National Medical Journal of China
Volume 91 · Issue 26 · 2011
Natl Med J China
Reflections on development of endoctrinology and metabolism in China
Although endocrine metabolism has a long history, it was not until the concept of hormone was put forward in 1905 that endocrine metabolism appeared officially as a discipline. The classical endocrinology defines hormone as a trace substance produced by endocrine organs and released into the blood and transported to target organs or tissues to exert its effect, and the endocrine system established according to this is limited to specific endocrine glands. However, the concept of hormone has been greatly expanded at present. It is defined as a chemical messenger that widely exists in the body for intercellular communication. Its function is to regulate in vivo metabolism, coordinate the activities of organs and systems of the body, maintain the stability of the internal environment, and participate in the regulation of cell growth, differentiation, development and apoptosis. Therefore, all cytokines, growth factors, neurotransmitters and neuropeptides are classified as hormones; Therefore, the endocrine system is no longer confined to the classical endocrine glands, but distributed more widely.
Increased liver fat content triggers metabolic disorders
Non-alcoholic fatty liver disease (NAFLD) is very common in western countries, with an estimated prevalence of 10% ~24% in general population, 57% ~74% in obese population [1], and 70% ~80% in diabetic population [2]. In recent years, its incidence is on the rise in Asia-Pacific region, and the number of patients is close to that in North America. The situation of NAFLD in China is also not optimistic, and the prevalence of NAFLD in community adults in Shanghai is as high as 15% [3].
Combined utility of hemoglobin A1c and glycated albumin in diabetic screening
Objective To assess the validity of combined detection of hemoglobin Alc (HbAlc)and glycated albumin (GA) in diabetic screening. Methods A total of 1480 subjects at our out-patient department from March 2007 to December 2009. Those suspected of diabetes or at a high risk of diabetes were enrolled. The study population included 677 males and 803 females with a mean age of 52. 7 years. All subjects received an oral glucose tolerance test ( OGTT) after a 10-hour fasting. Glycated albumin ( GA)and hemoglobin Alc (HbAlc) were measured with liquid enzyme method and high pressure liquid chromatography respectively. Results ( 1 ) According to World Health Organization diabetes diagnosis criteria, there were 562 subjects with normal glucose tolerance (NGT), 411 subjects with impaired glucose regulation (IGR) and 507 subjects with newly diagnosed diabetes mellitus (DM). The level of HbAlc and GA had a rising tendency among NGT, IGR and DM groups (P<0. 01). (2) Pearson correlation analysis demonstrated that HbAlc had a positive association with GA ( r = 0. 75, P < 0. 01). (3) Using OGTT as golden standard of diabetic diagnosis, receiver operator characteristic (ROC) curve indicated that HbAlc and GA were strong predictors of diabetes. The area under curve ( AUC) was 0. 882 and 0. 881 respectively with no significant difference ( P >0. 05). (4) The sensitivity of combined use of HbA1 c and GA at optimal cut-off points of 6. 1% and 17. 1% was significantly higher than that of single use of HbAlc or GA in diabetic screening (94. 7% vs 81. 1% , 88. 4% , P <0. 01). Conclusion A combined detection of HbAlc and GA may improve the efficacy of diabetic screening. The subject with HbAlc≥6. 1% or GA≥17.1% is recommended to undergo OGTT for confirming a diagnosis of diabetes.
