The mechanism of biological actions of quercetin was studied by using metabolomic method and biomolecular network. HPLC-MS was used to analyze the serum metabolome in rats of blank group and quercetin administration group rats, and MS data were processed by MATLAB software. With multivariate statistical analysis of serum metabolite profiles, a clear separation among blank group and quercetin administration group was achieved, potential biomarkers were selected according to the parameters of variable importance in the projection (VIP) and identified according to MS information and database retrieval. Four compounds, related enzymes, action targets and metabolic pathways had been confirmed, namely retinoic acid and RARbeta, arachidonate and COX-2, 3, 5-diodotyrosine and TPO, uridine diphosphate glucose and PDEs. The mechanism of quercetin enhancing ability of retinoic acid on the induction of RARbeta, activating TPO, using as COX-2 and PDEs inhibitor was approved by biomolecular network and related literatures. In this study, a mechanism of multiple biological actions of quercetin was evaluated at the level of the biomolecular network, metabolomics and biomolecular network can be used to investigate the biological effects mechanism of quercetin, which provided a new method to further revealing mechanism of drug action.
Animals ; Antioxidants ; pharmacology ; Biomarkers ; blood ; Chromatography, Liquid ; Mass Spectrometry ; Metabolic Networks and Pathways ; Metabolome ; Metabolomics ; Multivariate Analysis ; Quercetin ; pharmacology ; Rats

OBJECTIVETo investigate the role of CCL28 in hypoxia-induced cell migration of hepatocellular carcinoma (HCC).

METHODSResected liver tissues from 50 HCC patients were subjected to real-time (rt)-PCR analysis to evaluate the mRNA expression levels of the hypoxia-induced factor HIF-1a and the chemokine CCL28. Patient data on treatment and outcome were analyzed. The human HCC cell lines HepG2 and HCCLM3 were used to investigate effects of hypoxic conditions on HIF-1a and CCL28 expressions by rt-PCR, western blotting, and enzyme-linked immunoassay. The CCL28-mediated effects of hypoxic conditions on cell mobility and invasion were assessed by trans-well and matrigel assays, respectively, in HCCLM3 with CCL28 expression silenced by small-interfering (si)RNA transfection. Spearman's rank test was used to assess the correlation between CCL28 and effects on disease- and treatment-related factors.

RESULTSThe mRNA levels of CCL28 (0.025 +/- 0.075) were found to be strongly correlated with HIF-1a(0.065 +/- 0.098) in human clinical samples of HCC (r = 0.595, P less than 0.01), with higher expressions of both related to recurrence after surgery (P = 0.011 and 0.019, respectively). In vitro hypoxic conditions stimulated HIF-1a and CCL28 expression in a time-dependent manner in both HepG2 (HIF-1a: F = 873.5; CCL28: F = 151.6) and HCCLM3 (HIF-1a: F = 964.5; CCL28: F = 285.8) (all P less than 0.01). siRNA inhibition of CCL28 in HCCLM3 cells led to a significant reduction in hypoxia-induced invasion and migration (all P = 0.011).

CONCLUSIONChemokine CCL28 expression is up-regulated in human HCC and under in vitro hypoxic conditions, and may play an important role in hypoxia-induced HCC migration and invasion.

Carcinoma, Hepatocellular ; metabolism ; pathology ; Cell Hypoxia ; Cell Line, Tumor ; Chemokines, CC ; genetics ; metabolism ; Gene Silencing ; Hep G2 Cells ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; metabolism ; Liver Neoplasms ; metabolism ; pathology ; RNA, Messenger ; genetics

OBJECTIVETo investigate the role of renal sympathetic nerves in renal sodium transport in ouabain-hypertensive rats (OHR).

