Naples prognostic score as a predictor of outcomes in lung cancer: a systematic review and meta-analysis.

OBJECTIVE: The Naples prognostic score (NPS) is a newly developed indicator of inflammation and nutritional status. However, its role in predicting the prognosis of lung cancer is unclear. We hereby reviewed the association between NPS and outcomes of lung cancer. MATERIALS AND METHODS: PubMed, Web of Science, Embase, and Google Scholar were searched up to 15th April 2023 for studies assessing the predictive role of NPS for overall survival (OS) and disease-free survival (DFS) in lung cancer. RESULTS: Seven studies were included. All were from China. One study was on small cell lung cancer, while the rest were on non-small cell lung cancer. Meta-analysis demonstrated that a high NPS score was a significant predictor of OS (HR: 3.21 95% CI: 2.27, 4.54 I2=62%) and disease-free survival (DFS) (HR: 3.81 95% CI: 2.57, 5.64 I2=65%) in lung cancer patients. Subgroup analysis based on different NPS reference values also showed similar results. The results remained significant on sensitivity analysis. CONCLUSIONS: The NPS is a strong and independent prognostic indicator of lung cancer patients. Higher NPS scores are associated with worse OS and DFS. Further studies from non-Chinese populations are needed to supplement the results.

Could immune-related hepatitis rapidly progress to immune-related cirrhosis?

BACKGROUND: Immune-related hepatitis is one of the prevalent adverse events associated with immunotherapy, especially immune checkpoint inhibitors (ICIs). For patients without a history of liver disease, autoimmune disease, or alcohol consumption, it is not clear whether immune-related hepatitis could rapid progress to immune-related cirrhosis. CASE REPORT: We report the case of a 54-year-old female with stage IIIB primary pulmonary lymphoepithelioma-like carcinoma (PLELC) diagnosed with immune-related hepatitis. After 15 months, a liver biopsy demonstrated the rapid progression of liver cirrhosis although systematic corticosteroid administration. CONCLUSIONS: Long-term immune activation caused by ICIs may exacerbate the process of cirrhosis. Great attention should be paid to the rapid progression to liver cirrhosis of immune-related hepatitis in the clinic.

Shape-Guided Mixed Metro Map Layout.

Metro or transit maps, are schematic representations of transit networks to facilitate effective route-finding. These maps are often advertised on a web page or pamphlet highlighting routes from source to destination stations. To visually support such route-finding, designers often distort the layout by embedding symbolic shapes (e.g., circular routes) in order to guide readers' attention (e.g., Moscow map and Japan railway map). However, manually producing such maps is labor-intensive and the effect of shapes remains unclear. In this paper, we propose an approach to generalize such mixed metro maps that take user-defined shapes as an input. In this mixed design, lines that are used to approximate the shapes are arranged symbolically, while the remaining lines follow classical layout convention. A three-step algorithm, including (1) detecting and selecting routes for shape approximation, (2) shape and layout deformation, and (3) aligning lines on a grid, is integrated to guarantee good visual quality. Our contribution lies in the definition of the mixed metro map problem and the formulation of design criteria so that the problem can be resolved systematically using the optimization paradigm. Finally, we evaluate the performance of our approach and perform a user study to test if the embedded shapes are recognizable or reduce the map quality.

Upregulation of miR-335 reduces myocardial injury following myocardial infarction via targeting MAP3K2.

