A causal analysis of the relationship between exposure to sunlight and colorectal cancer risk: A Mendelian randomization study.

Several observational studies have found that exposure to sunlight reduces the risk of colorectal cancer (CRC). However, sun exposure remains ambiguous in its relationship to CRC. We carried out a Mendelian randomization (MR) study to explore the potential associations between them. We examined the exposure to sunlight summary statistics of the UK Biobank Consortium using a 2-sample MR analysis. Using data from the FinnGen consortium, we derived summary statistics for CRC. We conducted our analysis with various methods, incorporating inverse variance weighted (IVW) along with 4 other approaches. A Cochran Q statistic was used to measure the heterogeneity of instrumental variables (IVs). We screened 133 single nucleotide polymorphisms (SNPs) (time spent outdoors in summer), 41 SNPs (time spent outdoors in winter), and 35 SNPs (frequency of solarium/sunlamp use) representing sunlight exposure for MR analysis. All selected SNPs had an F-statistic >20, indicating that IVs did not weakly bias the results. The summer outdoor activity trait exhibited significant heterogeneity (Cochran Q statistic = 183.795, P = .002 < 0.05), but we found no horizontal polymorphisms or significant heterogeneity for the other exposure traits. According to IVW estimates, no causal association exists between time spent outdoors in summer and CRC (Odds Ratio, OR = 0.735, 95% confidence interval, CI = 0.494-1.017, P = .128 > 0.017). No causal relationship existed between time spent outdoors in winter and CRC, as indicated by Bonferroni-corrected adjusted p-values. The OR was 0.877 with a 95% CI of 0.334-2.299, and the P value was .789, more significant than the significance threshold of 0.017. The solarium/sunlamp use frequency was not associated with CRC (OR = 1.567, 95%CI = 0.243-10.119, P = .637 > .017). Also, an IVW with random effects was applied to determine the causal relationship between summer outdoor time and CRC. No causal association between summer outdoor time and CRC was found (OR = 0.735, 95% CI = 0.494-1.017, P = .128 > .017). Additionally, 4 additional analyses yielded similar results. The findings of our study suggest that exposure to sunlight may reduce CRC risk, but the causal relationship remains unsolved. There is no evidence to suggest that exposure to sunlight prevents CRC. Randomized, controlled trials are needed to determine whether sunlight exposure protects against CRC.

Safety and efficacy of low-dose esketamine in laparoscopic cholecystectomy: a prospective, double-blind randomized controlled trial.

BACKGROUND: Esketamine, recognized for its analgesic, sedative, and anti-inflammatory qualities, is integral in multimodal analgesia. However, the potential opioid-sparing effects of intravenous esketamine, along with its impact on inflammatory responses, and cognitive function during laparoscopic surgery, remain unexplored. METHODS: In this study, 90 patients scheduled for laparoscopic cholecystectomy were equally randomized into three groups: a normal saline control group (NS), a low-dose esketamine group (LS) and a high-dose esketamine group (HS). Subsequently, we monitored several parameters: hemodynamics, levels of stress and inflammatory responses, intraoperative doses of sufentanil, remifentanil, and propofol, and 24-hour postoperative sufentanil requirements. We also evaluated alterations in cognitive function, perioperative indicators, and potential adverse reactions among the three groups. RESULTS: Compared to their levels 5 minutes prior to anesthesia (T0) and 30 minutes post-operation (T4), the NS group exhibited a more significant decrease in Mean Arterial Pressure (MAP) and Heart Rate (HR) at various time intervals: 5 minutes after the skin incision (T1), 30 minutes post-incision (T2), and at the conclusion of the operation (T3), compared to the LS and HS groups(P < 0.05). Furthermore, the NS group exhibited a greater increase in levels of adrenaline (AD), noradrenaline (NE), endothelin (ET), C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) at T1, T2, and T3, more so than the other two groups(P < 0.05). 24 hours after the surgery, patients in the LS group and HS group had significantly higher Montreal Cognitive Assessment (MoCA) scores than those in the NS group(P < 0.05). The LS and HS groups required lower doses of propofol, remifentanil, and sufentanil during surgery (P < 0.05), experienced shorter postoperative recovery times, and had lower incidences of nausea, vomiting, and respiratory depression compared to the NS group (P < 0.05). CONCLUSION: The administration of low-dose esketamine has been shown to be safe, effective, and dependable in the context of laparoscopic gallbladder surgery. It has the capacity to stabilize hemodynamic responses, ameliorate both stress and inflammatory reactions from surgery, and hastens anesthesia recovery. Furthermore, it fosters the restoration of postoperative cognitive function. Notably, when combined with nalbuphine, it exhibits opioid-sparing effects, reducing postoperative adverse outcomes. TRIAL REGISTRATION: The trial is registered with the China Clinical Trials Registry Registration Number: ChiCTR2300067596. Retrospectively registered (date of registration: 12/01/2023).