METHODSSixteen male SD rats with sham renal denervation (Sham-RDNX) and 16 with renal denervation (RDNX) were randomly into normal control group and ouabain group to receive intraperitoneal injection of normal saline (1 ml/kg) and ouabain (27.8 µg/kg) once a day, respectively. Systolic blood pressure (SBP), heart rate and body weight were recorded weekly. Food consumption of the rats was determined twice a week. After a 4-week treatment, blood and 24 h urine samples were collected to measure the serum and urinary concentration of sodium, trace lithium and creatinine. Endogenous creatinine clearance rate (Ccr), fractional excretions of sodium (FENa), fractional excretions of lithium (FELi) and fractional reabsorption of sodium in the postproximal tubules (FDRNa) were calculated. Plasma renin activity was determined by radioimmunoassay. Norepinephrine was extracted from the renal tissue and assayed for norepinephrine content by HPLC.

RESULTSThe body weight, food intake and heart rate showed no significant difference among the 4 groups (P > 0.05). After 4 weeks, the SBP of control RDNX group (CDNX) was significantly lower than that of the control Sham-DNX group (Csham)(P < 0.05); the SBP of ouabain RDNX group (ODNX) was also significantly lower than that of ouabain Sham-DNX group (Osham) (P < 0.05); RNDX lowered SBP by about 10 mmHg in both ouabain groups and control groups. The SBP was significantly higher in Osham and ODNX groups than in the corresponding control groups (P < 0.01), also significantly higher in ODNX group than in Csham group (P < 0.01). Ccr showed no significant difference among the 4 groups(P > 0.05). FENa, FELi and FDRNa were significantly lower in ouabain groups than in the corresponding control groups (P < 0.05, P < 0.01, P < 0.05), but FENa, FELi and FDRNa of ODNX group were similar with those of Osham group (P > 0.05); FENa , FELi and FDRNa were similar between CDNX and Csham groups (P > 0.05). The plasma renin activity was comparable between the 4 groups (P > 0.05). Renal norepinephrine level was markedly reduced in RDNX group compared with that in Sham-RDNX group in both ouabain and control groups (P < 0.01).

CONCLUSIONThe increase of proximal tubule sodium reabsorption in OHR is not dependent on the renal sympathetic nerve.

Animals ; Hypertension ; chemically induced ; metabolism ; Kidney ; innervation ; Male ; Ouabain ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Sodium ; metabolism ; Sodium Channels ; metabolism ; Sympathetic Nervous System ; physiology

Objective To investigate the hemostatic effect of different administration Methods of hemabate in laparoscopic myomectomy, and to clarify the best mode of hemabate in laparoscopic myomectomy.Methods Ninety patients were randomly divided into two groups,group A and group B,45 patients in each group,group A was given intramuscular injection of hemabate 0.25 mg 30 minutes before operation,and in group B,the patients were injected with hemabate 0.25 mg at the muscular wall of uterine leiomyoma during operation.The preoperative,postoperative basic situation,intraoperative blood loss,operation time,intraoperative and postoperative adverse reactions and length of hospital stay were compared between the two groups.Results The average amount of blood loss during operation in the group B was(67.6±17.6)ml, significantly less than that in the group A((88.7±21.6)ml),the operation time in the group B was(68.1 ±18.1)min,shorter than that in the group A(83.1 ± 17.5)min(t=1.877,2.787,P<0.05).The systolic blood pressure of patients in the group A after 15,30,45 and 180 minutes of medication were(155.6±10.31) mmHg,(141.2±5.7)mmHg,(138.6±10.3)mmHg,(127.5±7.4)mmHg,respectively and the diastolic blood pressure were(90.5±8.8)mmHg,(85.5±8.0)mmHg,(80.6±6.3)mmHg,(72.2±7.1)mmHg,while the systolic blood pressure were(141.1±8.3)mmHg,(120.5±6.1)mmHg,(125.7±4.6)mmHg,(118.8±5.5) mmHg and diastolic blood pressure were(81.2 ± 11.4)mmHg,(70.4 ± 10.1)mmHg,(71.5 ± 5.8)mmHg, (66.5±1.2)mmHg in the group B,the differences were statistically significant(systolic blood pressure,Ftime=79.75,P<0.001;FgrouP=25.45,P<0.001; Finteraction=5.48,P=0.041; diastolic blood pressure,Ftime=46.61,P<0.001;FgrouP=11.97,P=0.021,Finteraction=4.05,P=0.034).Conclusion The application of hemabate for hemostasis in laparoscopic myomectomy surgery and uterine fibroids at the muscle wall injection medication can significantly reduce the amount of blood loss during operation,shorten the operation time,and at the same time,the effect on blood pressure was lower than that by preoperative hemabate,is beneficial to the development of operation,with obvious advantages.

