Located on chromosome 18q21.33, BCL2 gene is found in human B-cell lymphomas, which is first identi- fied through cloning the breakpoint of a translocation of t(14;18) . It has proven to be major negative regulator in apoptosis, playing key roles in neoplastic transform- ation and leukemogenesis . BCL2 protein plays crucial role in inhibiting the influx of adenine nucleotides through the outer mitochondrial membrane, resulting in reducing ATP hydrolysis and inhibiting cytochrome-C release . Based on its oncogenic role in cancer, a highly potent and selective inhibitor of BCL2, ABT-199, presents antitumor activity while sparing platelets . In 2016, venetoclax (ABT-199) has been authorized by FDA for relapsed/refractory chronic lymphoid leukemia (CLL) with 17p deletion. Although ABT-199 also in- duced cell death in AML , whether it can be applied to clinical treatment needs further studies. Notably, the FDA granted accelerated approval to venetoclax in combination with hypomethylating agents azacitidine or decitabine or low-dose cytarabine for the treatment of newly-diagnosed AML in adults who are age 75 years or older, or who have comorbidities that preclude use of in- tensive induction chemotherapy . Herein, we revealed clinical implication of BCL2 overexpression in de novo adult AML, and may provide theoretical basis for targeted therapy using BCL2 inhibitor venetoclax.
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hypotension,bradycardia and heart block after quinine therapy.She also stated that there is an inverse relationship between serum calcium level and parasite load (p<0.05). Serum calcium was found to return to normal with clinical recovery and lowering of parasite load. Though exact cause of hypocalcemia in malaria could not be found out,it was attributed to renal failure, hypomagnesemia and parathyroid dysfunction. She concluded that hypocalcemia in malaria is not uncommon and it can be used as a prognostic indicator in complicated malaria as it can cause cardiac conduction abnormalities and death, and serum calcium level returns to normal with clinical recovery and parasite clearance.
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Electrical impedance tomography (EIT) is a technique performed at the patient ’ s bedside. It is noninvasive and radiation-free and provides dynamic tidal images of gas distribution. Studies have reported that EIT provides useful information both in animal and clinical studies during mechanical ventilation. EIT has been shown to be useful during lung recruitment, titration of positive end-expiratory pressure, lung volume estimation, and evaluation of homogeneity of gas distribution in a single EIT measure or in combination with multiple EIT measures. EIT-guided mechanical ventilation preserved the alveolar architecture and maintained oxygenation and lung mechanics better than low-tidal volume ventilation in animal models. However, careful assessment is required for data analysis owing to the limited understanding of the results of EIT interpretation. Previous studies indicate monitoring regional ventilation by EIT is feasible in the intensive care setting and has potential to lead to lung protective ventilation. Further clinical studies are warranted to evaluate whether monitoring of regional ventilation using EIT can shorten the duration of ventilation or improve mortality in patients with acute respiratory distress syndrome.
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A total of 62 patients (30 males and 32 females with a median age of 35 years [range: 14–70 years]) with acute leukemia (AL) including 36 newly diagnosed, 6 relapsed, and 20 in CR were enrolled in the study. Clinical data for these patients presenting to Tangshan Kailuan Hospital from August 2012 to October 2013 were evaluated. AL was diagnosed by using morphology, immunophenotype, cytogenetics, and molecular biology (MICM) of bone marrow cells. The patients were classified according to the World Health Organization (WHO) criteria published in 2008. As a control, 30 healthy donors (14 males and 16 females) with a median age of 34 years (range: 18–48 years) were enrolled in this study (Table 1).