Development of a certified reference material for accurate determination of the leaching of Pb and Zn in solid waste.

Certified reference materials (CRMs) with high accuracy and traceability play a significant role in the calibration of equipment and validation of analytical methods. However, there is still a lack of suitable solid waste CRMs for quality assurance and quality control. Thus, a CRM (GBW(E)085538) was developed for accurate determination and reliable measurement of the leaching of Pb and Zn in solid waste according to the requirements of ISO 17034 and the recommendations of ISO Guide 35. This study describes the steps performed for the development of the CRM. These steps include material preparation, homogeneity, and stability during transport and storage, assignment of certified values, and their uncertainties. The material was dried, ground, sieved and well-mixed, and the final bulk material was bottled in 1 kg portions. Analytical techniques like inductively coupled plasma-mass spectrometry (ICP-MS), inductively coupled plasma-optical emission spectrometry (ICP-OES), and flame atomic absorption spectrometry (AAS) have been used for the characterization of property values. Concurrently, an inter-laboratory comparison study involving 9 qualified laboratories was implemented to support the certification study. The certified values of Pb and Zn were (4.66 ± 0.21) mg/L and (2.95 ± 0.14) mg/L with 7-month stability.

Multiple Aneurysms of the Subclavian-Axillary, Abdominal Aortoiliac, Lower Extremity, and Coronary Arteries in A Pediatric Patient of Takayasu Arteritis.

Takayasu arteritis is a chronic inflammatory vasculitis affecting mainly the aorta and its branches. Stenosis and occlusion of the involved vessels usually develop; however, their dilation and aneurysmal formation are extremely rare. Although aneurysmal disease has been reported in adults with Takayasu arteritis, it is a rare entity in children. The present report described an 11-year-old male found to have the subclavian-axillary, abdominal aortoiliac, lower extremity artery aneurysms with mural thrombi. Aneurysms were also found at the proximal and middle segments of the right coronary artery. The patient was conservatively treated with corticosteroid in addition to antiplatelet and anticoagulation agents.

Dysbiosis of lung commensal bacteria in the process of lung epithelial-mesenchymal transition in mice with silicosis / 中国职业医学

@#Objective - To investigate the effect of lung flora dysbiosis on the process of pulmonary fibrosis and lung epithelial （ ） Methods - mesenchymal transition EMT in mice with silicosis. Male C57BL/6 mice of specific pathogen free grade were ， ， ， （ ） randomly divided into the blank control group silicosis model group solvent control group vancomycin VM + ampicillin （ ） ， （ ） （ ） ， AMP group metronidazole MNZ + neomycin NEO group and mixed treatment group 12 mice in each group. Except for ， ， the blank control group which was given 20.0 µL of 0.9% NaCl solution the other five groups of mice were dosed with 20.0 µL of silica dust suspension at a mass concentration of 250.0 g/L using a single tracheal drip to establish the silicosis mouse model. ： The intranasal drip method was used to treat silicosis mice in each group as following mice in the solvent control group were - ； ； given double distilled water mice in the VM+AMP group were given VM at a mass concentration of 0.5 g/L and AMP at 1.0 g/L ； mice in the MNZ+NEO group were given MNZ at a mass concentration of 1.0 g/L and NEO at 1.0 g/L mice in the mixed ， treatment group were given the same doses of the four antibiotics mentioned above all in a drip volume of 50.0 µL. Silicosis ， ， mice were treated seven days and half an hour before silica dusting and 7 14 and 21 days after silica dusting. Mouse lungtissue was collected aseptically 28 days after silica dusting. Hematoxylin eosin and Masson trichrome staining methods were - used to observe the pathological changes. Western blotting was used to detect the relative protein expression of α smooth muscle （ - ）， - （ - ） （ ） actin α SMA E cadherin E CAD and vimentin VIM . Immunohistochemistry was used to detect the relative expression of - - E CAD and VIM. Real time fluorescence quantitative polymerase chain reaction was used to detect the expression levels of （Col1a2） Results collagen type Ⅰ alpha 2 mRNA in lung tissues. The histopathological results showed that the alveoli of the ， blank control group were thin and structurally intact with few surrounding infiltrating inflammatory cells and no abnormal ， distribution of collagen fibers. The alveoli of the silicosis model group were structurally disorganized with a large number of ， ， infiltrating inflammatory cells thickened alveolar walls and cellular fibrous nodules with abundant blue collagen deposit. In the ， ， VM+AMP group MNZ+NEO group and the mixed treatment group the inflammation and fibrosis were reduced with diferent degrees in the lung tissues compared to the silicosis model group and the solvent control group. The relative expression levels of - ， Col1a2 α SMA VIM protein and mRNA in lung tissues of mice in the silicosis model group were higher than those in the blank （ P ）， -CAD control group all <0.05 and the relative expression levels of E protein were lower than those in the blank control （P ） - ， Col1a2 group <0.05 . The relative expression levels of α SMA VIM protein and mRNA in lung tissues of mice in the MNZ+ （ P ）， -CAD NEO group and the mixed treatment group were lower all <0.05 and the relative expression levels of E protein were （P ）， Conclusion higher <0.05 when compared with the silicosis model group and the solvent control group. Pulmonary fibrosis ， - was reduced in silicosis mice with interventions in lung flora where anaerobic and gram negative bacteria affected pulmonary fibrosis and dysbiosis of the lung flora affected pulmonary EMT.