Effects of early insulin therapy on sterol regulatory element binding protein 1 pathway and lipid accumulation in liver of type 2 diabetic rats
Objective To explore the effect of early insulin therapy on sterol regulatory element binding protein 1 ( SREBP1) pathway and lipid accumulation in liver of type 2 diabetic rats ( DM ). Methods A high-fat diet plus a low-dose of streptozotocin (STZ) was administered to the Sprague-Dawley (SD) rats to create a type 2 diabetic animal model. Then the rats were divided into 3 groups: normal control ( NC) , DM (untreated diabetic rats) and INS (a 3-week treatment of NPH insulin initiated from day 3 of STZ injection). Insulin was delivered daily by a 3-week subcutaneous injection (6-8 U/day) . Liver homogenate was prepared. The protein levels of ER stress marker immunoglobulin binding protein ( Bip),oxygen-regulated protein 150 (ORP150) , insulin-induced gene 1 (Insig1) , SREBP1 and nuclear SREBP1 (nSREBPl) were assayed by Western blot. Adipose tissue mass was measured. Results In the DM group,ER (endoplasmic reticulum) stress marker Bip and ORP150 were up-regulated (0.67 ±0.02 vs 0.43 ±0. 01 for Bip; 1. 11 ±0. 04 vs 1. 83 ±0. 03 for ORP150, P <0. 05 for both) and Insigl decreased (0. 25 ±0. 02 vs 0. 80 ± 0. 07, P < 0. 05). And the expressions of SREBP1 and nSREBPl were elevated (1. 03 ±0. 14 vs 0. 41 ± 0.01 for SREBP1; 3. 63 ± 0. 77 vs 0. 96 ± 0. 20 for nSREBPl, P < 0. 05 for both) in comparison with the normal control rats. In the INS group, all aforementioned changes became attenuated or reversed (0.41 ±0.04 vs 0. 67 ±0. 02 for Bip; 1. 83 ±0. 03 vs 1. 11 ±0. 04 for ORP150; 0. 43 ±0.02 vs 0. 25 ± 0. 02 for Insigl; 0. 46 ± 0.01 vs 1. 03 ± 0. 14 for SREBP1; 1.65 ± 0. 18 vs 3. 63 ± 0. 77 for nSREBP1, P <0.05 for all). Furthermore, adipose tissue mass increased (22. 4 g ±3. 6g vs 12.0 g ±2. 6 g, P<0. 05). Conclusion The early insulin therapy induces a fat redistribution from liver to adipose tissue. The mechanism is probably through a reduction of ER stress and a down-regulated pathway of SREBP1 in liver of diabetic rats.
Histone H3 acetylation of tumor necrosis factor-alpha and cyclooxygenase-2 in patients with type 2 diabetes
Objective To investigate the expression of tumor necrosis factor-alpha (TNF-α) and cyclooxygenase-2(COX-2)mRNA and evaluate the status of histone H3 acetylation at TNF-α and COX-2 promoter in peripheral blood mononuclear cells ( PBMCs) from type 2 diabetics. Methods The PBMCs from 12 type 2 diabetics and 12 healthy controls were isolated by Ficoll-Hypaque density gradient centrifugation.The differential expression of TNF-α and COX-2 mRNA was measured by real-time PCR ( polymerase chain reaction). Chromatin immunoprecipitation analysis was used to detect the status of H3 acetylation at TNF-α and COX-2 promoter region. Results TNF-α and COX-2 mRNA were overexpressed in PBMCs from Type 2 diabetics as compared with normal controls ( 2. 28 ± 0. 09 fold and 2. 78 ± 0. 26 fold ) . ( P < 0. 05 ).Compared with normal controls, H3 acetylation at the TNF-α (1. 54 ± 0. 43 vs 0. 97 ± 0. 39, P = 0. 0094) and COX-2 (1. 20 ±0. 58 vs 0. 64 ±0. 21 ,P =0. 0161) gene promoter region was elavetedin PBMCs from Type 2 diabetic patients. Conclusion Increased H3 acetylation at TNF-α and COX-2 promoter in PBMCs from type 2 diabetics may contribute to the pathogenesis of type 2 diabetes through the elevated expressions of TNF-α and COX-2.
Laparoendoscopic single-site retroperitoneal adrenalectomy: a report of 7 cases
Objective To summarize our preliminary clinical experiences of laparoendoscopic single-site (LESS) retroperitoneal adrenalectomy. Methods Since October 2009 to January 2011, the investigators have performed LESS retroperitoneal adrenalectomy for 7 patients with adrenal tumors. A waist axillary midline incision of around 2 - 3 cm was made and a single incision for inserting a homemade port. Cambridge endo flexible laparoscopic instrument and other common laparoscopic accessories were used during the surgical procedures. Results LESS retroperitoneal adrenalectomies were technically successful in 6 cases with no extra skin incisions, no conversion into an open procedure or standard laparoscopy.Conversion to standard laparoscopy (3 ports) was inevitable in one case. The reason for conversion was due to tumor size (6 cm). No perioperative complication occurred. The mean operative duration was 139 min (95 -200 min), the mean volume of blood loss 96 ml(30 -350 ml) and the mean hospital stay 5 d(3 -8 d). Conclusion LESS retroperitoneal adrenalectomy is technically feasible and safe for the treatment of small adrenal tumors.
