Phosphocreatine promotes epigenetic reprogramming to facilitate glioblastoma growth through stabilizing BRD2.

Glioblastoma (GBM) exhibits profound metabolic plasticity for survival and therapeutic resistance, while the underlying mechanisms remain unclear. Here, we show that GBM stem cells (GSCs) reprogram the epigenetic landscape by producing substantial amounts of phosphocreatine (PCr). This production is attributed to the elevated transcription of brain-type creatine kinase (CKB), mediated by Zinc finger E-box binding homeobox 1 (ZEB1). PCr inhibits the poly-ubiquitination of the chromatin regulator bromodomain containing protein 2 (BRD2) by outcompeting the E3 ubiquitin ligase SPOP for BRD2 binding. Pharmacological disruption of PCr biosynthesis by cyclocreatine leads to BRD2 degradation and a decrease in its targets' transcription, which inhibits chromosome segregation and cell proliferation. Notably, cyclocreatine treatment significantly impedes tumor growth and sensitizes tumors to a BRD2 inhibitor in mouse GBM models without detectable side effects. These findings highlight that high production of PCr is a druggable metabolic feature of GBM and a promising therapeutic target for GBM treatment.

Evaluation of citrus pectin extraction methods: Synergistic enhancement of pectin's antioxidant capacity and gel properties through combined use of organic acids, ultrasonication, and microwaves.

The biological potency of pectin is intricately intertwined with its intricate molecular architecture. The fine structure of pectin is influenced by the extraction method, while the specific impact of these methods on the fine structure and the affected attributes thereof remains enigmatic. This study delves into the profound analysis of eight distinct extraction methods influence on the structure and biological activity of citrus peel pectin. The findings demonstrate that citric acid ultrasound-assisted microwave extraction yields pectin (PectinCA-US/MV) with higher viscosity and a dense, rigid chain. Pectin extracted with acetic acid ultrasound (PectinAA-US) and citric acid ultrasound (PectinCA-US) exhibits elevated galacturonic acid (GalA) levels and reduced D-galactose (Gal) content, enhancing antioxidant activity. Eight pectin-chitosan (CS) hydrogels, especially PectinCA-US/MV-CS, demonstrate commendable thermal stability, rheological properties, self-healing capability, and swelling behavior. This study characterizes citrus peel pectin properties from different extraction methods, laying a foundation for its application in food, pharmaceuticals, and industry.

Educational value of mixed reality combined with a three-dimensional printed model of aortic disease for vascular surgery in the standardized residency training of surgical residents in China: a case control study.

BACKGROUND: The simulated three-dimensional (3D) printed anatomical model of the aorta, which has become the norm in medical education, has poor authenticity, tactility, feasibility, and interactivity. Therefore, this study explored the educational value and effect of mixed reality (MR) combined with a 3D printed model of aortic disease in training surgical residents. METHOD: Fifty-one resident physicians who rotated in vascular surgery were selected and divided into traditional (27) and experimental (24) teaching groups using the random number table method. After undergoing the experimental and traditional training routines on aortic disease, both the groups took a theoretical test on aortic disease and an assessment of the simulation based on the Michigan Standard Simulation Experience Scale (MiSSES) template. Their scores and assessment results were compared. The study was conducted at the Department of Vascular Surgery of Peking University People's Hospital, Beijing, China. RESULTS: In the theoretical test on aortic disease, the experimental teaching group obtained higher mean total scores (79.0 ± 9.1 vs. 72.6 ± 7.5, P = 0.013) and higher scores in anatomy/ pathophysiology (30.8 ± 5.4 vs. 24.8 ± 5.8; P < 0.001) than the traditional teaching group. The differences in their scores in the differential diagnosis (25.8 ± 3.0 vs. 23.3 ± 4.9; P = 0.078) and treatment (22.5 ± 11.8 vs. 24.5 ± 8.2; P = 0.603) sessions were insignificant. The MR-assisted teaching stratified the vascular residents through the MiSSES survey. Overall, 95.8% residents (23/24) strongly or somewhat agreed that the MR was adequately realistic and the curriculum helped improve the ability to understanding aortic diseases. Further, 91.7% residents (22/24) strongly or somewhat agreed that the MR-assisted teaching was a good training tool for knowledge on aortic diseases. All residents responded with "Good" or "Outstanding" on the overall rating of the MR experience. CONCLUSIONS: MR combined with the 3D printed model helped residents understand and master aortic disease, particularly regarding anatomy and pathophysiology. Additionally, the realistic 3D printing and MR models improved the self-efficacy of residents in studying aortic diseases, thus greatly stimulating their enthusiasm and initiative to study.