OBJECTIVE: Acute myocardial infarction (AMI) is a serious cardiovascular disease with a high incidence worldwide and the main cause of sudden cardiac death. The aim of this article was to study the protective role of miR-335 in myocardial infarction (MI) and the underlying molecular mechanism. MATERIALS AND METHODS: Thirty Sprague Dawley (SD) rats were randomly divided into sham group, MI + NC group and MI + agomiR-335 group. The expression of miR-335 in rat myocardium was detected by quantitative Real Time-Polymerase Chain Reaction (RT-PCR). Western blot was performed to detect the expression of TNF-α, IL-6, IL-1ß, Caspase-3, Cleaved Caspase-3 (C-Caspase-3) and MAP3K2 in rat myocardium. On the 7th day of the establishment of the rat MI model, a high-resolution small animal ultrasound system was utilized to detect the cardiac function of the rats, and the heart tissues and blood samples of the rats were collected. The corresponding kits were purchased to detect the contents of LDH, CK-MB, MDA and SOD in rat serum, and HE staining was employed to observe the morphology of rat myocardial tissue. RESULTS: The expression of miR-335 in myocardial infarcted zones and border zones of MI rats decreased significantly. The upregulation of miR-335 remarkably inhibited myocardial inflammation and apoptosis after MI, thus improving the cardiac function of MI rats. Compared with the sham group, the MAP3K2 expression in the MI + NC group was observably increased, while the overexpression of miR-335 could inhibit the expression of this protein. Through the Luciferase reporter gene experiment, we found that miR-335 could directly target MAP3K2. CONCLUSIONS: The expression of miR-335 decreased in myocardial tissue after MI, and the overexpression of miR-335 reduced myocardial damage by inhibiting oxidative stress, inflammation, and apoptosis via targeting MAP3K2, thereby improving the cardiac function of MI rats.

CSE1L promotes proliferation and migration in oral cancer through positively regulating MITF.

OBJECTIVE: CSE1L (human chromosomal segregation 1-like) is reported to be able to affect cell apoptosis, invasiveness, and migration. The purpose of this study was to uncover the regulatory effects of CSE1L on cell phenotypes of oral cancer and the underlying mechanism. MATERIALS AND METHODS: CSE1L levels in oral cancer cells were determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blot. CSE1L overexpression and knockdown models were constructed in CAL-27 and HN6 cells, respectively. Changes in proliferative and migratory abilities in oral cancer cells affected by CSE1L and microphthalmia-associated transcription factor (MITF) were assessed by cell counting kit-8 (CCK-8), 5-Ethynyl-2'-deoxyuridine (EdU) and wound healing assay. Meanwhile, potential influences of CSE1L and MITF on relative levels of E-cadherin and Vimentin in oral cancer cells were detected. Finally, regulatory effects of CSE1L and MITF on the Akt/mTOR pathway were evaluated by detecting expression levels of p-Akt, Akt, p-mTOR, and mTOR. RESULTS: CSE1L was upregulated in oral cancer cells. Knockdown of CSE1L in HN6 cells attenuated proliferative and migratory abilities, as well as downregulated Vimentin and upregulated E-cadherin. Overexpression of CSE1L in CAL-27 cells yielded the opposite results. MIFT level was positively regulated by CSE1L. Overexpression of MITF partially reversed regulatory effects of CSE1L on proliferative ability of oral cancer cells. Moreover, silence of CSE1L suppressed the Akt/mTOR pathway, which was reversed by overexpression of MITF. CONCLUSIONS: CSE1L promotes the proliferative and migratory abilities in oral cancer cells by positively regulating MITF, thus activating the Akt/mTOR pathway.

The diagnostic and prognostic values of serum and urinary kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin in sepsis induced acute renal injury patients.

