Correlations between the femoral neck osteotomy angle and radiologic and clinical outcomes analyzed in patients undergoing total hip replacement with metaphyseal fixation.

OBJECTIVE: This study will explore whether the femoral neck osteotomy angle (FNOA) has an effect on hip anatomical functional reconstruction and clinical outcomes after total hip arthroplasty (THA). PATIENTS AND METHODS: The study included 254 patients (296 hips) who underwent primary total hip arthroplasty using the same uncemented short stem (Tri-Lock BPS) between December 2018 and December 2019. Correlations between FNOA and the radiologic and clinical outcomes of patients were analyzed. RESULTS: Patients were divided into 3 groups according to different FNOA. FNOA ≤50° is Group A, 50°< FNOA <55° Group B, and FNOA ≥55° Group C. There were significant differences among the three groups in distal D1 (p=0.029), sitting proud (SP) (p<0.001), varus and valgus alignment (p<0.001), FO (p=0.001), and caput-collum-diaphysis angle (CCD) (p<0.001). There were significant differences in the incidence of complications among the three groups (p<0.007). There was a significant linear correlation with D1 (B=0.005, CI=0.002 to 0.008, p=0.004), SP (B=-0.266, CI=-0.286 to 0.166, p<0.001), the femoral stem varus-valgus alignment angle (B=-0.359, CI=-0.422 to -0.297, p<0.001), femoral offset (FO) (B=-0.500, CI=-0.795 to -0.205, p=0.001), and CCD (B=0.696, CI=0.542 to 0.849, p<0.001). In logistic regression analysis, inappropriate FNOA increased the risk of dislocation (OR=0.892, CI=0.812 to 0.979, p=0.016) and thigh pain (OR=0.920, CI=0.851 to 0.995, p=0.037). CONCLUSIONS: The study demonstrates the relationship between FNOA and short-term radiological and clinical outcomes of patients after THA using a Tri-Lock femoral prosthesis. Inappropriate FNOA was significantly associated with failure of hip anatomical reconstruction and a higher risk of complications.

Levels of peripheral IL-6 and CD4+ and CD8+ T cells and their prognostic significance in COVID-19.

OBJECTIVE: The aim of this study was to discuss the prognostic significance of peripheral interleukin-6 (IL-6) and CD4+ and CD8+ T cells in COVID-19. PATIENTS AND METHODS: Eighty-four COVID-19 patients were retrospectively analyzed and classified into three groups, including the moderate group (15 cases), the serious group (45 cases), and the critical group (24 cases). The levels of peripheral IL-6, CD4+, and CD8+ T cells and CD4+/CD8+ were determined for each group. It was assessed whether these indicators were correlated to the prognosis and death risks of COVID-19 patients. RESULTS: The three groups of COVID-19 patients differed significantly in the levels of peripheral IL-6 and CD4+ and CD8+ cells. The IL-6 levels in the critical, moderate, and serious groups were increased successively, but the changed levels of CD4+ and CD8+ T cells were just opposite to that of IL-6 (p<0.05). The peripheral IL-6 level increased dramatically in the death group, while the levels of CD4+ and CD8+ T cells decreased significantly (p<0.05). The peripheral IL-6 level was significantly correlated with the level of CD8+ T cells and CD4+/CD8+ ratio in the critical group (p<0.05). The logistic regression analysis indicated a dramatic increase in the peripheral IL-6 level in the death group (p=0.025). CONCLUSIONS: The aggressiveness and survival of COVID-19 were highly correlated with the increases in IL-6 and CD4+/CD8+ T cells. The fatalities of COVID-19 individuals remained at increased incidence due to elevated peripheral IL-6 levels.

A 1:1 matched case-control study on dietary protein intakes and hip fracture risk in Chinese elderly men and women.

