[The influence of knocking down the expression of low-density lipoprotein receptor associated proteins on the vascular abnormalities in hepatocellular carcinoma and its mechanisms].

Objectives: To investigate the effect of the expression of low-density lipoprotein receptor associated protein (LDLR) on the vascular abnormalities in hepatocellular carcinoma (HCC) and its mechanisms. Methods: Based on the information of Oncomine Cancer GeneChip database, we analyzed the correlation between the expression level of LDLR and the expression level of carcinoembryonic antigen (CEA) and CD31 in hepatocellular carcinoma tissues. Lentiviral transfection of short hairpin RNA target genes was used to construct LDLR-knockdown MHCC-97H and HLE hepatocellular carcinoma cells. The differential genes and their expression level changes in LDLR-knockdown hepatocellular carcinoma cells were detected by transcriptome sequencing, real-time fluorescence quantitative polymerase chain reaction, and protein immunoblotting. The gene-related signaling pathways that involve LDLR were clarified by enrichment analysis. The effect of LDLR on CEA was assessed by the detection of CEA content in conditioned medium of hepatocellular carcinoma cells. Angiogenesis assay was used to detect the effect of LDLR on the angiogenic capacity of human umbilical vein endothelial cells, as well as the role of CEA in the regulation of angiogenesis by LDLR. Immunohistochemical staining was used to detect the expression levels of LDLR in 176 hepatocellular carcinoma tissues, and CEA and CD31 in 146 hepatocellular carcinoma tissues, and analyze the correlations between the expression levels of LDLR, CEA, and CD31 in the tissues, serum CEA, and alanine transaminase (ALT). Results: Oncomine database analysis showed that the expressions of LDLR and CEA in the tissues of hepatocellular carcinoma patients with portal vein metastasis were negatively correlated (r=-0.64, P=0.001), whereas the expressions of CEA and CD31 in these tissues were positively correlated ( r=0.46, P=0.010). The transcriptome sequencing results showed that there were a total of 1 032 differentially expressed genes in the LDLR-knockdown group and the control group of MHCC-97H cells, of which 517 genes were up-regulated and 515 genes were down-regulated. The transcript expression level of CEACAM5 was significantly up-regulated in the cells of the LDLR-knockdown group. The Gene Ontology (GO) function enrichment analysis showed that the differential genes were most obviously enriched in the angiogenesis function. The Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment analysis showed that the relevant pathways involved mainly included the cellular adhesion patch, the extracellular matrix receptor interactions, and the interactions with the extracellular matrix receptors. The CEA content in the conditioned medium of the LDLR-knockdown group was 43.75±8.43, which was higher than that of the control group (1.15±0.14, P＜0.001). The results of angiogenesis experiments showed that at 5 h, the number of main junctions, the number of main segments, and the total area of the lattice formed by HUVEC cells cultured with the conditioned medium of MHCC-97H cells in the LDLR-knockdown group were 295.3±26.4, 552.5±63.8, and 2 239 781.0±13 8211.9 square pixels, which were higher than those of the control group (113.3±23.5, 194.8±36.5, and 660 621.0±280 328.3 square pixels, respectively, all P＜0.01).The number of vascular major junctions, the number of major segments, and the total area of the lattice formed by HUVEC cells cultured in conditioned medium with HLE cells in the LDLR-knockdown group were 245.3±42.4, 257.5±20.4, and 2 535 754.5±249 094.2 square pixels, respectively, which were all higher than those of the control group (113.3±23.5, 114.3±12.2, and 1 565 456.5±219 259.7 square pixels, respectively, all P＜0.01). In the conditioned medium for the control group of MHCC-97H cells,the number of main junctions, the number of main segments, and the total area of the lattice formed by the addition of CEA to cultured HUVEC cells were 178.9±12.0, 286.9±12.3, and 1 966 990.0±126 249.5 spixels, which were higher than those in the control group (119.7±22.1, 202.7±33.7, and 1 421 191.0±189 837.8 square pixels, respectively). The expression of LDLR in hepatocellular carcinoma tissues was not correlated with the expression of CEA, but was negatively correlated with the expression of CD31 (r=-0.167, P=0.044), the level of serum CEA (r=-0.061, P=0.032), and the level of serum ALT(r=-0.147,P=0.05). The expression of CEA in hepatocellular carcinoma tissues was positively correlated with the expression of CD31 (r=0.192, P=0.020). The level of serum CEA was positively correlated with the level of serum ALT (r=0.164, P=0.029). Conclusion: Knocking down LDLR can promote vascular abnormalities in HCC by releasing CEA.

