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Chlorin e6 (Ce6) is a promising photosensitizer for tumor photodynamic therapy (PDT). However, the efficacy of Ce6 PDT is limited by Ce6's poor water solubility, rapid blood clearance, and inadequate accumulation in the tumor tissue. This problem is tackled in this work, wherein functionalized superparamagnetic iron oxide nanoparticles (IO-NPs) were used as carriers to deliver Ce6 to melanoma. The IO-NPs were coated with polyglycerol (PG) to afford good aqueous solubility. The chemotherapeutic agent doxorubicin (DOX) was attached to the PG coating via the hydrazone bond to afford affinity to the cell membrane and thereby promote the cell uptake. The hydrophobic nature of DOX also induced the aggregation of IO-NPs to form nanoclusters. Ce6 was then loaded onto the IO nanoclusters through physical adsorption and coordination with surface iron atoms, yielding the final composites IO-PG-DOX-Ce6. In vitro experiments showed that IO-PG-DOX-Ce6 markedly increased Ce6 uptake in mouse melanoma cells, leading to much-enhanced photocytotoxicity characterized by intensified reactive oxygen species production, loss of viability, DNA damage, and stimulation of tumor cell immunogenicity. In vivo experiments corroborated the in vitro findings and demonstrated prolonged blood clearance of IO-PG-DOX-Ce6. Importantly, IO-PG-DOX-Ce6 markedly increased the Ce6 distribution and retention in mouse subcutaneous melanoma grafts and significantly improved the efficacy of Ce6-mediated PDT. No apparent vital organ damage was observed at the same time. In conclusion, the IO-PG-DOX NPs provide a simple and safe delivery platform for efficient tumor enrichment of Ce6, thereby enhancing antimelanoma PDT.

An ex vivo heart perfusion device preserves the donor heart in a warm beating state during transfer between extraction and implantation surgeries. One of the current challenges includes the use of rigid and noncompliant plastic tubes, which causes injuries to the heart at the junction between the tissue and the tube. The compliant and rapidly strain-stiffening mechanical property that generates a "J-shaped" stress-strain behavior is necessary for producing the Windkessel effect, which ensures continuous flow of blood through the aorta. In this study, we mimic the J-shaped and anisotropic stress-strain behavior of human aorta in synthetic elastomers to replace the problematic noncompliant plastic tube. First, we assess the mechanical properties of human (n = 1) and porcine aorta (n = 14) to quantify the nonlinear and anisotropic behavior under uniaxial tensile stress from five different regions of the aorta. Second, fabric-reinforced elastomer composites were prepared by reinforcing silicone elastomers with embedded fabrics in a trilayer geometry. The knitted structures of the fabric provide strain-stiffening as well as anisotropic mechanical properties of the resulting composite in a deterministic manner. By optimizing the combination between different elastomers and fabrics, the resulting composites matched the J-shaped and anisotropic stress-strain behavior of natural human and porcine aorta. Finally, improved analytical constitutive models based on Gent's and Mooney-Rivlin's constitutive model (to describe the elastomer matrix) combined with Holzapfel-Gasser-Ogden's model (to represent the stiffer fabrics) were developed to describe the J-shaped behavior of the natural aortas and the fabric-reinforced composites. We anticipate that the suggested fabric-reinforced silicone elastomer composite design concept can be used to develop complex soft biomaterials, as well as in emerging engineering fields such as soft robotics and microfluidics, where the Windkessel effect can be useful in regulating the flow of fluids.

Aim To analyze the alterations of fecal microbiota in Chinese patients with inflammatory bowel disease (IBD). Methods Fecal samples from 15 patients with Crohn's disease (CD) (11 active CD, 4 inactive CD), 14 patients with active ulcerative colitis (UC) and 13 healthy individuals were collected and subjected to 16S ribosomal DNA (rDNA) gene sequencing. The V4 hypervariable regions of 16S rDNA gene were amplified from all samples and sequenced by the Illumina MiSeq platform. Quality control and operational taxonomic units classification of reads were calculated with QIIME software. Alpha diversity and beta diversity were displayed with R software. Results Community richness (chao) and microbial structure in both CD and UC were significantly different from those in normal controls. At the phyla level, analysis of the microbial compositions revealed a significantly greater abundance of Proteobacteria in IBD as compared to that in controls. At the genera level, 8 genera in CD and 23 genera in UC (in particular, the Escherichia genus) showed significantly greater abundance as compared to that in normal controls. The relative abundance of Bacteroidetes in the active CD group was markedly lower than that in the inactive CD group. The abundance of Proteobacteria in patients with active CD was nominally higher than that in patients with inactive CD; however, the difference was not statistically significant after correction. Furthermore, the relative abundance of Bacteroidetes showed a negative correlation with the CD activity index scores. Conclusion Our study profiles specific characteristics and microbial dysbiosis in the gut of Chinese patients with IBD. Bacteroidetes may have a negative impact on inflammatory development.