Association of inflammation biomarkers with food cravings and appetite changes across the menstrual cycle.

IMPORTANCE: Premenstrual symptoms, including food cravings, are often a regular complaint among menstruating women. However, existing evidence regarding the biological mechanisms by which these food cravings occur remains unclear. Inflammation may play an essential role in the occurrence of these food cravings before menstruation. OBJECTIVE: The purpose of the present study was to examine the associations between inflammatory markers and the risk of moderate/severe food cravings while accounting for changes in hormone levels and stress across the menstrual cycle. DESIGN, SETTING, AND PARTICIPANTS: The BioCycle Study followed women (n = 259) aged 18-44 for two menstrual cycles. Food cravings (via questionnaire) were assessed up to four times per cycle. Each assessment corresponded to menses and mid-follicular, ovulation, and luteal phases of the menstrual cycle. A wide range of cytokine and chemokine levels (hsCRP, GCSF, GMCSF, IL-4, IL-6, RANTES, MIP1B, etc.) were assessed in blood samples collected at up to 8 visits per cycle, with visits timed using fertility monitors. MAIN OUTCOMES AND MEASURES: Cravings for chocolate, sweets, salty, and other foods, and changes in appetite were determined to estimate the odds of moderate or severe cravings. Associations between inflammatory markers and risk of reporting a moderate/severe craving symptom at each cycle visit was determined using weighted generalized linear models (e.g., marginal structural models). Models were adjusted for age, BMI, and race, as well as time-varying covariates such as estradiol, stress, leptin, and total energy intake, and accounted for repeated measures (i.e., multiple cycles per woman). Both inflammatory markers and reports of cravings were modeled to account for variation at each visit. RESULTS: An association between higher inflammatory biomarkers such as hsCRP, GCSF, GMCSF, IL-4, IL-6, RANTES, MIP, and increased risk of moderate/severe cravings were identified across the menstrual cycle all risk ratio>1, all CIs range 0.71-2.38. hsCRP retained statistical significance after false discovery rate correction with chocolate, sweet, and salty cravings, while GCSF, GMCSF, IL-6, and RANTES retained significance with chocolate and sweet cravings only. CONCLUSION: and Relevance: The results suggest a potential role of inflammation in food cravings and appetite changes across the menstrual cycle.

SAG treatment ameliorates memory impairment related to sleep loss by upregulating synaptic plasticity in adolescent mice.

Adequate sleep during the developmental stage can promote learning and memory functions because synaptic protein synthesis at primed synapses during sleep profoundly affects neurological function. The Sonic hedgehog (Shh) signaling pathway affects neuroplasticity in the hippocampus during the development of the central nervous system. In this study, the changes in synaptic morphology and function induced by sleep deprivation and the potential therapeutic effect of a Shh agonist (SAG) on these changes were investigated in adolescent mice. Adolescent mice were subjected to sleep deprivation for 20 hrs (2 pm to 10 am the next day) and were free to sleep for the remaining 4 hrs per day for 10 consecutive days. Sleep-deprived mice were injected with SAG (10 mg/kg body weight, i.p.) or saline (i.p.) every day 5 min before the onset of the 20 h sleep deprivation period. Chronic sleep deprivation impaired recognition and spatial memory, decreased the number of dendritic spines and mEPSCs of hippocampal CA1 pyramidal neurons, decreased the postsynaptic density, and reduced Shh and glioma-associated oncogene homolog 1 (Gli1) expression. SAG significantly protected against sleep deprivation-induced memory dysfunction, increased the CA1 pyramidal neuronal dendritic spine number and mEPSC frequency, and increased Gli1 expression. In conclusion, sleep deprivation induces memory impairment in adolescent mice, and SAG treatment prevents this impairment, probably by enhancing synaptic function in the hippocampal CA1 region.

