Combined Intracoronary Prourokinase Thrombolysis on Myocardial Perfusion and Vascular Endothelial Function in STEMI.

BACKGROUND: This study aimed to investigate the effects of intracoronary prourokinase thrombolysis combined with emergency percutaneous coronary intervention (PCI) on myocardial perfusion and vascular endothelial function in patients with acute ST-segment elevation myocardial infarction (STEMI). METHODS: A total of 104 patients with STEMI were collected from August 2020 to August 2022, and were divided into control group and observation group in a random manner. The control group received PCI directly, and the observation group received intracoronary prourokinase thrombolytic therapy before PCI. The treatment effects were evaluated by measuring the cardiac function indexes, including left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), and left ventricular ejection fraction (LVEF), the TIMI myocardial perfusion grade, the vascular endothelial indexes, including soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1), the von Willebrand factor (vWF), the myocardial injury indexes, including cardiac troponin I (cTnI), creatine kinase isoenzyme MB (CK-MB), and lactate dehydrogenase (LDH), and the inflammatory factors, including myeloperoxidase (MPO), C-reactive protein (CRP), and interleukin-6 (IL-6). Furthermore, the treatment safety was assessed by recording the incidence of major MACE events, 6 months after the operation. RESULTS: After treatment, LVEDD and LVESD were lower in the observation group than in the control group, and LVEF was higher (p < 0.05). The TIMI myocardial perfusion grade in the observation group was higher than in the control group, after treatment (p < 0.05). The levels of sICAM-1, sVCAM-1, and vWF were higher in the observation group than in the control group (p < 0.05). The levels of cTnI, CK-MB, and LDH in the observation group were lower than those in the control group, 24 hours after surgery. At 3 days after surgery, MPO was lower in the observation group than in the control group, and CRP and IL-6 were higher (p < 0.05). The incidence of major MACE events in the observation group was lower than that in the control group, 6 months after surgery (p < 0.05). There was 1 case of puncture site bleeding in the observation group, 1 case of puncture site bleeding and 1 case of subcutaneous ecchymosis in the control group, but no serious bleeding events, such as internal bleeding or cerebral hemorrhage, in the two groups. CONCLUSIONS: Intracoronary prourokinase thrombolytic therapy combined with emergency PCI can promote the recovery of cardiac function, improve myocardial perfusion and vascular endothelial function, and reduce inflammation and the incidence of major postoperative MACE events in acute STEMI patients.

CircRNAs: emerging factors for regulating glucose metabolism in colorectal cancer.

Colorectal cancer is a malignant disease with a high incidence and low survival rate, and the effectiveness of traditional treatments, such as surgery and radiotherapy, is very limited. CircRNAs, a kind of stable endogenous circular RNA, generally function by sponging miRNAs and binding or translating proteins. CircRNAs have been identified to play an important role in regulating the proliferation and metabolism of CRC. In recent years, many reports have indicated that by regulating the expression of glycolysis-related proteins, such as GLUT1 and HK2, or directly translating proteins, circRNAs can promote the Warburg effect in cancer cells, thereby driving CRC metabolism. Moreover, the Warburg effect increases lactate production in cancer cells and promotes acidification of the TME, which further drives cancer progression. In this review, we summarized the remarkable role of circRNAs in regulating glucose metabolism in CRC in recent years, which might be useful for finding new targets for the clinical treatment of CRC.

Treatment of a Double Cancer Patient With Primary Inferior Vena Cava Sarcoma and Lung Adenocarcinoma: A Case Report and Literature Review.

Background: Leiomyosarcoma of the inferior vena cava (IVC) is a rare malignancy. Here, we present the case of a 38-year-old woman with a primary IVC leiomyosarcoma and lung adenocarcinoma. Case Report: The patient, a 38-year-old Chinese female, presented to the general surgical outpatients clinic with a 18-month history of intermittent right upper abdominal pain. Contrast-enhanced computed tomography (CT) showed a tumor of IVC (3.4*2.7 cm) extending to the renal veins. In addition, chest CT revealed a mass lesion in the upper left lung lobe. Then, the patient underwent resection of the IVC tumor and wedge resection of the upper lobe of the left lung. The patient then received gefitinib (250 mg/day) as a maintenance therapy until the tumor recurrence or metastasis in the follow-up period. Pulmonary metastasis of the sarcoma were first diagnosed 20 month after the resection of the IVC leiomyosarcoma. So the patient again received thoracoscopic wedge pneumonectomy, and it was confirmed to be metastasis of IVC leiomyosarcoma. The patient received oral anlotinib treatment (12 mg once daily) after the last operation. During on-going regular follow-up visits no evidence of recurrence or metastasis was observed from December 2020 to October 2021. Conclusions: The patient with a primary IVC leiomyosarcoma and lung adenocarcinoma is extremely rare. Surgery is still an effective treatment for patients with a primary IVC leiomyosarcoma and lung adenocarcinoma at present.