The role of protein intake in bone has been controversial. Our case-control study among Chinese elderly concluded that a higher consumption of protein, even substituted for fat, is associated with lowered hip fracture risk. Differences in protein sources, amino acids composition, gender, and calcium sufficiency may explain the inconsistency. PURPOSE: The aim of the study was to investigate the association of dietary protein intakes with hip fracture risk among Chinese elderly. METHODS: This was a 1:1 age and sex matched cross-sectional study of case-control design among 1070 pairs of elderly Chinese people aged 55 to 80 years. Patients who were newly diagnosed (within 2-week) hip fracture by X-ray were recruited from four hospitals in Guangdong Province of China. Dietary intakes were evaluated by a validated food frequency questionnaire for total protein, protein from different sources, amino acids profiles, and estimated renal acid load in diet. RESULTS: Daily average intakes of total protein were 58.1±27.0 (women) and 65.7±31.8 (men) g/d for cases, and 66.8±21.5 (women) and 72.1±24.4 (men) for controls (p<0.001). Multivariable regression indicated that, compared with the lowest quartile, the highest quartile of consumption of energy adjusted total protein [OR: 0.360 (0.206~0.630) for women and 0.381 (0.153~0.949) for men] and animal protein [0.326 (0.183, 0.560) for women and 0.335 (0.136~0.828) for men] was significantly associated with the lowered risk of hip fracture in a dose-response manner (all p for trend <0.05). A significant hip fracture risk reduction was observed in women with higher intakes of sulfur amino acids [OR: 0.464 (0.286~0.753)] and aromatic amino acids [0.537 (0.326~0.884)] but not in men. Subgroup analysis suggested that these associations were more evident in elderly with lower body mass index and dietary calcium intake less than 400 mg/d. CONCLUSIONS: A higher level of protein intake, even substituted for fat, is associated with lowered hip fracture risk.

LncRNA GAS5 induces chondrocyte apoptosis by down-regulating miR-137.

OBJECTIVE: Long non-coding RNA (lncRNA) participates in the pathogenesis of human knee osteoarthritis (KOA). Growth arrest specificity 5 (GAS5) is a member lncRNA, but its role in pathological regulation of KOA is still unknown. This study aims to explore the mechanism of GAS5 in KOA on chondrocyte apoptosis and other pathological processes. PATIENTS AND METHODS: The serum and cartilage tissues were collected from 35 patients with KOA and 30 patients with traumatic amputation admitted to our hospital from April 2016 to April 2020. The expressions of GAS5 and miR-137 were detected and analyzed. Chondrocytes were extracted from cartilage tissues of KOA patients, and the genes were regulated by transfection. Then, the cells were detected, including apoptosis, apoptosis-related proteins (caspase-3, Bax/Bcl-2), and proliferation. The targeting relationship between GAS5 and miR-137 was verified. RESULTS: GAS5 was up-regulated in serum and cartilage tissues of KOA patients, and down-regulation of GAS5 could inhibit the apoptosis process of chondrocytes and promote proliferation. MiR-137 was down-regulated in samples of KOA patients and was negatively regulated by GAS5. GAS5 induced apoptosis of chondrocytes and inhibited its proliferation through targeted down-regulating miR-137. CONCLUSIONS: GAS5 is up-regulated in KOA serum, cartilage tissues and cells, and can induce chondrocyte apoptosis through down-regulating miR-137.

MiR-1301 promotes adipogenic and osteogenic differentiation of BMSCs by targeting Satb2.