Inhibition of macrophages inflammasome activation via autophagic degradation of HMGB1 by EGCG ameliorates HBV-induced liver injury and fibrosis.

Background: Liver fibrosis is a reversible wound-healing response that can lead to end-stage liver diseases without effective treatment, in which HBV infection is a major cause. However, the underlying mechanisms for the development of HBV-induced fibrosis remains elusive, and efficacious therapies for this disease are still lacking. In present investigation, we investigated the effect and mechanism of green tea polyphenol epigallocatechin-3-gallate (EGCG) on HBV-induced liver injury and fibrosis. Methods: The effect of EGCG on liver fibrosis was examined in a recombinant cccDNA (rcccDNA) chronic HBV mouse model by immunohistochemical staining, Sirius red and Masson's trichrome staining. The functional relevance between high mobility group box 1 (HMGB1) and inflammasome activation and the role of EGCG in it were analyzed by Western blotting. The effect of EGCG on autophagic flux was determined by Western blotting and flow cytometric analysis. Results: EGCG treatment efficiently was found to alleviate HBV-induced liver injury and fibrosis in a recombinant cccDNA (rcccDNA) chronic HBV mouse model, a proven suitable research platform for HBV-induced fibrosis. Mechanistically, EGCG was revealed to repress the activation of macrophage NLRP3 inflammasome, a critical trigger of HBV-induced liver fibrosis. Further study revealed that EGCG suppressed macrophage inflammasome through downregulating the level of extracellular HMGB1. Furthermore, our data demonstrated that EGCG treatment downregulated the levels of extracellular HMGB1 through activating autophagic degradation of cytoplasmic HMGB1 in hepatocytes. Accordingly, autophagy blockade was revealed to significantly reverse EGCG-mediated inhibition on extracellular HMGB1-activated macrophage inflammasome and thus suppress the therapeutic effect of EGCG on HBV-induced liver injury and fibrosis. Conclusion: EGCG ameliorates HBV-induced liver injury and fibrosis via autophagic degradation of cytoplasmic HMGB1 and the subsequent suppression of macrophage inflammasome activation. These data provided a new pathogenic mechanism for HBV-induced liver fibrosis involving the extracellular HMGB1-mediated macrophage inflammasome activation, and also suggested EGCG administration as a promising therapeutic strategy for this disease.

Can Patients with HER2-Low Breast Cancer Benefit from Anti-HER2 Therapies? A Review.

Breast cancer (BC) poses a severe threat to the health of women worldwide. Currently, different therapeutic regimens are used for BC according to the pathological classification of HER2-positive or HER2-negative. Clinical reports of HER2-low expression indicate that the condition is HER2-negative, which was ineligible for HER2-targeted therapy. In contrast to HER2-zero tumors, however, HER2-low BC is a heterogeneous disease with unique genetic characteristics, prognoses, and different therapeutic responses. Clinical efficacy has been demonstrated by numerous potent and innovative anti-HER2 medications, particularly antibody-drug conjugates (ADCs). Certain ADCs, including T-DXd, have demonstrated good efficacy in some trials either used alone or in conjunction with other medications. To enhance outcomes in individuals with HER2-low BC, immunotherapy and other treatments are frequently combined with HER2-targeted therapy. There are also alternative strategies that target both HER2 and HER3 or other antigenic sites. We hope more individuals with HER2-low BC will benefit from more precise treatment regimens in the future. This article provides a review of existing research and clinical trials.

Endovascular Repair for Abdominal Aortic Aneurysm in Mainland China: A Systematic Review and Meta-Analysis.

