Mechanism of Gegen Qinlian Decoction in improving glucose metabolism in vitro and in vivo by alleviating hepatic endoplasmic reticulum stress / 中国中药杂志

This study investigated the mechanism of Gegen Qinlian Decoction(GQD) in improving glucose metabolism in vitro and in vivo by alleviating endoplasmic reticulum stress(ERS). Molecular docking was used to predict the binding affinity between the main effective plasma components of GQD and ERS-related targets. Liver tissue samples were obtained from normal rats, high-fat-induced diabetic rats, rats treated with metformin, and rats treated with GQD. RNA and protein were extracted. qPCR was used to measure the mRNA expression of ERS marker glucose-regulated protein 78(GRP78), and unfolded protein response(UPR) genes inositol requiring enzyme 1(Ire1), activating transcription factor 6(Atf6), Atf4, C/EBP-homologous protein(Chop), and caspase-12. Western blot was used to detect the protein expression of GRP78, IRE1, protein kinase R-like ER kinase(PERK), ATF6, X-box binding protein 1(XBP1), ATF4, CHOP, caspase-12, caspase-9, and caspase-3. The calcium ion content in liver tissues was determined by the colorimetric assay. The ERS-HepG2 cell model was established in vitro by inducing with tunicamycin for 6 hours, and 2.5%, 5%, and 10% GQD-containing serum were administered for 9 hours. The glucose oxidase method was used to measure extracellular glucose levels, flow cytometry to detect cell apoptosis, glycogen staining to measure cellular glycogen content, and immunofluorescence to detect the expression of GRP78. The intracellular calcium ion content was measured by the colorimetric assay. Whereas Western blot was used to detect GRP78 and ERS-induced IRE1, PERK, ATF6, and eukaryotic translation initiation factor 2α(eIF2α) phosphorylation. Additionally, the phosphorylation levels of insulin receptor substrate 1(IRS1), phosphatidylinositol 3-kinase regulatory subunit p85(PI3Kp85), and protein kinase B(Akt), which were involved in the insulin signaling pathway, were also measured. In addition, the phosphorylation levels of c-Jun N-terminal kinases(JNKs), which were involved in both the ERS and insulin signaling pathways, were measured by Western blot. Molecular docking results showed that GRP78, IRE1, PERK, ATF4, and various compounds such as baicalein, berberine, daidzein, jateorhizine, liquiritin, palmatine, puerarin and wogonoside had strong binding affinities, indicating that GQD might interfere with ERS-induced UPR. In vivo results showed that GQD down-regulated the mRNA transcription of Ire1, Atf6, Atf4, Grp78, caspase-12, and Chop in diabetic rats, and down-regulated GRP78, IRE1, PERK, as well as ERS-induced apoptotic factors ATF4 and CHOP, caspase-12, caspase-9, and caspase-3, while up-regulating XBP1 to enhance adaptive UPR. In addition, GQD increased the calcium ion content in liver tissues, which facilitated correct protein folding. In vitro results showed that GQD increased glucose consumption in ERS-induced HepG2 cells without significantly affecting cell viability, increased liver glycogen synthesis, down-regulated ATF6 and p-eIF2α(Ser51), and down-regulated IRE1, PERK, and GRP78, as well as p-IRS1(Ser312) and p-JNKs(Thr183/Tyr185), while up-regulating p-PI3Kp85(Tyr607) and p-Akt(Ser473). These findings suggested that GQD alleviates excessive ERS in the liver, reduces insulin resistance, and improves hepatic glucose metabolism in vivo and in vitro.

MicroRNA-375 Suppresses the Tumor Aggressive Phenotypes of Clear Cell Renal Cell Carcinomas through Regulating YWHAZ / 中华医学杂志(英文版)