Clinical comparative study of neoadjuvant chemotherapy outcome in locally advanced breast cancer:docetaxel versus paclitaxel plus pirarubicin hydrochloride and cyclophosphamide
Objective To compare the efficacy and toxicity of neoadjuvant chemotherapy of docetaxel with paclitaxel plus pirarubicin hydrochloride (THP) and cyclophosphamide ( CTX) in locally advanced breast cancer ( LABC). Methods A total of 97 LABC cases were randomly divided into 2 groups: docetaxel group (n = 49, taxotere plus THP & CTX ) and paclitaxel group (n = 48, paclitaxel plus THP & CTX). Neoadjuvant chemotherapy had four cycles of 21 days each. Results The clinical and pathological complete remission rates of docetaxel group was 28. 6% and 26. 5% respectively. They were significantly higher than those of paclitaxel group ( 10. 4% and 8. 3% ) . Furthermore the pathological negative rate of regional lymph node in docetaxel group was also significantly higher than that of paclitaxel group (40.6% vs. 12.9%). However, grade Ⅲ - Ⅳ blood system toxic reaction was found in 71.4% cases, grade Ⅱ - Ⅳ liver dysfunction in 53. 1% cases and edema in 24. 5% cases among docetaxel group.They were higher than those among paclitaxel group (46. 9%, 27. 1% & 4. 2% ). Conclusion Compared with paclitaxel, the combined regimen of docetaxel plus THP and CTX offers better outcomes for locally advanced breast cancer.
Short-term efficacy comparison of laparoscopic-assisted versus open distal gastrectomy
Objective To compare the short-term efficacy of laparoscopic-assisted verus open distal gastrectomy for gastric cancer. Methods The data of 29 patients with distal gastric cancer from January 2008 to October 2010 were analyzed. Results Twenty-eight underwent laparoscopic-assisted distal gastrectomy while 1 was switched to open surgery. The operative duration was (253. 1 ± 32. 6) min and the blood loss volume (268.5 ± 101.4) ml. The postoperative recovery time of gastrointestinal peristalsis was (2. 1 ± 0. 6) d. The length of incision was (5.6 ±1.6) cm, the hospital stay duration (10. 6 ±2. 4) d and the number of dissected lymph nodes (34. 5 ± 5. 2 ). Conclusion Laparoscopic-assisted distal gastrectomy for gastric cancer is both safe and feasible. And it offers many advantages of minimal invasion, less pain and shorter hospital stay.
Influence of minor back trauma on surgical outcomes in patients with thoracic ossification of ligamentum flavum
Objective To retrospectively explore the influences of minor back trauma on surgical outcomes in patients with thoracic ossification of ligamentum flavum (TOLF) and preliminarily detect its possible causes. Methods A total of 94 TOLF patients were divided into two groups according to the absence or presence of minor back trauma: MT (minor trauma, n = 16) and NT (no trauma, n = 78). They were compared in terms of gender, age, duration of symptoms, levels of involvement, numbers of involved segments, ratio of intramedullary signal changes (IMSC) , pre- & post-operative JOA (Japanese Orthopedic Association) score, recovery rate (RR) at the final follow-up. Multiple regression analysis was employed to elucidate the causes related with the surgical outcomes. The MT group was further divided into two subgroups according to the intervals between trauma and surgery to clarify the influences of surgical timing on the efficacies. Results The JOA scores were 4. 0 ± 1. 4 and 8.4 ± 1. 7 respectively in MT and NT groups at the final follow-up. The neurological status of patients improved in both groups (MT: P =0.009, NT: P =0. 000). The patients were younger in MT groups (50 ±11 years ) than those in NT groups (58 ± 8 years )(P = 0.046). The ratio of IMSC was higher in MT groups(75. 0% ) than that in NT groups(25. 6% ) (P =0. 000). The pre- & post-operative JOA scores were lower in MT groups than those in NT groups (both P =0. 000). Multiple regression analysis revealed that the postoperative JOA score at the final follow-up was positively related with the preoperative JOA score (r = 0. 60, P = 0. 000) and negatively with trauma and IMSC (r = - 1. 82 and r =- 1. 87, P = 0. 000) while the final postoperative RR were negatively related with trauma and IMSC (r = - 26. 26 and r = - 33. 70, P = 0. 000). The surgical timing after trauma did not influence the efficacies (P =0. 147). Conclusion The TOLF patients with minor back trauma have a worse post-operative recovery. A minor trauma might be a risk factor of adverse surgical outcomes.