CircRNAs: promising factors for regulating angiogenesis in colorectal cancer.

Colorectal cancer (CRC) is one of the most common cancers in the world. The incidence rate of cancer is high. The overall response to traditional treatment methods such as surgery, radiotherapy, and chemotherapy is not very satisfactory. Therefore, finding new therapeutic targets is very important for improving CRC treatment. In recent reports, the role of circRNAs in regulating colorectal angiogenesis has been gradually revealed. CircRNAs can indirectly act on angiogenesis pathways and regulate the expression of growth factors such as vascular endothelial growth factor (VEGF). CircRNAs are endogenous noncoding RNAs formed by pre-mRNAs through exon circular splicing. The covalent closed-loop structure makes these RNAs highly conserved and stable. CircRNAs have been found in human plasma, serum, urine, and other body fluids. Their highly conserved characteristics play important roles in many biological activities. CircRNAs can participate in the progression of many diseases by sponging miRNAs, interacting with proteins, and regulating transcription. Angiogenesis can provide nutrients and oxygen for tumour proliferation and metastasis. Angiogenesis is an important sign of the formation of the tumour microenvironment. Here, we will summarize the role of the latest circRNAs in the mechanism of angiogenesis in CRC and provide potential therapeutic targets for clinical treatment.

Structure and mechanism of a phage-encoded SAM lyase revises catalytic function of enzyme family.

The first S-adenosyl methionine (SAM) degrading enzyme (SAMase) was discovered in bacteriophage T3, as a counter-defense against the bacterial restriction-modification system, and annotated as a SAM hydrolase forming 5'-methyl-thioadenosine (MTA) and L-homoserine. From environmental phages, we recently discovered three SAMases with barely detectable sequence similarity to T3 SAMase and without homology to proteins of known structure. Here, we present the very first phage SAMase structures, in complex with a substrate analogue and the product MTA. The structure shows a trimer of alpha-beta sandwiches similar to the GlnB-like superfamily, with active sites formed at the trimer interfaces. Quantum-mechanical calculations, thin-layer chromatography, and nuclear magnetic resonance spectroscopy demonstrate that this family of enzymes are not hydrolases but lyases forming MTA and L-homoserine lactone in a unimolecular reaction mechanism. Sequence analysis and in vitro and in vivo mutagenesis support that T3 SAMase belongs to the same structural family and utilizes the same reaction mechanism.

Bacteria can be infected by viruses known as bacteriophages. These viruses inject their genetic material into bacterial cells and use the bacteria's own machinery to build the proteins they need to survive and infect other cells. To protect themselves, bacteria produce a molecule called S-adenosyl methionine, or SAM for short, which deposits marks on the bacteria's DNA. These marks help the bacteria distinguish their own genetic material from the genetic material of foreign invaders: any DNA not bearing the mark from SAM will be immediately broken down by the bacterial cell. This system helps to block many types of bacteriophage infections, but not all. Some bacteriophages carry genes that code for enzymes called SAMases, which can break down SAM, switching off the bacteria's defenses. The most well-known SAMase was first discovered in the 1960s in a bacteriophage called T3. Chemical studies of this SAMase suggested that it works as a 'hydrolase', meaning that it uses water to break SAM apart. New SAMases have since been discovered in bacteriophages from environmental water samples, which, despite being able to degrade SAM, are genetically dissimilar to one another and the SAMase in T3. This brings into question whether these enzymes all use the same mechanism to break SAM down. To gain a better understanding of how these SAMases work, Guo, Söderholm, Kanchugal, Isaksen et al. solved the crystal structure of one of the newly discovered enzymes called Svi3-3. This revealed three copies of the Svi3-3 enzyme join together to form a unit that SAM binds to at the border between two of the enzymes. Computer simulations of this structure suggested that Svi3-3 holds SAM in a position where it cannot interact with water, and that once in the grip of the SAMase, SAM instead reacts with itself and splits into two. Experiments confirmed these predictions for Svi3-3 and the other tested SAMases. Furthermore, the SAMase from bacteriophage T3 was also found to degrade SAM using the same mechanism. This shows that this group of SAMases are not hydrolases as originally thought, but in fact 'lyases': enzymes that break molecules apart without using water. These findings form a starting point for further investigations into how SAM lyases help bacteriophages evade detection. SAM has various different functions in other living organisms, and these lyases could be used to modulate the levels of SAM in future studies investigating its role.

