Screening of miRNAs associated with lymph node metastasis in Her-2-positive breast cancer and their relationship with prognosis / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

The aim of this study was to identify some biomarkers for predicting lymph node metastasis and prognosis of human epidermal growth factor receptor 2 (Her-2)-positive breast cancer (BC). We analyzed correlations between microRNAs (miRNAs) and the prognosis of patients with BC based on data collected from The Cancer Genome Atlas (TCGA) database. The expression levels of miR-455, miR-143, and miR-99a were measured in clinical samples of Her-2-positive BC patients with different degrees of lymph node metastasis. We investigated the impacts of overexpressed miR-455 on the proliferation and invasiveness of MDA-MB-453 cells and measured its effects on the expression of long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) by quantitative real-time polymerase chain reaction (qRT-PCR). The expression of miR-455 was significantly and positively correlated to the prognosis and overall survival (OS) of the BC (P=0.028), according to TCGA information. The expression level of miR-455 was positively correlated with OS and relapse-free survival (RFS) of patients with Her-2-positive BC, and was negatively correlated with the number of metastatic lymph nodes (P<0.05). Transwell assay suggested that MDA-MB-453 cells became much less invasive (P<0.01) after being transfected with miR-455 mimics. During the qRT-PCR, the expression level of MALAT1 declined significantly after transfection (P<0.01). Overexpressed miR-455 significantly inhibited the proliferation and migration of MDA-MB-453 cells and the expression of MALAT1. We conclude that miR-455 may be a useful potential biomarker for forecasting lymph node metastasis and the prognosis of Her-2-positive BC patients. miR-455 may play an important role in lymph node metastasis of BC by interacting with MALAT1.

Protective effects of Radix Astragali injection on multiple organs of rats with obstructive jaundice / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the protective effects and mechanisms of Radix Astragali Injection on multiple organs of rats with obstructive jaundice (OJ).</p><p><b>METHODS</b>A total of 180 rats were randomly divided into the sham-operated, model control and treated groups (60 in each group). On 7, 14, 21 and 28 days after operation, the serum contents of alanine aminotransferase (ALT), aspartate aminotransferase (AST), r-glutamyl transpeptidase (r-GT), total bilirubin (TBil), direct bilirubin (DBil), blood urine nitrogen (BUN), and creatinine (CREA) were determined. And the pathological changes of livers, kidneys and lungs, and protein expressions of toll-like receptor-4 (TLR-4) of livers, intercellular adhesion molecule-1 (ICAM-1) of lungs, Bax and nuclear factor-kappa B (NF-κB), as well as apoptotic indexes of multiple organs were observed, respectively.</p><p><b>RESULTS</b>The pathological severity scores of multiple organs (including livers on 7, 14, 21 and 28 days, kidneys on 14 and 28 days, and lungs on 14 days), serum contents of ALT (14 and 21 days), AST (14 days), TBil (7, 14, 21 and 28 days), DBil (14 and 21 days), BUN (28 days), protein expressions of TLR-4 (in livers, 28 days), Bax (in livers and kidneys, 21 days), and apoptotic indexes in livers (7 and 21 days) in the treated group were significantly lower than those in the model control group (P<0.05 or P<0.01).</p><p><b>CONCLUSION</b>Radix Astragali Injection exerts protective effects on multiple organs of OJ rats by improving the pathological changes of lung, liver and kidney, decreasing the serum index of hepatic and renal function as well as inhibiting the protein expression of TLR-4 and Bax in the livers and Bax in the kidneys.</p>