Association of IL-8 gene polymorphisms with inflammatory bowel disease in Chinese patients
Objective To investigate the association of interleukin 8 (IL-8 ) gene polymorphisms with the risks of inflammatory bowel disease( IBD). Methods Single nucleotide polymorphisms(SNPs) of IL-8 gene at -845 T/C, -738 T/A, -353 A/T, -251 T/A and +678 T/C were analyzed in 183 IBD patients. They included Crohn's disease( CD, n =41) , ulcerative colitis( UC, n = 142) and healthy controls (n= 160). The methods of polymerase chain reaction-restriction fragment length polymorphism ( PCR-RFLP) and polymerase chain reaction-sequence specific primers ( PCR-SSP) were employed. Results No association was observed between any of these five SNPs in IL-8 gene with the occurrence of IBD. A specific haplotype AAT(-353 A/T, -251 T/A & +678 T/C) was over-represented in UC cases when compared with controls(31. 0% vs 23.7%, P= 0.046). But the distributions of this haplotype did not show significant difference between CD cases and controls. Conclusion Our data support a significant but modest association between the AAT haplotype of IL-8 gene and UC( OR = 1. 441, 95% CI 1. 007 -2. 063).
Prevalence and risk factors of retinal arterial atherosclerosis in urban subjects participating in routine physical examinations
Objective To determine the prevalence and risk factors of atherosclerotic lesions in retinal arteries of an urban population undergoing routine physical examinations. Methods Demographic and clinical information of subjects participating in annual routine physical examinations at Peking Union Medical Center from January to October of 2010 were collected and summarized. Univariate and multivariate Logistic regression analyses were conducted to evaluate the demographic and clinical factors associated with retinal arterial atherosclerosis. Results Among a total of 17 886 non-diabetic adults evaluated during the study period, retinal arterial atherosclerosis was diagnosed in 1721 (9.6% ). There were predominantly grade 1 (88% ) and grade 2 (11% ) lesions. Prevalence of retinal arterial atherosclerosis increased with age. And traditional risk factors for cardiovascular diseases included overweight or obesity, hypertension, dyslipidemia and elevated fasting serum glucose. In a multivariate Logistic regression model, advanced age, male gender,obesity or overweight, hypertension and dyslipidemia were independently associated with a higher risk of retinal arterial atherosclerosis. Hypertension was prevalent in subjects above 40 years old while overweight or obesity had a high prevalence in all age groups. Conclusion Retinal arterial atherosclerosis is common in this urban population. And aging, overweight/obesity and hypertension are the dominant risk factors.Routine physical examination is valuable for both the prevention and an early diagnosis of this disease.
Clinicopathologic characteristics and prognosis in young Chinese women with breast cancer
Objective To analyze the clinicopathologic characteristics and evaluate the prognosis in young Chinese women with breast cancer. Methods A total of 1538 female patients with operable primary breast cancer (stage Ⅰ - Ⅲ) treated at our hospital from December 1994 to December 2003 were analyzed retrospectively. Among them, 1075 patients (≤60 yrs) with the complete follow-up data were divided into two groups according to age: young breast cancer group ( ≤40 yrs, n = 208) and control group (41-60 yrs, n = 867) to analyze the differences in their clinicopathologic characteristics and evaluate the prognosis of both groups. Results The patients with young breast cancer were more likely to have positive lymph nodes (P=0.016) , a negative expression of ER (estrogen receptor) (P = 0.016) and a positive expression of HER2 (P = 0. 001). The 5-year disease-free survival (DFS) rates of young breast cancer group and control group were 73. 3% and 84. 1% (P <0. 001) and the 5-year overall survival (OS) rates 83. 5% and 89. 1% (P = 0.004) respectively. Moreover, the patients with young breast cancer had a worse DFS than control group in patients with stage Ⅰ - Ⅱ disease but not in those with stage Ⅲ disease. And ≤40 years was an independent unfavorable prognostic factor of DFS (HR = 1. 78, 95% CI: 1. 19 - 2. 66, P = 0. 005) and OS (HR = 1. 71, 95%CI: 1.01 -2.90, P = 0.046) in the patients with stage Ⅰ - Ⅱ disease. Conclusion Chinese women with young breast cancer have a worse prognosis, particularly in those with stage Ⅰ - Ⅱ disease.
