Laryngeal and hypopharyngeal squamous cell carcinoma: association between quantitative parameters derived from dual-energy CT and histopathological prognostic factors.

BACKGROUND: Dual-energy computed tomography (DECT) can provide objective evaluation of laryngeal and hypopharyngeal squamous cell carcinoma (LHSCC). PURPOSE: To investigate the relationship between quantitative parameters acquired from DECT and histopathological prognostic factors in LHSCC. MATERIAL AND METHODS: A total of 65 patients with LHSCC who underwent arterial phase and venous phase DECT scans were retrospectively enrolled. Iodine concentration (IC) and normalized IC (NIC) of the tumor were calculated in both the arterial (ICA and NICA) and venous (ICV and NICV) phases, and compared among different pathological grades, T stages, and lymph node stages. Receiver operating characteristic (ROC) curves were generated to evaluate their diagnostic performance. RESULTS: There were significantly differences on ICA and NICA among three pathological grades (ICA, P = 0.001; NICA, P = 0.002). For differentiating moderately and poorly differentiated from well-differentiated LHSCC using ICA and NICA, the areas under curve (AUCs) were 0.753 and 0.726, respectively. High T stage (T3/4) LHSCC showed significantly higher ICA (P = 0.012) and NICA (P = 0.005) than low T stage (T1/2) LHSCC. The AUCs of the ICA and NICA were 0.674 and 0.703, respectively, in discriminating high from low T stage LHSCC. Lymph node metastasis (LNM)-positive (N1/2/3) LHSCC showed significantly higher ICA (P = 0.008) and NICA (P = 0.003) than LNM-negative (N0) LHSCC. For discriminating the LNM-positive from the LNM-negative group using ICA and NICA, the AUCs were 0.697 and 0.744, respectively. CONCLUSION: ICA and NICA might be helpful in assessing histopathological prognostic factors in patients with LHSCC.

[Molecular mechanism of Ganoderma against gastric cancer based on network pharmacology and experimental test].

This study aims to explore the molecular mechanism of Ganoderma against gastric cancer based on network pharmacology, molecular docking, and cell experiment. The active components and targets of Ganoderma were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), and gastric cancer-related targets from GeneCards and Online Mendelian Inheritance in Man(OMIM). The protein-protein interaction(PPI) network of the common targets was constructed with STRING, followed by Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis of the common genes based on Bioconductor and R language. The medicinal-disease-component-target network and medicinal-disease-component-target-pathway network were established by Cytoscape. Molecular docking was performed between ß-sitosterol(the key component in Ganoderma) and the top 15 targets in the PPI network. Cell experiment was performed to verify the findings. A total of 14 active components and 28 targets of Ganoderma were retrieved, and the medicinal and the disease shared 25 targets, including caspase-3(CASP3), caspase-8(CASP8), caspase-9(CASP9), and B-cell lymphoma-2(BCL2). The common targets involved 72 signaling pathways and apoptosis and p53 signaling pathway may play a crucial role in the effect of Ganoderma against gastric cancer. ß-sitosterol had strong binding activity to the top 15 targets in the PPI network. The in vitro cell experiment demonstrated that ß-sitosterol inhibited gastric cancer AGS cell proliferation by inducing cell apoptosis and cell cycle arrest in the S phase, which might be related to the regulation of the p53 pathway. This study shows the multi-component, multi-target, and multi-pathway characteristics of Ganoderma against gastric cancer, which lays a scientific basis for further research on the molecular mechanism.

Genomic landscape and tumor mutation burden analysis of Chinese patients with sarcomatoid carcinoma of the head and neck.