OBJECTIVE: The kidney injury molecule-1 (uKIM-1) and neutrophil gelatinase-associated lipocalin (uNGAL, sNGAL) have been demonstrated to be diagnostic biomarkers for acute kidney injury (AKI) in a variety of diseases. However, both of them were not well validated in sepsis patients with acute kidney injury. PATIENTS AND METHODS: This was a prospective and observational study which was performed in the three intensive care units of the Beijing Chao-Yang Hospital. Over a 12-month period, 174 patients (70 sepsis patients, 69 sepsis with AKI and 35 controls) were enrolled. Blood and urinary specimens were collected at admission as soon as possible (within 24 hours) and KIM-1 and NGAL levels were tested. RESULTS: Levels of uKIM-1, uNGAL, sNGAL were significantly higher in the sepsis patients who developed AKI compared to those sepsis with no-AKI (0.88 ng/ml (0.37, 2.14) vs. 1.21 ng/ml (0.67, 3.26) p=0.003, 63.54 ng/ml (21.66, 125.45) vs. 249.85 ng/ml (86.60, 585.97) p<0.001, and 108.08 ng/ml (67.74, 212.22) vs. 200.01 ng/ml (102.76, 300.77) p=0.001, respectively). sKIM-1 also had significant differences between the two groups (83.98 pg/ml (54.00,147.08) vs. 193.41 pg/ml (106.90, 430.60) p<0.001). The four biomarkers (uKIM-1, sKIM-1, uNGAL, sNGAL) all could be predictive for AKI, and the areas under the receiver operating characteristic curves (AUROC) were 0.607, 0.754, 0.768, 0.658, respectively. The uNGAL was an independent risk factor for septic AKI, and the AUROC was 0.768 (95% CI: 0.689 to 0.835). The uNGAL and sNGAL were related to the prognosis of sepsis. CONCLUSIONS: Our results showed that NGAL was a promising biomarker of septic AKI. Like the uKIM-1, the sKIM-1 could early predict the occurrence of septic AKI too, but both of them did not have the predictive value in judging the severity of AKI and the prognosis of sepsis.

Exogenous IL-19 mediates downregulation of TGF-ß through Erk and p38 pathway to inhibit epidural fibrosis.

OBJECTIVE: To evaluate the effect of interleukin-19 (IL-19) treatment on epidural fibrosis and its mechanism of action with transforming growth factor ß (TGF-ß). MATERIALS AND METHODS: Initially, IL-19 (10, 20, 50 and 100 ng/L) was used to pretreat rat fibroblasts. TGF-ß (10 µg/L) was then applied to activate fibroblasts. The protein expression levels of TGF-ß receptor, extracellular-signal-regulated kinase (Erk) and p-38 were measured by Western blotting. In addition, we performed laminectomy at T10 vertebral plate in rats, followed by injection of IL-19 in caudal vein one week after injury. Furthermore, IL-19, TGF-ß and fibrosis indexes were measured by quantitative Real-time polymerase chain reaction (qRT-PCR) and Western blotting at 7 and 28 days after injury, respectively. RESULTS: Concentration-dependent IL-19 significantly down-regulated TGF-ß receptor expression and inhibited phosphorylated Erk (p-Erk) and phosphorylated p38 (p-p38). In vivo, IL-19 reduced the expressions of TGF-ß and connective tissue growth factor (CTGF) at 7 days. Furthermore, IL-19 significantly suppressed extracellular matrix productions formation, including α smooth muscle actin (α-SMA) and collagen-1 (COL-1), and fibronectin at 28 days. CONCLUSIONS: IL-19 inhibited TGF-ß expression via Erk and p38 pathway. Moreover, it decreased CTGF expression to suppress α-SMA, COL-1 and fibronectin in scar tissues, thereby preventing spinal cord from compression of scar tissues.

Association of Serum 25(OH) D Levels with Infarct Volumes and Stroke Severity in Acute Ischemic Stroke.

BACKGROUND: The aim of this study is to investigate whether 25-hydroxyvitamin D [25(OH) D] is associated with initial stroke severity and infarct volume, using diffusion-weighted imaging (DWI) in patients with acute ischemic stroke. METHODS: We studied a total of 235 patients who were admitted within 24 hours of acute ischemic stroke onset. Initial stroke severity was assessed using the NIH Stroke Scale (NIHSS) score. Infarct volume was measured using DWI. Multivariable linear and logistic regression analyses were used to test whether 25(OH) D represents an independent predictor of infarct volume and stroke severity (NIHSS score of ≥6). RESULTS: Among 235 study patients, the median age was 64 years (IQR 56-75 years), and 125 (53.2%) were women. In multivariable models adjusted for other significant risk factors, 25(OH) D levels in the lowest and second interquartiles were associated with an increased risk of a NIHSS≥6 (with highest 25 (OH) D quartile as reference) with odd ratios (OR) 3.02(95% confidence interval [CI]:1.59-6.34) and 5.85(2.90-11.54). The median DWI infarct volumes for the serum 25(OH) D level quartiles (lowest to highest) were 12.35, 6.55, 2.44, and 1.59 ml. The median DWI infarct volume in the lowest serum 25(OH) D level quartile was larger than that in the other 3 quartiles (P<0.001). The median adjusted DWI infarct volume in the lowest serum 25(OH) D level quartile was statistically significantly larger than that in the other 3 quartiles (P<0.01). CONCLUSION: In conclusion, reduced serum 25(OH) D levels in acute ischemic stroke are an early predictor of larger volumes of ischemic tissue and worse neurological deficit (assessed by the NIHSS).