Protection of penehyclidine hydrochloride on renal tissue injury induced by limb ischemia/reperfusion
Objective To evaluate the protection of penehyclidine hydrochloric postconditioning on HIF-1α (hypoxia-inducible factor -1α) in renal tissue injury induced by lower limb ischemia/reperfusion (I/R). Methods A total of 72 adult male Wistar rats weighing 230 - 250 g were randomly divided into 3 groups: control ( group C ) , limb ischemia-reperfusion ( group R/I) and penehyclidine hydrochloride postconditioning (group P). The animals were anesthetized by inhaling 2% isoflurane and blood flow of bilateral lower limbs was blocked with rubber bands for 3 h in groups P and R/I. In group P, penehyclidine hydrochloride 0. 15 mg/kg was injected via caudal vein at 3 min pre-reperfusion. After sacrificing, their kidneys were removed at 3 h of ischemia and 1, 3, 6 h of reperfusion respectively. The blood urea nitrogen (BUN) and creatinine ( Cr) were detected by colorimetric method, plasma tumor necrosis factor-α (TNF-α) by ELISA ( enzyme-linked immunosorbent assay ) and HIF-1α of renal tissue by immunohistochemistry. Renal pathological changes were observed under light microscope. Results Compared with group C, the serum levels of BUN and Cr increased while TNF-α and HIF-1α were upregulated in groups I/R and P (P < 0. 05). As compared with group I/R, the serum levels of BUN, Cr and MDA decreased while TNF-α and HIF-lα were down-regulated in group P . [at T2: (15. 10 ± 1. 88) mmol/L vs(19.46±2. 76) mmol/L, (113 ±10) μmol/L vs(143 ± 11) μmol/L, (13. 8 ±1.7) nmol/g vs (15.5 ±1.8) nmol/g, (53.1 ±3. 1)ng/L vs(53.9 ±4. 8) ng/L, 0.298 ±0.015 vs 0.471 ±0.032, all P<0.05 ]. Conclusion Penehyclidine hydrochloride can down-regulate the expression of HIF-lα and attenuate the renal injury induced by lower limb I/R. And the mechanisms may be through inhibiting the inflammatory reactions, reducing the release of oxygen free radicals and improving the conditions of hypoxia and ischemia.
Pathogenic mechanism of CD8 + CD28 - T cell and the effect of dexamethasone in asthmatic mouse
Objective To explore whether or not CD8+ CD28- T cell play a pathogenic role in asthma and detect the effects of dexamethasone ( DXM ). Methods A total of 30 mice were randomly divided into 3 groups: asthmatic group, DXM group and control group ( n = 10 each). The asthmatic and DXM groups were sensitized twice and inhaled ovalbumin. The DXM Group received an intraperitoneal injection of DXM lmg/kg before inhaling ovalbumin. After successful modeling, 3 mice were selected randomly from each group to measure the airway responsiveness. Also a bronchoalveolar lavage cytological study was performed and lung tissue sections were prepared for histopathologic examination to evaluate the airway inflammation. The content of IgE in bronchoaleolar lavage fluid ( BALF) was detected with a murine IgE ELISA kit. And the fractions of CD8 + CD28- T cell of peripheral blood and BALF were tested by flow cytometry to analyze the correlation between IgE, eosinophils ( EOS) of BALF and CD8 + CD28 - T cell of blood. Results The airway hyperresponsiveness in asthmatic and DXM groups were significantly higher than that in the control group. The number of total cells and EOS of BALF in the asthmatic group [ ( 5. 56 ±4. 06) × 102/L; (3. 29 ±2. 23) × 102/L] were significantly higher than that in control group [ (0. 91 ±0.65)×102/L, P = 0.003; (0.43 ±0.37) × 102/L, P = 0.001] and DXM group [(2.59 ±1.69) ×102/L, P =0.044; (1. 11 ±0.73) ×l02/L, P = 0.008]; while the DXM group was insignificantly higher than the control group (P=0. 