BACKGROUND: The aim of this study was to evaluate the safety, applicability, and outcomes of the endovascular aneurysm repair (EVAR) technique for patients in mainland China with abdominal aortic aneurysm (AAA) by performing a systematic review. METHODS: We conducted a systematic search using the PubMed, Embase, Chinese National Knowledge Infrastructure, and Chinese Biomedical databases to identify Chinese studies on the management of AAAs using the EVAR technique published in English between January 2000 and December 2020. Two independent observers selected studies for inclusion in the study, assessed the methodological quality of the included studies, and extracted the data. The included studies investigated the clinical outcomes and postprocedural complications of using EVAR techniques. RESULTS: Sixteen studies reported a total of 3,024 AAA patients. The follow-up period ranged from 1 to 133 months. The mean follow-up time was 38.5 months, the mean age was 69.2 years, and the mean aneurysm diameter was 56.1 mm. The pooled technical success rate was 95% (95% confidence interval [CI]: 92-96%). The endoleak rate was 7% (95% CI: 6-8%). The rate of endoleak requiring reintervention was 3% (95% CI: 3-4%). The 30-day morbidity rate was 9% (95% CI: 6-14%). The 30-day mortality rate was 2% (95% CI: 1-3%). The follow-up mortality was 5% (95% CI: 3-8%). CONCLUSIONS: The results of the study showed that using the EVAR technique for treating patients in mainland China with AAAs produced encouraging mid-term outcomes. Long-term outcomes should be examined in future research.

Changes in the Relative Displacement between the Supra-Aortic Branches with Age.

BACKGROUND: This study aimed to determine the normal ranges for the height and deflection angle of the aortic arch and the displacement distances between the supra-aortic branches in relation to age, sex, body mass index (BMI), and body surface area (BSA) in adults without aortic disease using non-contrast chest computed tomography (CT). METHODS: The CT scans of 700 patients were analyzed. We measured the height and deflection angle of the aortic arch based on the lower level of the pulmonary artery bifurcation. The displacement distances between the supra-aortic branches in the coronal and sagittal planes were measured, and the deflection angles between these branches were calculated. Multiple linear regression analysis was used to investigate the associations of age, sex, BMI, and BSA with these aortic arch parameters. RESULTS: The height of the aortic arch was significantly higher (74 ± 15 mm vs. 65 ± 12 mm, P < 0.001) and the left-posterior displacement distance of the left subclavian artery (LSA) to the innominate artery (IA) was greater in men than that in women. The height and deflection angle of the aortic arch increased with age. The distance by which the LSA was shifted to the left posterior of the left common carotid artery and to the left of the IA increased with age. CONCLUSIONS: The normal aging process is accompanied by morphological changes in the aortic arch and relative displacement between the supra-aortic branches. Identifying these parameters could lead to a comprehensive understanding of the anatomy and morphology of the aortic arch.

Symptoms and Comorbidities Differ Based on Race and Weight Status in Persons with HIV in the Northern United States: a Cross-Sectional Study.

BACKGROUND: Persons with HIV (PWHIV) on highly active antiretroviral treatments (HAART) may require specialized care based on health and demographic indicators. This study investigated the association of comorbidities, race, weight status, and gastrointestinal (GI) and cardiovascular (CV) symptoms among PWHIV. METHODS: The Symptom Checklist, Co-Morbidity Questionnaire, and Sociodemographic Questionnaire were used to assess weight status and GI and CV symptoms among 283 PWHIV. Data were analyzed using latent class analysis on John's Macintosh Project 13 Platform. RESULTS: Participants were majority Black (50%), 69% male, and 35% AIDS diagnosed. Ages were 25 to 66. Clusters included least symptomatic status, weight gain, and weight loss by Black and non-Black participants. The non-Black weight gain cluster reported a higher incidence of AIDS (70.6% vs 38.2%), nausea (70.6% vs 17.6%), diarrhea (70.6% vs 26.5%), and shortness of breath (58.8% vs 20.6%) compared to the Black weight gain cluster. The Black weight loss cluster reported a higher incidence of CV symptoms such as chest palpitations (42.2% vs 2.7%), chest pain (44.4% vs 8.1%), and shortness of breath (73.3% vs 35.1%). Moreover, the Black weight loss cluster reported a higher incidence of all GI symptoms with the most prominent being diarrhea (71.1% vs 48.6%) compared to the non-Black weight loss cluster. CONCLUSIONS: The existing racial disparities in health-related quality of life for PWHIV may be improved through precision health and nutrition modifications. Continued research is needed investigating differential health outcomes among PWHIV on HAART. CLINICAL TRIAL REGISTRATION NUMBER: NCT00222716. Registered 22 September 2005. Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT00222716?term=NCT00222716&draw=2&rank=1.