BACKGROUND: Sarcomatoid carcinoma (SC) of the head and neck (HN) is a rare disease that has both sarcomatoid and cancerous components. The genetic background and mechanisms of tumorigenesis remain largely unrevealed, and the progress of precision therapy has been limited. METHODS: Targeted DNA-based next-generation sequencing (NGS) was performed by a 539 genes panel of pan-cancer in 12 patients with SC of the HN to identify their genetic alterations and investigate clinically actionable mutations for use in precision treatment. RESULTS: TP53 was identified as the most frequently mutated gene. Genes related to the cell cycling, chromatin remodeling and histone modification were found to be frequently mutated in patients with SC of the HN. Alterations in receptor tyrosine kinases (RTKs) were also found in six patients. In addition, four patients had mutations in members of the downstream RAS and PI3-kinase pathways, PIK3CA was identified as the most frequently mutated gene in this pathway. The tumor mutation burden (TMB) value ranged from 0.71 to 14.71 per megabase, with a median of 4.34. The TMB value of PIK3CA mutation patients was significantly higher than that of PIK3CA wild-type patients. CONCLUSIONS: This was the first study to investigate genomic alterations specifically in Chinese patients with SC of the HN. Our research results showed that 10 out of 12 patients can match the targeted therapies or immunotherapy currently available in clinical practice or active clinical trials, suggesting precision therapy has the potential utility to improve the long-term prognosis for patients with the rare disease. Due to the small number of patients in this study, the findings need to be validated in a larger cohort.

Outcomes of preoperative endoscopic nasobiliary drainage and endoscopic retrograde biliary drainage for malignant distal biliary obstruction prior to pancreaticoduodenectomy.

AIM: To compare the outcomes of preoperative endoscopic nasobiliary drainage (ENBD) and endoscopic retrograde biliary drainage (ERBD) in patients with malignant distal biliary obstruction prior to pancreaticoduodenectomy (PD). METHODS: Data from 153 consecutive patients who underwent preoperative endoscopic biliary drainage prior to PD between January 2009 and July 2016 were analyzed. We compared the clinical data, procedure-related complications of endoscopic biliary drainage (EBD) and postoperative complications of PD between the ENBD and ERBD groups. Univariate and multivariate analyses with odds ratios (ORs) and 95% confidence intervals (95%CIs) were used to identify the risk factors for deep abdominal infection after PD. RESULTS: One hundred and two (66.7%) patients underwent ENBD, and 51 (33.3%) patients underwent ERBD. Endoscopic sphincterotomy was less frequently performed in the ENBD group than in the ERBD group (P = 0.039); the EBD duration in the ENBD group was shorter than that in the ERBD group (P = 0.036). After EBD, the levels of total bilirubin (TB) and alanine aminotransferase (ALT) were obviously decreased in both groups, and the decreases of TB and ALT in the ERBD group were greater than those in the ENBD group (P = 0.004 and P = 0.000, respectively). However, the rate of EBD procedure-related cholangitis was significantly higher in the ERBD group than in the ENBD group (P = 0.007). The postoperative complications of PD as graded by the Clavien-Dindo classification system were not significantly different between the two groups (P = 0.864). However, the incidence of deep abdominal infection after PD was significantly lower in the ENBD group than in the ERBD group (P = 0.019). Male gender (OR = 3.92; 95%CI: 1.63-9.47; P = 0.002), soft pancreas texture (OR = 3.60; 95%CI: 1.37-9.49; P = 0.009), length of biliary stricture (≥ 1.5 cm) (OR = 5.20; 95%CI: 2.23-12.16; P = 0.000) and ERBD method (OR = 4.08; 95%CI: 1.69-9.87; P = 0.002) were independent risk factors for deep abdominal infection after PD. CONCLUSION: ENBD is an optimal method for patients with malignant distal biliary obstruction prior to PD. ERBD is superior to ENBD in terms of patient tolerance and the effect of biliary drainage but is associated with an increased risk of EBD procedure-related cholangitis and deep abdominal infection after PD.

Relationship between waist circumference and elevation of carotid intima-media thickness in newly-diagnosed diabetic patients.