234, P=0. 363). There were significant differences in the contents of IgE of BALF for the asthmatic, DXM and control groups [ (23. 85 ±5. 97) g/L, (13. 15 ±2.22) g/L, (6.54±1. 03) g/L, F = 38. 558, P = 0. 000 ] . The percentages of CD8 + CD28- T cell in peripheral blood in asthmatic and DXM groups [ (18. 68 ±4. 12)% and ( 13.43 ± 2. 91) % ] were significantly higher than those in control mice [ (8. 43 ± 4. 60) % , both P < 0. 05 ]. The percentages of CD8 + CD28 - T cell of BALF in asthmatic group and DXM group [(1.25±0. 40)% and (0. 66 ± 0. 49) % ] were also significantly higher than those in control mice [ (0. 21 ± 0. 19) % , both P < 0. 05 ]. The percentages of CD8 + CD28 - T cell of blood and BALF in the DXM mice were significantly lower than those in asthmatic group. The correlations between IgE ( r = 0. 864, P = 0. 012), EOS ( r = 0. 804, P = 0.029) and CD8 + CD28- T cell were significant. Conclusion The fraction of CD8 + CD28- T cell is closely correlated with the inflammation of asthmatic airway. The airway hyperresponsiveness and inflammation in asthmatic mice may be relieved by DXM through its effect of inhibiting the expression of CD8 + CD28- T cell.
Effects of simvastatin plus all-trans retinoic acid on WT1/hDMP1 gene expression profiles of human promyelocytic leukemia cell line NB4
Objective To investigate the effects of simvastatin (SV) plus all-trans retinoic acid ( ATRA) on the proliferation, differentiation, apoptosis and WT1/hDMP1 gene expression profiles of human promyelocytic leukemia cell line NB4. Methods The NEW cell was incubated with simvastatin and ATRA alone or in combination. And the NB4 cell without any treatment was adopted as a normal control. The cells of different groups were collected at24, 48 and 72 h post-incubation. Their morphological changes were observed after Wright staining. The method of MTT was employed to assay the growth inhibition rate and flow cytometry was used to detect the early-stage ratios of apoptosis and cell necrosis. Real-time quantitative reverse transcriptase-polymerase chain reaction ( RT-PCR) was used to detect the WT1/hDMP1 gene expression levels. Results The cell inhibition rates increased gradually (F = 7. 15, P = 0.000) at 15, 10 and 5 μmol/L SV respectively. And so did the expression levels of CD11b ( F= 3. 41, P = 0. 014) and Annexin-V ( F = 43. 38, P = 0. 000). However the expression levels of WT1 decreased gradually ( F =5. 35, P = 0. 001) reversely with the elevated levels of hDMP1 ( F= 22. 61, P = 0. 000 ). Furthermore the NB4 cell exhibited the most significant changes at 15 μmol/L SV. After a 72-hour incubation, the expression levels of GD11b(89. 46% ±9. 13% )and hDMP1(626. 9 ±56.9)in NB4 cells at 15 μmol/L SV plus 0. 5 μmol/L ATRA were significantly higher than those with ATRA(71. 27% ±7. 27% , P =0. 000 and 421. 8 ±38. 3, P =0.003 in each) and SV alone(62.41% ±6.37%, P =0.003 and 241. 4 ±21. 9, P =0.003 in each). A combination of 15 μmol/L SV with 0.5 μmol/L ATRA displayed obvious interactions with the expressions of CD11b and hDMPl (F = 4. 09, P = 0. 025 and F = 29. 58, P = 0. 000 in each). And there was no significant interaction for cell inhibition rates and Annexin-V expression. Conclusion Simvastatin in vitro inhibits the proliferation of NB4 cell, induces its differentiation and promotes its apoptosis. And the lowered expression of WT1 has a dose-dependent correlation with the elevated expression of hDMP1. It indicates that simvastatin has the synergistic in vitro anti-promyelocytic potency.