Treatment of Chemotherapy Related Leukocytopenia by Oral Administration of Multiple Leucogenic Drugs Combined with G-CSF: an Experimental Study / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To evaluate efficacies of three commonly used oral drugs including Berbamine Hydrochloride Tablet (B), Qijiao Shengbai Capsule (Q), and Leucogen Tablet (L) (by single drug, two drugs or three drugs) combined with granulocyte colony-stimulating factor (G-CSF) for treat ment of chemotherapy related leukocytopenia in mice.</p><p><b>METHODS</b>Totally 156 Kunming male mice were divided into the normal control group (A, n=24), the model group (B, n=24), the G-CSF group (C, n =24), the G-CSF+Q group (D, n=12), G-CSF+ B (E, n=12), the G-CSF+L group (F, n=12), the G-CSF + Q + B group (G, n=12), the G-CSF + Q + L group (H, n=12), the G-CSF + L + B group (I, n=12), and the G-CSF + L + Q + B (J, n=12). Mouse models of chemotherapy related leukocytopenia were established by intraperitoneal injection of cyclophosphamide (CTX). A G-CSF group was set up as a positive control. Mice were treated by a single oral drug, a single oral drug combined with G-CSF, and two or three drugs combined with G-CSF respectively, and the death rate calculated. Hemocytes [such as white blood cells (WBC) and its classification, red blood cells (RBC), platelet (PLT), hemoglobin (Hb)] were calculated by hematology analyzer. Mice were anatomized and important organs weighed. Organ indices were calculated.</p><p><b>RESULTS</b>There was no statistical difference in the mortality rate among all groups (P > 0.05). Compared with Group B, WBC was elevated in all other groups (P < 0.01). WBC and PLT were elevated most in Group J, Hb and RBC were also increased at the same time (P < 0.05, P < 0. 01). Compared with Group B, RBC increased in Group E, F, G, I, and J (P < 0.01); Hb obviously increased in Group C, E, F, H, I, and J (P<0.01). Compared with Group B and D, the promotion of erythroid hematopoiesis by G-CSF could be elevated in any group contained drug B and L (P < 0.05, P < 0.01). The spleen index of model mice could be significantly improved in Group C, D, and G (P < 0.01). The thymus index of model mice could be significantly improved in Group H (P < 0.05).</p><p><b>CONCLUSIONS</b>The best scheme to treat mice with chemotherapy related leukopenia or decreased three blood series was to administrate three commonly oral drugs combined with G-CSF. Authors speculated that G-CSF and Q might have a certain effect on CTX induced immune inhibition.</p>

Therapeutic mechanisms of single Chinese medicine herb or their extracts for extrahepatic obstructive jaundice / 中国结合医学杂志

Obstructive jaundice (OJ) is classified as extrahepatic OJ or intrahepatic OJ. Extrahepatic OJ is attributed to a variety of intricate etiological factors. Research has begun with Chinese medicine (CM), which can be used as an adjunctive therapy for extrahepatic OJ. Particular attention has been paid to the therapeutic effects and their mechanisms of single CM herb and relevant extracts. The roles of single CM or their extracts during adjunctive therapy for extrahepatic OJ have been described briefly. This review focuses on the effects and their mechanisms of relevant herbal medicines.

Protective effects of Salvia miltiorrhizae on the hearts of rats with severe acute pancreatits or obstructive jaundice / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

<p><b>OBJECTIVE</b>To investigate the therapeutic effects and mechanisms of Salvia miltiorrhizae (Danshen) in the treatment of severe acute pancreatitis (SAP)- or obstructive jaundice (OJ)-induced heart injury.</p><p><b>METHODS</b>A total of 288 rats were used for SAP- (n=108) and OJ-associated (n=180) experiments. The rats were randomly divided into sham-operated, model control, and Salvia miltiorrhizae-treated groups. According to the difference of time points after operation, SAP rats in each group were subdivided into 3, 6 and 12 h subgroups (n=12), whereas OJ rats were subdivided into 7, 14, 21, and 28 d subgroups (n=15). At the corresponding time points after operation, the mortality rates of the rats, the contents of endotoxin and phospholipase A2 (PLA2) in blood, and pathological changes of the hearts were investigated.</p><p><b>RESULTS</b>The numbers of dead SAP and OJ rats in the treated groups declined as compared with those in the model control group, but not significantly (P>0.05). The contents of endotoxin (at 6 and 12 h in SAP rats and on 7, 14, 21, and 28 d in OJ rats, respectively) and PLA2 (at 6 and 12 h in SAP rats and on 28 d in OJ rats, respectively) in the treated group were significantly lower than those in the model control group (P<0.01 and P<0.001, respectively). Besides, myocardial pathological injuries were mitigated in SAP and OJ rats.</p><p><b>CONCLUSION</b>In this study, we found that Salvia miltiorrhizae improved myocardial pathological changes, reduced the content of PLA2 in blood, and decreased the mortality rates of SAP and OJ rats, exerting protective effects on the hearts of the rats.</p>