Remodeling of Aortic Configuration and Abdominal Aortic Branch Perfusion After Endovascular Repair of Acute Type B Aortic Dissection: A Computed Tomographic Angiography Follow-Up.

Background: Thoracic endovascular aortic repair (TEVAR) for type B aortic dissection (TBAD) induces false lumen (FL) thrombosis, promotes favorable aortic remodeling, and makes an impact on abdominal aortic branch perfusion patterns. However, little is known about the long-term fate of aortic remodeling and abdominal aortic branch perfusion after TEVAR for TBAD and the effect of FL thrombosis status on these changes. Materials and methods: Between January 2014 and May 2021, 59 enrolled patients with acute TBAD were treated with TEVAR and had post-operative or follow-up images. Pre-operative, post-operative, and latest follow-up CT angiography (CTA) data were analyzed for the largest diameter of true lumen (TL), FL, and transaorta and for the FL thrombosis status on the stented thoracic aorta, unstented thoracic aorta, and abdominal aorta. Abdominal aorta perfusion patterns were characterized. Results: The mean follow-up period was 17.1 months. In the stented thoracic aorta, average TL diameters increased, average FL diameters decreased, and average transaortic diameters did not change; 82.6% of the patients had either a stable or shrinking transaortic size and 87% of the patients achieved total FL thrombosis. In the unstented thoracic aorta, average TL diameters increased, transaortic growth and no changes occurred in 39.1 and 45.7% of the patients, respectively, and complete FL thrombosis was present in 50% of the patients. In the abdominal aorta, average FL and transaortic diameters increased, aorta was expanded in 52.2% of the patients, and FL remained patent in 65.2% of the patients. Of the 354 branches, 37 branches (10.5%) exhibited changes in perfusion patterns, 22 branches (6.2%) demonstrated an increased TL perfusion, and 15 branches (4.2%) had an increased FL contribution. Compared with patent or partially thrombosed FL, complete FL thrombosis was accompanied by a bigger decrease in FL diameters, a larger increase in TL diameters, and a higher percentage of abdominal branch TL perfusion. Conclusions: In majority of the patients, TEVAR stabilized the size of the stented thoracic aorta, namely TL expansion and FL obliteration. However, abdominal aortic FL remained patent FL, and it was expanded with the resultant transaortic growth over a long follow-up period. Abdominal aortic branch perfusion patterns remained largely stable after TEVAR. The failure to achieve FL thrombosis negatively affects the remodeling of a contagious abdominal aortic dissection.

Probiotic Interventions Alleviate Food Allergy Symptoms Correlated With Cesarean Section: A Murine Model.