Glioblastoma stem cell-specific histamine secretion drives pro-angiogenic tumor microenvironment remodeling.

The communication between glioblastoma stem cells (GSCs) and the surrounding microenvironment is a prominent feature accounting for the aggressive biology of glioblastoma multiforme (GBM). However, the mechanisms by which GSCs proactively drive interactions with microenvironment is not well understood. In this study, we interrogated metabolites that are preferentially secreted from GSCs and found that GSCs produce and secrete histamine to shape a pro-angiogenic tumor microenvironment. This histamine-producing ability is attributed to H3K4me3 modification-activated histidine decarboxylase (HDC) transcription via MYC. Notably, HDC is highly expressed in GBM, which is associated with poor survival of these patients. GSC-secreted histamine activates endothelial cells by triggering a histamine H1 receptor (H1R)-Ca2+-NF-κB axis, thereby promoting angiogenesis and GBM progression. Importantly, pharmacological blockage of H1R using antihistamines impedes the growth of GBM xenografts in mice. Our findings establish that GSC-specific metabolite secretion remodels the tumor microenvironment and highlight histamine targeting as a potential strategy for GBM therapy.

Permeation Characteristics of CH4 in PVDF with Crude Oil-Containing.

The liner of reinforced thermoplastic composite pipes (RTPs) used for oil and gas gathering and transportation experienced blister failure due to gas permeation. Few reports have appeared on the problem of gas permeation in thermoplastics with absorbed crude oil. Accordingly, the permeability of CH4 in polyvinylidene fluoride (PVDF) containing crude oil was studied at the normal service conditions by molecular simulations. The results showed that the solubility coefficients of CH4 in PVDF containing crude oil were much lower than those in pure PVDF. It can be concluded that the crude oil molecules absorbed into PVDF occupied certain adsorption sites, resulting in a decrease in the adsorption capacity of CH4 molecules in PVDF. The diffusion coefficients of CH4 in oil-containing PVDF were significantly greater than in PVDF. This is because the absorption of oil molecules leads to the volume swelling of PVDF and then increases the free volume for diffusion. The permeation process showed that CH4 molecules were selective-aggregate adsorbed in the region with low potential energy in oil-containing PVDF firstly, and then they vibrated within the holes of PVDF containing oil in most cases and jumped into the neighboring holes at high temperatures and pressures.

Inhibition of endoplasmic reticulum stress and the downstream pathways protects CD4+ T cells against apoptosis and immune dysregulation in sepsis.

Immunosuppression mediated by CD4+ T cell apoptosis and dysfunction is a key factor in promoting the progression of sepsis. Endoplasmic reticulum (ER) stress participates in the apoptosis and dysfunction of immune cells. We aimed to investigate the role of ER stress inhibition in CD4+ T cells in both in vitro and in vivo models of sepsis. In vitro model of sepsis was established with lipopolysaccharide (LPS) and the rat model of sepsis was established using cecal ligation and puncture (CLP). After the LPS treatment or CLP, ER stress inhibitors including 4-PBA, SNJ-1945, and SP600125 were used to treat cells or rats, and the CD4+ T cells were obtained by magnetic bead sorting. The effects of ER stress inhibitors on apoptosis and the function of CD4+ T cells were evaluated. After the LPS stimulation or CLP, the levels of ER stress and downstream markers (PERK, eIF2α, IRE-1α, ATF6, ATF4, XBP-1 s, GRP78, CHOP, and p-JNK) were increased in CD4+ T cells at the beginning of sepsis. Meanwhile, the number of apoptotic CD4+ T cells markedly increased. In addition, sepsis impaired the function of CD4+ T cells, manifested by the increased population of Th1, Th2, Th17, and Treg, as well as the production of TNF-α, interleukin (IL)-6, IL-4, and IL-10. However, inhibitors of ER stress, JNK, and calpain all decreased the induction of Th1 and Th17, enhanced the increase of Th2 and Treg, decreased the production of TNF-α and IL-6, and enhanced the production of IL-4 and IL-10. Our findings indicate that ER stress inhibitors may play a protective role by reducing CD4+ T cell apoptosis and maintaining CD4+ T cell function, which may be useful for enhancing the immune function and poor prognosis of patients with sepsis.