Effects of Montessori education on the intellectual development in children aged 2 to 4 years / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To compare the effects of Montessori education and traditional education on the intellectual development in children aged 2 to 4 years.</p><p><b>METHODS</b>Children aged between 2 to 3 years who were enrolled in a kindergarten in September 2006 were randomly assigned to the Montessori education and the traditional education groups. In addition to receiving the traditional education, the Montessori education group participated in the two-hour Montessori pedagogical activities every day. The intellectual development was evaluated by the Neuropsychological Development Examination Format for Children Aged 0~6 years published by Capital Pediatrics Research Institute at enrollment and one year after the trial.</p><p><b>RESULTS</b>There were no significant differences in the intelligence growth level between the Montessori education and the traditional education groups at enrollment. After one year, the levels of fine movements, adaptation ability, language, and social behavior developments in the Montessori education group were significantly higher than those in the traditional education group (p<0.05 or 0.01). The intelligence increasing scores of the large motor ability, fine movements, language, social behavior and development quotient in the Montessori education group were also higher than those in the traditional education group (p<0.05 or 0.01).</p><p><b>CONCLUSIONS</b>Montessori education can promote the development of large motor ability, fine movements, language, and social behavior in children.</p>

Prospective study of early application of immune-enhanced enteral nutrition and recombined human growth hormone on patients with gastric neoplasms after total gastrectomy / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To explore the effect of immune-enhanced enteral nutrition (IEN) together with recombined human growth hormone (rhGH) on patients after total gastrectomy.</p><p><b>METHODS</b>Forty-eight patients after total gastrectomy were randomly divided into EN group (n=16), IEN group (n=16) and IEN+ rhGH(n=16) group. Nitrogen balance, nutritional status, immune function and lassitude degree were compared among 3 groups.</p><p><b>RESULTS</b>IEN+rhGH group had better efficacy as compared to EN and IEN group in improving postoperative nutritional status, immune function, nitrogen balance and lassitude degree, and recovered to normal level after 7 days. All the indexes of IEN+rhGH group except CD8 were improved significantly on the 10th day after operation as compared to those of EN group[total protein(66.8 +/- 2.0)g/L vs (65.8 +/- 0.9)g/L, CD3(66.1 +/- 6.3)% vs (60.5 +/- 5.6)%, Christensen score (4.6 +/- 0.9) vs (6.3 +/- 0.9), all P<0.05].</p><p><b>CONCLUSION</b>Early application of IEN combined with rhGH plays an effective role in improving protein metabolism and immune function for patients after total gastrectomy in short period.</p>

Mechanism of acute pancreatitis complicated with injury of intestinal mucosa barrier / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Acute pancreatitis (AP) is a common acute abdomen in clinic with a rapid onset and dangerous pathogenetic condition. AP can cause an injury of intestinal mucosa barrier, leading to translocation of bacteria or endotoxin through multiple routes, bacterial translocation (BT), gut-origin endotoxaemia, and secondary infection of pancreatic tissue, and then cause systemic inflammatory response syndrome (SIRS) or multiple organ dysfunction syndrome (MODS), which are important factors influencing AP's severity and mortality. Meanwhile, the injury of intestinal mucosa barrier plays a key role in AP's process. Therefore, it is clinically important to study the relationship between the injury of intestinal mucosa barrier and AP. In addition, many factors such as microcirculation disturbance, ischemic reperfusion injury, excessive release of inflammatory mediators and apoptosis may also play important roles in the damage of intestinal mucosa barrier. In this review, we summarize studies on mechanisms of AP.