Background@#MicroRNAs (miRNAs) are key regulators during tumor initiation and progression. MicroRNA-375 (MiR-375) has been proven to play a tumor-suppressive role in various types of human malignancies; however, its biological role in clear cell renal cell carcinoma (ccRCC) remains unclear. The purpose of this study was to explore the biologic role as well as the underlying mechanism of miR-375 in ccRCC progression.@*Methods@#Quantitative polymerase chain reaction (qPCR) was applied to test the expression of miR-375 in tissues and cell lines by t-test. Functional experiments were used to investigate the biological role of miR-375 utilizing a gain-of-function strategy. The target of miR-375 was investigated by bioinformatic analysis and further verified by luciferase reporter assay, qPCR, Western blotting, and functional experiments in vitro.@*Results@#Our study demonstrated that miR-375 was significantly downregulated in ccRCC tissues (cancer vs. normal, 0.804 ± 0.079 vs. 1.784 ± 0.200, t = 5.531 P < 0.0001) and cell lines, and loss of miR-375 expression significantly associated with advanced Fuhrman nuclear grades (Grade III and IV vs. Grade I and II, 1.000 ± 0.099 vs. 1.731 ± 0.189, t = 3.262 P = 0.003). Functional studies demonstrated that miR-375 suppressed ccRCC cell proliferation, migration, and invasion (all P < 0.05 in both 786-O and A498 cell lines). Multiple miRNA target prediction algorithms indicated the well-studied oncogene YWHAZ as a direct target of miR-375, which was further confirmed by the luciferase reporter assay, qPCR, and Western blotting. Moreover, restoration of YWHAZ could rescue the antiproliferation effect of miR-375.@*Conclusions@#The data provide the solid evidence that miR-375 plays a tumor-suppressive role in ccRCC progression, partially through regulating YWHAZ. This study expands the antitumor profile of miR-375, and supports its role as a potential therapeutic target in ccRCC treatment.

Surgical Treatment of Double Outlet Right Ventricle Complicated by Pulmonary Hypertension / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Double outlet right ventricle (DORV) is a group of complex congenital heart abnormalities. Preoperative pulmonary hypertension (PH) is considered an important risk factor for early death during the surgical treatment of DORV. The aim of this study was to report our experience on surgical treatment of DORV complicated by PH.</p><p><b>METHODS</b>From June 2004 to November 2016, 61 patients (36 males and 25 females) aged 2 weeks to 26 years (median: 0.67 years and interquartile range: 0.42-1.67 years) with DORV (two great arteries overriding at least 50%) complicated by PH underwent surgical treatment in our center. All patients were categorized according to surgical age and lesion type, respectively. Pulmonary artery systolic pressure (PASP), pulmonary artery diastolic pressure (PADP), and mean pulmonary artery pressure (mPAP) were measured directly before cardiopulmonary bypass (CPB) was established and after CPB was removed. An intracardiac channel procedure was performed in 37 patients, arterial switch procedure in 19 patients, Rastelli procedure in three patient, Senning procedure in one patients, and Mustard procedure in one patient. The Student's t-test and Chi-squared test were performed to evaluate clinical outcomes of the surgical timing and operation choice.</p><p><b>RESULTS</b>Fifty-five patients had uneventful recovery. PASP fell from 55.3 ± 11.2 mmHg to 34.7 ± 11.6 mmHg (t = 14.05, P < 0.001), PADP fell from 29.7 ± 12.5 mmHg to 18.6 ± 7.9 mmHg (t = 7.39, P < 0.001), and mPAP fell from 40.3 ± 10.6 mmHg to 25.7 ± 8.3 mmHg (t = 11.85, P < 0.001). Six (9.8%) patients died owing to complications including low cardiac output syndrome in two patients, respiratory failure in two, pulmonary hemorrhage in one, and sudden death in one patient. Pulmonary artery pressure (PAP) dropped significantly in infant and child patients. Mortality of both infants (13.9%) and adults (33.3%) was high.</p><p><b>CONCLUSIONS</b>PAP of patients with DORV complicated by PH can be expected to fall significantly after surgery. An arterial switch procedure can achieve excellent results in patients with transposition of the great arteries type. Higher incidence of complications may occur in patients with ventricular septal defect (VSD) type before 1 year of age. For those with remote VSD type, VSD enlargement and right ventricle outflow tract reconstruction are usually required with acceptable results. The degree of aortic overriding does not influence surgical outcome.</p>

One-stage repair of congenital aortic arch disease with other cardiac defects by using autologous pulmonary artery tissue / 中华外科杂志

<p><b>OBJECTIVE</b>To analyze the surgical strategy and result of one-stage repair for congenital aortic arch disease associated with other cardiac anomalies.</p><p><b>METHODS</b>Between April 1993 and November 2009, 25 consecutive patients aged 26 d to 6.5 years underwent one-stage repair for congenital aortic arch disease with other cardiac anomalies. Among them, 6 patients had coarctation of aorta, 6 patients had interrupted aortic arch, and 13 cases had hypoplasia of aortic arch. The surgical techniques include excision of the anterior wall of pulmonary artery, resection of patent ductus arteriosus tissue, aortic arch reconstruction with autologous pulmonary artery wall, reconstruction of the pulmonary artery and repair of the associated defects.</p><p><b>RESULTS</b>Twenty-four patients survived and recovered uneventfully. One patient died of pulmonary hypertension crisis in hospital. The reconstruction of the aorta and the correction of the intracardiac anomalies were proved by postoperative echocardiography and CT scan. There were no neurological or other complications. The follow-up showed that all patients developed normally and there were no restenosis of the aorta arch.</p><p><b>CONCLUSIONS</b>With the benefits of growth potential and less tension, autologous pulmonary artery tissue is an optimal choice in aortic arch reconstruction. One-stage repair of congenital aortic arch disease associated with other cardiac anomalies can achieve good results.</p>