The novel COVID-19 outbreak has affected more than 200 countries and territories as of March 2020. Given that patients with cancer are generally more vulnerable to infections, systematic analysis of diverse cohorts of patients with cancer affected by COVID-19 is needed. We performed a multicenter study including 105 patients with cancer and 536 age-matched noncancer patients confirmed with COVID-19. Our results showed COVID-19 patients with cancer had higher risks in all severe outcomes. Patients with hematologic cancer, lung cancer, or with metastatic cancer (stage IV) had the highest frequency of severe events. Patients with nonmetastatic cancer experienced similar frequencies of severe conditions to those observed in patients without cancer. Patients who received surgery had higher risks of having severe events, whereas patients who underwent only radiotherapy did not demonstrate significant differences in severe events when compared with patients without cancer. These findings indicate that patients with cancer appear more vulnerable to SARS-CoV-2 outbreak. Significance: Because this is the first large cohort study on this topic, our report will provide much-needed information that will benefit patients with cancer globally. As such, we believe it is extremely important that our study be disseminated widely to alert clinicians and patients. This article is highlighted in the In This Issue feature, p. 747

Background Deubiquitinating enzymes (DUBs) are linked to cancer progression and dissemination, yet less is known about their regulation and impact on epithelial–mesenchymal transition (EMT). Methods An integrative translational approach combining systematic computational analyses of The Cancer Genome Atlas cancer cohorts with CRISPR genetics, biochemistry and immunohistochemistry methodologies to identify and assess the role of human DUBs in EMT. Results We identify a previously undiscovered biological function of STAM-binding protein like 1 (STAMBPL1) deubiquitinase in the EMT process in lung and breast carcinomas. We show that STAMBPL1 expression can be regulated by mutant p53 and that its catalytic activity is required to affect the transcription factor SNAI1. Accordingly, genetic depletion and CRISPR-mediated gene knockout of STAMBPL1 leads to marked recovery of epithelial markers, SNAI1 destabilisation and impaired migratory capacity of cancer cells. Reversely, STAMBPL1 expression reprogrammes cells towards a mesenchymal phenotype. A significant STAMBPL1-SNAI1 co-signature was observed across multiple tumour types. Importantly, STAMBPL1 is highly expressed in metastatic tissues compared to matched primary tumour of the same lung cancer patient and its expression predicts poor prognosis. Conclusions Our study provides a novel concept of oncogenic regulation of a DUB and presents a new role and predictive value of STAMBPL1 in the EMT process across multiple carcinomas.

BACKGROUND Gene polymorphisms are associated with sensitivity to platinum drugs. This study aimed to investigate the polymorphisms of GSTP1 rs1695 locus and ABCC2 rs717620 locus, and the sensitivity of patients with advanced non-small cell lung cancer (NSCLC) to platinum drugs in a Xinjiang Uygur population. MATERIAL AND METHODS The gene polymorphisms of GSTP1 rs1695 and ABCC2 rs717620 of Uygur NSCLC patients were assessed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The relationship between the prognosis of advanced NSCLC Uygur patients and the gene polymorphisms of GSTP1 rs1695 and ABCC2 rs717620 was analyzed using progression-free survival (PFS) and overall survival (OS) as the major outcome indicators. RESULTS The median PFS of patients with advanced NSCLC was 6.9 months and the OS of Uygur patients with advanced NSCLC was 10.8 months. Kaplan-Meier survival analysis indicated that survival time of patients with GSTP1 AG + GG was significantly longer than in patients with AA gene (P

Two new species of the genus Stilicoderus Sharp, 1889 from China are described and illustrated: S. maolini sp. nov. (Jiangxi, Hunan) of the S. var iolosus group and S. chengrani sp. nov. (Xizang) of the S. signatus group. Additional records of eleven described species of Stilicoderus are given.

