Objective To investigate the expressions of insulin receptor substrate-1 (IRS-1) and insulin receptor sub-strate-2 (IRS-2) in adipocytes during catch-up growth in neonatal rats with intrauterine growth restriction (IUGR) and their correlations with the insulin resistance. Methods Sprague-Dawley rats (clean grade) were randomly divided into control group and food-restricted group after fertilization. Food-restricted group were received about 30%of food amount consumed in control group every day through the whole pregnant period to establish IUGR animal model, and were fed increased amount of breast-milk from postnatal day 1 to 21 to establish the period of catch-up growth in IUGR animal model (IUGR-CG). Fasting serum glu-cose, insulin and triglyceride were measured in blood from heart ventricles of 4-week old SD rats and insulin resistance index was calculated. Pre-adipocytes and mature adipocytes were obtained from SD rats at different age (1-week, 3-week, 5-week and 7-week old) and the former were induced to differentiate toward mature adipocytes. The levels of IRS-1, IRS-2 in the two kinds of mature adipocytes were detected by Real-Time PCR and Western blot. Results The expression levels of IRS-1, IRS-2 mRNA in mature adipocytes of IUGR-CG rats were signiifcantly lower than those of IUGR rats at 5-weeks and 7-weeks old (P<0.05) while the ex-pression levels of IRS-1, IRS-2 mRNA in differentiated adipocytes of IUGR-CG rats were signiifcantly lower than those of IUGR rats at 5-weeks old (P<0.05). The expression levels of IRS-1, IRS-2 protein in two kinds of adipocytes (mature and differentiated adipocytes) of IUGR-CG rats were signiifcantly lower than those of IUGR rats from postpartum week 1 through 7 (P<0.05). Conclusions IRS-1 and IRS-2 expression levels are downregulated in adipocytes during catch-up growth of IUGR rats, which may be closely related with insulin resistance.

OBJECTIVETo evaluate the clinical efficacy of the ARAR0331 protocol for treatment of childhood nasopharyngeal carcinoma.

METHODSThe clinical data of eight children with nasopharyngeal carcinoma between May 2004 and May 2012 were retrospectively studied. The eight patients included six boys and two girls, and the onset age was between 3 and 13 years. Six patients were in AJCC Stage Ⅲ, one was in StageⅡA and one was in Stage ⅣA. One patient had been treated with combined radiotherapy and chemotherapy which mainly included EAP, BEP and EA. The other seven patients had been treated with the ARAR0331 protocol provided by the America Children's Oncology Group (COG).

RESULTSThe patient who had been treated with combined radiotherapy and chemotherapy developed multiple bony metastasis during the chemotherapeutic period. Four out of seven patients who had been treated with ARAR0331 protocol achieved complete remission, and two achieved partial remission. The seven patients were followed-up from 8 to 75 months and the survival rate was 100%. The ARAR0331 protocol treatment-related complications included radiodermatitis, mucocitis and nausea. Late toxicity was not found.

CONCLUSIONSBased on the limited cases, ARAR0331 protocol appears to be effective and safe for childhood nasopharyngeal carcinoma.

Adolescent ; Carcinoma ; Chemoradiotherapy ; adverse effects ; Child ; Child, Preschool ; Female ; Humans ; Male ; Nasopharyngeal Neoplasms ; pathology ; therapy ; Neoplasm Staging ; Retrospective Studies

OBJECTIVETo investigate the association between HPV16 infection, E6/E7 variations and the cervical lesions.

METHODSHPV subtypes were detected by using flow-through hybridization technique, E6/E7 gene was extracted from cervical lesions in 80 patients with HPV16 infection, PCR amplified, cloned into plasmid pMD18-T and sequenced.

RESULTSHPV 16 was the most common type which accounted for 33.3% (154/463), the HPV16 infection rates increased with the severity of cervical lesions (P < 0.05). Totally in 72 cases the complete E6 and E7 regions were successfully sequenced, the DNA mutation rate of E6/E7 was 88.9% (64/72). A mutation, E6-D32E (T96G) coincided with a specific type of E7 mutation, N29S (A86G). D32E/N29S mutation rate was 38.9% (28/72), the detection rate increased with the severity of cervical lesions (P < 0.05).