Study progress in therapeutic effects of traditional Chinese medicine monomer in severe acute pancreatitis / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Severe acute pancreatitis (SAP) is a common acute abdomen clinical problem characterized by high mortality, multiple complications, complicated pathogenesis and difficult treatment. Recent studies found traditional Chinese medicine (TCM) monomers have markedly good effect for treating SAP. Many TCM monomers can inhibit pancreatin, resist inflammation, improve microcirculation and immunoloregulation, etc. to block the pathological progress of SAP in multiple ways, reduce complications and lower mortality with rapid effects. It is significant for enhancing SAP treatment to deeply understand the current situation in TCM monomers for treating SAP and take precious references therein. This article summarizes the treating effects and mechanisms of TCM monomers for SAP in recent years.

Study progress on mechanism of severe acute pancreatitis complicated with hepatic injury / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Study on the action mechanism of inflammatory mediators generated by the severe acute pancreatitis (SAP) in multiple organ injury is a hotspot in the surgical field. In clinical practice, the main complicated organ dysfunctions are shock, respiratory failure, renal failure, encephalopathy, with the rate of hepatic diseases being closely next to them. The hepatic injury caused by SAP cannot only aggravate the state of pancreatitis, but also develop into hepatic failure and cause patient death. Its complicated pathogenic mechanism is an obstacle in clinical treatment. Among many pathogenic factors, the changes of vasoactive substances, participation of inflammatory mediators as well as OFR (oxygen free radical), endotoxin, etc. may play important roles in its progression.

Soy isoflavones with supplemental calcium provide protection against the loss of bone mass and influence insulin-like growth factor (IGF)-I after ovariectomy in rat / 中华预防医学杂志

<p><b>OBJECTIVE</b>To compare the effects of soy isoflavone with supplemental calcium to soy isoflavone or Ca alone on preservation of bone mineral density (BMD) and the expression of insulin-like growth factor (IGF)-I.</p><p><b>METHODS</b>Sprague-Dawley (SD) female Rats, 6 months old, were ovariectomized and randomized into five groups: sham-operated group (n = 10) or ovx (n = 40) group. Shams were fed a 3.272 g/kg Ca diet. Ovx rats were randomized to a 3.272 g/kg Ca diet alone (OVX) or with soy isoflavone (SI) extract (37.95 mg/kg.bw) or to a supplemental Ca diet (Ca, 4.676 g/kg) alone or a supplemental Ca diet with the isoflavone extract (SI + Ca) for 12 weeks. BMD of femur was measured by scanner of bone mineral density. The level of IGF-1 mRNA expression was measured by reverse transcriptase-polymerase chain reaction (RT-PCR), respectively.</p><p><b>RESULTS</b>There was no significant difference between group Sham (0.267 +/- 0.008) and group SI + Ca (0.263 +/- 0.007) g/cm(2) (P > 0.05) on femur BMD of distal end. Femur BMD of distal end in group Sham and group SI + Ca was greater (P < 0.05) as compared to group OVX (0.245 +/- 0.005) g/cm(2), SI (0.258 +/- 0.011) g/cm(2) or Ca (0.255 +/- 0.004) g/cm(2), P < 0.05. The liver tissue IGF-1 mRNA contents (IGF-1 cDNA/B-actin cDNA) were significantly decreased in group Sham (0.200 +/- 0.023) g/cm(2), SI (0.278 +/- 0.019) g/cm(2), Ca (0.302 +/- 0.026) g/cm(2) or SI + Ca (0.231 +/- 0.025) g/cm(2) as compared to group OVX (0.362 +/- 0.031) g/cm(2), P < 0.05; The liver tissue IGF-1 mRNA contents (IGF-1 cDNA/B-actin cDNA) were significantly decreased in group SI + Ca (0.231 +/- 0.025) g/cm(2) compared to group SI (0.278 +/- 0.019) g/cm(2) and Ca (0.302 +/- 0.026) g/cm(2), P < 0.05.</p><p><b>CONCLUSIONS</b>Soy isoflavones combined with supplemental Ca are more protective against the loss of femur BMD than soy isoflavones or supplemental Ca diet alone. The dose of SI (37.95 mg/kg.bw) might significantly restrain the rising of the liver tissue IGF-1 mRNA contents caused by ovariectomy.</p>