AIM To investigate the effects of berberine-evodiamine compatibility on expressions of intestinal acyl-CoA:cholesterol acyltransferase 2 (ACAT2),apolipoprotein B48 (ApoB48),and Niemann-Pick C1 Like 1 (NPC1L1) proteins in hypercholesterolemic rats.METHODS Fifty SD rats were assigned to control and model groups.After establishing the hypercholesterolemic rat model by feeding high fat and high cholesterol food,forty SD rats were equally divided into model control group,atorvastatin group,berberine-evodiamine compatibility groups (89.2 mg/kg,178.4 mg/kg).After four weeks treatment,serum triglycerides (TG),total cholesterol (TC),low-density lipoprotein cholesterol (LDL-C),high density lipoprotein cholesterol (HDL-C) were detected.Then the contents of cholesterol and β-sitoesterol in serum were determined by GC.The expressions of ACAT2,ApoB48 and NPC1 L1 proteins in the small intestine were assayed with immunohistochemistry technology.RESULTS Serum TC,TG and liver TC were significantly decreased in 89.2 mg/kg and 178.4 mg/kg berberineevodiamine compatibility groups compared with those in the model control group (P ＜ 0.01).Serum LDL-C and liver TC were also significantly decreased in 89.2 mg/kg berberine-evodiamine compatibility group (P ＜ 0.05).GC analysis indicated that the amount of cholesterol level and β-sitoesterol in serum were decreased in 178.4 mg/kg berberine-evodiamine compatibility group (P ＜ 0.05) and 89.2 mg/kg berberine-evodiamine compatibility group (P ＜ 0.01).Immunohistochemistry analysis manifested that the average luminous density of ACAT2,ApoB48 and NPC1L1 proteins in two dosages of berberine-evodiamine compatibility group were descended markedly compared with those in the model control group (P ＜ 0.05 or P ＜ 0.01).CONCLUSION The mechanisms underlying the cholesterol metabolism activity of berberine-evodiamine compatibility are mediated most likely by down-regulating the expressions of intestinal ACAT2,ApoB48 and NPC1 L1 proteins in hypercholesterolemic rats.

Objective To examine the hemostatic effect of oxytocin in laparoscopic myomectomy,and to clarify the optimal dosage of oxytocin in laparoscopic myomectomy. Methods From January 2016 to July 2017, ninety patients with myoma of uterus who underwent laparoscopic myomectomy in Tangshan Union Medical College Hospital were divided into two groups: group A and group B,45 cases in each group. In group A,the patients were given 20U oxytocin and 5％ glucose injection 250 ml via intravenous drip, and in group B, the patients were injected with 20U oxytocin on the muscular wall of uterus myoma during operation. The preoperative, postoperative basic situation, intraoperative blood loss, operation time, intraoperative and postoperative adverse reactions and the time of hospitalization were compared between the two groups. Results The average amount of blood loss during operation in group B was (76. 5±15. 8) ml,significantly lower than that in group A((99. 8±20. 7) ml),and the operation time in group B was (71. 2±10. 7) min,shorter than that in group A ((90. 1±18. 4) min) The difference was statistically significant (t=1. 788、2. 878,P<0. 05). At 5 minutes,30 minutes and 180 minutes after medication, the systolic blood pressure of patients in group A was (132. 2±1. 4) mmHg,(120. 7±5. 3) mmHg,(110. 9±1. 8) mmHg and the diastolic blood pressure was (80. 9 ±12. 5) mmHg,(71. 4±12. 6)mmHg,(70. 1±2. 8) mmHg,while the systolic blood pressure in the group B was (140. 4±11. 1) mmHg,(131. 2±4. 5) mmHg,(121. 4±11. 2) mmHg and the diastolic blood pressure was (93. 4±8. 1) mmHg,(86. 4±7. 1) mmHg,(81. 1±1. 5) mmHg,the differences were statistically significant (systolic blood pressure:Ftime=68. 57,P<0. 001;FgrouP=16. 54,P<0. 001;Finteraction=4. 34,P=0. 011;diastolic blood pressure:Ftime=45. 16,P<0. 001;FgrouP=10. 79,P=0. 024;F interaction=4. 16,P=0. 037);at the same treatment time,the systolic blood pressure and diastolic blood pressure in group B were higher than those in group A,the differences were statistically significant (P<0.05).Conclusion Laparoscopic uterine myomectomy with oxytocin hemostasis, intrauterine myoma wall injection method can significantly reduce intraoperative blood loss and shorten the operation time,the effect is obviously better than intravenous drip,and it is conducive to the operation.