OBJECTIVE: Bone marrow mesenchymal stem cells (BMSCs) have the ability to differentiate into several cell lines and are critical for skeletal microenvironment and bone development. MiR-1301 is involved in multiple pathological and physiological processes. However, miR-1301's role in BMSCs adipogenic and osteogenic differentiation remains unclear. MATERIALS AND METHODS: Rat BMSCs were isolated and randomly divided into control group, miR-1301 group, and miR-1301 siRNA group followed by analysis of the expression of miR-1301, Bax, Bcl-2, UNX2, and OPN, as well as FABP4 and PPARγ2 by Real Time-PCR. Cell proliferation was assessed by MTT assay and the relationship between miR-1301 and Satb2 was evaluated by the Dual-Luciferase reporter assay. Satb2 expression was detected by Western blot. RESULTS: The pcDNA-miR-1301 plasmid was transfected into BMSCs to upregulate the expression of miR-1301, which promoted cell proliferation, decreased Bax expression, and increased Bcl-2 expression and ALP activity. In addition, it also elevated the expression of RUNX2 and OPN and decreased the expression of FABP4, PPARγ2, and Satb2. Compared with the control group, the difference was statistically significant (p<0.05); Satb2 was the target gene of miR-1301. MiR-1301 siRNA transfected into BMSCs down-regulated miR-1301 expression, inhibited cell proliferation, increased Bax expression and decreased Bcl-2 expression and ALP activity. Meanwhile, miR-1301 siRNA also reduced RUNX2 and OPN expression and increased expression of FABP4, PPARγ2 and Satb2. The difference was statistically significant compared with control group (p<0.05). CONCLUSIONS: Regulation of miR-1301 expression in BMSCs can improve BMSCs proliferation and regulate their adipogenic and osteogenic differentiation by regulating Satb2.

MiR-96-5p promotes the proliferation, invasion and metastasis of papillary thyroid carcinoma through down-regulating CCDC67.

OBJECTIVE: MicroRNAs (miRNAs) have been identified to play an important regulatory role in various biological behaviors of papillary thyroid carcinoma (PTC). However, the specific role and function of miR-96-5p in PTC remain unclear. Therefore, the aim of this study is to detect the expression of miR-96-5p in PTC, and to explore its exact function. PATIENTS AND METHODS: The relative expression level of miR-96-5p in PTC tissues and cell lines was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). MiR-96-5p mimics or inhibitors were then constructed and transfected into cells to upregulate or downregulate miR-96-5p expression. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay and colony formation assay were employed to evaluate the proliferation of PTC cells. Meanwhile, transwell assay was employed to detect the invasion and metastasis of PTC cells. In addition, the underlying mechanism of miR-96-5p was identified by Luciferase reporter gene assay and Western blot analysis. RESULTS: The expression of miR-96-5p in PTC tissues and PTC-derived cell lines was significantly higher than that of normal controls. The overexpression of miR-96-5p remarkably promoted the proliferation, invasion and migration of PTC cells. However, knockdown of miR-96-5p significantly decreased cell growth and metastasis. CCDC67 was verified as a target gene of miR-96-5p in PTC. Further experiments demonstrated that the restoration of CCDC67 could significantly reduce the carcinogenic function of miR-96-5p. CONCLUSIONS: MiR-96-5p was remarkably upregulated in PTC tumor tissues and cells. In addition, it promoted cell growth, invasion, and migration via repressing CCDC67 expression.

A meta-analysis of the effect of microRNA-34a on the progression and prognosis of gastric cancer.

OBJECTIVE: To explore the value of microRNA-34a (miR-34a) as a diagnostic biomarker of gastric cancer development and prognosis. MATERIALS AND METHODS: PubMed, Web of Science, Embase, CNKI, Wanfang Database and Gene Expression Omnibus (GEO) were searched according to the key words for the literature about the expression of microRNA-34a in the serum or tissues of gastric cancer patients. The data of gene expression were extracted and the data were analyzed by Stata 14.0 software to explore the significance of the difference of microRNA-34a expression in the development and prognosis of gastric cancer patients. RESULTS: The expression of microRNA-34a was significantly lower in gastric cancer tissues and significantly lower in metastatic gastric cancer tissues. The 5-year survival rate of gastric cancer patients was also significantly lower. CONCLUSIONS: The low expression of microRNA-34a can promote the progression of gastric cancer and reduce the prognosis of patients. MicroRNA-34a can be used as an important biomarker of gastric cancer progression and prognosis.

Molecular mechanism for P38 signaling pathway in autophagy of skin cancer cell line HS-1.