Interleukin-armed chimeric antigen receptor-modified T cells for cancer immunotherapy.

Chimeric antigen receptor-modified T cells (CAR-T) are endowed with cytotoxic specificity to tumor cells. Although CAR-T-based cancer immunotherapy presents curable therapeutic potential for hematological malignancies, achieving substantial efficacy for solid tumors remain challenging. Researchers have exploited many strategies to enhance the anti-tumor efficacy of CAR-T cells for solid tumors, among which cytokine-armed CAR-T cells improve the proliferation, survival, homing and other properties of CAR-T cells. Interleukins (ILs), pivotal cytokines that affect the function of immune cells, were co-expressed in CAR-T cells or combinatorially administered to enhance the therapeutic potential in clinical trials. In this review, we summarize the strategies exploited by ILs to improve the anti-cancer ability of CAR-T cells and the different impacts of different ILs on CAR-T cells.

Molecular characterizations of DNA methyltransferase 3 and its roles in temperature tolerance in the whitefly, Bemisia tabaci Mediterranean.

The Bemisia tabaci Mediterranean (MED) cryptic species is an invasive pest, distributed worldwide, with high ecological adaptability and thermotolerance. DNA methylation (a reversible chromatin modification) is one possible change that may occur within an organism subjected to environmental stress. To assess the effects of temperature stress on DNA methyltransferase 3 (Dnmt3) in MED, we cloned and sequenced BtDnmt3 and identified its functions in response to high and low temperatures. The full-length cDNA of BtDnmt3 was 3913 bp, with an open reading frame of 1962 bp, encoding a 73.89 kDa protein. In situ hybridization showed that BtDnmt3 was expressed mainly in the posterior region. BtDnmt3 messenger RNA expression levels were significantly down-regulated after exposure to heat shock and significantly up-regulated after exposure to cold shock. Furthermore, after feeding on double-stranded RNA specific for BtDnmt3, both heat resistance and cold resistance were significantly decreased, suggesting that BtDnmt3 is associated with thermal stress response and indicating a differential response to high- and low-temperature stress in MED. Together, these results highlight a potential role for DNA methylation in thermal resistance, which is a process important to successful invasion and colonization of an alien species in various environments.

The safety profile of subcutaneous allergen immunotherapy in children with asthma in Hangzhou, East China

Background: The aim of the current study is to evaluate the prevalence, severity and possible risk factors of systemic reactions (SRs) to subcutaneous allergen immunotherapy (SCIT) in children and adolescents with asthma in Hangzhou, east China's Zhejiang province. Methods: From January 2011 to December 2016, this survey analysed the SCIT-related SRs involving 429 patients (265 children and 134 adolescents) affected by allergic asthma. Recorded data included demographics, diagnosis, patient statuses, pulmonary function testing results before and after each injection, allergen dosage, and details of SRs. Results: All patients finished the initial phase and six patients withdrew during the maintenance phase. There were 2.59% (328/12,655) SRs in all injections (3.28% in children and 1.47% in adolescents); 15.62% (67/429) patients experienced SRs (18.49% children and 10.98% adolescents). There were 54.57% SRs of grade 1; 42.37% SRs of grade 2; 3.05% SRs of grade 3; and no grades 4 or grade 5 SRs occurred in patients. Most reactions were mild, and were readily controlled by immediate emergency treatment. There was no need for hospitalisation. The occurrence of SRs was significantly higher in children than that in adolescents (p < 0.01). A higher ratio of SRs was found among patients with moderate asthma. Conclusion: This retrospective survey showed that properly-conducted SCIT was a safe treatment for children and adolescents with asthma in Hangzhou, East China. Children and patients with moderate asthma may be prone to develop SRs (AU)

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Clinical significance of SCCRO (DCUN1D1) in prostate cancer and its proliferation-inhibiting effect on Lncap cells.