OBJECTIVE: Waist circumference, as a brief indicator of visceral obesity, is associated with multi-metabolic disorders and cardiovascular diseases. The present study was aimed to find out the relationship between waist circumference and carotid intima media thickness (C-IMT), as well as the best waist circumference cutoff for identifying C-IMT elevation in Chinese male patients with newly-diagnosed diabetes. METHODS: Five hundred and seventy-eight patients from Department of Endocrinology and Metabolism in Shanghai Sixth People's Hospital affiliated to Shanghai Jiao Tong University were enrolled. Both physical examination (for measurement of waist circumference) and carotid ultrasonography (for measurement of C-IMT) were performed. RESULTS: After grouping according to the quartiles of C-IMT, the waist circumference increased across all its quartiles. The waist circumference in 3rd and 4th quartiles (90.7±9.8 cm and 90.8±9.6 cm) was significant higher than in 1st and 2nd quartiles (P<0.05). When subjects were divided into 4 groups according to waist circumference, the C-IMT of subjects with waist circumference 90-95 cm was significant higher than that of subjects with waist circumference 85-90 cm and less than 85 cm respectively (P<0.05). Both spearman and partial correlation analysis showed that C-IMT was positively correlated with waist circumference (P<0.01). C-IMT was found significantly elevated with the increase of waist circumference. Multiple stepwise regression analysis showed that waist circumference was one of the independent risk factors of C-IMT. After an average of 2.23±0.85 years follow up, there was a significant elevation of C-IMT in the group with baseline waist circumference over 90 cm P<0.05), while no significant difference was detected in the group with baseline waist circumference less than 90 cm (P=0.27). Logistic regression showed that baseline waist circumference over 90 cm was associated with a relative risk to C-IMT elevation of 1.132 (95% CI 1.043-1.431, P<0.05). CONCLUSION: Among newly-diagnosed diabetic male patients, waist circumference over 90 cm not only reflects sub-clinical atherosclerosis in early stage, but also predicts the progression of atherosclerosis.

[Change and significance of urinary smad3 in type 2 diabetic nephropathy].

OBJECTIVE: To explore the significance of urinary smad3(usmad3) protein level change in diabetic nephropathy (DN) in type 2 diabetes mellitus and examine its relationship with the progression of DN. METHODS: From May 2010 to August 2011, a total of 282 patients with type 2 diabetes were selected for the experimental group according to instant urine specimen albumin-creatinine ratio (UACR). Another 100 healthy subjects were taken as the control group. Then the diabetics were divided into 3 groups, including 110 with normal albuminuria (NA group), 114 with microalbuminuria (MA group) and 58 with macroalbuminuria (DN group). Enzyme-linked immunosorbent assay (ELISA) was used to detect the content of usmad3. The parameters of age, systolic blood pressure, body mass index (BMI), blood glucose, blood lipids, urinary albumin/creatinine (ACR), estimated glomerular filtration rate (eGFR) and glycosylated hemoglobin were measured. And non-mydriatic fundus camera was used to evaluate retinopathy, the DN group (n = 58) was then divided into two groups of those without retinopathy (n = 25) and with retinopathy (n = 33). RESULTS: (1) The usmad3 level in type 2 diabetes group was significantly higher than that in the control group (489(273,1193) vs 311 (179, 497) ng/mmol Cr (P < 0.01). (2) According to UACR, type 2 diabetes group was divided into 3 different groups to compare the relative level differences of usmad3 in different groups: MA group versus NA group, 552 (316,1338) vs 317 (200,594), DN group versus NA group, 1035 (503,3035)vs 317 (200,594), DN group versus MA group, 1035(503,3035)vs 552(316,1338), all P < 0.01. (3) Pearson correlation test showed the level of usmad3 was significantly correlated with age, SBP, HbA1c, blood urea nitrogen, creatinine, total cholesterol, low density lipoprotein, eGFR and UACR (r = 0.57, P < 0.01). And multiple linear regression analysis showed that usmad3 and UACR were independently correlated (ß = 0.754, P < 0.01). (4) The usmad3 level in DN with retinopathy were significantly higher than that in DN without retinopathy (1905(806,4303) vs 595 (331,1183), P < 0.01). No significant difference existed in uACR level between DN with retinopathy and DN without retinopathy(P > 0.05). CONCLUSIONS: Urinary level of smad3 is significantly elevated in type 2 diabetics and it is significantly associated with ACR. It suggests that usmad3 is a potential marker in the diagnosis of DN and may be used to predict the severity of DN.

Associations of IL-10 gene polymorphisms with acute myeloid leukemia in Hunan, China.