CONCLUSIONHPV 16 was the most common type in women with cervical lesions in Beijing, D32E/N29S variant associated with the cervical lesions.

Adult ; Aged ; China ; epidemiology ; Female ; Gene Frequency ; Genotype ; Host-Pathogen Interactions ; Human papillomavirus 16 ; genetics ; physiology ; Humans ; Middle Aged ; Mutation ; Oncogene Proteins, Viral ; genetics ; Papillomavirus E7 Proteins ; Papillomavirus Infections ; epidemiology ; pathology ; virology ; Repressor Proteins ; genetics ; Severity of Illness Index ; Uterine Cervical Diseases ; epidemiology ; pathology ; virology ; Uterine Cervical Neoplasms ; epidemiology ; pathology ; virology ; Young Adult

It is one of the key points for modernization and internationalization of traditional Chinese medicines to construct the Good Agricultural Practice (GAP) base of Chinese materia medica (CMM).GAP helps to minimize contamination and improve the quality of CMM during the plantation and the production of Chinese crude drugs.In this article,the status and development of CMM production bases of GAP in Guangdong Province,China,are presented.The suggestions upon the problems during the development of GAP for Chinese crude drugs are also provided.

OBJECTIVETo investigate the clinicopathologic and prognostic implications of phosphoinositide 3 kinase (PI3K)/AKT pathway alterations in endometrial cancers of Chinese women.

METHODSThe expression of PTEN, p-AKT, and ER/PR was assessed in 71 cases of endometrial carcinoma by immunohistochemistry (EnVision method). The PIK3CA mutation at exon 9 and exon 20 was analyzed by PCR and direct sequencing in 34 tumors.

RESULTS(1) Of the 71 cases of endometrial carcinoma, 65 cases were endometrioid adenocarcinoma (EEC) and 6 cases were nonendometrioid adenocarcinoma (NEEC). PTEN loss of expression was found in 63.4% (45/71) of tumors, and more commonly occurred in EEC (66.2%, 43/65) than that in NEEC (2/6, P = 0.18). Patients with PTEN loss in their tumors (45 cases) had a better survival than those without (26 cases, P = 0.07). In ER negative subgroup, the patients with PTEN loss of expression (12 cases) had longer survival than those with normal PTEN expression (7 cases; P = 0.04). (2) The frequency of PIK3CA mutation was 41.2% (14/34) with a hot mutation spot at T544 in exon 9. PIK3CA mutations more commonly occurred in EEC (44.8%, 13/29) than in NEEC (1/5, P > 0.05). The mutations at exon 9 more commonly occurred in EEC, well- and moderately-differentiated EEC, and tumors at early stage (P > 0.05). On the contrary, in tumors at early stages, the frequency of mutations in exon 20 (14.3%, 4/28) was significantly lower than that at late stages (4/6, P = 0.01). (3) p-AKT was positive in 59.2% (42/71) of tumors that were more frequently found in EEC (60.0%, 39/65) than that in NEEC (3/6, P = 0.68). However, the significant difference of p-AKT expression was found between well- and moderately-differentiated EEC (75.0%, 21/28; 53.6%, 15/28) and poorly-differentiated EEC (3/9, P = 0.02). Moreover, p-AKT expression was significantly correlated with positive ER (r = 0.339, P = 0.00).

CONCLUSIONSEndometrial carcinoma patients with loss of PTEN and p-AKT positivity have a favorable prognosis. PIK3CA mutations at exon 9 or 20 may have different impact on the prognosis. The function of PTEN loss and p-AKT expression may vary according to different hormone status.

Adult ; Aged ; Carcinoma, Endometrioid ; genetics ; metabolism ; pathology ; surgery ; Class I Phosphatidylinositol 3-Kinases ; Endometrial Neoplasms ; genetics ; metabolism ; pathology ; surgery ; Exons ; Female ; Follow-Up Studies ; Humans ; Hysterectomy ; Middle Aged ; Mutation ; Neoplasm Invasiveness ; Neoplasm Staging ; PTEN Phosphohydrolase ; metabolism ; Phosphatidylinositol 3-Kinases ; genetics ; metabolism ; Phosphorylation ; Proto-Oncogene Proteins c-akt ; metabolism ; Receptors, Estrogen ; metabolism ; Receptors, Progesterone ; metabolism ; Signal Transduction ; Survival Rate

OBJECTIVETo investigate the significance of human papillomavirus test in triage of patients with atypical squamous cell of undetermined significance (ASCUS) diagnosed by cervical cytology.