OBJECTIVE:   SCCRO/DCUN1D1/DCN1 (squamous cell carcinoma-related oncogene/defective in cullin neddylation 1 domain containing 1/defective in cullin neddylation) is considered as an oncogene, but its role in the prostate cancer (PC) is still not clear. The current study aims to investigate the expression of SCCRO in PC tumor tissues, further its clinical significance, and proliferation inhibiting effect on PC cells in vitro. PATIENTS AND METHODS: RT-PCR was used to detect the expression of SCCRO in PC tissue and corresponding adjacent normal tissues from 160 cases, and its relationship with clinical pathological characteristics was analyzed. Small interfering RNA (siRNA) expression plasmid targeting SCCRO gene was constructed and transferred into PC cell line Lncap. The effect on proliferation was observed by CCK8 assay, and its influence on invasion and migration of Lncap cells was studied by Transwell Matrigel assay after SCCRO gene was silenced. The expression of focal adhesion kinase (FAK) and matrix metalloproteinase-2 (MMP-2) influenced by SCCRO silencing were detected by Western blot. RESULTS: mRNA expression of SCCRO protein increased significantly in cancer tissues compared to adjacent normal tissue, especially for T3+T4, N+, and III+IV patients (p<0.05). SCCRO expression was an independent prognostic factor (p<0.05). After SCCRO gene was knocked down by siRNA, the SCCRO protein level decreased 78.4% in the siRNA-3 group. By CCK8 assay, knocking down SCCRO in Lncap significantly reduced the cell proliferation, as well as its migration and invasion capability compared to siRNA-control group (p<0.01) by transwell invasion and migration assay. The expression of FAK and MMP-2 also reduced in siRNA-3 group compared to siRNA control group (p<0.01). CONCLUSIONS: SCCRO is associated with progression and prognosis of PC. After SCCRO gene was transferred, the growth of Lncap cells was inhibited, and ability of invasion and migration decreased by reducing the expression of FAK and MMP-2. SCCRO has potential to become a new target for the treatment of PC.

Multi-detector spiral CT diagnosis of common bile duct ampullary carcinoma.

OBJECTIVE: The aim of this project was to study the imaging characteristics of multi-detector CT (MDCT) in different types of malignant tumor in the common bile duct ampulla. PATIENTS AND METHODS: We examined 30 cases of pancreatic head cancer, 35 of terminal cholangiocarcinoma, 26 of ampullary carcinoma, and 40 of benign lesions, all confirmed by pathology. We used 64-slice spiral CT plain scan and multi-phase enhanced scan with multi-planar reconstruction (MPR) and curved planar reconstruction (CPR) post-processing to obtain three-dimensional images. From these images, we analyzed intrahepatic and extrahepatic bile ducts, gallbladder and common bile duct dilation, and morphology and enhancement pattern of lesions and surrounding tissue. RESULTS: The dilatation rate of intrahepatic, extrahepatic bile duct and gallbladder in terminal cholangiocarcinoma was the highest. The double duct sign was most evident in pancreatic head cancer. Ampullary carcinoma fell in between, and the benign lesions had no intrahepatic or extrahepatic bile duct and pancreatic duct dilation. Pancreatic cancer had a larger diameter, a higher internal rate of necrosis, and the surrounding tissues had a higher vulnerability to invasion. Terminal cholangiocarcinoma had a smaller diameter and a thicker wall. Benign lesions showed isodensity and hyperdensity shadow in the lumen, but no other significant changes were observed. Pancreatic head carcinoma had lower enhancement degree than normal pancreatic tissue, no enhancement in the internal necrotic area, and the borderline was unclear. Thickened ductal wall of the terminal cholangiocarcinoma showed equal density, enhancement and commonly delayed enhancement. The enhancement degree was higher than in the cancer of the pancreatic head and slightly lower than in ampullary cancer. Ampullary cancer had a regular margin and a significant enhancement, with enhancement degree higher than in pancreatic cancer and lower than in common bile duct cancer. Arterial and venous phases showed enhancement, but benign lesions did not show enhancement. CONCLUSIONS: MDCT imaging and post-processing techniques have significant application in the diagnosis of benign and malignant lesions, as well as a malignant tumor of the common bile duct ampulla.