OBJECTIVE: Abnormal cell autophagy is correlated with aging, neurodegenerative disease, and skin cancer. The signal transduction pathway of autophagy in skin cancer is still unclear. This study aimed to investigate the role of P38 signal pathway-induced cell autophagy in skin cancer onset and potential clinical application value. MATERIALS AND METHODS: Skin cancer cell line HS-1 was used as the model for ultraviolet (UV) irritation. Western blot tested autophagy signal molecules P38 activation in skin cancer cell line HS-1. Cells were then treated with P38 pathway agonist and antagonist to test autophagy condition and P38 pathway activation. Correlation analysis was performed to investigate the correlation between P38 pathway and cell autophagy level. RESULTS: UV irradiation treated skin cancer cell line HS-1 led to cell autophagy and P38 activation. AICAR and SB203580 potentiated and inhibited UV-induced HS-1 cell autophagy, respectively. P38 signal pathway activation condition was positively correlated with autophagy level. CONCLUSIONS: UV irradiation can induce skin cancer cell autophagy via the P38 signal pathway, indicating that the regulation of the P38 signal pathway activation might be one potential strategy treating skin cancer.

Low expression of miR-203 promoted diabetic nephropathy via increasing TLR4.

OBJECTIVE: To investigate the relationship between microRNA-203 (miR-203) and diabetic nephropathy and its potential mechanism. MATERIALS AND METHODS: The expression of microRNA-203 in mice with diabetic nephropathy and M4200 cells cultured with high glucose was detected by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Toll-like receptor 4 (TLR4), the target gene of microRNA-203, was predicted and screened by bioinformatics method. Real-time quantitative PCR and Western blot were used to detect the endogenous TLR4 level in renal cortex of db/db mice with diabetic nephropathy and glomerular mesangial cells cultured in high glucose or low glucose. The expression of microRNA-203 and TLR4 mRNA were evaluated by RT-PCR after treatment of miR-203 mimics and inhibitor. The protein of TLR4 level was detected by Western blot. Additionally, the proliferation ability of cells was evaluated by Cell Counting Kit-8 (CCK8). The target relationship between microRNA-203 and TLR4 3' UTR was confirmed by luciferase reporter assay RESULTS: The expression of miR-203 was significantly decreased in the kidney of mice with diabetic nephropathy and M4200 cells cultured in high glucose. On the contrary, TLR4 expression was significantly increased. Results of in vitro experiments showed that miR-203 could bind to 3'UTR region of TLR4. Overexpression of microRNA-203 significantly decreased the levels of TLR4 mRNA and protein. Meanwhile, low expression of miR-203 leaded to increased TLR4 expression, resulting in an enhanced proliferation of M4200 cells. CONCLUSIONS: The downregulation of microRNA-203 leaded to an increased level of TLR4, thus promoting proliferation of M4200 cells in the pathogenesis of diabetic nephropathy.

Dietary sugar intake was associated with increased body fatness but decreased cardiovascular mortality in Chinese elderly: an 11-year prospective study of Mr and Ms OS of Hong Kong.

BACKGROUND/OBJECTIVES: Epidemiological studies suggest that sugar intake contributes to weight gain and increased risk of cardiovascular diseases (CVDs). However, this association is largely undefined in the elderly population. Our aim was to investigate the effect of sugar consumption on the subsequent changes in body fatness and CVD mortality in Chinese elderly. METHODS: A total of 2000 men and 2000 women aged ⩾65 years were recruited from 2001 to 2003. Dietary sugar intake was estimated based on a validated 329-item food frequency questionnaire and a local sugar database. Adiposity was measured using dual-energy X-ray absorptiometry at baseline and follow-up after 4 years. Mortality was ascertained by local death registry until March 2014. Multivariable linear and Cox regression were conducted to evaluate the association of sugar consumption on the changes in body fatness and CVD mortality. RESULTS: A total of 174 CVD deaths were documented within the total 37 999 person-years' follow-up. Significant positive association between sugar intake and increase in body fatness at follow-up after 4 years was found in men but not in women. After adjustment for potential confounders, men who consumed 1% increase in added sugar had an increase in whole body fat by 0.043 kg (P=0.006), central fat by 0.029 kg (P=0.016) and peripheral fat by 0.026 kg (P=0.006). However, in both genders, after an average of 11.1-year follow-up, compared with the lowest quintile, the highest intakes of added sugar were associated with significantly lowered CVD mortality by 74.9% (hazard ratio (HR) (95% confidence interval (CI)): 0.251(0.070, 0.899)) in a dose-response manner (Ptrend=0.011). This association was attenuated to non-significance by further adjustment of the change in body fatness (Ptrend=0.055). CONCLUSIONS: Thus higher sugar intake of the Chinese elderly was associated with increased adiposity in men but decreased CVD mortality. The current World Health Organization recommendation for the elderly should be reviewed.