Phenotypic homogeneity of emetic Bacillus cereus isolates in China.

Emetic Bacillus cereus strains produce a potent cereulide cytotoxin, which can cause acute and fatal cases of food poisoning. We isolated 18 emetic B. cereus strains from a food poisoning event, and from clinical and non-random food surveillance in China and phenotypic characteristics of haemolysis, starch hydrolysis, salicin fermentation, gelatin liquefaction, cytotoxicity, and susceptibility to antibiotics were assessed. All isolates were positive for haemolysis and gelatin liquefaction, and negative for starch hydrolysis and salicin fermentation. Their haemolytic potentials were intermediate to Bacillus anthracis and B. cereus ATCC 14579 (a non-emetic strain). All isolates were cytotoxic to CHO, Hep-2, and Vero cells, and were sensitive to ampicillin. The homogeneous phenotypes of emetic isolates from China are similar to the corresponding traits of European and Japanese isolates that have been characterized, suggesting highly similar phenotypes of emetic B. cereus worldwide.

[Visual outcome of cataract surgery and its influencing factors in China].

Objective: To explore the visual outcome of cataract surgery and its influencing factors in China. Methods: A case-control study. The information of 2 078 479 patients who underwent cataract extraction of 31 provinces (municipalities and autonomous regions) recorded in the National Cataract Surgery Information Reporting System during January to December, 2017 were analyzed. The postoperative visual outcomes of 3 days after surgery and 3 months after surgery were analyzed. The effects of age, gender, preoperative corrected visual acuity, past medical history, and surgical methods on the results of cataract surgery were analyzed. Surgery effect was divided into ideal effect, moderate effect and poor effect according to the best corrected visual acuity after operation. Wilcoxon rank sum test and multinomial logistic regression model were used for statistical analysis. Results: There were 1 197 942 female patients (57.64%) and 880 537 male patients (42.36%) in all 2 078 479 cases. The average age was (69±11) years old. The main type of cataract was age-related (1 928 440 cases; 92.78%). There were 1 608 385 cases, 1 126 961 cases and 389 020 cases with complete corrected visual acuity before surgery, 3 days after surgery and 3 months after surgery, respectively. The median difference of corrected visual acuity of preoperative versus three days after surgery, and preoperative versus three months after surgery were -0.48, -0.52 respectively (after logarithm of the minimum angle of resolution conversion). The interquartile ranges were 0.60 and 0.73 respectively. The differences were statistically significant (Z=551 599.30, 206 815.35; both P<0.01). Multivariate analysis showed that postoperative complications (moderate effect: OR=0.50, 95%CI: 0.46 to 0.55; ideal effect: OR=0.31, 95%CI: 0.28 to 0.33), preoperative pupil abnormal (moderate effect: OR=0.52, 95%CI: 0.44 to 0.61; ideal effect: OR=0.55, 95%CI: 0.47 to 0.63), preoperative intraocular pressure abnormalities (moderate effect: OR=0.86, 95%CI: 0.79 to 0.93; ideal effect: OR=0.45, 95%CI: 0.42 to 0.49), history of hypertension (moderate effect: OR=0.90, 95%CI: 0.85 to 0.95; ideal effect: OR=0.88, 95%CI: 0.83 to 0.93) and history of diabetes (moderate effect: OR=0.86, 95%CI: 0.80 to 0.93; ideal effect: OR=0.92, 95%CI: 0.86 to 0.99) were predictors of worse outcome. Good preoperative corrected visual acuity (0.2 to 0.4 for moderate effect: OR=2.20, 95%CI: 2.06 to 2.34; for ideal effect: OR=5.25, 95%CI: 4.94 to 5.59; 0.5 to 0.7 for moderate effect: OR=1.08, 95%CI: 0.96 to 1.21; for ideal effect: OR=6.35, 95%CI: 5.69 to 7.08; above 0.8 for moderate effect: OR=0.73, 95%CI: 0.60 to 0.89; for ideal effect: OR=6.58, 95%CI: 5.51 to 7.86), small incision extracapsular extraction (moderate effect: OR=3.19, 95%CI: 2.35 to 4.33; ideal effect: OR=6.79, 95%CI: 5.13 to 8.97) and phacoemulsification (moderate effect: OR=2.12, 95%CI: 1.60 to 2.81; ideal effect: OR=3.34, 95%CI: 2.59 to 4.32) were predictors of better outcome. Conclusions: Visual acuity of patients in China improve significantly after cataract surgery. However, some patients still suffer moderate visual impairment. The effect of surgery can be affected by many factors, such as preoperative corrected visual acuity, preoperative intraocular pressure, preoperative pupil status, surgical approach and postoperative complications, etc. (Chin J Ophthalmol, 2021, 57: 63-70).