Establishment and characterization of serial subpopulations with highly metastatic potential via different metastatic routes
Objective To establish the serial cell lines, derived from the same parental gallbladder cancer cell line GBC-SD, with highly metastatic potential via different routes and characterize their biological behaviors to understand the different metastasis mechanisms via lymph and blood. Methods The spleenliver metastasis model and footpad-inguinal lymph node metastasis model were established. GBC-SD was injected into spleen or footpad of nude mice. Then the highly metastasized subpopulations via lymph and blood were isolated. Their differences in morphology, genetic background, proliferation, migration, invasion and adhesion were revealed by comparing the lymphatic-disseminating and hematogenous-disseminating subpopulations with parental cells. Results The lymphatic-disseminating and hematogenous-disseminating subpopulations were successfully isolated and designated as GBC-SD/HL and GBC-SD/M3 respectively.They demonstrated the identical genetic background with GBC-SD. In comparison with parental cells, the hematogenous-disseminating subpopulation was morphologically characterized with epithelial-mesenchymal transition (EMT) while it was not shown in the lymphatic-disseminating subpopulation. Furthermore, the hematogenous-disseminating subpopulation showed the strongest migrating capacity but the lymphaticdisseminating subpopulation demonstrated a stronger invasive and adhesive ability. Conclusion The whole parental cell GBC-SD, hematogenous-metastasized subpopulation GBC-SD/M3 and lymphatic-disseminating subpopulation GBC-SD/HL is an ideal tool for metastatic mechanism study of gallbladder cancer. EMT plays an important role in hematogenous metastasis while lymphatic metastasis relies more on enhanced invasiveness and adhesion. It may be a target for interfering the lymphatic metastasis of gallbladder cancer.
Transplantation of marrow mesenchymal stem cells transfected with vascular endothelial growth factor gene for the treatment of pulmonary hypertension in rats
Objective To explore the therapeutic effect and the mechanism of marrow mesenchymal stem cells (MMSCs) transfected with vascular endothelial growth factor ( VEGF) gene in the treatment of pulmonary hypertension in rats. Methods MMSCs from the bone marrow of Sprague-Dawley rats were isolated, cultured and propagated in vitro. pIRES2-EGFP-VEGF165 was transfected into MMSC. The healthy male SD rats were divided randomly into 4 groups: normal control group, pulmonary hypertension model group, MMSCs transplantation group and transfer gene transplantation group. A single subcutaneous monocrotaline (50 mg/kg) was injected to induce the model of pulmonary hypertension. The normal control group received a single subcutaneous dose of L-DMEM (low glucose Dulbecco's modified Eagle's medium).All four groups of rats were fed similarly. At Day 21 post-modeling, 5 × 106 MMSCs in 1 ml L-DMEM were injected into the MMSC group. 5 × 105 MMSC transfected by pIRES2-EGFP-VEGF165 were injected into the gene transplantation group. A same volume L-DMEM solution was also injected into the pulmonary hypertension model group and normal control group. The parameters of right ventricular systolic pressure (RVSP) , right ventricular hypertrophy index, blood gas analysis and microstructure as well as pulmonary microvascular changes were observed after 30 days. Results At Day 30 post-transplantation of MMSCs, the outcomes were as follows; RVSP was (30. 2 ±2. 1) and (29. 2 ± 1. 1) mm Hg (1 mm Hg =0. 133 kPa) in the MMSCs transplantation and gene transplantation groups respectively. The right ventricular hypertrophy indices were (37. 9 ±3. 2) % and (27. 2 ±3.4)% respectively. The media thickness of pulmonary artery ( MT) was (21.3 ± 3. 4 ) and ( 14. 3 ± 2. 8 ) μm respectively. The ratios of vascular area to total arterial area (V/T) were (39.3 ±4.3) % and (43.0±1.5) % respectively. As compare with the pulmonary hypertension model group, the above parameters were of statistical significances (P <0. 01). A comparison of right ventricle hypertrophy index, MT and V/T was of statistical significance between MMSC and gene transplantation groups ( P < 0. 05 ) . The blood gas analysis of the MMSCs transplantation and gene transplantation groups were better than the pulmonary hypertension mode group. Ultramicrostructure showed that neovascularization and small pulmonary arterial repair appeared in two transplantation groups. Conclusion MMSCs transfected by pIRES2-EGFP-VEGF165 transplantation may improve and reverse the MCT-induced progress of pulmonary hypertension in rats. And it is better than the MMSC transplantation. The potential mechanism is through arterial repair and neovascularization.