Objective:To explore the efficacy of the oncoplastic round block technique in surgical management of idiopathic granulomatous mastitis (IGM).Methods:From January 2014 to December 2019, a total of 18 patients (24 to 38 years old, 32.2 years in average) with IGM underwent excision of the inflammatory breast mass with oncoplastic round block technique, the postoperative clinical efficacy was summarized and analyzed.Results:All 18 patients with IGM underwent excision of the inflammatory breast mass with oncoplastic round block technique, among them 2 patients underwent round-block reduction surgery of contralateral breast at the same time. The median follow-up duration was 16.1 months (from 6 to 36 months). Incision poor healing occurred in two cases which was cured after dressing change. Recurrence occurred in one case at 6 months after operation, and then cured with conservative measures. No other severe complications occurred. All patients were satisfacted with the results.Conclusions:Application of oncoplastic round block technique in surgical management of IGM may remove more tissue in order to reduce the recurrent rate, and get a better cosmetic results.

OBJECTIVETo explore significance of high-risk human papillomavirus (HR-HPV) testing in atypical squamous cells, cannot exclude high grade squamous intraepithelial lesion (ASC-H).

METHODSPresence of HR-HPV DNA was examined in 45 patients with ASC-H using hybrid capture II (HC-II) test. Colposcopic examination and biopsy were taken all results were evaluated.

RESULTSOverall, 33 of 45 (73.3%) ASC-H cases were biopsy proven cervical intraepithelial lesion (CIN). 36 of 45 ASC-H cases were HPV-DNA positive, including 19 cases of HSIL and over lesion; whereas no HSIL or over was found in 9 HR-HPV negative cases. Sensitivity and negativity predictive value of HR-HPV in ASC-H with HSIL and over lesion were both 100%.

CONCLUSIONSASC-H strongly predicts the presence of HSIL, HR-HPV may serve as a predict select whether a patient with ASC-H should take colposcopic examination immediately, patients with positive HR-HPV should undergo immediate colposcopic examination, while negative HR-HPV is an excellent predictor of the absence of HSIL.

Adult ; Aged ; Biopsy ; Carcinoma, Squamous Cell ; pathology ; virology ; Cervical Intraepithelial Neoplasia ; pathology ; virology ; Colposcopy ; DNA, Viral ; analysis ; Female ; Humans ; Middle Aged ; Papillomaviridae ; isolation & purification ; Papillomavirus Infections ; Precancerous Conditions ; pathology ; virology ; Uterine Cervical Neoplasms ; pathology ; virology ; Uterine Cervicitis ; pathology ; virology ; Vaginal Smears ; Young Adult

OBJECTIVETo assess the sensitivity and positive predictive value (PPV) of intraoperative frozen section diagnosis of the borderline tumor of ovary (BTO).

METHODSA retrospective analysis and comparison were done respectively between the accuracies of diagnoses made by using frozen and paraffin sections from the same tissue blocks for BTO from March 1995 to May 2008 achieved in the Department of Pathology, Guangdong General Hospital. Univariate and multivariate regression models were used to assess the influence of patient and tumor characteristics on the likelihood of underdiagnosis and overdiagnosis.