Retraction RETRACTION of "Efficacy and safety of nucleoside analogues in preventing vertical transmission of the hepatitis B virus from father to infant", by L.-H. Cao, P.-L. Zhao, Z.-M. Liu, S.-C. Sun, D.-B. Xu, J.-D. Zhang and Z.-H. Shao - Genet. Mol. Res. 14 (4): 15539-15546 (2015).

The retracted article is: Cao L-H, Zhao P-L, Liu Z-M, Sun S-C, et al. (2015). Efficacy and safety of nucleoside analogues in preventing vertical transmission of the hepatitis B virus from father to infant. Genet. Mol. Res. 14: 15539-15546. The article published in Genetics and Molecular Research 14 (4): 15539-15546 (2015) is a very good paper, but it appears that the authors' group submitted this manuscript to multiple journals, which is ethical misconduct. This manuscript (similar language and identical data) was published in the Experimental and Therapeutic Medicine Journal prior to being submitted to GMR. There are parts copied from "Efficacy and safety of nucleoside analogs on blocking father-to-infant vertical transmission of hepatitis B virus", by Li-Hau Cao, Pei-Li Zhao, Zhi-Min Liu, Shao-Chun Sun, et al. Exp. Ther. Med. 9 (6): 2251-2256 (2015) - DOI: 10.3892/etm.2015.2379. The GMR editorial staff was alerted and after a thorough investigation, there is strong reason to believe that the peer review process was failure. Also, after review and contacting the authors, the editors of Genetics and Molecular Research decided to retract this article in accordance with the recommendations of the Committee on Publication Ethics (COPE). The authors and their institutions were advised of this serious breach of ethics.

Efficacy and safety of nucleoside analogues in preventing vertical transmission of the hepatitis B virus from father to infant.

We examined the efficacy and safety of nucleoside analogues in preventing the vertical transmission of hepatitis B virus (HBV) from father to infant. We included 201 patients who visited the liver clinic of our hospital. The patients were positive for HBV surface antigen (HBsAg), HBeAg, anti-HBc, and HBV DNA; 189 patients (94%) had abnormal liver function. In all couples, the fathers were HBV DNA-negative and had normal liver function, and the mothers were anti-HB-positive before pregnancy. The control group comprised 188 couples who visited our hospital during the same time period. The fathers in the control group were positive for HBsAg, HBeAg, anti-HBc, and HBV DNA. The mothers were HBsAg-negative and anti-HBs-positive. No infants in the case group were HBsAg-positive and HBV DNA-positive, and all were anti-HBs-positive, indicating that father to infant HBV vertical transmission was prevented in the case group. In the control group, 147 of 188 newborns (78.2%) were anti-HBs-positive at birth, 28 (14.9%) were HBV DNA-positive, and 19 (10.1%) were HBsAg-positive. A significant difference was observed between the two groups. No statistically significant difference was observed in the gestational age, birth weight, birth length, 1-min and 8-min Apgar score, jaundice, other internal and surgical diseases, delivery mode, and other birth information between the neonates born to couples in the case and control groups; there were no fetal malformations and stillbirths in the two groups. Our results showed that administration of antiretroviral therapy to HBV DNA-positive fathers before pregnancy can cause a decrease in the viral load and prevent father to infant HBV vertical transmission. The use of antiviral nucleoside analogues before pregnancy was safe in fathers, and the fathers who wanted children could continue to use anti-viral therapy. The sample size in our study was small, and further studies with a large sample size and longer follow-up time are required for determining the use of nucleoside analogues from the point view of prenatal and postnatal care.