To investigate the expression level of NEK2 in 40 tissue specimens of primary liver cancer and to search for clues whether the effect of NEK2 depletion plays a role on biological behaviors of HepG2 cells and the relevant molecular mechanism are the objectives of this study. Real-time PCR and immunohistochemistry assessed expression level of NEK2 in specimens of cancerous tissues and carcinoma-adjacent tissues. The NEK2 expression level in HepG2, Huh7, SMMC, and 7402 cells was detected by real-time PCR and western blot to screen experimental cell line. To assess the expression levels of NEK2 mRNA and protein, an effective siRNA transfected into the HepG2 cells was designed. CCK8 and colony-forming assays were performed to verify short-term and long-term proliferative activities, respectively. Capacity of apoptosis and cell cycle changes were assessed by flow cytometry. Ability of transference and invasion was measured by Transwell Chambers. Western blot approach was used to determine the protein expression levels. There was significantly high expression level of NEK2 in cancerous tissues compared to adjacent tissues. The expression of NEK2 was higher in HepG2 cells than other cell lines. Real-time PCR and western blot shown there were obviously down-regulated NEK2 expression in the NEK2-siRNA group compared to control groups. The capacity of amplification and invasion was inhibited distinctly, and FCM revealed the apoptosis rate was increased and G1 phase was arrested in NEK2-siRNA group. Western blot indicated that low expression of NEK2 in HepG2 cells could increase the expression levels of Bax, caspase-3, P21, and TIMP-1, but significantly suppressed the c-myc, c-jun, Bcl-2, cyclinD1, CDK4, MMP2, and MMP9 expression levels and the phosphorylation levels of ERK, JNK, and P38 compared with the control groups. Our findings demonstrated that NEK2 could be a valuable carcinogenic factor and a promising therapeutic target for primary liver cancer; NEK2 may regulate proliferation, apoptosis, and other biological behaviors of HepG2 cells via MAPK signal pathway.

Vasohibin-1 (VASH1) is a newly discovered angiogenesis inhibitor that is specifically expressed in human vascular endothelial cells in response to vascular endothelial growth factor and fibroblast growth factor-2. This study aimed to evaluate the expression of VASH1 in non-small cell lung cancer (NSCLC) and correlates its expression with the clinicopathological parameters and prognosis of the disease. Immunohistochemical analysis was used to determine the expression of VASH1 in NSCLC tissue and adjacent normal tissue from 84 patients. The relationship between VASH1 expression and clinicopathological indicators was examined with the chi-squared test. Moreover, the survival rate was calculated with the Kaplan–Meier survivor curve. Finally, the correlation between the indicators and patient survival was estimated with Cox analysis. VASH1 was high expressed in 63.1 % of NSCLC tissues versus 21.4 % of adjacent tissues (P < 0.01). High VASH1 expression in NSCLC tissue was correlated with clinicopathological features including lymph node status (P = 0.024) and TNM stage (P = 0.036). The Kaplan–Meier curve indicated that the patients with high VASH1 expression had significantly shorter survival than those with low VASH1 expression. In the multivariate Cox regression model, high VASH1 expression was identified as an independent prognostic factor for patients with NSCLC. High VASH1 expression is predictive of poor prognosis of NSCLC, implying that VASH1 may be a promising new target for targeted therapies for NSCLC.

Background and Objective: Lung cancer is one of the malignant diseases which most seriously threat humansurvival and development. This study aimed to assess osteopontin (OPN) expression in non-small cell lung cancer (NSCLC) and any relationship with clinicopathological features. Methods: Immunohistochemistry was used to determine OPN expression and microvascular density (MVD) in 120 cases of NSCLC also undergoing clinical assessment. Results: Moderately positive expression of OPN was found in 34.6% (41/120) and strong expression in 47.5% (57/120) of the NSCLCs; OPN expression in carcinomas was higher than in pericarcinoma tissues (P

Background: Use of epidermal growth factor receptor inhibitors (EGFR-TKIs ) is now standard for non- small-cell lung cancer (NSCLC). However, the effects of EGFR-TKIs in maintenance therapy for advanced NSCLC patients are still unclear. The preent meta-analysis was performed to examine pooled data of randomized control trials (RCT) where EGFR-TKIs were compared against placebo in maintenance regimens for patients with advanced NCSLC to quantify potential benefits and determine safety. Methods: Several data bases were searched, including PubMed, EMBASE and CENTRAL, and we performed an internet search of conference literature. The endpoints were objective response rates (ORR), progression-free survival (PFS) and overall survival (OS). We performed a meta-analysis of the published data, using Comprehensive Meta Analysis software (Version 2.0). with a fixed effects model and an additional random effects model, when applicable. The results of the meta-analysis are expressed as hazard ratios (HRs) or risk ratios (RRs), with their corresponding 95% confidence intervals (95%CIs). Results: The final analysis included six trials, covering 3,758 patients. Compared with placebo, EGFR-TKIs maintenance therapy improved ORR and PFS for patients with advanced NSCLC, the difference being statistically significant ( P