[Molecular epidemiology of Listeria monocytogenes isolated from ready-to-eat food in 2017 in China].

Objective: To analyze the molecular characteristics of Listeria monocytogenes strains from ready-to eat food in China. Methods: A total of 239 Listeria monocytogenes strains isolated from ready-to-eat food in 2017, all strains underwent whole-genome sequencing (WGS) , and comparisons uncovered population structure derived from lineages, clonal complex, serogroups, antimicrobial susceptibility and virulence, which were inferred in silico from the WGS data. Core genome multilocus sequence typing was used to subtype isolates. Results: All strains were categorized into three different lineages, lineage Ⅱ was the predominant types in food, and IIa was the main serogroups. CC8, CC101 and CC87 were the first three prevalent CCs among 23 detected CCs, accounting for 49.4%. Only 4.6% (11 isolates) of tested strains harbored antibiotic resistance genes, which were mostly trimethoprim genes (7 isolates, 2.9%). All strains were positive for LIPI-1, and only a part of strains harbored LIPI-3 and LIPI-4, accounting for 13.8% (33 isolates) and 14.2% (34 isolates), respectively. ST619 carried both LIPI-3 and LIPI-4. 51.5% (123 isolates) of strains carried SSI-1, and all CC121 strains harbored SSI-2. Different lineages, serogroups and CCs can be separated obviously through cgMLST analysis, and 24 sublineages were highly concordant with CCs. Conclusion: Ⅱa was the main serogroups in ready-to-eat food isolates in China; CC8, CC101 and CC87 were the prevalent CCs, and CC87 isolates was hypervirulent isolates, cgMLST method can be adopted for prospective foodborne disease surveillance and outbreaks detection.

Influence of the Klotho/FGF23/Egr1 signaling pathway on calcium-phosphorus metabolism in diabetic nephropathy and the intervention of Shenyuan granules.

This study aimed to explore the effects of Shenyuan granules on the Klotho/FGFR23/Egr1 signaling pathway and calcium-phosphorus metabolism in diabetic mice models with impairment of renal function. Streptozotocin-induced diabetic nephropathy (DN) mice models were randomly divided into three groups: Shenyuan granules group (n=10), model control group (n=10), and blank control group (n=10). Corresponding drugs were given by gavage for 8 weeks. Blood glucose and serum creatinine (SCr), urea nitrogen (BUN), calcium (Ca), phosphorus (P) and mLAB were detected before and after administration. Moreover, RT-qPCR was performed to detect the expression of CYP24 and CYP27 mRNA in kidney tissue. Blood FGF23 was detected by ELISA. Western-blot and immunohistochemistry were performed to detect the expressions of Klotho, FGFR1, Egr1, CYP24, CYP27, ERK1/2 and p-ERK1/2. Compared with the blank control group, in the model control group serum FGF23,P, SCr and 24-hour proteinuria levels increased (P<0.05), serum Ca significantly decreased (P<0.05), expressionss of Egr1, CYP24, CYP27 and p-ERK1/2 were up-regulated (P<0.05), and the expressions of Klotho and FGFR1 were down-regulated (P<0.05). After treatment, compared with the model control group, in the Shenyuan granule group serum FGF23, P, SCr levels decreased (P<0.05), serum Ca increased (P<0.05), expressions of Egr-1, CYP24, CYP27 and p-ERK1/2 were down-regulated (P<0.05), and the expressions of Klotho and FGFR1 were up-regulated (P<0.05). Shenyuan granules may partly intervene in the expressions of CYP24 and CYP27 through the Klotho/FGF23/Egr1 signaling pathway, thereby improving calcium and phosphorus metabolism and alleviating renal injury in diabetic nephropathy.

Perioperative analgesia during thymectomy via median sternotomy : Ultrasound-guided bilateral parasternal block.