Delivery by cesarean section (CS) is linked to an increased incidence of food allergies in children and affects early gut microbiota colonization. Furthermore, emerging evidence has connected disordered intestinal microbiota to food allergies. Here, we investigated the impact of CS on a rat model for food allergy to ovalbumin (OVA). Rats delivered by CS were found to be more responsive to OVA sensitization than vaginally born ones, displaying a greater reduction in rectal temperature upon challenge, worse diarrhea, and higher levels of OVA-specific antibodies and histamine. 16S rRNA sequencing of feces revealed reduced levels of Lactobacillus and Bifidobacterium in the CS rats. Preventative supplementation with a probiotic combination containing Lactobacillus and Bifidobacterium could protect CS rats against an allergic response to OVA, indicating that the microbiota dysbiosis contributes to CS-related response. Additionally, probiotic intervention early in life might help to rebuild aberrant Th2 responses and tight junction proteins, both of which have been linked to CS-related high allergic reactions. Taken together, this study shows that disordered intestinal microbiota plays an essential role in the pathogenesis of food allergy mediated by CS. More importantly, interventions that modulate the microbiota composition in early life are therapeutically relevant for CS-related food allergies.

Complete genome sequencing of Peyer's patches-derived Lactobacillus taiwanensis CLG01, a potential probiotic with antibacterial and immunomodulatory activity.

BACKGROUND: The genus Lactobacillus is an important component of the gastrointestinal tract of human and animals and commonly considered as probiotic. L. taiwanensis has long been proposed to be a probiotic whereas understanding on this species is still in its infancy. Genomic information of L. taiwanensis is fairly limited. Extensive characterization of its beneficial traits is needed. RESULTS: A new strain CLG01 of L. taiwanensis was isolated from mouse Peyer's patches. We established its probiotic profile through in vitro experiments. Complete genome of this strain was also sequenced and analyzed. L. taiwanensis CLG01 showed robust tolerance to acid and a degree of tolerance to bile salt with a promising antibacterial activity against a broad spectrum of pathogenic bacteria. In vitro treatment of mouse RAW 264.7 macrophage cells with heat-killed bacteria and bacterial supernatant of L. taiwanensis CLG01 resulted in enhancement of immune responses and upregulated expression of TNF-α and IL-6. The strain CLG01 also increased the IL-10 production of macrophages when co-treated with lipopolysaccharide (LPS). Complete genome of L. taiwanensis CLG01 contained a 1.89 Mb chromosome and two plasmids. Further genomic analysis revealed the presence of genes related to its resistance to different stresses and the beneficial effects mentioned above. Moreover, biosynthetic gene clusters (BGCs) encoding antimicrobial peptides, like bacteriocin, linear azol(in)e-containing peptide (LAP) and lanthipeptide, were also identified in the genome of L. taiwanensis CLG01. CONCLUSIONS: L. taiwanensis CLG01, isolated from mouse Peyer's patches, is the first L. taiwanensis strain with both phenotypes and genotypes systematically studied. These preliminary data confirmed the role of L. taiwanensis CLG01 as a potential probiotic candidate with antibacterial and immunomodulatory activity, which provide insight for further investigation to this species.

Clinical features and management strategy of symptomatic spontaneous isolated celiac artery dissection.

OBJECTIVES: The aim of this study was to evaluate the clinical features and management strategy for patients with symptomatic spontaneous isolated celiac artery dissection (SICAD). METHODS: In this retrospective study, consecutive patients with symptomatic SICAD from two institutions were included. The demographics, clinical manifestations, comorbidities, imaging findings and treatment strategy selection were obtained from the medical records. The general epidemiological data, treatment regimens and clinical and follow-up outcomes were analysed. RESULTS: Patients were divided into the conservative treatment group (group A, n = 26) and endovascular treatment group (group B, n = 11). Of these 37 patients, extent of dissection in both groups included only celiac trunk (61.54%% vs. 18.18%, p = 0.03), common hepatic artery (CHA) and splenic artery (SA) (3.85%% vs. 54.55%, p = 0.001), CHA (7.69% vs. 18.18%, p = 0.57), SA (23.08% vs. 9.09, p = 0.65) and left gastric artery (LGA) (3.85% vs. 54.55%, p = 0.99). Of note, the extension of the lesion in group A was shorter than that in group B. In addition, there were significantly more type IIb in group A than in group B (42.31% vs. 9.09%, p = 0.06) and the mean length of dissection in group A was 42.3 ± 54.71 mm which was significantly shorter than that in the group B 58.45 ± 3.71 mm (p =0.04). During a median follow-up of 11.5 months, the 1, 3, 6 and 12 month follow-ups were completed in 100% (37/37), 100% (37/37), 94.59% (35/37) and 91.19% (34/37) of patients, respectively. The cumulative rate of persistent disease stability in patients with endovascular treatment group was higher than in that conservative treatment group at the 3, 6, 9 and 12 months (50% vs. 16.67%, p = 0.001; 80% vs. 37.5%, p =0.03; 100% vs. 62.5%, p = 0.012;100% vs. 91.67%, p = 0.02 respectively). CONCLUSION: Most symptomatic SICAD have a tendency to persistent disease stability after conservative treatment. Risk factors for failed conservative treatment were length of dissection and branch involvement. Furthermore, endovascular treatment was associated with a high technical success and persistent disease stability rate, which might be reserved for patients with failed conservative treatment.