METHODSHuman papillomavirus test,colposcope and cervical biopsy were performed in 184 patients with a referral diagnosis of ASCUS by cervical cytology.

RESULTSConfirmed by pathological diagnosis of cervical biopsy, 112 cases were chronic inflammation (60.87%), 33 CIN I (17.93%), 17 CIN II (9.24%), 8 CIN III (4.35%), 4 cervical squamous carcinoma (2.17%) and 10 condyloma (5.43%). Of the 184 women with cytological ASCUS, 124 (67.39%) cases were positive in high-risk HPV test among which 66 cases were histologically confirmed as chronic inflammation (53.23%), 22 as CIN I (17.74%), 16 as CIN II (12.90%), 8 as CIN III (6.45%), 4 as cervical squamous carcinoma (3.23%) and 8 as condyloma (6.45%). The positive rate of HPV in groups of ASCUS were higher than those with negative HPV (P < 0.003).

CONCLUSIONWomen with ASCUS should be tested for HPV. Cervical biopsy under colposcopy is recommended for women with HR-HPV infection.

Adult ; Aged ; Alphapapillomavirus ; isolation & purification ; Carcinoma, Squamous Cell ; diagnosis ; pathology ; virology ; Female ; Humans ; Middle Aged ; Papillomavirus Infections ; diagnosis ; pathology ; virology ; Uterine Cervical Neoplasms ; diagnosis ; pathology ; virology ; Vaginal Smears ; Young Adult

OBJECTIVETo detect the effect of Nocardia rubra cell wall skeleton (Nr-CWS) on tumorigenicity induced by TC-1 cells and to clinically study anti-human papillomavirus effect of Nr-CWS in lower genital tract of women.

METHODSTumor model was established by injecting TC-1 cells subcutaneously in SCID mice, then divided them into 3 groups randomly and injected with isovolumetric physiological saline, 60 micrograms/ml Nr-CWS and 120 micrograms/ml Nr-CWS respectively, the growth of tumors was measured one week later. Nr-CWS was applied on 45 HPV positive women whose TCT test was normal and without cervical erosion 2-3 days after menstruation. HPV was detected again 3 months later to explore the effect of Nr-CWS on HPV infection in female lower genital tract.

RESULTSThe animal experiment showed the weight of transplanted tumors in treated group was less than that of control group (chi2=12.5, P= 0.002). The tumor inhibition rate was 59.1 percent and 84.2 percent in the groups treated with Nr-CWS 60 and 120 micrograms/ml Nr-CWS; the results of HPV detection in 23 out of the 45 cases (51.1 percent) became negative after the 3-month treatment; the viral load was reduced in 9, and there was no change in viral load in 13 cases. Significant difference was found between the rates of undetectable viral load and the natural viral disappearance rate (P less than 0.05).

CONCLUSIONNr-CWS has an inhibitory effect to TC-1 cell tumorigenesis and clinical application of Nr-CWS may eliminate the HPV infection in lower genital tract of a considerable proportion of women with HPV infection.

Adult ; Animals ; Cell Wall Skeleton ; therapeutic use ; Cervix Uteri ; virology ; DNA, Viral ; analysis ; Female ; Humans ; Mice ; Mice, SCID ; Middle Aged ; Papillomavirus Infections ; complications ; drug therapy ; Uterine Cervical Neoplasms ; drug therapy ; virology ; Viral Load

OBJECTIVETo investigate the antiproliferation effect of cardamonin (CAR) and its possible mechanisms on human umbilical artery smooth muscle cells (HUASMCs) cultured in the mimicking insulin resistance (IR) medium.