Thymectomy is sometimes carried out via median sternotomy; however, patients undergoing thymectomy via median sternotomy may experience severe postoperative pain. In this study, an ultrasound-guided regional anesthetic technique called a parasternal block, which can be used to relieve postoperative surgical pain after thymectomy via median sternotomy by blocking the medial nerve branch of the anterior cutaneous branch is presented. In this patient bilateral parasternal blocks provided long-lasting analgesia (18 h) with no side effects. While these are preliminary findings, further confirmatory clinical trials will be conducted. In summary, ultrasound-guided bilateral parasternal block appears to be a safe, simple, effective and minimally invasive technique for surgery via median sternotomy.

[Effect of different plasma treated zirconia on the adhensive behaviour of human gingival fibroblasts].

OBJECTIVE: To evaluate the effect of different cold atmospheric plasma (CAP) treatment on the surface chemical and physical properties of zirconia and adhensive behaviour of human gingival fibroblasts (HGFs) cultured on zirconia disks. METHODS: The zirconia disks were divided into four groups and treated using helium, argon and mixture of argon and oxygen cold atmospheric plasma for 90 s or left untreated. The surface morphology, wettability and chemical elements were analyzed right after treatment. Human gingival fibroblasts were grown from biopsies obtained from a periodontally healthy human subject during periodontal surgery. HGFs were seeded on zirconia disk, and cells density was measured at the time point of 3 hours. Indirect immunofluorescence (IIF) was performed for morphometric examination at the time point of 3 hours. RESULTS: The crystallographic structure of zirconia was analyzed previously and the results suggested that it fitted the properties of zirconium yttrium oxide. After helium, argon and mixture of argon and oxygen cold atmospheric plasma treatment, the surface morphology and roughness of zirconia disks remained the same. The contact angle of zirconia decreased significantly(P<0.05)after CAP treatment: from 68.38° to 17.90°. After different CAP plasmas treatment, the atomic percentage of carbon on the outermost surface of the three groups decreased, as did the surface C/O ratio. The surface C/O ratio of zirconia decreased from 1.07 to 0.33. Fibroblasts density increased on CAP treated disks, especially the ones treated by mixture of argon and oxygen CAP(P<0.05). Cells of the three CAP plasma treatment groups spread better and had more protrusions, as well as larger surficial areas. CONCLUSION: Based on the results of this study after being treated by different kinds of CAP plasmas for 90 s, the surface wettability increased and the elements changed significantly with no changes in the tomography and roughness of the materials. The CAP treatment enhances the adhensive behavior of fibroblasts on zirconia by increasing the oxygen functional groups and promoting the cell density. Wettability of zirconia, an important physicochemical property, has a vital influence on the cell behaviors.

Disrupted topology of the resting state structural connectome in middle-aged APOE ε4 carriers.

The apolipoprotein E (APOE) ε4 allele is the best characterized genetic risk factor for Alzheimer's disease to date. Older APOE ε4 carriers (aged 60 + years) are known to have disrupted structural and functional connectivity, but less is known about APOE-associated network integrity in middle age. The goal of this study was to characterize APOE-related differences in network topology in middle age, as disentangling the early effects of healthy versus pathological aging may aid early detection of Alzheimer's disease and inform treatments. We performed resting state functional magnetic resonance imaging (rs-fMRI) and diffusion tensor imaging (DTI) in healthy, cognitively normal, middle-aged adults (age 40-60; N = 76, 38 APOE ε4 carriers). Graph theoretical analysis was used to calculate local and global efficiency of 1) a whole brain rs-fMRI network; 2) a whole brain DTI network; and 3) the resting state structural connectome (rsSC), an integrated functional-structural network derived using functional-by-structural hierarchical (FSH) mapping. Our results indicated no APOE ε4-associated differences in network topology of the rs-fMRI or DTI networks alone. However, ε4 carriers had significantly lower global and local efficiency of the integrated rsSC compared to non-carriers. Furthermore, ε4 carriers were less resilient to targeted node failure of the rsSC, which mimics the neuropathological process of Alzheimer's disease. Collectively, these findings suggest that integrating multiple neuroimaging modalities and employing graph theoretical analysis may reveal network-level vulnerabilities that may serve as biomarkers of age-related cognitive decline in middle age, decades before the onset of overt cognitive impairment.

Rebalancing the Caries Microbiome Dysbiosis: Targeted Treatment and Sugar Alcohols.