Melatonin Mitigates Oxazolone-Induced Colitis in Microbiota-Dependent Manner.

Levels of type 2 cytokines are elevated in the blood and intestinal tissues of ulcerative colitis (UC) patients in the active phase; this phenomenon indicates the participation of type 2 immune response in UC progression. The beneficial effects of melatonin in dextran sodium sulfate (DSS) and 2,4,6-trinitrobenzene sulfonic acid (TNBS) colitis models have been illustrated, but its role in the oxazolone (Oxa)-induced colitis model (driven by type 2 immune response) remains relatively unknown. We investigated the relationship between melatonin concentration and the severity of UC, revealing a significantly negative correlation. Subsequently, we investigated the effects of melatonin in Oxa-induced colitis mice and the potential underlying mechanisms. Administration of melatonin significantly counteracted body weight loss, colon shortening, and neutrophil infiltration in Oxa-induced colitis mice. Melatonin treatment mitigated Oxa-induced colitis by suppressing type 2 immune response. In addition, melatonin attenuated intestinal permeability by enhancing the expression of ZO-1 and occludin in colitis mice. Interestingly, the protective effect of melatonin was abolished when the mice were co-housed, indicating that the regulation of gut microbiota by melatonin was critical in alleviating Oxa-induced colitis. Subsequently, 16S rRNA sequencing was performed to explore the microbiota composition. Decreased richness and diversity of intestinal microbiota at the operational taxonomic unit (OTU) level resulted from melatonin treatment. Melatonin also elevated the abundance of Bifidobacterium, a well-known probiotic, and reduced proportions of several harmful bacterial genera, such as Desulfovibrio, Peptococcaceae, and Lachnospiraceae. Fecal microbiota transplantation (FMT) was used to explore the role of microbiota in the function of melatonin in Oxa-induced colitis. Microbiota transplantation from melatonin-treated mice alleviated Oxa-induced colitis, suggesting that the microbiome participates in the relief of Oxa-induced colitis by melatonin. Our findings demonstrate that melatonin ameliorates Oxa-induced colitis in a microbiota-dependent manner, suggesting the therapeutic potential of melatonin in treating type 2 immunity-associated UC.

Outcomes and radiographic findings of symptomatic isolated mesenteric artery dissection with conservative management.

OBJECTIVES: The aim of this study was to evaluate the computed tomography follow-up outcomes and radiographic findings of symptomatic isolated mesenteric artery dissection (IMAD) after conservative management. METHODS: In this retrospective study, 130 consecutive patients with symptomatic IMAD from three institutions were enrolled from January 2011 to December 2019. The general epidemiological data, clinical manifestations, first-episode symptoms, imaging findings, and treatment strategy selection were analyzed from the medical records. RESULTS: Among 130 patients diagnosed with symptomatic IMAD, positive remodeling of the SMA was achieved in 75.38% (98/130), and negative remodeling of the SMA was achieved in 24.62% (32/130). In the positive remodeling group, complete remodeling was achieved 39.23% (51/130) (type I 6 patients, type IIa 10 patients, type IIb 35 patients), in which type IIb was the most (p = 0.004). Moreover, of the 32 patients in whom negative remodeling of the SMA was achieved, significant differences were observed between the type IIa with respect to dissecting aneurysm formation (p = 0.04).Of the seven factors analyzed with a logistic regression model identified three factors significantly associated with negative remodeling: length of dissection (Waldχ2 13.331; OR 6.945; 95% CI 2.762-10.498; p = 0.014), true lumen residual diameter (TLRD) (Waldχ2 9.626; OR 7.85; 95% CI 1.892-19.063; p = 0.022), and branch involvement (Waldχ2 11.812; OR 7.247; 95% CI 1.245-14.830; p = 0.011). CONCLUSION: The prognosis of most symptomatic IMAD has a tendency to positive remodeling after conservative management, in which the initial type IIb classification is common. In contrast, risk factors for negative remodeling were type IIa, length of dissection, TLRD, and branch involvement. Patients with these morphological characteristics may not benefit from conservative management.