ROS-related enzyme expressions in endothelial cells regulated by tea polyphenols / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>Elevation of reactive oxygen species (ROS), especially the level of superoxide is a key event in many forms of cardiovascular diseases. To study the mechanism of tea polyphenols against cardiovascular diseases, we observed the expressions of ROS-related enzymes in endothelial cells.</p><p><b>METHODS</b>Tea polyphenols were co-incubated with bovine carotid artery endothelial cells (BCAECs) in vitro and intracellular NADPH oxidase subunits p22phox and p67phox, SOD-1, and catalase protein were detected using Western blot method.</p><p><b>RESULTS</b>Tea polyphenols of 0.4 microg/mL and 4.0 microg/mL (from either green tea or black tea) down-regulated NADPH oxidase p22phox and p67phox expressions in a dose-negative manner (P < 0.05), and up-regulated the expressions of catalase (P < 0.05).</p><p><b>CONCLUSIONS</b>Tea polyphenols regulate the enzymes involved in ROS production and elimination in endothelial cells, and may be beneficial to the prevention of endothelial cell dysfunction and the development of cardiovascular diseases.</p>

Induction of heme oxygenase-1 in human hepatocytes to protect them from ethanol-induced cytotoxicity / 生物医学与环境科学（英文）

<p><b>UNLABELLED</b>We investigated the relationship between ethanol exposure and heme oxygenase (HO-1) in human hepatocytes in order to ascertain if induction of HO-1 can prevent ethanol induced cellular damage.</p><p><b>METHODS</b>Dose-dependent (25-100 mmol/L) and time-dependent (0-24 h) ethanol exposure were used in the present study. HO-1 mRNA and protein expression were detected by PT-PCR and Western blot respectively. HO-1 activity was indicated by bilirubin and Fe2+ formation. Cytotoxicity was investigated by means of lactate dehydrogenate (LDH) and aspartate transaminase (AST) level in culture supernatants, as well as the intracellular formation of malondialdehyde (MDA), cellular glutathione (GSH) status and CYP 2E1 activity.</p><p><b>RESULTS</b>We first demonstrated a dose-dependent response between ethanol exposure and HO-1 mRNA and protein expression in human hepatocytes. We further observed a time-dependent increase of HO-1 mRNA expression using 100 mmol/L ethanol starting 30 minutes after ethanol exposure, reaching its maximum between 3 h and 9 h. Being similar increased protein expression started to what had been demonstrated with the mRNA level, at 6 h after ethanol exposure, and kept continuous elevated over 18 h. In addition, we found that ethanol exposure to hepatocytes markedly increased HO-1 enzyme activity in a time-dependent manner measured as bilirubin and Fe2+ formation in human hepatocytes. Our results clearly showed that ethanol exposure caused a significant increase of LDH, AST, and MDA levels, while the antioxidant GSH was time-dependently reduced. Furthermore, we demonstrated that pre-administration of cobalt protoporphyrin (CoPP) induced HO-1 in human hepatocytes, and prevented an increase of MDA and a decrease of GSH. These effects could be partially reversed by zinc protoporphyrin (ZnPP), an antagonist of HO-1 induction.</p><p><b>CONCLUSION</b>HO-1 expression in cells or organs could lead to new strategies for better prevention and treatment of ethanol-induced oxidative damage in human liver.</p>

Influence of alcohol on insulin sensitivity and insulin receptor substrate-1 mRNA expression in rat skeletal muscle / 中华预防医学杂志