Selective Esophagogastric Devascularization in the Modified Sugiura Procedure for Patients with Cirrhotic Hemorrhagic Portal Hypertension: A Randomized Controlled Trial.

Aim: Portal hypertension is a series of syndrome commonly seen with advanced cirrhosis, which seriously affects patient's quality of life and survival. This study was designed to access the efficacy and safety of selective esophagogastric devascularization in the modified Sugiura procedure for patients with cirrhotic hemorrhagic portal hypertension. Methods: Sixty patients with hepatitis B cirrhotic hemorrhagic portal hypertension and meeting the inclusion criteria were selected and randomly divided by using computer into the selective modified Sugiura group (sMSP group, n = 30) and the modified Sugiura group (MSP group, n = 30). The primary endpoint measurement is the postoperative rebleeding rate. Secondary endpoint measurements included free portal venous pressure, liver Child-Pugh score, liver volume, portal vein width and blood flow velocity, survival rate, quality of life, and dysphagia as well as other complications one year postoperatively. This trial is registered with ChiCTR, number ChiCTR2000033468. Results: There was no statistically significant difference in rebleeding rates within one year after surgery between patients in the sMSP and MSP groups (χ = 0.11, p=0.73). In comparison with the MSP group, the Child-Pugh score of liver function in the sMSP group significantly increased (χ = 6.4, p=0.04) and the incidence of dysphagia was significantly reduced (χ = 6.23, p=0.01) one year after surgery. There was a statistically significant difference in the quality of life between the two groups. However, there were no statistically significant differences in free portal venous pressure (MD = -3.44, 95% CI: -7.87 to 0.98, p=0.12), postoperative liver volume (3 months: MD = -258.81, 95% CI: -723.21 to 205.57, p=0.24; 1 year: MD = -320.12, 95% CI: -438.43 to 102.78, p=0.16), postoperative portal vein width (3 months: MD = -0.06, p=0.50; 1 year: MD = 0.17, p=0.21), portal vein flow velocity (3 months: MD = 1.64, p=0.21; 1 year: MD = -1.19, p=0.57), 1-year survival rate (χ = 1.01, p=0.31), and other complications between the two groups. Conclusions: Selective esophagogastric devascularization in the modified Sugiura procedure may not lower the incidence of rebleeding in the short term based on our findings. However, it may significantly improve quality of life of patients with cirrhotic hemorrhagic portal hypertension, improve liver function, and reduce postoperative dysphagia.

Post-gadolinium 3-dimensional spatial, surface, and structural characteristics of glioblastomas differentiate pseudoprogression from true tumor progression.

PURPOSE: Pseudoprogression is often indistinguishable from true tumor progression on conventional 2-dimensional (2D) MRI in glioblastoma multiforme (GBM) patients. The aim of this study was to determine the association between post-gadolinium 3-dimensional (3D) characteristics and clinical state in GBM patients. METHODS: Standardized 3D brain MRI studies were performed, and contrast enhancing portions of each tumor were segmented and analyzed, blinded to clinical state, using principal component analysis (PCA), medial axis transformation (MAT), and coverage analysis. Associations between the 3D characteristics of the post-gadolinium enhanced regions and the clinical status of patients were performed. RESULTS: A total of 15 GBM patients [male: 11 (73%); median age (range): 62 years (36-72)] with a median disease duration of 6 months (range 2-24 months) were studied cross-sectionally with 6 (40%) patients identified with tumor progression. Post-gadolinium features corresponding to the group with progressive disease exhibited a more spherical and symmetric shape relative to their stable counterparts (p = 0.005). The predictive value of a more uniformly full post-gadolinium enhanced shell to clinical progression was determined with a sensitivity of 66.7% (95% CI 29.9-92.5), specificity of 100% (54.1-100), and PPV of 100% (p = 0.028, 2-tailed Fisher's exact test). There did not appear to be an association between the thickness of the contrast enhanced shell to clinical state. CONCLUSIONS: The application of 3D technology with post-gadolinium imaging data may inform healthcare providers with new insights into disease states based on spatial, surface, and structural patterns.