Mid-term outcomes of symptomatic isolated superior mesenteric artery dissection with endovascular management.

OBJECTIVES: The clinical outcomes, safety, and efficacy of endovascular management are explored for symptomatic isolated superior mesenteric artery dissection (ISMAD). METHODS: In this retrospective study, 51 consecutive patients with symptomatic ISMAD received endovascular management from three institutions between January 2011 and December 2019.These patients were categorized into group A (endovascular treatment was used as the first-line therapy) and group B(endovascular treatment was used as the second-line therapy). The general epidemiological data, clinical manifestations, first-episode symptoms, treatment process, imaging findings, follow-up outcomes were analyzed from the medical records. RESULTS: A total of 51 patients with endovascular management were collected in this study. Significant differences were observed between the two groups with respect to the course (150 h vs. 57 h; p < 0.001), intestinal ischemia (26.32% vs. 6,25%; p = 0.04) and dissection length (45.26 ± 13.78 mm vs. 63.37 ± 12.73 mm; p < 0.001). Technical success rate was 90.2% (46/51). There was significant difference in the MOD (42.27 ± 23.41 min vs. 76.63 ± 28.62 min p < 0.001), MPSRT (4.67 ± 2.65 h vs. 7.32 ± 2.49 h, p = 0.02), LOS (9.52 ± 3.72 days vs. 11.86 ± 4.13 days; p = 0.01) between the two groups. The bleeding complication rate was 7.84% (one patient in group A and three patients in group B). A total of 48 (94.12%, 48/51) patients were followed up for a median of 36.51 months (range, 4-87 months). Positive events of the SMA were achieved in 81.25% (39/48), and negative events of the SMA were achieved in 18.75% (8/48) based on the follow-up contrast-enhanced CT scan. CONCLUSIONS: Endovascular management of symptomatic ISMAD has a high technical success rate and efficient at controlling symptoms. Furthermore, as more positive events occur, endovascular management should be encouraged early when pain persists after conservative management or there are signs of disease progression.

S100A10 Accelerates Aerobic Glycolysis and Malignant Growth by Activating mTOR-Signaling Pathway in Gastric Cancer.

S100 calcium-binding protein A10 (S100A10) is crucially involved in the tumorigenesis of multiple malignant tumors. Reprogrammed glucose metabolism is emerging as a hallmark of various human cancers. However, the function of S100A10 in aerobic glycolysis is unclear. The expression of S100A10 was analyzed using the Oncomine database, Gene Expression Profiling Interactive Analysis (GEPIA), The Cancer Genome Atlas (TCGA), and the UALCAN cancer database. Prognostic analysis was performed using the Kaplan-Meier Plotter. The correlation between S100A10 and key glycolytic factors was assessed by GEPIA. The glycolysis level was examined by determining glucose consumption, lactate production, adenosine triphosphate production, cellular oxygen consumption rate, and extracellular acidification rate. Cell apoptosis was investigated by flow cytometry. Colony formation and BrdU assays were performed to detect cell proliferation. A subcutaneous xenograft mouse model was established to evaluate the effects of S100A10 in vivo. Gene Set Enrichment Analysis and western blotting were performed to explore the downstream signaling pathway. S100A10 was significantly upregulated in gastric cancer. Its expression was associated with poor survival. S100A10 increased glucose consumption, lactate production, and the switch from oxidative phosphorylation to aerobic glycolysis. S100A10 promoted malignant proliferation and suppressed cell apoptosis in gastric cancer. S100A10 activated the mTOR pathway by interacting with annexin A2 (ANXA2) to accelerate tumor glycolysis, resulting in tumor malignant progression. S100A10 contributed to aerobic glycolysis and accelerated malignant growth by modulating the Src/ANXA2/AKT/mTOR signaling pathway. Thus, S100A10 may have pivotal roles in gastric cancer.

Integrative genomic analyses identify WDR12 as a novel oncogene involved in glioblastoma.