Dental caries is a disease that results from microbiome dysbiosis with the involvement of multiple cariogenic species, including mutans streptococci (MS), lactobacilli, Scardovia wiggsiae, and several Actinomyces species that have the cariogenic traits of acid production and acid tolerance. Sugar consumption also plays an important role interacting with microbiome dysbiosis, determining the fate of caries development. In addition, the MS transmission that encompasses multiple sources can have long-term impacts on the oral microbiome and caries development in children. Intervention in MS transmission in early childhood may promote effective long-term caries prevention. Anticaries regimens aimed against the above mechanisms will be important for successful caries management. Xylitol and erythritol may serve as good components of anticaries regimens as oral microbiome modifiers, sugar substitutes, and agents to prevent MS transmission in early childhood with both oral and systemic benefits. Further studies are needed to elucidate the mechanism of the anticaries effects of xylitol and erythritol with consideration of their impacts on the microbiome and bacterial virulence, in addition to cariogenic bacteria levels as well as their benefits for overall health. On the other hand, the anticaries agent C16G2, specifically targeting Streptococcus mutans, the most common cariogenic bacterial species, has shown good safety for short-term oral topical use and promising effects in reducing S. mutans in vitro and in vivo with the promotion of oral commensal bacteria. Future study on its anticaries effect will need to include its long-term impact on the oral microbiome and effects on other important cariogenic bacteria.

Dehydration of sludge using the polyethylene glycol solution dialysis method and the mechanism of dehydration.

This study was undertaken to develops a new sludge dewatering technology based on polyethylene glycol solution dialysis. This method significantly reduced the final water content of sludge when compared to conventional dewatering methods. It was found that when the osmotic pressure difference between the polyethylene glycol solution and the sludge reached 8 MPa, the moisture content in the sludge was reduced to 28.6%, facilitating deep dehydration. To further improve the dehydration effect and explore the technical feasibility of dialysis dehydration, a dehydration experiment was designed using the polyethylene glycol solution dialysis method combined with external pressure. By applying external pressure to the dialysis membranes, the particles in the sludge were compacted, which reduced the internal voids of the sludge and propelled continuous water discharge. The results demonstrated that the dehydration effect was significantly improved when compared to single dialysis. A scanning electron microscope (SEM) was used to observe and quantitatively analyze the microstructure of the sludge before and after dehydration and to compare the variations in sludge microstructure throughout the dehydration process. The relationships between the sludge moisture content and the porosity and pore equivalent diameter were obtained. This demonstrated the effectiveness of the dewatering experiment using sludge dialysis combined with external pressure. This study also investigates the dehydration mechanism of this method during the sludge dehydration process. This study provides a novel solution for sludge volume reduction that can be applied to sewage treatment in the future.

[Analysis on ophthalmic human resource allocation and service delivery at county level in Mainland China in 2014].

Objective: To master the status of ophthalmic human resource allocation and service delivery at county level in Mainland China, and to provide the basis for strengthening the construction of grassroots ophthalmic personnel team and formulating feasible medium and long-term eye health plans. Methods: All the medical institutions that provided ophthalmic service at county level or above were investigated by online reporting. This study only included medical institutions at county level. Descriptive statistics were used. Results: Three thousand three hundred and fifty-nine medical institutions were included, of which 1 463 hospitals had independent departments of ophthalmology (43.55%). Each medical institution has 3.93 ophthalmologists, 4.59 ophthalmic nurses, 0.30 full-time optometrist and 0.21 full-time optician. Ophthalmologists are mainly undergraduate, and the ratio of senior, intermediate and junior titles is 1.0∶1.7∶1.9. The ophthalmic nurses are mainly graduated from junior colleges or secondary schools, and the ratio of senior, intermediate and junior titles is 1.0∶7.3∶22.3. There were statistically differences in the distribution of job titles of ophthalmologists (χ(2)=106.21, P<0.01) and nurses (χ(2)=128.54, P<0.01) in the eastern, central and western regions. Of each ophthalmologist, the annual number of outpatient, outpatient surgery, inpatient and inpatient operation was 2 377.62, 109.79, 124.03, and 85.97 respectively. Four thousand one hundred and sixty ophthalmologists were able to carry out cataract surgeries independently, accounting for 31.50% of all ophthalmologists. The quantity for annual per capita cataract operation among ophthalmologists who can perform cataract surgery independently was 181.81 per capita. The average beds rate of utilization was 68.91%, and that was less than 60% in 52.99% of medical institutions. Conclusions: Compared with 1998, ophthalmic health personnel at county level in Mainland China has expanded rapidly. But cataract ability of ophthalmologists and the number of cataract surgeries still need to be improved. The structure of ophthalmic nursing staff is irrational. The full-time optometrists and opticians are extremely scarce. It is necessary to cultivate high-quality ophthalmic health personnel and improve beds rate of utilization at county level. (Chin J Ophthalmol, 2018, 54:929-934).