Uniportal versus biportal video-assisted thoracoscopic sympathectomy for palmar hyperhidrosis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Video-assisted thoracoscopic sympathectomy had replaced open surgery. The aim of this study was to compare the outcomes of using a single port and two ports to perform video-assisted thoracoscopic sympathectomy for palmar hyperhidrosis.</p><p><b>METHODS</b>Between April 2006 and February 2008, 20 cases underwent video-assisted thoracoscopic sympathectomy through one port (uniportal group) and 25 cases through two ports (biportal group). The variables including the operating time, hospital stay, pain scores, postoperative complications, incidence of symptom recurrence and patient satisfaction were compared. The mean postoperative follow-up period was 11.5 months (range, 3 - 25 months).</p><p><b>RESULTS</b>The hands of all patients were warm and dry after operation. No conversion to open surgery was necessary, and no operative mortality was recorded in either group. The mean inpatient pain scores were significantly higher in the biportal group (1.2 +/- 0.6) than that in the uniportal group (0.8 +/- 0.5, P = 0.025). For the first three weeks after operation, four out of 20 (20%) patients in the uniportal group constantly suffered from mild or moderate residual pain while eight out of 25 (32%) cases in the biportal group (P = 0.366). Among them, two cases in the uniportal group and five cases in the biportal group need to take analgesics. Our mean operative time (bilateral sympathectomy) in the uniportal group ((39.5 +/- 10.0) minutes) was shorter than that in biportal group ((49.7 +/- 10.6) minutes, P = 0.02). There were no significant differences between two groups in terms of the mean hospital stay, compensatory sweating, and patient satisfaction. Two patients in the biportal group and three in the uniportal group experienced a unilateral pneumothorax. None of them required chest drainage. No patient experienced Horner's syndrome, and no recurrent symptoms were observed in either groups.</p><p><b>CONCLUSIONS</b>Both uniportal and biportal video-assisted thoracoscopic sympathectomy are effective, safe, and minimally invasive for palmar hyperhidrosis. Comparing with the biportal approach, the uniportal approach causes less postoperative pain and less operative time, and is a more reasonable procedure in treatment of palmar hyperhidrosis.</p>

Surgical treatment of anomalous origin of coronary artery from the pulmonary artery / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Anomalous origin of coronary artery from the pulmonary artery is a rare congenital cardiac malformation with a mortality rate of up to 90% within the first year of life without surgical intervention. Direct implantation of the anomalous coronary artery (ACA) into the aorta is successful in early life, but it may have increased surgical difficulty and risk with age. This retrospective study summarized our operative experience in direct implantation for treatment of this coronary anomaly in pediatric and adult patients.</p><p><b>METHODS</b>From August 2000 to January 2003, 4 consecutive patients aged from 9 months to 41 years underwent dual coronary repair. Among them, two children and one infant with anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) and one adult was anomalous origin of right coronary artery from the pulmonary artery (ARCAPA). Coronary arteries were directly implanted into the ascending aorta in 4 patients. In a boy with ALCAPA associated with moderate mitral insufficiency (MI), whose ACA arose remotely from the ascending aorta, we created a tube-shaped graft using part of the pulmonary arterial wall in continuity with the origin of the left coronary artery (LCA). Concomitant moderate MI was repaired in 2 patients, including this boy, after a dual-coronary repair.</p><p><b>RESULTS</b>All patients survived. There were no hospital or late deaths and no major complications as well. Echocardiography revealed that the left ventricular (LV) function including LV end-diastolic dimension (EDD) and ejection fraction (EF) was markedly improved at hospital discharge. At 3 - 6 years follow-up after surgery all patients were asymptomatic and currently in NYHA class I.</p><p><b>CONCLUSIONS</b>The best results are achieved with direct implantation of the ACA into the ascending aorta and simultaneous mitral valve repair if needed. Direct implantation is feasible in pediatric and adult patients with ALCAPA or ARCAPA including the coronary artery in a location remote from the ascending aorta. It is a good procedure to lengthen the ACA by creating a tube-shape graft using part of the pulmonary arterial wall in continuity with the origin of ACA.</p>