Mucosolvan serves to optimize perioperative airway management for NSCLC patients in fast track surgery: a randomized placebo controlled study.

OBJECTIVE: This study is conducted to investigate whether mucosolvan may offer therapy optimization initiatives for airway perioperative management of patients with non-small cell lung cancer (NSCLC) in fast track surgery (FTS). PATIENTS AND METHODS: The patients in FTS were treated with and without aerosol (90 mg/day) of mucosolvan in combination of intravenous administration of the agent (180 mg/day) for 8 consecutive days. Postoperative complications and length of time of hospital stay were examined in the patients treated with and without mucosolvan. RESULTS: Prevalence rate for the overall postoperative complication was significantly decreased in the mucosolvan-treated patients as compared to the untreated ones (p < 0.05). In further analysis, an appearance of postoperative pulmonary complication was reduced in the treated patients as well (p < 0.05). There was no statistical difference in a morbidity rate of postoperative cardiac complications between these two groups. Furthermore, treatment with mucosolvan resulted in significantly decreasing length of time of hospital stay as compared to the untreated patients (p < 0.05), indicating that this agent may facilitate early recovery of the patients in FTS after major surgical approaches. CONCLUSIONS: Mucosolvan optimizes the perioperative airway management for NSCLC patients in FTS through reducing postoperative complications and shortening time of hospital stay.

Efficacy of combined hepatitis B immunoglobulin and hepatitis B vaccine in blocking father-infant transmission of hepatitis B viral infection.

The aim of this study was to examine the efficacy of combined immunization of hepatitis B immunoglobulin (HBIG) and hepatitis B vaccine (HBVac) in blocking father-infant transmission of hepatitis B virus (HBV). Newborns positive at birth for blood HBV sur-face antigen (HBsAg) and/or HBV DNA were selected and immunized with HBIG combination HBVac. At 7 months, HBV markers and HBV DNA of each neonate were measured using electrochemiluminescence with the Cobas-e-411 Automatic Electrochemiluminescence Immuno-assay Analyzer and fluorescence quantitative polymerase chain reaction. Among all 7-month-old subjects, the negative conversion rates of HBV DNA and HBsAg were 48/61 (78.7%) and 19/41 (46.3%), respectively. Therefore, this study demonstrated that prompt combination injection of HBIG and HBVac can protect some of the HBV DNA- and/ or HBsAg-positive newborns from HBV.

Dual priming oligonucleotide (DPO)-based multiplex PCR assay for specific detection of four diarrhoeagenic Escherichia coli in food.

UNLABELLED: In this study, a dual priming oligonucleotide (DPO)-based multiplex PCR assay was developed for the specific detection of four foodborne diarrhoeagenic Escherichia coli (DEC) in food, including enterotoxigenic E. coli (ETEC), enteropathogenic E. coli (EPEC), enterohemorrhagic E. coli (EHEC) O157:H7 and enteroinvasive E. coli (EIEC). Species-specific DPO primers were designed based on rfbE, LT, ipaH and bfpA genes for EHEC O157:H7, ETEC, EIEC and EPEC respectively. Our optimized DPO-based multiplex PCR assay was able to simultaneously detect these DEC from pure cultures, spiked food or environmental sample with an analytical detection limit of <120 CFU ml(-1) (or g(-1) ) for each at annealing temperature from 45 to 65°C. A total of 336 bacterial strains including 51 target and 285 other bacterial strains were used to evaluate the specificity of the assay, and results showed that specific PCR products were only amplified in strains belonging to target bacteria. Applying the assay to 982 samples collected from food, clinical patients and environmental sources revealed that 73 samples were positive, which were confirmed by conventional culture-based assays combined with serological tests. Taken together, the DPO-based multiplex PCR assay developed in this study is a rapid, specific and reliable tool for efficient screening single or multiple DEC from food in laboratory diagnosis. SIGNIFICANCE AND IMPACT OF THE STUDY: The high specificity of the DPO-based multiplex PCR assay developed in this study without false positive results indicates its great potential to be a rapid, reliable, practical and cost-effective method for the monitoring of diarrhoeagenic E. coli in food.