Long non-coding RNA CPS1-IT1 is a positive prognostic factor and inhibits epithelial ovarian cancer tumorigenesis.

OBJECTIVE: The aim of the present study was to explore the prognostic value of long non-coding RNA CPS1-IT1 (CPS1-IT1) expression in epithelial ovarian cancer (EOC) patients and identify the effect of CPS1-IT1 on cell proliferation and apoptosis of EOC cells. PATIENTS AND METHODS: Expression levels of CPS1-IT1 in tissues and cells were detected by the Real-time quantitative RT-PCR assay. The χ2-test was used to analyze the relationship between CPS1-IT1 expression and the clinicopathological characteristics. Survival analysis was performed using the Kaplan-Meier method and Cox's proportional hazards model. The capacity for cellular proliferation was measured with cell counting Kit-8. Cell apoptosis assays were performed using flow cytometry. Western blot was used to detect the expression levels of cell apoptosis-related proteins. RESULTS: We observed that CPS1-IT1 was significantly downregulated in EOC cell lines and tissue samples. The expression of CPS1-IT1 was significantly associated with FIGO stage and lymph node metastases. In addition, EOC patients in the low tissue CPS1-IT1 expression group had significantly shorter 5-year overall survival time than those in the high tissue CPS1-IT1 expression group. Furthermore, univariate and multivariable Cox regression analysis identified low CPS1-IT1 expression in EOC tissues as an independent poor prognostic marker of overall survival. It was also found that over-expression of CPS1-IT1 markedly promoted proliferation of EOC cells. Further studies revealed that over-expression of CPS1-IT1 induced cell apoptosis by through regulating apoptosis-related proteins. CONCLUSIONS: CPS1-IT1 may be a functional tumor suppressor in EOC. It may also serve as an independent prognostic factor for patients with EOC.

Influence of VEGF/BMP-2 on the proliferation and osteogenetic differentiation of rat bone mesenchymal stem cells on PLGA/gelatin composite scaffold.

OBJECTIVE: To investigate the influence of VEGF/BMP-2 on the proliferation and osteogenic differentiation of rat bone mesenchymal stem cells BMSCs) on PLGA/gelatin composite scaffold. MATERIALS AND METHODS: Randomly-oriented nanofibers with different ratios of Poly Lactic-co-Glycolic Acid (PLGA)/gelatin were produced through electrospinning. The mixture of nanofibers and BMSCs was pipetted onto the surface of the scaffolds, and BMSCs/PLGA/gelatin composite was obtained. The surface morphology, chemical structure, hydrophilicity and mechanical property of PLGA/gelatin nanofibers were revealed by scanning electron microscope. In vitro release kinetics of bone morphogenetic protein (BMP-2) and vascular endothelial growth factor (VEGF) were studied using ELISA kits. The cell adhesion, growth and proliferation of BMSCs on scaffolds were observed by scanning electron microscopy. The CCK-8 assay was used to evaluate the effects of VEGF/BMP-2 slow release system on the proliferation of BMSCs on scaffolds. RT-PCR was used to examine the activities of alkaline phosphatase (ALP), runt-related transcription factor 2 (RUNX-2), and osteocalcin (OCN). RESULTS: In each group of cells in the in-vitro experiment, through electron microscope scanning, fiber scaffolds were interconnected three-dimensional reticular structure, BMSCs firmly attached to the fiber surface and internal stent, cells experienced a long spindle, polygon change, and branch-like protrusions on the cell surface were connected. Under the electron microscope, cell proliferation curve and osteogenesis markers (ALP, RUNX-2, OCN) expression in the dual factor group on cell adhesion, proliferation and differentiation were much better than those of blank control group and single factor groups. CONCLUSIONS: In the successfully constructed gelatin/PLGA nanofiber scaffold, VEGF and BMP-2 can be sequentially released, during which VEGF and BMP-2 can promote the adhesion, proliferation, and differentiation of BMSCs.