An absence of donor TH17 differentiation ameliorates dermal tissue damage
Objective To explore the functions of TH17 cell in cutaneous graft-versus-host disease (GVHD). Methods A model of acute GVHD (aGVHD) was established with a major histocompatibility complex class Ⅰ /Ⅱ -disparate allogeneic bone marrow transplantation( BMT). Bone marrow monocytes and splenic T cells from donor C57/BL6 were enriched. The recipient BABL mice were irradiated ( Co source)with 7. 5 Gy total body irradiation (TBI) and injected with 5 × 106 marrow monocytes and 5 × 105 T cells.The experimental mice were divided into 3 groups: lethal total body irradiation (TBI); allogeneic bone marrow transplantation (BMT) and recipients of holafugine ( HF). The symptoms of aGVHD were observed daily and detailed histopathologic analyses of recipient skin were performed at Day 6 post-transplantation.And Tri-color flow cytometry ( FCM) was performed at Day 6 post-transplantation to measure the levels of interleukin (IL)-17, interferon (IFN)-γ and TH1/TH17. Results Clinical GVHD symptoms were observed in recipient mice. The administration of HF to lethally irradiated recipients led to very modest GVHD-induced cutaneous changes manifested predominantly by fur loss. However, the experimental animals receiving only allogeneic BMT showed significant fur loss and pathologic skin conditions. Consistent with the clinical evaluations, the histopathologic results demonstrated significantly increased pathologic cutaneous lesions in recipients undergoing only BMT. The median ratios of TH1/TH17 cells were 17. 57 and 5. 31 in the HF and BMT groups respectively. The difference had statistical significance (P < 0. 05). The serum levels of IL-17 were(1.47 ±0. 18)and(2. 81 ±0. 19)pg/ml in the TBI and BMT groups respectively(P <0. 05). But IL-17 could not be detected in the HF group. The serum levels of IFN-γ were (3. 86 ±0. 32) ,(42. 97 ± 0. 42) and (9. 89 ± 0. 51) pg/ml in the TBI, BMT and HF groups respectively. The inter-group differences had statistical significance (P <0. 05). Conclusion An absence of TH17 cell may alleviate the cutaneous GVHD but exacerbate the systemic GVHD.
American scientists discover an enzyme that can promote the growth of breast cancer
Researchers at Chicago Medical University have found an enzyme that promotes the production of estrogen in breast cancer tissues, thereby promoting the progression of breast cancer. The results of the study were published in May 2011<MolecularEndocrinology>Part 1. A large number of studies have confirmed that excess estrogen, also known as estradiol, is associated with the worsening of breast cancer in the body. Researchers have discovered an unknown protein product in ovarian tissue, which can be increased in content under the influence of estrogen.
High doses of atorvastatin before percutaneous coronary intervention prevent contrast-agent nephropathy
The Italian research team published online April 27 in<AmericanJouvllall of Cardiology>on "High doses of atorvastatin before coronary intervention prevent contrast-agent nephropathy". Dr. Gernlallo Di SMascio of Campus Bio-Medlico University in Rome and colleagues previously found that patients treated with long-term statins were less susceptible to postoperative contrast-induced nephropathy (CIN) after percutaneous coronary intervention (PCI), prompting them to conduct a randomized trial to see whether high-dose, short-term statin therapy could prevent CIN.
Research progress of diabetic skin diseases
In recent years, with the obvious increase of the incidence of diabetes in China, there are many reports of skin lesions complicated and/or complicated by diabetes [1-2]. Skin lesions caused by diabetes are called diabetic skin diseases, or diabetic dermatosis for short [3]. Type 1 or type 2 diabetes can lead to skin lesions, and the data show that more than 2/3 of diabetic patients have skin problems at a certain stage in the whole disease process, and skin diseases can be the first symptom of diabetes [4]. Diabetic dermatosis ranges from general skin changes to special skin lesions, and the disease is mostly stubborn. If not treated in time, the lesions will progress, and even lead to serious fatal symptoms [3-4]. Therefore, it is necessary to understand the etiology, mechanism and clinical manifestations of diabetic dermatosis [5].
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