The effect of fibroblast growth factor 15 deficiency on the development of high fat diet induced non-alcoholic steatohepatitis.

Non-alcoholic steatohepatitis (NASH) is a form of non-alcoholic fatty liver disease (NAFLD) characterized by steatosis, inflammation, and fibrosis often associated with metabolic syndrome. Fibroblast growth factor 15 (FGF15), an endocrine factor mainly produced in the distal part of small intestine, has emerged to be a critical factor in regulating bile acid homeostasis, energy metabolism, and liver regeneration. We hypothesized that FGF15 alters the development of each of the listed features of NASH. To test this hypothesis, four-week old male Fgf15-/- and their corresponding wild-type (WT) mice were fed either a high fat diet (HFD) or a control chow diet for six months. The results confirmed that HFD feeding for six months in WT mice recapitulated human NASH phenotype, including macrovesicular steatosis, inflammation, and fibrosis. Whereas FGF15 deficiency had no effect on the severity of liver steatosis or inflammation, it was associated with decreased liver fibrosis. Furthermore, FGF15 deficiency resulted in abnormal bile acid homeostasis, increased insulin resistance, increased HFD-induced serum triglycerides, decreased inductions of hepatic cholesterol content by HFD, and altered gene expression of lipid metabolic enzymes. These data suggest that FGF15 improves lipid homeostasis and reduces bile acid synthesis, but promotes fibrosis during the development of NASH.

Patient-reported quality-of-life analysis of radium-223 dichloride from the phase III ALSYMPCA study.

BACKGROUND: Radium-223 dichloride (radium-223), a first-in-class α-emitting radiopharmaceutical, is recommended in both pre- and post-docetaxel settings in patients with castration-resistant prostate cancer (CRPC) and symptomatic bone metastases based on overall survival benefit demonstrated in the phase III ALSYMPCA study. ALSYMPCA included prospective measurements of health-related quality of life (QOL) using two validated instruments: the general EuroQoL 5D (EQ-5D) and the disease-specific Functional Assessment of Cancer Therapy-Prostate (FACT-P). PATIENTS AND METHODS: Analyses were conducted to determine treatment effects of radium-223 plus standard of care (SOC) versus placebo plus SOC on QOL using FACT-P and EQ-5D. Outcomes assessed were percentage of patients experiencing improvement, percentage of patients experiencing worsening, and mean QOL scores during the study. RESULTS: Analyses were carried out on the intent-to-treat population of patients randomized to receive radium-223 (n = 614) or placebo (n = 307). The mean baseline EQ-5D utility and FACT-P total scores were similar between treatment groups. A significantly higher percentage of patients receiving radium-223 experienced meaningful improvement in EQ-5D utility score on treatment versus placebo {29.2% versus 18.5%, respectively; P = 0.004; odds ratio (OR) = 1.82 [95% confidence interval (CI) 1.21-2.74]}. Findings were similar for FACT-P total score [24.6% versus 16.1%, respectively; P = 0.020; OR = 1.70 (95% CI 1.08-2.65)]. A lower percentage of patients receiving radium-223 experienced meaningful worsening versus placebo measured by EQ-5D utility score and FACT-P total score. Prior docetaxel use and current bisphosphonate use did not affect these findings. Treatment was a significant predictor of EQ-5D utility score, with radium-223 associated with higher scores versus placebo (0.56 versus 0.50, respectively; P = 0.002). Findings were similar for FACT-P total score (99.08 versus 95.22, respectively; P = 0.004). CONCLUSIONS: QOL data from ALSYMPCA demonstrated that improved survival with radium-223 is accompanied by significant QOL benefits, including a higher percentage of patients with meaningful QOL improvement and a slower decline in QOL over time in patients with CRPC.

Brain connectome modularity in weight-restored anorexia nervosa and body dysmorphic disorder.