Glioblastoma (GBM) is the most malignant primary brain tumor in adults. Due to its invasive nature, it cannot be thoroughly eliminated. WD repeat domain 12 (WDR12) processes the 32S precursor rRNA but cannot affect the synthesis of the 45S/47S primary transcript. In this study, we found that WDR12 is highly expressed in GBM according to the analysis results of mRNA expression by The Cancer Genome Atlas database. The high expression level of WDR12 is dramatically related to shorter overall survival and reduced disease-free survival. Next, we knocked down WDR12 and found that knockdown of WDR12 promoted the apoptosis and inhibited the proliferation by cell biology experiments. Differential expression genes in gene-chip revealed that WDR12 knockdown mainly inhibited cell cycle. Finally, we also found that WDR12 is associated with PLK1 and EZH2 in cell proliferation of GBM. Resumptively, this report showed a possible evidence that WDR12 drove malignant behavior of GBM, whose expression may present a neoteric independent prognostic biomarker in GBM.

Intravascular Leiomyomatosis Extending to Right Atrium: A Rare Caused Syncope.

Intravascular leiomyomatosis (IVL) is a variant of leiomyoma characterized by intravascular proliferation of a histologically benign smooth muscle tumor extending beyond the uterus into distant great vessels or the heart. It is a rare disease and results in death. Here, we reported the case of 48-year-old, otherwise well woman, who presented to the emergency department with syncope. Pulmonary computed tomography (CT) demonstrated a large low-density shadow originating from the inferior vena cava (IVC) extending into the right atrium (RA). Magnetic resonance venography (MRV) showed that a neoplasm was "snakelike," which completely occluded the right internal iliac vein (RIIV), the common iliac vein (CIV), and IVC. A multidisciplinary team of specialists consisting of vascular surgeons, cardiac surgeons, gynecologists, anesthesiologists, and radiologists reviewed the history, clinical examination findings, and diagnostic imaging of the patient. A decision was made to proceed with one-stage surgery (resection of thoracoabdominal tumor extension at one operative setting). After surgery, the patient's vital signs were restored, and her symptoms were disappeared. She was discharged on hospital day 21 without complications. One-stage surgical approach to completely remove an IVL with RA involvement is an optimal choice if the patient's physical condition permits.

A Randomized, Double-Blind, Placebo-Controlled Phase II Study of Hepatocyte Growth Factor in the Treatment of Critical Limb Ischemia.

NL003 is a plasmid engineered to simultaneously express two isoforms of hepatocyte growth factor. This phase II study was performed to assess the clinical safety and efficacy of intramuscular injection of NL003 in critical limb ischemia (CLI) patients for 6 months. Two hundred patients (Rutherford scale 4-5) were randomly assigned: placebo (n = 50), low-dose NL003 (n = 50), middle-dose NL003 (n = 50), or high-dose NL003 (n = 50). The drug was administered in the affected limb of 197 patients on days 0, 14, and 28. No significant differences in the incidence of adverse events (AEs) or serious AEs were found among the groups. At 6 months, pain severity was significantly reduced in all NL003 groups, but not in the placebo group (p < 0.05). The proportion of patients with complete ulcer healing in the high-dose group was significantly higher than that of the placebo group (p = 0.0095). There were no statistically significant differences in transcutaneous oxygen pressure (TcPO2), ankle-brachial index (ABI), or toe-brachial index (TBI) value among the four groups throughout the study period. These results provide the first effective evidence of significant improvements in total healing of ulcers in treated legs, complete pain relief without analgesics, and safety for NL003 in patients with Rutherford stage 4-5.

Diagnosis and surgical management of inferior vena cava leiomyomatosis.