METHODProliferation of HUASMCs was assayed by MTT method. The mRNA expression of mTOR, Raptor and Rictor was detected by a real-time PCR. The expression content was calculated by Livak method using internal control of beta-actin.

RESULTThe proliferation of HUASMCs cultured in the mimicking IR medium was significantly increased. Both in normal and mimic IR culture medium, cells proliferation was inhibited by CAR (1 x 10(-5), 1 x 10(-4) mol x L(-1)). Pretreated with PD98059 and LY294002, cell proliferation induced by phosphatidic acid (PA) was inhibited, and the mRNA expression of mTOR, Raptor and Rictor was significantly decreased by CAR in the mimic IR medium.

CONCLUSIONIt is implicated that antiproliferation of CAR is involved in mRNA expression decrease of mTOR and its relative protein Raptor and Rictor.

Adaptor Proteins, Signal Transducing ; genetics ; metabolism ; Carrier Proteins ; genetics ; metabolism ; Cell Proliferation ; drug effects ; Cells, Cultured ; Chalcones ; pharmacology ; Gene Expression Regulation ; drug effects ; Growth Inhibitors ; pharmacology ; Humans ; Myocytes, Smooth Muscle ; cytology ; drug effects ; metabolism ; RNA, Messenger ; genetics ; metabolism ; Rapamycin-Insensitive Companion of mTOR Protein ; Regulatory-Associated Protein of mTOR ; TOR Serine-Threonine Kinases ; genetics ; metabolism

Serum samples from endometrial cancer (EC) patients and healthy females were analyzed using surface-enhanced laser desorption-ionization time-of-flight mass spectrometry (SELDI-TOF-MS) to discover the potential diagnostic biomarker for detection of EC. A preliminary training set of spectra derived from 40 EC patients and 30 healthy women were used to develop a proteomic model that effectively discriminated cancer patients from healthy women. The training set had a specificity of 100% and sensitivity of 92.5% in the EC detection. A blind test set, including 20 new cancer cases and 10 healthy women, was used to validate the sensitivity and specificity of this multivariate model, which had a corresponding results of 60% in specificity and 75% in sensitivity, respectively. The combination of SELDI-TOF-MS with bioinformatics tools could help find new biomarkers and establish the detection of EC with high sensitivity and specificity.
Biomarkers, Tumor ; metabolism ; Case-Control Studies ; Endometrial Neoplasms ; diagnosis ; metabolism ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Medical Oncology ; methods ; Models, Biological ; Neoplasm Proteins ; Neoplasm Staging ; Protein Array Analysis ; Proteomics ; methods ; Sensitivity and Specificity ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; methods

BACKGROUND:Delayed graft function (DGF) occurs frequently in kidney transplants from donation after cardiac death if creatinine level is high in kidney recipients. OBJECTIVE:To analyze the clinical effects of renal transplantation with kidneys from donors dying of cardiac death in organophosphate poisoning. METHODS:Data were col ected from kidney transplants from two donors dying of cardiac death in organophosphate poisoning. After some donor maintenance, donor organ were obtained and perfused with impulse type machine. Recipients were treated with intervention of immunity induction, anti-rejection drugs and infection prevention drugs during and after renal transplantation. Pathological data of donor kidney zero needle biopsy, DGF after kidney transplantation, complication rate (such as acute rejection), renal al ograft recovery situation, the survival rate of recipients and kidney transplants were col ected and analyzed. RESULTS AND CONCLUSION:Needle biopsy results from four donor kidneys showed that glomerular morphology was normal, but there were edema and degeneration in kidney tubules in some degree. Donor DGF rate was 75%(3/4), acute rejection rate was 0%(0/4), perioperative period donor kidney and recipient survival rate were 100%(4/4). Al recipients showed a good result of transplanted kidney, their creatinine and urea nitrogen were at low level, and had no proteinuria. One recipient died of severe pulmonary infection 4 months after surgery. For some organophosphate poisoning donors dying of cardiac death, donor kidney quality can be improved by suitable donor maintenance and high-quality donor kidney preservation using machine perfusion. Kidney transplants from donors dying of cardiac death in organophosphate poisoning who receive the maintenance of organ function may be a promising candidate for renal transplantation due to a severe lack of kidney donor sources.