systolic constriction at angiography had stress-induced isch- emia on SPECT. Although the number of subjects was too small to have clinical significance in our study, a higher rate of revers- ible perfusion defect was observed in MB subjects than those without MB. Another potential explanation of ER in MB pa- tients is that MB can lead to irreversible myocardial damage. MB produces not only myocardial ischemia but also may even result in myocardial infarction. 15,21 And a high incidence of ER
The biceps brachii muscle is present in the anterior aspect of the arm. Its morphological variations have great clinical significance for surgeons, orthopaedic surgeons, anaes- thetists, neurologists and anatomists. This study aimed to describe the incidence and morphology of the extra-heads of the biceps brachii muscle. Hundred upper limbs of 50 adult human cadavers (30 men and 20 women) were used in this study after the approval of the medical ethical committee. These cadavers were obtained from the Anatomy Department, Faculty of Medicine, King Abdul-Aziz University. The incidence of anatomical variations of biceps muscle was equal in both male and female cadavers (10%) with predominance of the left side (7%). The 3-headed biceps brachii muscle was noticed in 7% (4% male and 3% female), while the 4-headed biceps was seen in 2 (2%) left limbs, 1 male and 1 female. The third head of the biceps muscle arose from the anteromedial aspect of humerus, between the coracobrachialis insertion and the brachialis origin, in 6% and from middle of the medial border of humerus in 3%. While the fourth head originated from the articular capsule of shoulder joint in 1 (1%) limb and from the coracoid process of scapula in the other limb. The biceps common tendon of insertion received the supernumerary heads in 7% of the limbs. However, the extra-head fused with the long head in 2 (2%) limbs and united with the short head in 1 (1%) limb. The mean of the third head length was 118.8 ± 10.9 in all limbs, where it was 121.8 ± 12.3 in male and 113.5 ± 8.1 in female cadavers. The third head length/arm length ratio was 38.4 ± 2.6 in all, 38.3 ± 3.4 in male and 38.8 ± 1.8 in female cadavers. The length of the extra-head was extremely significant with those of the corresponding limb in all, male and female cadavers (p < 0.0001). Knowledge of the morphological variations of biceps muscle provides better pre-operative evaluation, safe surgical intervention within the arm and better postoperative outcomes. (Folia Morphol 2013; 72, 4: 349–356)
autoantibodies and tumor markers), pulmonary function, electrocardiogram, ultrasonic cardiogram, and computed tomography. All enrolled patients were followed until the individual was medically stable enough to leave the hospital and not prone to acute exacerbation again. Patients who had adverse clinical outcomes were also excluded, including death from any cause in hospital, requiring mechanical ven- tilation and length of hospitalization time shorter than 1 day or longer than 30 days. Finally, 93 cases met the required inclusion and exclusion criteria, and were further evaluated 8 (interquartile range [IQR]: 7–11) days after the onset of exacerbation when they were convalescent. Healthy controls were recruited from the health examination center of the hospital, and 88 controls were matched with COPD patients for age, gender, body mass index, and smoking index. The present research was approved by the Research Committee of Human Investigation of Medical College of Xi’an Jiaotong University. All participants gave written informed consent.
Statistical analyses were conducted using SPSS version 15.0 (SPSS, Chicago, IL, USA). A one-way ANOVA test was performed to analyze differences in the percentage of the region methylation among pancreatic cancer tissues, adjacent normal pancreatic tissues, chronic pancreatitis tissues, and normal pancreatic tissues. General linear model univariate analysis was performed to determine the correlations of SPARC methylation with clinical char- acteristics of pancreatic cancer. All variables were subse- quently analyzed using a stepwise multiple regression to assess their independent contribution to the methylation level, with entry and removal at the 0.05 and 0.1 signifi- cance levels, respectively.
DOI: 10.4236/ijmpcero.2019.83012 133 Int. J. Medical Physics, Clinical Engineering and Radiation Oncology occational episodes of convulsion or headache without any obvious bleeding) were confirmed by digital subtraction angiography (DSA) and were planned for SRS with robotic radiosurgery system. Planning scans done as per the protocol with plain CT scan brain, CT angiography and MR angiography. After fusion of the images in “Multiplan” system and assessment of diagnostic DSA images, the nidus volume and organ at risk (OARs) were contoured. No PTV margin was generated in the nidus (target) and normal brain volume contoured without ex- cluding the nidus volume. Robotic Radiosurgery (CyberKnife®) treatment plans were generated in Multiplan treatment planning algorithm. Computed tomo- graphy images of the patients acquired with 1 mm spacing were used to create treatment plans. Treatment plans are generated using the sequential optimiza- tion method. Radiosurgery plans were generated with treatment paths that con- trol the beam orientations specific to different anatomical sites. Treatment plans for patients with AVM were generated using the head path with 6D skull track- ing method to deliver a dose of 20 Gy marginal dose in a single treatment ses- sion. Multiple shells with asymmetric margins around the target were used to limit the dose to critical structures near the target. The dose distribution in the computed tomography images of the patient’s head was calculated using the “Raytracing” algorithm. Collimator sizes of 7.5 and 10 mm were used in the treatment plan. Number of beams, monitor unit (MU), nodes, CI, nCI, HI and 12 Gy normal brain volumes in all the plans were documented in Table 1. Ap- proved plan had nidus coverage more than 98%, optimal number of beams, ac- ceptable CI, nCI and HI values and adjacent critical structure dose within nor- mal limits. The nidus volumes were small, ranging from 0.32 cc to 9.4 cc [Table 1]. As the nidus