We investigated the possible association of interleukin-10 (IL-10) single nucleotide polymorphisms (SNPs) and susceptibility to acute myeloid leukemia (AML) in 115 patients and 137 healthy controls. Genetic analysis of IL-10 SNPs at -819 and -592 was carried out with the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) approach. The IL-10 mRNA expression of AML patients and controls with different genotype was detected by real-time quantitative polymerase chain reaction (RT-PCR). Genetic analysis of IL-10 revealed that the -819AA genotype frequencies and the -819A allele frequencies in the AML group were higher than in the controls (59.1% vs 40.9%; 75.6% vs 63.9%, respectively); there were remarkable differences in -819T/C and -592A/C gene distribution (P<0.05) and the TA haploid frequencies were higher in the AML group (75.6% vs 63.9%, P<0.05). IL-10 mRNA expression in incipient AML patients was obvious higher than the non- tumor group and the remission group (7.78?10-3 vs 2.43?10-3, 3.64?10-3, P<0.05).The study suggested that the haploid TA and genotype TA/TA may be associated with AML in Han people in Hunan province.The IL-10 SNPs at -819 and -592 sites were associated with AML and may affect IL-10 mRNA expression in AML patients.

The protective effect of the RAS inhibitor on diabetic patients with nephropathy in the context of VEGF suppression.

AIM: The aim of the present study was to explore whether renin angiotensin system (RAS) inhibitor can reduce the production of vascular endothelium growth factor (VEGF). Further, we sought to elucidate the correlation between VEGF level and certain clinical parameters, such as albumin excretion rate (AER), before and after treatment with angiotensin type 1 receptor blocker. METHODS: We recruited 166 type 2 diabetic patients at various stages of diabetic nephropathy (DN) and 46 healthy control subjects for a cross-sectional study. We recruited another 42 hypertensive type 2 diabetic patients with microalbuminuria for a longitudinal study involving a 6-month irbesartan treatment protocol. Urinary VEGF (uVEGF) levels were determined using ELISA. RESULTS: In the cross-sectional study, hypertensive type 2 diabetic patients who received RAS inhibitor presented lower uVEGF levels than those who did not receive the RAS inhibitor. Statistical analysis indicated that uVEGF level was independently correlated with the AER. In the longitudinal study involving the 6-month irbesartan treatment, we demonstrated that uVEGF levels decreased significantly in patients who achieved a 50% AER reduction (remission group, n=32). In contrast, uVEGF levels remained unchanged in patients who did not exhibit a 50% AER reduction (nonremission group, n=10). Furthermore, the change in uVEGF was significantly correlated with the change in AER (r=0.65, P<0.01) before and after 6 months of irbesartan treatment. This result held true even after we had adjusted for the decrease in average blood pressure. CONCLUSION: The protective effect of the RAS inhibitor in DN patients is associated with the suppression of VEGF. Accordingly, it may be possible to use uVEGF as a marker of DN progression. We suggest that uVEGF may be an important target for therapeutic intervention in the context of DN.

Localized-statistical quantification of human serum proteome associated with type 2 diabetes.

BACKGROUND: Recent advances in proteomics have shed light to discover serum proteins or peptides as biomarkers for tracking the progression of diabetes as well as understanding molecular mechanisms of the disease. RESULTS: In this work, human serum of non-diabetic and diabetic cohorts was analyzed by proteomic approach. To analyze total 1377 high-confident serum-proteins, we developed a computing strategy called localized statistics of protein abundance distribution (LSPAD) to calculate a significant bias of a particular protein-abundance between these two cohorts. As a result, 68 proteins were found significantly over-represented in the diabetic serum (p<0.01). In addition, a pathway-associated analysis was developed to obtain the overall pathway bias associated with type 2 diabetes, from which the significant over-representation of complement system associated with type 2 diabetes was uncovered. Moreover, an up-stream activator of complement pathway, ficolin-3, was observed over-represented in the serum of type 2 diabetic patients, which was further validated with statistic significance (p = 0.012) with more clinical samples. CONCLUSIONS: The developed LSPAD approach is well fit for analyzing proteomic data derived from biological complex systems such as plasma proteome. With LSPAD, we disclosed the comprehensive distribution of the proteins associated with diabetes in different abundance levels and the involvement of ficolin-related complement activation in diabetes.