The safety profile of subcutaneous allergen immunotherapy in children with asthma in Hangzhou, East China.

BACKGROUND: The aim of the current study is to evaluate the prevalence, severity and possible risk factors of systemic reactions (SRs) to subcutaneous allergen immunotherapy (SCIT) in children and adolescents with asthma in Hangzhou, east China's Zhejiang province. METHODS: From January 2011 to December 2016, this survey analysed the SCIT-related SRs involving 429 patients (265 children and 134 adolescents) affected by allergic asthma. Recorded data included demographics, diagnosis, patient statuses, pulmonary function testing results before and after each injection, allergen dosage, and details of SRs. RESULTS: All patients finished the initial phase and six patients withdrew during the maintenance phase. There were 2.59% (328/12,655) SRs in all injections (3.28% in children and 1.47% in adolescents); 15.62% (67/429) patients experienced SRs (18.49% children and 10.98% adolescents). There were 54.57% SRs of grade 1; 42.37% SRs of grade 2; 3.05% SRs of grade 3; and no grades 4 or grade 5 SRs occurred in patients. Most reactions were mild, and were readily controlled by immediate emergency treatment. There was no need for hospitalisation. The occurrence of SRs was significantly higher in children than that in adolescents (p<0.01). A higher ratio of SRs was found among patients with moderate asthma. CONCLUSION: This retrospective survey showed that properly-conducted SCIT was a safe treatment for children and adolescents with asthma in Hangzhou, East China. Children and patients with moderate asthma may be prone to develop SRs.

The involvement of senescence induced by the telomere shortness in the decline of osteogenic differentiation in BMSCs.

OBJECTIVE: BMSC (Bone marrow mesenchymal stem cells) is an important seed cell for the repair of bone and cartilage defect in the tissue engineering. The proliferation rate and differentiation capacity of BMSCs from the old donors were less than that from young donors; however, the related mechanism remained unclear. MATERIALS AND METHODS: Sprague Dawley (SD) rats BMSCs were cultured and treated. Hydrogen peroxide (H2O2) and continual passage of BMSCs were performed to induce senescence. Senescence was detected by the SA-b-Gal staining and the telomere length analysis. Cell proliferation and osteogenic differentiation were also observed. Finally, Olaparib was used to maintain the telomere length and investigate the role of telomere length and senescence on the cell proliferation and differentiation. RESULTS: H2O2 could increase the positive rate of SA-b-Gal staining in BMSCs and shorten the length of the telomere. The proliferation rate and ALP activity were also decreased by the H2O2. The senescence and decline of osteogenic differentiation could also be observed after prolonged passage of BMSCs. Inhibition of telomere length decline could attenuate the increased positive rate of SA-b-Gal staining induced by the H2O2, promote the cell proliferation, and enhance the capacity of osteogenic differentiation. CONCLUSIONS: Senescence induced by the decline of telomere length could reduce the capacity of osteogenic differentiation and inhibit cell proliferation in BMSCs.

LKB1 inhibits HPV-associated cancer progression by targeting cellular metabolism.