To explore the relationship between aggressive behaviors, parent-child separation and experience of childhood abuse among junior high school students.A total of 1417 students in ordinary junior high schools from 3 townships in Huoshan, Anhui were involved in this study. Self-made questionnaire was used to estimate aggressive behaviors, parent-child separation in childhood, child abuse and social demographic information of the students under this study.Related scores (2.52 ± 0.78) on physical aggression in boys was higher than in girls (2.29 ± 0.79) while the scores related to anger (2.60 ± 0.82) and hostility (2.58 ± 0.80) in girls, were higher than those in boys (2.41 ± 0.75, 2.47 ± 0.78), all with statistically significant differences (P0.05). Scores related to different types of aggressive behaviors and the scores in total, were higher in students from the senior class (P0.001). Scores on items as verbal aggression, hostility and in total, were higher in those adolescents which had undergone maternal-child separation during their childhood (P0.05). Scores on hostility and in total, were higher in those adolescents which had suffered from father-child separation during their childhood (P0.05). Scores related to anger, hostility and in total, were higher in those adolescents which had undergone both parent-child separation when they were much younger (P0.05). Students who had suffered from various types of repeated abuse showed higher scores in various types of aggressive behaviors and in total, than those who did not have the same experience. Most of the differences among groups were statistically significant (P0.05).Students that suffered parent-child separation in their earlier childhood and with repeated experiences of abuse in childhood appeared to be risk factors causing aggressive behaviors to develop during the age of adolescence.

OBJECTIVE To observe the effect of compound granule prescription of thunberg fritillary bulb in relieving the post-chemotherapy bone marrow depression in refractory acute leukemia (RAL) patients. METHOD Two hundred and thirty eight RAL patients collected from 7 third-grade class-A hospitals were randomly divided into the treatment group and the control group. Both groups were treated with conventional chemotherapy. They were administered with compound granule prescription of thunberg fritillary bulb or placebo three days before chemotherapy for consecutively 14 days. A standardized chemotherapy course was a treatment cycle. The changes in peripheral hemogram of two groups were detected before and after chemotherapy. RESULT After the treatment, the white blood cell counts of the two groups were significantly different (P < 0.05), but there was no statistical significance in qualitative comparison. Before and after the treatment, the difference of the white cell counts of the two groups detected had significant statistics (P < 0.05). The white cell counts of both groups declined after chemotherapy, but the treatment group decreased more significantly than the control group. Before and after the treatment, there were no statistical significances in quantitative and qualitative comparisons both in HGB and PLT. After the treatment, HGB and PLT contents of both groups declined, but there was no statistical difference between the two groups. CONCLUSION Compound granule prescription of thunberg fritillary bulb can relieve the bone marrow suppression in RAL patients caused by the chemotherapy, which is mainly reflected by the slowdown of reduction in white blood cells.

To find the major risk factors associated with gastric cardia cancer.We selected five high incidence areas of esophageal cancer and gastric cancer which have cancer registration system, i.e. Cixian and Shexian of Hebei Province, Linxian of Henan Province, Feicheng of Shandong Province and Zhuanghe of Liaoning Province. Fifty newly diagnosed cases of cardiac cancer after January 1, 2008 were selected from each cancer registration database. A uniform questionnaire, which was fully consulted by experts, was used. Population-based 1:3 case-control study was conducted in those areas. The study recruited 250 cases of cardiac cancer and 750 matched controls, which were investigated with the uniform questionnaire. The data were statistically analyzed by fitting-conditional Logistic analysis.Smoking, passive smoking, alcohol drinking, irregular meal, improper dining posture, heavy taste, dried food, pickled food, fried food, hot food, gastrointestinal history, gastroesophageal reflux disease (GERD) can increase the risk of cardiac cancer. To eat more bean and high BMI are protective factors of the single factor logistic analysis. Gastrointestinal history (OR = 42.899), dried food (OR = 5.932), irregular meal (OR = 4.911), hot food (OR = 4.144), pickled food (OR = 3.287), passive smoking (OR = 2.355), and GERD (OR = 1.930) can increase the risk of cardiac cancer, eat more bean (OR = 0.254) and BMI ≥ 25 (OR = 0.492) are protective factors of the mixture factors logistic analysis.Gastric cardia cancer is caused by environmental risk factors and genetic factors. Health education in high cardiac cancer incidence areas and primary prevention popularized into people's daily life will be beneficial to decreasing the incidence of gastric cardia cancer.