[Change and significance of serum pigment epithelium-derived factor in type 2 diabetic nephropathy].

OBJECTIVE: To investigate the change of pigment epithelium-derived factor (PEDF) in type 2 diabetic nephropathy, and to explore the significance of PEDF in the development of diabetic nephropathy. METHODS: ELISA was used to detect the serum PEDF and immunoturbidimetry was used to measure the urinary albumin excretion (UAE) in 49 healthy controls and 132 type 2 diabetic patients, including 48 with normal urinary albumin excretion rate (NA group), 50 with microalbuminuria (MA group), and 34 with overt diabetic nephropathy (PR group). HbA1c, triglyceride (TG), total cholesterol, high density lipoprotein cholesterol (HDL-c), and highly sensitive C-reactive protein (hs-CRP) were simultaneously determined. RESULTS: The serum PEDF levels of the NA, MA, and PR groups were (3.7 +/- 2.2) mg/L, (4.7 +/- 2.9) mg/L, and (5.7 +/- 2.8) mg/L respectively, all significantly higher than that of the control group (2.7 +/- 1.3) mg/L. P < 0.05, 0.01, and 0.01 respectively). The serum PEDF levels of the MA and PR groups were significantly higher than that of the NA group (both P < 0.01), and that of the PR group was significantly higher than that of the MA group (P < 0.05). Correlation analysis demonstrated that serum PEDF level was positively correlated with HbA1c (r = 0.198, P < 0.01), FPG (r = 0.231, P < 0.01), TG (r = 0.302, P < 0.01), hs-CRP (r = 0.214, P < 0.01), and urinary albumin excretion rate (UAER) (r = 0.169, P < 0.05), significantly, but negatively correlated with HDL-c (r = -0.237, P < 0.01). Stepwise multiple linear regression analysis showed that TG (beta = 0.314, P < 0.01), hs-CRP (beta = 0.260, P < 0.01), and UAER (beta = 0.148, P < 0.05) were significant independent determinants for serum PEDF. CONCLUSION: Serum PEDF level significantly increases in type 2 diabetic patients, and the magnitude of PEDF is related to the severity of diabetic nephropathy. TG, hs-CR and UAER are significant independent determinant for serum PEDF. The increase of PEDF may involve in the development of diabetic nephropathy.

Effect of targeted magnetic nanoparticles containing 5-FU on expression of bcl-2, bax and caspase 3 in nude mice with transplanted human liver cancer.

AIM: To investigate the anti-tumor effect and mechanisms of magnetic nanoparticles targeting hepatocellular carcinoma. METHODS: Human hepatocellular carcinoma was induced in nude mice, and the mice were randomly divided into group A receiving normal saline, group B receiving magnetic nanoparticles containing 5-fluorouracil (5-FU), group C receiving 5-FU, and group D receiving magnetic nanoparticles containing 5-FU with a magnetic field built in tumor tissues. The tumor volume was measured on the day before treatment and 1, 4, 7, 10 and 13 d after treatment. Tumor tissues were isolated for examination of the expression of bcl-2, bax and caspase 3 by immunohistochemical method, reverse transcription polymerase chain reaction and Western blotting. RESULTS: The tumor volume was markedly lower in groups C and D than in groups A and B (group C or D vs group A or B, P<0.01). The volume was markedly lower in group D than in group C (P<0.05). The expression of protein and mRNA of bcl-2 was markedly lower in groups C and D than in groups A and B (group C or D vs group A or B, P<0.01), and was markedly lower in group D than in group C (P<0.01). The expression of bax and caspase 3 in groups C and D was significantly increased, compared with that in groups A and B (P<0.01). CONCLUSION: The targeted magnetic nanoparticles containing 5-FU can improve the chemotherapeutic effect of 5-FU against hepatocellular carcinoma by decreasing the expression of bcl-2 gene, and increasing the expression of bax and caspase 3 genes.