RESULTSOf the 73 patients analyzed, 39 cases (53.42%) were histologically serous tumors, 32 (43.84%) were mucinous and 2 (2.74%) were endometrioid tumors. Diagnoses identical in those made by using either frozen or routine paraffin sections were 55/73 (75.34%). The sensitivity and positive predictive value of frozen section diagnosis were 87.30% and 85.94%, respectively. Underdiagnosis of frozen section were 18/73 (24.66%). There was no overdiagnosis cases obtained. Univariate analysis showed that tumor diameter and tumor histology were the predictors of underdiagnosis in frozen section analysis. And in multivariate analysis, only tumor diameter, rather than patient age, tumor histology and stage, bilateral side tumor, serum CA-125 and concurrent presence of endometriosis was a predictor of underdiagnosis.

CONCLUSIONSIntraoperative frozen section diagnosis of BTO has a low sensitivity and PPV. Underdiagnosis is not uncommon. Surgical management based on intraoperative frozen section diagnosis should be used with caution.

Adult ; Aged ; Aged, 80 and over ; CA-125 Antigen ; metabolism ; Carcinoma, Endometrioid ; metabolism ; pathology ; surgery ; Cystadenoma, Mucinous ; metabolism ; pathology ; surgery ; Cystadenoma, Serous ; metabolism ; pathology ; surgery ; Female ; Frozen Sections ; Humans ; Intraoperative Period ; Middle Aged ; Neoplasm Staging ; Ovarian Neoplasms ; metabolism ; pathology ; surgery ; Paraffin Embedding ; Predictive Value of Tests ; Retrospective Studies ; Sensitivity and Specificity ; Young Adult

OBJECTIVETo summarize the experience of surgical treatment of secundum atrial septal defects in adults over 30 years old.

METHODSThere were 469 patients with secundum atrial septal defects in our study (male 144, female 325; ages 30-68, mean 38.6 years old). There were 105 cases with pulmonary hypertension and 458 cases with arrhythmia in the group. Surgical closure of defects were performed in all patients. Surgical closure of 358 cases were done by patches including 305 autologous pericardial patches. The low dose (6 x 10(-6)) nitric oxide inhalation was used in 25 postoperative patients with pulmonary hypertension. Right sided maze procedures were done in 5 cases with atrial fibrillation.

RESULTSSurgical mortality was 0.6% (3 cases), the others were healed. In the group, there were 180 cases with arrhythmia, 27 cases with left ventricular function amyoplasia, 28 cases with low cardiac output syndrome, 12 cases in secondary operation for bleeding and 1 case with air-embolism. The level of mean pulmonary artery pressure of 25 postoperative patients with pulmonary hypertension inhaled nitric oxide was down 28.5%. After right sided maze procedures were done in 5 cases with atrial fibrillation, atrial fibrillation disappeared. 352 cases were followed up from 3 months to 20 years (mean 5.6 years). Twenty-nine cases were in class I-II of cardiac function, and the others were better than class I of cardiac function.

CONCLUSIONSAtrial septal defects in adult should be operated as early as possible. When patch is needed, an autologous pericardial patch is the first selection. Inhaled nitric oxide is an effective method to postoperative pulmonary hypertension. The maze operation should be performed for atrial septal defect with atrial fibrillation while the surgical closure of defect was done. During and after operation, much attention should be paid to preventing and curing arrhythmia and protecting and supporting left heart function.

Administration, Inhalation ; Adult ; Age Factors ; Aged ; Atrial Fibrillation ; surgery ; Endothelium-Dependent Relaxing Factors ; therapeutic use ; Female ; Heart Septal Defects, Atrial ; surgery ; Humans ; Hypertension, Pulmonary ; complications ; drug therapy ; Male ; Middle Aged ; Nitric Oxide ; therapeutic use ; Postoperative Complications ; drug therapy ; Retrospective Studies