To investigate the characteristics of glycemic excursions in people with normal glucose tolerance (NGT) in Chengdu.A total of 50 non-obese people with normal glucose tolerance (NGT, 23-68 years old), normal blood pressures and lipid profiles participated in the study. The fluctuations of glucose levels in the participants were measured by a continuous glucose monitoring system (CGMS) for three days 72 h. The 48 h mean blood glucose (MBG), mean amplitude of glycemic excursions (MAGE), Largest amplitude of glycemic excursions (LAGE), Postprandial peak glucose (PPG), Postprandial glucose excursion (PPGE), Mean of postprandial glucose excursion (MPPGE), and absolute means of daily differences (MODD) were measured.The number of glucose values detected by CGMS amounted to 861+/-7 with a mean absolute difference (MAD) of 11.3%+/-10.6%. The CGMS values were significantly correlated with the capillary glucose measurements (n=1076, r=0.761, P0.005). The participants had a MBG of (5.9+/-1.2) mmol/L, a MAGE of (1.7+/-0.7) mmol/L, a LAGE of (4.4+/-1.9) mmol/L, a daily glycemic peak (PPG) of (8.7+/-1.7) mmol/L, a nadir level of (4.3+/-0.7) mmol/L, a MPPGE of (2.3+/-1.6) mmol/L, and a MODD of (0.75+/-0.79) mmol/L. The post-breakfast Postprandial glycemic excursions (PPGE) were lower than those of post-lunch and post-dinner (P=0.01 and P=0.05). The postprandial glucose excursions in the 60-70 year-old participants were the highest (P0.022). In 95% (77%-100%) of the daytime, the glycose levels fluctuated between 4.1 and 8.8 mmol/L, and 78% of the participants (n=39) had hyperglycemia (BG7.8 mmol/L) and 10% (n=5) had asymtomatic hypoglycemia (BG2.8 mmol/L).CGMS tests may be important for detecting asymptomatic hyperglycemia and hypoglycemia. The NGT people in Chengdu have exhibited abnormal blood glucose values in CGMS, revealing problems in people with normal range of blood glucose.

To identify the differences and contributing factors of plasma total homocysteine (tHcy) in people with type II diabetes mellitus (T2DM) and people who had normal glucose tolerance (NGT), and to explore the association between plasma tHcy and diabetic vascular complications.One hundred and thirty-five people (fifty-five in NGT group, eighty in T2DM group) were enrolled in this cross sectional study. The height, weight, waist circumference, hip circumference, and blood pressure of the participants were measured. The body mass index (BMI) and waist-hip ratio (WHR) were calculated. The fasting plasma tHcy, serum vitamin B12, and plasma folic acid were determined. Oral glucose tolerance test and insulin releasing test were performed to assess insulin secretion area under the curve (AUC) and insulin sensitivity (HOMA-IR). Lipid profiles were also assessed at the same time.T2DM patients had significantly higher plasma tHcy [(21.09 +/- 10.99) micromol/L] than the people in the NGT group [(3.70 +/- 5.54) micromol/L, P=0.000). The stepwise multiple regression analysis showed that LnAUCGlu and WC were independent contributors to the increase of plasma tHcy (adjusting R2=0.378, P=0.000). The logistic regression analysis showed that tHcy (OR=1.109) and age (OR=1.146) were associated with diabetic macroangiopathy.Plasma tHcy increase in patients with type II diabetes. Glucose and WC are important contributors to the increase of plasma tHcy in T2DM patients. The increase of plasma tHcy contributes to diabetic macroangiopathy.

To assess the effectiveness and security of autologous platelet-rich gel (APG) in the treatment of refractory diabetic dermal ulcers.Thirteen diabetic patients with refractory skin lesions were enrolled for this study, and APG was produced by platelet (PLT)-rich plasma (PRP) with thrombin and calcium gluconate. APG treatment consisted of wound dressed with APG, followed by topical washing and cleaning. The APG was then covered with Vaseline gauze and left for 48 to 72 hours, after which the wounds were treated conventionally until the next PLT-gel treatment. The clinical endpoints of the study were the healing rate.A total of 13 patients entered the pilot study. There were no drop-outs in the study. 69.2% ulcers were cured, and especially the ulcer areas were reduced significantly in the first 3 weeks; no adverse reactions were observed.Topical therapy with APG may be considered as an effective adjuvant method to treating refractory diabetic dermal ulcer.