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cancer, but up to 30% of patients will experience bio- chemical failure (rising PSA) or gross disease recurrence after surgery. These findings may be due to significant clinical under-staging and suggests that many sub-clinical metastases are not diagnosed at the time of surgery for presumed localized disease. Improved prediction of bio- logically aggressive tumors with a high propensity towards early metastasis would allow for either more aggressive or more appropriate primary treatment. We describe here our finding that CD10-positive tumors are of a more aggressive cancer type predictive of lymph node metastasis and biochemical recurrence after primary ther- apy. Osman et al.  have earlier reported a study on prostate cancer CD10 expression. Although our immuno- histochemistry data are similar in that a majority of tumors are CD10-negative and CD10 + cancer cells tend to
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and proliferation. These genes included COL1A2, COL3A1, CLO6A3 , FABP7 [16, 34-37], GDF-15, SH3GL2 [38, 39], ADM, VEGFA, and PTX3 [40, 41]. Our gene signature also contained proneural genes, BMP2, DCX, IGFBP2, PDPN, and PLAT, which are associated with anaplastic oligodendroglioma harboring 1p/19q co-deletion . The proneural genes indicate a better prognosis of malignant glioma . The 89-gene signature consists of a number of hypoxia and inflammation- related genes such as AKR1C3 , PTX3, PLAT  and IGFBP2 , showing that these two inseparable hallmarks are involved in tumor progression [47, 48] and play significant roles in glioma pathogenesis. Purinergic signaling related genes such as GPR17 , VEGFA  and CCL2  are involved in inflammation leading to glioma growth [52, 53]. In addition, BCAT1 was reported to promote cell proliferation in gliomas carrying wild-type IDH1 . Our gene signature also possessed several genes related to clinical characteristics of recurrent glioblastoma. Furthermore, genes such as AKR1C3, ETNPPL, FXYD1, SH3GL2, SH3GL3, SNAP91, and SYT1 have important role in reprograming and are also involved in drug resistance . Additionally, IPA revealed that most of the genes were controlled by NF-KB, STAT3, and AP-1 transcription factors. These transcription factors play a vital role in cancer and are important regulators of immune and inflammatory functions [56–58]. Finally, many novel genes including CHRNA9, CNGA3, FERMT1, FZD7, GABRB3, METTL7B, USD5, and SYT4 were also identified, suggesting that our 89-gene signature contains novel information which may provide new biomarkers to assist in clinical decision making concerning new opportunities for targeted treatment of individual patients.
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[32–34]. The reduction of 5hmC in high-grade glioma was indeed noted in our study (Figure 2C). It is well established that epigenetic modifications and associated proteins function in a cooperative manner. As the DNA modification per se is not convenient to quantify, it is rational to exploit some relevant epigenetic proteins as the alternative in clinical applications. In this regard, a group of patients bearing correlated levels of MBD3 and 5hmC in tumor biopsies were recruited. In the 60-month follow-up, MBD3 – as well as 5hmC – exhibited a positive correlation with the patients’ survival. The PFS of GBM patients who received gross total resection in surgery and adjuvant therapies (i.e., radiotherapy and temozolomide) was highly proportional to the intra-tumor levels of MBD3 and 5hmC (Figure 7). This correlation was also observed in the WHO grades II-III patients (Figures S12-S13). From MRI imaging, tumors with a relatively high abundance of MBD3 and 5hmC showed a more confined growth whereas low abundance of MBD3 and 5hmC contributed to a more aggressive, pre-multifocal growth (Figure 8). Therefore, this set of data supports the potential of MBD3 as a novel epigenetic marker to complement 5hmC in the clinical management of malignant glioma.
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KA, Vasko V, Larin A, Tallini G, Tolaney S, Holt EH, Hui P, Umbricht CB, Basaria S, Ewertz M, Tufaro AP, Califano JA, Ringel MD, Zeiger MA, Sidransky D, Ladenson PW: BRAF mutation predicts a poorer clinical prognosis for papillary thyroid cancer. J Clin Endocrinol Metab 2005, 90:6373 – 6379. 17. Lupi C, Giannini R, Ugolini C, Proietti A, Berti P, Minuto M, Materazzi G, Elisei
There are different concepts on bala and it is of wide use in health and treatment of an individual. There is a necessity to un- derstand the concept of bala pareeksha in patients and healthy individuals. Charaka, Vaghbata and Sushruta have explained about concepts of bala. The present review was done in order to collect the concept of bala, its pareeksha and its implication. MATERIALS & METHODS
I understand that sponsor of the clinical study, others working on the sponsor’ s behalf, the Ethics committee and the regulatory authorities will not need my permission to look at my health records, both in respect of current study and any further research that may be conducted in relation to it, even if I withdraw from the study I agree to this access. However, I understand that my identity will not be revealed in any information released to third parties or published, unless as required under the law. I agree not to restrict the use of any data or results that arise from this study.