ZUFSP Deubiquitylates K63-Linked Polyubiquitin Chains to Promote Genome Stability.

Deubiquitylating enzymes (DUBs) enhance the dynamics of the versatile ubiquitin (Ub) code by reversing and regulating cellular ubiquitylation processes at multiple levels. Here we discovered that the uncharacterized human protein ZUFSP (zinc finger with UFM1-specific peptidase domain protein/C6orf113/ZUP1), which has been annotated as a potentially inactive UFM1 protease, and its fission yeast homolog Mug105 define a previously unrecognized class of evolutionarily conserved cysteine protease DUBs. Human ZUFSP selectively interacts with and cleaves long K63-linked poly-Ub chains by means of tandem Ub-binding domains, whereas it displays poor activity toward mono- or di-Ub substrates. In cells, ZUFSP is recruited to and regulates K63-Ub conjugates at genotoxic stress sites, promoting chromosome stability upon replication stress in a manner dependent on its catalytic activity. Our findings establish ZUFSP as a new type of linkage-selective cysteine peptidase DUB with a role in genome maintenance pathways.

3D-2D Deformable Image Registration Using Feature-Based Nonuniform Meshes.

By using prior information of planning CT images and feature-based nonuniform meshes, this paper demonstrates that volumetric images can be efficiently registered with a very small portion of 2D projection images of a Cone-Beam Computed Tomography (CBCT) scan. After a density field is computed based on the extracted feature edges from planning CT images, nonuniform tetrahedral meshes will be automatically generated to better characterize the image features according to the density field; that is, finer meshes are generated for features. The displacement vector fields (DVFs) are specified at the mesh vertices to drive the deformation of original CT images. Digitally reconstructed radiographs (DRRs) of the deformed anatomy are generated and compared with corresponding 2D projections. DVFs are optimized to minimize the objective function including differences between DRRs and projections and the regularity. To further accelerate the above 3D-2D registration, a procedure to obtain good initial deformations by deforming the volume surface to match 2D body boundary on projections has been developed. This complete method is evaluated quantitatively by using several digital phantoms and data from head and neck cancer patients. The feature-based nonuniform meshing method leads to better results than either uniform orthogonal grid or uniform tetrahedral meshes.

Sensitivity of tumor motion simulation accuracy to lung biomechanical modeling approaches and parameters.

Finite element analysis (FEA)-based biomechanical modeling can be used to predict lung respiratory motion. In this technique, elastic models and biomechanical parameters are two important factors that determine modeling accuracy. We systematically evaluated the effects of lung and lung tumor biomechanical modeling approaches and related parameters to improve the accuracy of motion simulation of lung tumor center of mass (TCM) displacements. Experiments were conducted with four-dimensional computed tomography (4D-CT). A Quasi-Newton FEA was performed to simulate lung and related tumor displacements between end-expiration (phase 50%) and other respiration phases (0%, 10%, 20%, 30%, and 40%). Both linear isotropic and non-linear hyperelastic materials, including the neo-Hookean compressible and uncoupled Mooney-Rivlin models, were used to create a finite element model (FEM) of lung and tumors. Lung surface displacement vector fields (SDVFs) were obtained by registering the 50% phase CT to other respiration phases, using the non-rigid demons registration algorithm. The obtained SDVFs were used as lung surface displacement boundary conditions in FEM. The sensitivity of TCM displacement to lung and tumor biomechanical parameters was assessed in eight patients for all three models. Patient-specific optimal parameters were estimated by minimizing the TCM motion simulation errors between phase 50% and phase 0%. The uncoupled Mooney-Rivlin material model showed the highest TCM motion simulation accuracy. The average TCM motion simulation absolute errors for the Mooney-Rivlin material model along left-right, anterior-posterior, and superior-inferior directions were 0.80 mm, 0.86 mm, and 1.51 mm, respectively. The proposed strategy provides a reliable method to estimate patient-specific biomechanical parameters in FEM for lung tumor motion simulation.

The effects of bariatric procedures versus medical therapy for obese patients with type 2 diabetes: meta-analysis of randomized controlled trials.