Liver kinase B1 (LKB1) is mutationally inactivated in Peutz-Jeghers syndrome and in a variety of cancers including human papillomavirus (HPV)-caused cervical cancer. However, the significance of LKB1 mutations in cervical cancer initiation and progress has not been examined. Herein, we demonstrated that, in mouse embryonic fibroblasts, loss of LKB1 and transduction of HPV16 E6/E7 had an additive effect on constraining cell senescence while promoting cell proliferation and increasing glucose consumption, lactate production and ATP generation. Knockdown of LKB1 increased and ectopic expression of LKB1 decreased glycolysis, anchorage-independent cell growth, and cell migration and invasion in HPV-transformed cells. In the tumorigenesis and lung metastasis model in syngeneic mice, depletion of LKB1 markedly increased tumor metastatic colonies in lungs without affecting subcutaneous tumor growth. We showed that HPV16 E6/E7 enhanced the expression of hexokinase-ll (HK-II) in the glycolytic pathway through elevated c-MYC. Ectopic LKB1 reduced HK-II along with glycolysis. The inverse relationship between HK-II and LKB1 was also observed in normal and HPV-associated cervical lesions. We propose that LKB1 acts as a safeguard against HPV-stimulated aerobic glycolysis and tumor progression. These findings may eventually aid in the development of therapeutic strategy for HPV-associated malignancies by targeting cell metabolism.

Size of bone flap and bone window area may impact the outcome of decompressive craniectomy using standard bone flap.

OBJECTIVE: To verify if the size of the bone flap and the bone window area may have an impact on the outcome of decompressive craniectomy. PATIENTS AND METHODS: From February 2012 to February 2014, 42 patients with acute intracranial hypertension were enrolled in this study. We conducted standard craniotomy and decompressive hemicraniectomy on all patients. The intracranial pressure was measured before the hemicraniectomy operation, at the time of bone flap removal, at the time of the incision of the dura mater and 24 hours after the operation. RESULTS: Intracranial pressure readings at the time of bone flap removal, incising dura mater and 24 hours postoperation were significantly lower than the pressure measured before the operation. The highest pressure was recorded at the time of the dura mater incision followed by pressure recorded at 24 hours post-operation and at the time of bone flap removal. The lowest pressure was recorded during the preoperative period. Postoperative GOSE and GCS scores were significantly higher than those scores recorded before the operation. A positive correlation between the diameter of the bone disc and the amount of drop in pressure at 24 h post-operation was detected. Also, the bone window area showed a positive correlation with the amount of drop in pressure at 24 h post-operation. CONCLUSIONS: The bone flap decompressive craniectomy is safe and effective, and the depressurizing range has a positive correlation with the diameter of the bone disc and the area of the bone window.

The clinical research of off-pump coronary artery bypass grafting by small incision at the left chest.

OBJECTIVE: To explore the clinical value of off-pump coronary artery bypass grafting by small incision at the left chest, and develop a better surgical regimen for coronary heart disease patients. PATIENTS AND METHODS: 201 coronary heart disease patients who need coronary artery bypass grafting were required and randomly divided into 2 groups including a control group and an observation group. There were 107 cases in the control group who received coronary bypass grafting by extracorporeal circulation; there were 103 cases in the observation group who received off-pump coronary bypass grafting by small incision at the left chest. The duration of the mechanism ventilation, length of stay in ICU, hospitalization time, postoperative drainage volume, and the occurrence rate of complications were recorded and compared. RESULTS: The duration of mechanism ventilation, length of stay in ICU, hospitalization time and postoperative drainage volume in the control group were (19.21 ± 1.33) hours, (5.08 ± 0.57) days, (21.20 ± 2.34) days and (997.68 ± 96.35) mL, which were (7.73 ± 0.74) hours, (2.83 ± 0.16) days, (15.67 ± 1.18) days and (901.53 ± 89.32) mL in the observation group respectively, with statistical difference between the two groups (p<0.05). The occurrence rates of renal insufficiency and arrhythmia were both 6.54% and 0.97% in the control group and the observation group, respectively. The occurrence rates of postoperative renal insufficiency and arrhythmia in the observation group were both significantly lower than those in the control group, with statistical significance analysis (p < 0.05). Postoperative low cardiac output, second thoracotomy, cerebrovascular disease, pulmonary infection, perioperative cardiac infarction and mortality did not display a significant difference between the two groups (p > 0.05). CONCLUSIONS: Off-pump coronary artery bypass grafting by small incision at the left chest is a surgical method with less injury and fast recovery, which can be used as the preferred therapeutical method for the coronary heart disease patients who need coronary artery bypass grafting.