BACKGROUND: Anorexia nervosa (AN) and body dysmorphic disorder (BDD) frequently co-occur, and have several overlapping phenomenological features. Little is known about their shared neurobiology. The aim of the study was to compare modular organization of brain structural connectivity. METHOD: We acquired diffusion-weighted magnetic resonance imaging data on unmedicated individuals with BDD (n = 29), weight-restored AN (n = 24) and healthy controls (HC) (n = 31). We constructed connectivity matrices using whole-brain white matter tractography, and compared modular structures across groups. RESULTS: AN showed abnormal modularity involving frontal, basal ganglia and posterior cingulate nodes. There was a trend in BDD for similar abnormalities, but no significant differences compared with AN. In AN, poor insight correlated with longer path length in right caudal anterior cingulate and right posterior cingulate. CONCLUSIONS: Abnormal network organization patterns in AN, partially shared with BDD, may have implications for understanding integration between reward and habit/ritual formation, as well as conflict monitoring/error detection.

Socioeconomic burden of hand, foot and mouth disease in children in Shanghai, China.

In the near future, the inactivated enterovirus 71 (EV71) vaccine is expected to become available on the market in China. Since EV71 is a major cause of hand, foot and mouth disease (HFMD), the vaccine is expected to significantly reduce the number of cases, as well as the detrimental economic effect of the disease. However, for a national vaccination strategy to be developed, policy-makers need more information on the socioeconomic burden of EV71 HFMD infection. Based on the 2011 population data, we estimated the clinical and economic effect of EV71 HFMD infection in children aged 0-9 years in Shanghai, China. The annual cost related to HFMD is >US$7.66 million for a population of 1·42 million children aged 0-9 years with an average cost of US$208.2/case. The extrapolated cost for EV71 HFMD infection was US$3.53 million, comprising 46·1% of the overall cost associated with HFMD. Around 97% of all of the HFMD-related expenses were paid for by the families creating a considerable economic burden. Our findings could provide the necessary recommendations on the most effective national EV71 vaccine implementation, as well as a baseline data for assessing the cost-effectiveness of the vaccine in China.

Leptospira in breast tissue and milk of urban Norway rats (Rattus norvegicus).

Leptospirosis is a zoonosis caused by bacteria of the genus Leptospira. The disease is globally distributed and a major public health concern. The Norway rat (Rattus norvegicus) is the main reservoir of the pathogen in urban slums of developing and developed countries. The potential routes of intra-specific leptospire transmission in rats are largely unknown. Herein, we identified pathogenic Leptospira spp. in breast tissue and milk of naturally infected rats. We examined kidney, breast tissue and milk from 24 lactating rats for the presence of leptospires using immunofluorescence, immunohistochemistry, polymerase chain reaction (PCR) and scanning electronic microscopy. All 24 rats had evidence for Leptospira in the kidneys, indicating chronic carriage. The majority of kidney-positive rats had detectable leptospires in milk (18, 75%) and breast tissue (16, 67%), as evidenced by immunofluorescence assay and immunohistochemistry. Four (17%) milk samples and two (8%) breast tissue samples were positive by quantitative real-time PCR. Scanning electron microscopy confirmed the presence of leptospires in breast tissue. No major pathological changes in breast tissue were found. This study, for the first time, identified leptospires in the milk and breast tissue of wild Norway rats, suggesting the possibility of milk-borne transmission of leptospirosis to neonates.

Novel poly (ADP-ribose) polymerase inhibitor, AZD2281, enhances radiosensitivity of both normoxic and hypoxic esophageal squamous cancer cells.