OBJECTIVE: We aimed to review our experience in the diagnosis and surgical management of patients diagnosed with inferior vena cava leiomyomatosis (IVL). METHODS: We retrospectively evaluated all patients diagnosed with IVL between 1999 and 2015. Patient demographics, diagnostic imaging, operative techniques, and perioperative outcomes were reviewed. RESULTS: Over the study period, 16 patients with an IVL diagnosis were identified. In all patients, the diagnosis was made with ultrasound and magnetic resonance imaging. In 15 patients who underwent operative intervention, we observed three tumor extension routes from the uterus to the inferior vena cava: (i) via the internal iliac vein, (ii) via the ovarian vein, and (iii) via the anterior sacral vein. Complete tumor removal was achieved in all patients who underwent a one-stage operation (12 patients). Among these patients, antegrade tumor extraction from the right atrium was performed in nine patients, and retrograde extraction from iliac veins was performed in three. A two-stage operation with direct tumor transection and resection was necessary in a subset of patients to facilitate complete resection in one patient, and near-complete resection in two patients. Preoperative imaging and intraoperative findings demonstrated four distinct types of gross tumor morphologies: (i) type A solid cast (43.8%), (ii) type B hallow tube-like (12.5%), (iii) type C thread-like (18.7%), and (iv) type D mixed morphology (25%). Types A and B were the easiest tumor types to extract, and types C and D tumors were more difficult to remove given their fragility. Postoperative surgical pathology confirmed the diagnosis of IVL. All patients recovered successfully with no major complications; there were no deaths. One patient early in our experience had an incomplete resection and developed a recurrence that required re-intervention at 26 months from the initial operation. CONCLUSIONS: IVL can be accurately diagnosed with ultrasound and magnetic resonance imaging. Surgical tumor resection with a one-stage operation can lead to reasonable outcomes and successful cure rates. The surgical plan can be tailored to the type of tumor morphology observed on preoperative imaging.

Improvement in Cerebral and Ocular Hemodynamics Early after Carotid Endarterectomy in Patients of Severe Carotid Artery Stenosis with or without Contralateral Carotid Occlusion.

Purpose. To investigate the alternation in cerebral and ocular blood flow velocity (BFV) in patients of carotid stenosis (CS) with or without contralateral carotid occlusion (CO) early after carotid endarterectomy (CEA). Patients and Methods. Nineteen patients underwent CEA for ≥50% CS. Fourteen patients had the unilateral CS, and five patients had the ipsilateral CS and the contralateral CO. Transcranial Doppler (TCD) and Color Doppler Imaging (CDI) were performed before and early after CEA. Results. In patients with unilateral CS, significant improvements in BFV were observed in anterior cerebral artery (ACA) and middle cerebral artery (MCA) on the ipsilateral side after CEA. In patients of ipsilateral CS and contralateral CO, significant improvements in BFV were observed in the ACA and MCA not only on the ipsilateral side but also on the contralateral side postoperatively. The ipsilateral ophthalmic artery (OA) retrograde flows in two patients were recovered to anterograde direction following CEA. The BFV in short posterior ciliary artery (SPCA) of the ipsilateral side significantly increased postoperatively irrespective of the presence of contralateral CO. Conclusions. CEA improved cerebral anterior circulation hemodynamics especially in patients of unilateral CS and contralateral CO, normalized the OA reverse flow, and increased the blood perfusion of SPCA.

A Primary Primitive Neuroectodermal Tumor Arising from Left Subclavian Vein and Extending along Left Brachiocephalic Vein and Superior Vena Cava into Right Atrium.

Primitive neuroectodermal tumor (PNET) is an extremely rare malignancy thought to be derived from fetal neuroectodermal precursor cells. It usually occurs in central and peripheral nervous system or soft tissue and bone, while intravenous or intracavitary PNET is considered as an extremely rare tumor. We reported a case of a 44-year-old woman who presented with the left unilateral facial and neck swelling. Magnetic resonance imaging revealed a tape-shaped solid mass within left subclavian vein, left brachiocephalic vein, superior vena cava, and right atrium; the proximal end proportion occupied almost the entire right atrium with a pedicle flip protruded into the right ventricle. Ultrasonography revealed an irregular hypoechnoic mass arising from the left subclavian vein, which extended along the left brachiocephalic vein and superior vena cava into the right atrium and up to the right ventricle. Positron emission tomography-computed tomography revealed several hypermetabolic thyroid nodules with no evidence of intravenous hyperactive lesion. The patient underwent tumor resection under cardiopulmonary bypass. At 15 days postoperatively, total thyroidectomy and resection of the left subclavian vein were simultaneously performed. The patient received chemotherapy and radiotherapy later. Histologically, the neoplasm displayed small, round, blue cells with hyperchromatic nuclei and scant cytoplasm. The neoplastic cells showed a strong immunopositivity for CD99, synaptophysin, CD56, CD57, and friend leukemia integration 1, thus confirming a diagnosis of the PNET. Histopathological examination of the thyroid showed papillary carcinoma. Thus, this PNET had no definitive organ or tissue of origin, which primarily originated from the left subclavian vein with tumor extension along the superior vena cava to the right ventricle.