OBJECTIVE: To assess the effects of bariatric surgery versus medical therapy for type 2 diabetes mellitus. METHODS: The Cochrane library, PubMed, Embase, Chinese biomedical literature database, and Wanfang database up to February 2012 were searched. The literature searches strategies contained terms ("diabetes*", "surg*", and "medic*" were used), combined with the medical subject headings. Randomized controlled trails (RCTs) of frequently used bariatric surgery for obese patients with type 2 diabetes were included. Study selection, data extraction, quality assessment, and data analyses were performed according to the Cochrane standards. RESULTS: Three randomized controlled trials (RCTs) involving 170 patients in the bariatric surgery groups and 100 patients in the medical therapy group were selected. Compared with medical therapy, bariatric surgery for type 2 diabetes can significantly decrease the levels of HbA1c, FBG, weight, triglycerides, and the dose of hypoglycemic, antihypertensive, and lipid-lowering medicine, while increasing the rate of diabetes remission (RR = 9.74, 95%CI, (1.36, 69.66)) and the levels of high-density lipoprotein. However, there are no statistical differences in serious adverse events between the surgical and medical groups (RR = 1.23, 95%CI, (0.80, 1.87)). CONCLUSIONS: Surgical procedures were more likely to help patients achieve benefits than medical therapy alone. Further intensive RCTs of high-quality, multiple centers and long-term followup should be carried out to provide more reliable evidence.

A novel markerless technique to evaluate daily lung tumor motion based on conventional cone-beam CT projection data.

PURPOSE: In this study, we present a novel markerless technique, based on cone beam computed tomography (CBCT) raw projection data, to evaluate lung tumor daily motion. METHOD AND MATERIALS: The markerless technique, which uses raw CBCT projection data and locates tumors directly on every projection, consists of three steps. First, the tumor contour on the planning CT is used to create digitally reconstructed radiographs (DRRs) at every projection angle. Two sets of DRRs are created: one showing only the tumor, and another with the complete anatomy without the tumor. Second, a rigid two-dimensional image registration is performed to register the DRR set without the tumor to the CBCT projections. After the registration, the projections are subtracted from the DRRs, resulting in a projection dataset containing primarily tumor. Finally, a second registration is performed between the subtracted projection and tumor-only DRR. The methodology was evaluated using a chest phantom containing a moving tumor, and retrospectively in 4 lung cancer patients treated by stereotactic body radiation therapy. Tumors detected on projection images were compared with those from three-dimensional (3D) and four-dimensional (4D) CBCT reconstruction results. RESULTS: Results in both static and moving phantoms demonstrate that the accuracy is within 1 mm. The subsequent application to 22 sets of CBCT scan raw projection data of 4 lung cancer patients includes about 11,000 projections, with the detected tumor locations consistent with 3D and 4D CBCT reconstruction results. This technique reveals detailed lung tumor motion and provides additional information than conventional 4D images. CONCLUSION: This technique is capable of accurately characterizing lung tumor motion on a daily basis based on a conventional CBCT scan. It provides daily verification of the tumor motion to ensure that these motions are within prior estimation and covered by the treatment planning volume.

[Effects of soy isoflavone on the reproductive system development and ER-beta expression in male rat offspring in different postnatal periods].

OBJECTIVE: To investigate the effects of pre- and post-natal exposure to soy isoflavones (SIF) on the related indicators of the reproductive system development and ER-beta expression in male rat offspring. METHODS: Pregnant SD rats were randomly divided into a corn oil group (control), 3 SIF groups (50, 200 and 400 mg/kg body weight), and a diethylstilbestrol (DES, 0.1 mg/ kg body weight) group to be treated respectively by intragastric gavage from pregnancy day 0. On postnatal day (PND) 21, the male offspring were treated in the same manner till sexual maturity, and on PND 49 and 90, 6 male rats from each group were killed for observation of the related indicators of the reproductive system development and the detection of the expression of ER-beta in the testis. RESULTS: The mean daily food intake showed no evident differences among the SIF and DES groups, but the food efficiency ratio (FER) was significantly decreased in the 200 and 400 mg/kg SIF and 0.1 mg/kg DES groups (P < 0.05) at 49 and 90 PND. At the dose of > or = 50 mg/kg, SIF markedly reduced the body weight of the rats (P < 0.05), even more so at 90 PND than at 49 PND. The increased dose of SIF was correlated with the reduction of testis weight, sperm head count and daily sperm production, and so was it with the elevation of the ER-beta expression, both more obviously at 90 PND than at 49 PND. CONCLUSION: Pre- and post-natal exposure to SIF affects the reproductive system development of male rat offspring, and the elevation of ER-beta expression may be one of its mechanisms.