Radiotherapy plays an important role in the treatment of esophageal squamous cell carcinoma (ESCC). However, the outcome of radiotherapy in ESCC remains unsatisfactory because esophageal squamous cancer cells, particularly those under hypoxic condition, exhibit radioresistance. The aim of this study was to determine whether or not AZD2281, a potent poly (ADP-ribose) polymerase (PARP) inhibitor, could enhance the radiation sensitivity of two ESCC cell lines, namely ECA109 and TE13. The radiosensitizing effect of AZD2281 was evaluated on the basis of cell death, clonogenic survival and tumor xenograft progression. AZD2281 alone was slightly toxic to ESCC cell lines. Apoptosis was increased and clonogenic survival was decreased in both cell lines when AZD2281 was combined with ionizing radiation (IR) under normoxic condition. AZD2281 enhanced IR-induced apoptosis to a more significant level under chronic hypoxic condition (0.2% O(2), 48 hour) than under normoxic condition. AZD2281 also slightly enhanced clonogenic cell death under chronic hypoxic condition compared with that under normoxic condition. This result could be associated with increased radiation-induced DNA double-strand breaks (DSB), decreased DSB repair and increased apoptosis of ESCC cells. Furthermore, homologous recombination (HR) protein Rad51 expression and focus formation were decreased in ESCC cells exposed to moderate chronic hypoxic condition (0.2% O(2), 48 hour); this result indicated that chronic hypoxic ESCC cells were HR deficient, possibly causing contextual synthetic lethality with PARP inhibitor in radiation sensitization. AZD2281 was also a radiation sensitizer in ESCC tumor xenograft models. Hence, in vitro and in vivo findings provide evidence that AZD2281 potently sensitizes ESCC cells to X-ray irradiation. The selective cell killing of HR-defective hypoxic cells contributes to radiosensitization by PARP inhibitor in ESCC cells under hypoxic condition.

Study of the expression of GABA(A) receptor in rats during acute lung injury caused by endotoxin.

The objective of the present study was to investigate the role of γ-aminobutyric acid type A receptor (GABA(A)R) in lipopolysaccharide (LPS)-induced acute lung injury (ALI) in rats. Thirty-two male wistar rats were randomly divided into four groups. Rats in the GABA group were pretreated with LPS and GABA, while those in the bicuculline (BIC) group were pretreated with LPS and bicuculline. We assessed the arterial blood gas, dry/wet ratio, and the level of tumor necrosis factor-α (TNF-α), IL-6, malondialdehyde, and superoxide dismutase 6 h after the immunization. Paraffin sections of samples were detected using the steptavidin-peroxidase method. Protein expression was detected using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and western blotting. PaO2 in the LPS group was significantly lower than that in the control rats. Activation of GABA-mediated signaling by GABA increased the expression of GABA(A)R in airway bronchial and alveolar epithelial cells. Blockade of the GABA(A)R by bicuculline limited the expression of this receptor. The GABA group rats had higher levels of tissue TNF-α and IL-6 than in ALI rats and control rats. The BIC group rats demonstrated an opposite expression level compared to the GABA group rats. Our results suggest that the GABA(A)R could aggravate the inflammatory response syndrome and oxidative stress in the lungs and play an essential role in LPS-induced acute lung injury. It provides a novel method to study the incidence and mortality of ALI during the peroperative period.

Single organ metastatic sites in non-small cell lung cancer: Patient characteristics, treatment patterns and outcomes from a large retrospective Canadian cohort.

BACKGROUND: There is a paucity of information about the characteristics, treatment patterns, and outcomes of non-small cell lung cancer (NSCLC) patients with single organ metastasis (SOM). METHODS: This retrospective cohort study includes all patients with a diagnosis of stage IV NSCLC diagnosed from 2014 to 2016 and treated at Princess Margaret Cancer Centre. We compared baseline characteristics and patterns of metastatic sites between patients with SOM versus multiple (M)OM. Additionally, we identified treatment modalities and outcomes for patients with SOM. Cox multivariable models (MVA) were utilized to evaluate differences in overall survival (OS) between the SOM and MOM cohorts. RESULTS: Of 893 pts analyzed, 457 (51 %) had SOM, while 436 (49 %) had MOM at initial diagnosis. Demographics were comparable between the two groups. Brain was the most common site of metastasis for SOM patients. When compared to the MOM group, the SOM group had lower percentages of liver and adrenal metastases. Amongst SOM patients, 54 % received single modality treatment, and 20 % did not receive any treatment for their SOM. In MVA, patients with liver (HR 2.4), bone (HR 1.8), and pleural (HR 1.7) metastasis as their SOM site had the worst outcomes, with median OS of 6.8 months, 12.1 months, and 13.0 months respectively. Patients with SOM had a significantly improved median OS compared to those with MOM (15.9 months vs. 10.6 months; HR 0.56, 95 % CI 0.47-0.66, p < 0.001). CONCLUSION: In NSCLC patients who presented with SOM, survival correlated with the initial organ involved and was better overall compared to patients with MOM. SOM NSCLC may benefit from specific management strategies and SOM patients could be considered as a specific subgroup for survival analyses in observational and non-randomized interventional studies. In clinical trials, SOM can be considered as a stratification factor in the future.