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The mechanisms of CD147 in CSCC tumouri- genesis, progression and invasion remain to be elucidated. Previous studies have demonstrat- ed that CD147 promotes tumour cell move- ment and metastasis. It has been reported that the interaction of CD147 with Annexin A2 and the DOCK3-β-catenin-WAVE2 signalling path- way  and its involvement in TGF-β-induced epithelial-mesenchymal transition helps indu- ce hepatocellular carcinoma invasion . In our study, the clinical implication of CD147- HPV16E6 co-expression suggested that the CD147-HPV16 interaction might be involved in CSCC progression. Therefore, we investigated p53 and pRB expression, each of which is directly affected by HPV16E6 and HPV16E7, respectively. In our statistical studies, we found that p53 expression is statistically associated with CD147 and CD147-HPV16E6. Therefore, we hypothesize that CD147, HPV16E6 and p53 exist in a signalling pathway to promote CSCC tumourigenesis and progression. This hypothe- sis requires further studies on the exact mech- anism of CD147, HPV16E6 and p53 interaction using cytobiological and molecular biological methods.
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issues may become a primary concern in clinical decisions for situations where survival benefits with current therapy are modest. For some, the number of days, months, or years given following a diagnosis of metastatic melanoma may not be as concerning as the quality of that time period and the absence of underlying side effects (see Table 1). In one study of patients with melanoma, those who demonstrated optimism and positivity about their disease prognosis or who minimized the influence of cancer in their daily lives were found to live longer than those who did not. 62 Patients
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The situation of bone in ankylosing spondylitis (AS) is more complex. Clearly the same systemic bone loss is obvious in these patients with the extreme frailty of ver- tebral bone. In sharp contrast is the situation in the syn- desmophytes in AS. There the opposite is seen with ectopic new bone formation. In that case, excessive bone formation is the issue, resulting in the clinical spinal stiffness. In this context of AS, if, as discussed above, cytokines induce bone destruction, how can we justify the use of TNF inhibitors if inhibition of destruc- tion and even induction of repair is the consequence of such treatment? Either there should be a contraindica- tion or short-term use, unless there is another explan- ation. Inhibition of TNF has been registered for AS and PsA and this has been extended to IL-17A inhibition.
Artemisinin and its derivatives have successfully been used in treatment of falciparum malaria infections in various parts of the world. More importantly, they have proved effective against strains resistant to conventional antimalarials such as chloroquine and mefloquine in those parts of the world where malaria is endemic. Only one clinically relevant artemisinin-resistant human malaria has been reported recently in South East Asia, although there are reports published on development of the rodent malaria parasite strains resistant to the drug earlier. This article reviews the implications of combination therapy on the pharmacokinetics and hence clinical efficacy of Artemisinins using relevant and published papers. It gives detailed account on the general chemistry and mechanism of action of the parent compound Artemisinin before considering its pharmacokinetics. Artemisinin-based combination treatments (ACTs) are now generally accepted as the best treatment options for uncomplicated falciparum malaria. They are rapidly and reliably effective. The article would focus on combination therapy & its implication on the pharmacokinetics & clinical efficacy of artemisinin & its derivatives and also presents the scientific rationale for the need of combining Artemisinins to enhance their clinical efficacy and also minimize the likelihood of the emergence of resistant strains of the malarial parasites. INTRODUCTION: The Chinese medicinal plant qinghao
patients. This ﬁ nding may provide a novel perspective for prognosis evaluation of LUAD patients. The prognosis of lung cancer is a key issue for clinicians. Although the related research has gradually increased in recent years, there is no uniform prognostic standard. The current prognostic indica- tors for evaluating lung cancer include epidermal growth factor receptor (EGFR), K-ras gene mutation, TTF-1, Napsin A 34–36 ; however, these indicators certain limitations in speci ﬁ city and sensitivity. ERR α may be able to perform an auxiliary assessment in cases where other indicators are not valid, especially in distinguishing between LUAD and LSCC, which can play an important role in clinical application.
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