Effect of whole soy and purified daidzein on ambulatory blood pressure and endothelial function--a 6-month double-blind, randomized controlled trial among Chinese postmenopausal women with prehypertension.

BACKGROUND/OBJECTIVES: Although observational studies suggest that soy foods or isoflavones are cardio-protective, clinical trials on whole soy or isoflavone daidzein (one major isoflavone and the precursor of equol) on blood pressure (BP) and endothelial function (EF) are few and have not been specifically conducted among equol producers, a population most likely to benefit from soy treatment. SUBJECTS/METHODS: We performed a 6-month double-blind, randomized, placebo-controlled trial to examine the effect of whole soy (soy flour) or purified daidzein on BP and EF in prehypertensive or untreated hypertensive postmenopausal women verified to be equol producers. A total of 270 eligible women were recruited and randomized to either one of the three treatment groups, 40 g soy flour (whole soy group), 40 g low-fat milk powder+63 mg daidzein (daidzein group) or 40 g low-fat milk powder (active control group) daily, each given as a solid beverage powder for 6 months. The primary outcome measures were 24 h ambulatory BP (ABP) and EF assessed by flow-mediated dilation using brachial artery ultrasound. RESULTS: A total of 253 subjects completed the study according to protocol. Urinary isoflavones indicated good compliance with the interventions. Intention to treat and per-protocol analysis indicated that there was no significant difference in the 6-month changes or % changes in parameters of ABP and brachial flow-mediated dilation among the three treatment groups. A further subgroup analysis among hypertensive women (n=138) did not alter the conclusions. CONCLUSIONS: Whole soy and purified daidzein had no significant effect on BP and vascular function among equol-producing postmenopausal women with prehypertension or untreated hypertension.

VEGF Trapon inhibits tumor growth in papillary thyroid carcinoma.

OBJECTIVE: Vascular endothelial growth factor (VEGF) is the most potent inducer of neovasculature, and its increased expression has been related to a worse clinical outcome in many disease. Angiogenesis from thyroid cancer cell plays the important roles in post-surgical persistent, recurrent, and metastatic papillary thyroid cancer (PTC). Vascular endothelial growth factor (VEGF) Trapon is a newly developed VEGF-blocking agent with stronger affinity and broader activity than the anti-VEGF antibody bevacizumab. In this study, we tested the activity of VEGF Trapon on a PTC model in vivo. MATERIALS AND METHODS: BC-PAP (derived from papillary carcinomas) transfected with a luciferase-expressing vector were injected into the back to mice. I.p. treatment with VEGF Trapon or control protein (25 mg/kg twice weekly) was started shortly after tumor injection to prevent tumor development (prevention model) or after established tumors were formed to inhibit tumor growth and metastasis formation (intervention model). RESULTS: In the prevention model, VEGF Trapon inhibited tumor growth by 73 ± 12% compared with control (p = 0.014) and significantly prolonged survival. In the intervention model, VEGF Trapon inhibited tumor growth by 68 ± 7% (p < 0.01). Microvascular density was reduced by 56% due to VEGF Trapon treatment (p < 0.01). CONCLUSIONS: VEGF Trapon is a potent inhibitor of BC-PAP tumor growth, angiogenesis and blocks the biological function of VEGF in vivo. These results support further clinical development of VEGF Trapon for PTC and other cancer types.

siRNA-directed clusterin silencing promotes cisplatin antitumor activity in human non-small cell lung cancer xenografts in immunodeficient mice.