Papillary renal neoplasm with reverse polarity with a favorable prognosis should be separated from papillary renal cell carcinoma.

Papillary renal neoplasm with reverse polarity (PRNRP) is a newly documented renal entity with an easily recognizable morphology, distinct immunohistochemical profiles, and frequent KRAS mutations. The latest practice guidelines regard PRNRP as a subtype of papillary renal cell carcinoma due to the documented chromosomal alterations of 7, 17, and Y. This study included 20 patients with PRNRP and 30 patients with PRCC. Statistically significant differences were observed in size, WHO/ISUP grade, macrophages in the papillae, reverse polarity, CK7, basolateral positivity for Claudin7, GATA3 expression, KRAS mutation, and chromosomal alterations. No adverse events such as perinephric invasion, lymphovascular invasion, sarcomatoid of rhabdoid differentiation, metastasis, or recurrence were found in PRNRP. However, PRCC can cause these adverse events. Basolateral positivity for Claudin7 together with GATA3 expression indicated distal tubule derivation of PRNRP. KRAS mutations were detected in 89% (16/18) of PRNRP. No KRAS mutations were detected in PRCC. Six patients with PRNRP had one chromosomal alteration and the other 12 had no chromosomal alterations. However, only four patients with PRCC showed no chromosomal alterations. Eighteen patients had two or three chromosomal alterations. PRCC can metastasize, recur, and even cause death, whereas PRNRP has a favorable prognosis. We recommend that PRNRP should be separated from PRCC and partial nephrectomy is more suitable for PRNRP.

Molecular Simulation on Permeation Behavior of CH4/CO2/H2S Mixture Gas in PVDF at Service Conditions.

Reinforced thermoplastic composite pipes (RTPs) have been widely used for oil and gas gathering and transportation. Polyvinylidene fluoride (PVDF) has the greatest potential as a thermoplastic liner of RTPs due to its excellent thermal and mechanical properties. However, permeation of gases is inevitable in the thermoplastic liner, which may lead to blister failure of the liner and damage the safe operation of the RTPs. In order to clarify the permeation behavior and obtain the permeation mechanism of the mixture gas (CH4/CO2/H2S) in PVDF at the normal service conditions, molecular simulations were carried out by combining the Grand Canonical Monte Carlo (GCMC) method and the Molecular Dynamics (MD) method. The simulated results showed that the solubility coefficients of gases increased with the decrease in temperature and the increase in pressure. The adsorption isotherms of all gases were consistent with the Langmuir model. The order of the adsorption concentration for different gases was H2S > CO2> CH4. The isosteric heats of gases at all the actual service conditions were much less than 42 kJ/mol, which indicated that the adsorption for all the gases belonged to the physical adsorption. Both of the diffusion and permeation coefficients increased with the increase in temperature and pressure. The diffusion belonged to Einstein diffusion and the diffusion coefficients of each gas followed the order of CH4 > CO2 > H2S. During the permeation process, the adsorption of gas molecules in PVDF exhibited selective aggregation, and most of them were adsorbed in the low potential energy region of PVDF cell. The mixed-gas molecules vibrated within the hole of PVDF at relatively low temperature and pressure. As the temperature and pressure increase, the gas molecules jumped into the neighboring holes occasionally and then dwelled in the holes, moving around their equilibrium positions.

Mid-term Efficacy and Safety of Drug-coated Balloon versus Nitinol Bare Metal Stent for Primary Lesions in Femoropopliteal Artery Disease.