<p><b>OBJECTIVE</b>To investigate the molecular mechanism of the effect of alcohol on insulin sensitivity.</p><p><b>METHODS</b>Four groups of Wistar rats were used, i.e. control (C) group, and low (L), moderate (M) and high (H) alcohol group. Alcohol doses of each group were 0, 0.6, 1.8 and 3.0 ml.(kg.bw)(-1).day(-1). Each group was comprised of 10 male and 10 female rats. Alcohol was given to rats by gastric intubation. Thirteen weeks later, serum was collected for testing of fasting plasma glucose and insulin. HOMA-IR index of each group were calculated. Total muscle RNA was extracted using Trizol Reagent (Promega). The expression level of IRS-1 mRNA in muscle was detected by RT-PCR.</p><p><b>RESULTS</b>In female rats, the fasting plasma glucose of group (8.36 +/- 0.57) mmol/L was higher and the fasting plasma insulin (15.25 +/- 3.32) was lower than those of group C (7.56 +/- 0.85, 20.80 +/- 3.25). The HOMA-IR of group L (1.775 3 +/- 0.138 1) was lower than that of group C (1.982 6 +/- 0.124 6) (P < 0.05), while IRS-1 mRNA (0.766 1 +/- 0.076 9) was up-regulated (P < 0.05); HOMA-IR of group M (2.202 2 +/- 0.271 0) was higher than that of group C (P < 0.01), while IRS-1 mRNA (0.501 8 +/- 0.049 2) was suppressed (P < 0.01); HOMA-IR of group H (1.850 1 +/- 0.162 8) was not significantly changed as compared with that of group C (1.982 6 +/- 0.124 6) (P > 0.05), while IRS-1 mRNA (0.418 1 +/- 0.049 1) was significantly suppressed (P < 0.01). In male rats, the fasting plasma glucose and insulin had the similar change as those of female rats. The HOMA-IR of group M (1.878 5 +/- 0.250 2) was lower than that of C group (2.147 3 +/- 0.330 8) (P < 0.05), IRS-1 mRNA was up-regulated (0.824 9 +/- 0.064 7) (P < 0.05).</p><p><b>CONCLUSIONS</b>The present study showed that low-to-moderate dose of alcohol could increase insulin sensitivity; while alcohol abuse could decrease insulin sensitivity. Sex difference in this effect was found. Changes of IRS-1 mRNA expression may be involved in the molecular mechanism of the effects of alcohol on insulin sensitivity.</p>

Combination of hemofiltration and peritoneal dialysis in the treatment of severe acute pancreatitis / 中华外科杂志

<p><b>OBJECTIVE</b>To study the therapeutic effects and its mechanism of combination of hemofiltration (HF) and peritoneal dialysis (PD) in the treatment of severe acute pancreatitis (SAP).</p><p><b>METHODS</b>Forty patients with SAP were divided at random into the HF + PD group (therapeutic group, 25 patients) and the non-HF + PD group (contrast group, 15 patients). Both groups were treated by the conventional mode of therapy. The release time of abdominal pain and distention, CT scores, APACHE II scores, the time of hospital stay, cost of treatment in hospital, operative rate and rate of complications and recovered rate of the two groups were compared. Simultaneously, the concentration of serum and fluid filtrated pro-inflammatory cytokines TNF, IL-6 and IL-8 were also determined pro and post the therapy.</p><p><b>RESULTS</b>The time needed for the disappearance of abdominal pain and the amelioration of abdominal distension, CT scores, APACHE II scores, the average hospital stay and hospital cost of the therapeutic group were significantly decreased compared with those of the contrast group. The cytokines detected at the end of 1d, 2d after HF + PD were decreased significantly compared with those observed in pro HF + PD and the contrast group.</p><p><b>CONCLUSIONS</b>The above results show that the cytokines overproduced during the development of SAP can be removed effectively from the circulation and the fluid filtrated by means of HF + PD. The continual deterioration of the local focus and systemtic presentation could be prevented effectively too, and the earlier the treatment of HF + PD, the better the prognosis.</p>