OBJECTIVES: In a previous analysis using a lung cancer cell lines model, we have found that therapies directed against sCLU and its downstream signaling targets pAkt and pERK1/2 may have the potential to enhance the efficacy of cisplatin (DDP)-based chemotherapy in vitro. Here, we investigated the therapies directed against sCLU on the DDP-based chemotherapy in vivo, and explored the mechanism. MATERIALS AND METHODS: Using lung cancer cell lines, A549 cells and DDP-resistant A549 cells (A549DDP), we determined the effect of sCLU silencing using short interfering double-stranded RNA (siRNA) on chemosensitivity in immunocompromised mice bearing A549DDP tumors. We then determined the effect of sCLU overexpression via stable sCLU transfection on chemosensitivity in immunocompromised mice bearing A549 tumors. The effect of sCLU silencing or overexpression on pAkt and pERK1/2 expression and chemosensitivity in vivo was detected by western blot assay. RESULTS: The results showed sCLU silencing increased the chemosensitivity of A549DDP cells to DDP in vivo via downregulation of pAkt and pERK1/2 expression. And sCLU overexpression decreased the chemosensitivity of A549 cells to DDP in vivo via upregulation of pAkt and pERK1/2 expression. CONCLUSIONS: DDP-induced sCLU activation, which involved induction of pAkt and pERK1/2 activation that confer DDP resistance in immunocompromised mice. Alteration of this balance allows sensitisation to the antitumor activity of cisplatin chemotherapy.

Bioinformatic analysis of microarray data reveals several key genes related to heart failure.

OBJECTIVES: Heart failure is a major public health problem worldwide. However, the molecular mechanism is still unclear. This study aims to discover differentially expressed genes (DEGs) between non-ischemic or ischemic heart failure samples and healthy control, which may be used for diagnosis and treatment of heart failure. MATERIALS AND METHODS: Gene expression profile GSE9128 was downloaded from Gene Expression Omnibus, including 3 normal samples, 4 non-ischemic heart failure samples and 4 ischemic samples. Data processing and differential analysis were carried out with packages of R. Cluster analysis was also performed for all the samples to globally observe the difference among the three groups of samples. Interactors of the DEGs were retrieved with Osprey and then networks were constructed. The overlapping part of the network was selected out using Cytoscape, for which functional enrichment analysis was applied with DAVID tools. RESULTS: A total of 293 and 133 DEGs were obtained for non-ischemic and ischemic heart failure, respectively. Two networks were established and then functional enrichment analysis revealed that "regulation of programmed cell death" was most significantly over-represented in common DEGs. CONCLUSIONS: Genes differentially expressed in non-ischemic and ischemic heart failure can be biomarkers to distinguish the two types of heart failure. Besides, these genes can be targets to develop treatments.

Clinical research in individual information of celiac artery CT imaging and gastric cancer surgery

OBJECTIVE: The objective of this study is to acquire CT images of the celiac artery by 64-multi-slice spiral CT angiography (64-MSCTA) in gastric cancer patients to facilitate gastric cancer surgery. METHODS: Preoperative 64-MSCTA was performed to observe the origin, course and anatomical variations of the celiac artery and vascular calcifications in 102 gastric cancer patients. RESULTS: (1) The celiac trunk mostly arose at the level between the 12th thoracic vertebra and the 1st lumbar vertebra; the mean inferior angle with the abdominal aorta was 63.5° (14°-159°), the mean length was 36.29 mm (5.80-73.58 mm), and its course showed many styles. (2) Of 102 gastric cancer patients, 34 patients (33.33 %) were observed with celiac artery variations of whom there were 27 patients with anatomical variations of the hepatic artery, 3 patients with anatomical variation of the left gastric artery and 1 patient with anatomical variation of the splenic artery; in 1 patient, the celiac trunk and the superior mesenteric artery originated from a common trunk. In other cases, it was observed with another variation. (3) The abdominal aortic calcified plaque was observed in 48 patients (47.1 %), and among them, 34 patients were more than 60 years old, and the existence of the abdominal aortic calcified plaque was related to age, significantly (P < 0.01). CONCLUSIONS: The 64-MSCTA largely improves our understanding of the origin, course and anatomical variations of the celiac artery and vascular calcifications in individual patient with gastric cancer. It is recommended that the 64-MSCTA of the celiac artery should be classified as a routine preoperative procedure in gastric cancer patients (AU)