OBJECTIVES: To compare drug-coated balloon (DCB) and bare metal stent (BMS) for primary lesions in femoropopliteal artery disease in Chinese population and to make subgroup analysis between the groups. METHODS: Patients with primary lesions who underwent BMS or DCB treatment of a single tertiary vascular center were included and followed up for 24 months. Clinical and anatomic status were reported using the criteria recommended by the Society for Vascular Surgery. The primary endpoint included primary patency, clinically target limb revascularization, composite safety endpoint and all-cause death over 24 months assessed by Kaplan-Meier. Secondary endpoints included technical success rate and stent-related complications. RESULTS: A total of 284 patients with 324 limbs were pooled into analysis and most of the baseline characteristics did not show significant difference. A total of 74 in BMS group and 71 in DCB group were claudicants while 83 in BMS group and 56 in DCB group suffered from chronic limb threatening ischemia (CLTI). The mean cumulative lesion length was 18.7 ± 9.8cm in BMS group while 17.2 ± 10.3cm in DCB group. Kaplan-Meier estimates of primary patency were 75.3% and 80.9% for BMS and DCB groups at 12 months while decreased to 63.9% and 70.2% at 24 months (log-rank P = 0.167), respectively. Freedom from clinically driven target limb revascularization was 86.8% and 92.7% for BMS and DCB groups at 12 months while dropped to 82.5% and 85.9% at 24 months (log-rank P = 0.342). Estimates of primary patency between BMS and DCB group did not show significant difference on lesions with poor runoff (58.8% vs. 67.3%, log-rank P = 0.127), severe calcification (64.5% vs. 69.4%, log-rank P = 0.525) and popliteal artery involvement (59.3% vs. 60.3%, log-rank P = 0.695) at 24 months. The overall survival (92.6% for BMS, 90.3% for DCB, log-rank P = 0.391) and freedom from composite safety endpoint (79.3% for BMS, 79.2% for DCB, log-rank P = 0.941) showed no significant difference at 24 months. CONCLUSIONS: Over the 24 month follow-up, BMS and DCB showed equivalent efficacy and safety outcomes for primary femoropopliteal artery disease, which indicated the reduction of permanent metallic implant insertion might be possible.

Tumor-Specificity Growth Factor Combined with Tumor Markers in Nuclear Medicine Imaging to Identify Prostate Cancer Osteonosus.

Objective: This study has explored the application value of malignant tumor SPE growth factor (TSGF) combined with tumor markers (TM) (TSGF + TM) in nuclear medicine imaging to identify prostate cancer osteonosus (PCO). Methods: A retrospective analysis for 70 patients with prostate cancer and bone disease admitted to our hospital was performed, 30 healthy persons in the same period were selected as the control group, and the advantages and disadvantages of various examinations were analyzed. All patients were diagnosed with PET whole body bone imaging. Suspicious lesions could be examined by MRI or CT. According to the results of imaging examination, patients were divided into 40 cases of malignant prostate cancer and 30 cases of benign prostate cancer. All the patients underwent 18F-FDG-PET imaging, alpha-fetoprotein (AFP), and TSGF + TM determination. The case diagnosis results were compared and analyzed, and the sensitivity (SEN), specificity (SPE), and accuracy (ACC) of various detection methods were calculated. The SEN, SPE, and ACC of positron emission tomography (PET) were 90.9%, 57.8%, and 81.2%, respectively; those of TM were 79.2%, 94.6%, and 69.8%, respectively; and those of TSGF + TM were 95.9%, 100%, and 97.3%, respectively. The accuracy of combined diagnosis of tumors can reach 100%. The AFP and TSGF levels of serum TM were compared and analyzed, and it was found that the benign lesion group and the malignant lesion group showed significant increases compared with the control group, and the difference between the malignant lesion group and the control group was obvious (P < 0.05). SGF combined with TM could obtain a more definite diagnosis in PCO. Conclusion: TSGF + TM combined with 18F-FDG-PET imaging showed important clinical value to diagnose the PCO. The imaging accuracy of TSGF + TM combined with 18F-FDG-PET is 97.3%, and the specificity of tumor diagnosis is 100%. Therefore, the TSGF + TM applied in medical imaging and identification of PCO was worthy of clinical promotion.

[The prevention and management of approach-specific complications of abdominal aortic balloon occlusion in pelvic and sacral surgery].

Objective: To investigate the causes,prevention and treatment of femoral artery puncture related complications caused by the application of resuscitative endovascular balloon occlusion of the aorta (REBOA) in the resection of pelvic and sacral tumors. Methods: Clinical data of 23 patients with femoral artery puncture related complications who received REBOA in the resection of pelvic and sacral tumors from August 2010 to August 2018 at the Musculoskeletal Tumor Center,Peking University People's Hospital were retrospectively analyzed.There were 8 males and 15 females,with the an age of (37.0±16.2) years (range:15 to 65 years).Arterial access via the Seldinger technique for REBOA was obtained in the right common femoral artery of 18 cases,and in the left of 6 cases.An arterial sheath with a diameter of 11 to 12 F(1 F≈0.33 mm) was used for the patient.The occurrence and treatment of postoperative complications were analyzed. Results: Acute femoral arterial thrombosis occurred in 18 patients,which was managed by open repair 48 hours postoperatively.Among the 349 patients admitted before 2015 who received hemostasis by compression after femoral artery sheath removal,12 patients (3.4%) developed acute femoral artery thrombosis.While the 476 patients admitted after 2015 who used a vascular stapler to close the femoral artery wound,6 patients (1.3%) developed acute femoral artery thrombosis.One case of retroperitoneal hematoma and 1 case of femoral pseudoaneurysm were found and surgically fixed.Postoperative follow-up was (40±18) months (range:13 to 108 months).Three cases with chronic lower extremity ischemia were confirmed by Doppler ultrasonography during 1 to 5 years follow-up.Two of them had minimal symptoms and denied further treatment,while the other one received femoral-femoral artery bypass surgery to restore distal flow for pain and numbness relief. Conclusions: Acute femoral arterial thrombosis was the most common femoral artery puncture.Technique refinement of REBOA,the use of percutaneous suture device and close follow-up can reduce the approach-specific complications,and help to detect and treat the complications timely,which may popularize the clinical application of REBOA.

Comprehensive Metabolomic Analysis Reveals Dynamic Metabolic Reprogramming in Hep3B Cells with Aflatoxin B1 Exposure.

Hepatitis B virus (HBV) infection and aflatoxin B1 (AFB1) exposure have been recognized as independent risk factors for the occurrence and development of hepatocellular carcinoma (HCC), but their combined impacts and the potential metabolic mechanisms remain poorly characterized. Here, a comprehensive non-targeted metabolomic study was performed following AFB1 exposed to Hep3B cells at two different doses: 16 µM and 32 µM. The metabolites were identified and quantified by an ultra-performance liquid chromatography-mass spectrometry (UPLC-MS)-based strategy. A total of 2679 metabolites were identified, and 392 differential metabolites were quantified among three groups. Pathway analysis indicated that dynamic metabolic reprogramming was induced by AFB1 and various pathways changed significantly, including purine and pyrimidine metabolism, hexosamine pathway and sialylation, fatty acid synthesis and oxidation, glycerophospholipid metabolism, tricarboxylic acid (TCA) cycle, glycolysis, and amino acid metabolism. To the best of our knowledge, the alteration of purine and pyrimidine metabolism and decrease of hexosamine pathways and sialylation with AFB1 exposure have not been reported. The results indicated that our metabolomic strategy is powerful to investigate the metabolome change of any stimulates due to its high sensitivity, high resolution, rapid separation, and good metabolome coverage. Besides, these findings provide an overview of the metabolic mechanisms of the AFB1 combined with HBV and new insight into the toxicological mechanism of AFB1. Thus, targeting these metabolic pathways may be an approach to prevent carcinogen-induced cancer, and these findings may provide potential drug targets for therapeutic intervention.