Effects on lymphangiogenesis and angiogenesis of lung cancer with antisense oligonucleotides of vascular endothelial growth factor C / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the effects on lymphangiogenesis and angiogenesis of orthotopic implantation of lung cancer in nude mice with antisense oligonucleotides of VEGF-C.</p><p><b>METHODS</b>The model in nude mice was established with orthotopic implantation for the human lung cancer cell line A549. Thirty nude mice were randomized into three groups: PBS control group, sense oligonucleotides control group and antisense oligonucleotides group (AODN group). After treatments were completed, the expression of VEGF-C and lymphatic microvessel density (LMVD) and microvessel density (MVD) of lung cancer were detected by RT-PCR,Western Blot and immunohistochemistry.</p><p><b>RESULTS</b>The expression of VEGF-C in AODN group was inhibit significantly (P < 0.05). The LMVD in AODN group was decreased significantly (P < 0.1). Though the MVD in AODN group was also decreased, but there were no significant differences compared with control groups (P > 0.05).</p><p><b>CONCLUSIONS</b>The antisense oligonucleotides of VEGF-C can inhibit the expression of VEGF-C in nude mice of orthotopic implantation of lung cancer. It could inhibit the lymphangiogenesis.</p>

Surgical treatment of myocardial bridging: report of 31 cases / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Myocardial bridging (MB) is usually considered a benign condition but may result in myocardial ischemia, myocardial infarction (MI), exercise-induced tachycardia, atrioventricular conduction block or even sudden cardiac death. This retrospective study summarizes our operative methods and outcomes for treatment of 31 cases of MB.</p><p><b>METHODS</b>From January 1997 to December 2006, 31 consecutive patients (24 men and 7 women; aged 35 - 67 years; mean 52.3 years) with MB underwent surgical treatment. Thirteen patients had MB only and 18 patients had MB associated with other heart diseases. In preoperative cardiac function grading, 5 patients were in NYHA class I and 18 in NYHA class II and 8 in NYHA class III. Among them, 15 underwent myotomy and 16 underwent coronary artery bypass grafting (CABG).</p><p><b>RESULTS</b>All patients survived and recovered uneventfully. Neither hospital or late death nor major complications occurred. Postoperative exercise testing in all patients failed to reveal any persistent ischemia. Follow-up time was 3 - 115 months (mean 31 months). Follow-up angiographic studies in 21 patients (68%) demonstrated restoration of coronary blood flow and myocardial perfusion without significant residual compression of the artery. All patients were symptom-free and currently in NYHA class I - II.</p><p><b>CONCLUSION</b>The patients who are refractory to medication should actively undergo the surgical procedures such as myotomy and CABG. Myotomy should be advocated as the first choice because of its safety and satisfactory results.</p>

Change of nerve growth factor mRNA in human detrusor in bladder outlet obstruction with benign prostatic hyperplasia and their implication / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the change of nerve growth factor (NGF) mRNA in human detrusor in bladder outlet obstruction (BOO) with benign prostatic hyperplasia (BPH) and their implication.</p><p><b>METHODS</b>Eight cases of bladder cancer and 40 patients with BPH were included in this study. All patients were divided into three groups, a control group, an obstructive detrusor stability group and an obstructive detrusor instability group. NGF mRNA in detrusor from all patients was measured using a RT-PCR.</p><p><b>RESULTS</b>The RT-PCR study indicated that NGF mRNA was expressed in detrusor of three groups of patients. There were significant differences among the three groups (P < 0.01). The expression of NGF mRNA in the obstructive instability group was higher than that in the obstructive stability group and in the control group. The NGF mRNA level in the obstructive stability group was higher than that in the control group.</p><p><b>CONCLUSION</b>The expression of NGF mRNA in detrusor was elevated in BOO with BPH. The elevated expression of NGF mRNA might be correlated with detrusor instability (DI) due to BOO.</p>

Basic fibroblast growth factor in human detrusor muscle in bladder outlet obstruction due to benign prostatic hyperplasia / 中华老年医学杂志

Objective To investigate the change of the basic fibroblast growth factor(bFGF) leve in human detrusor muscle(DM)in bladder outlet obstruction(BOO)due to benign prostatic hyperplasia(BPH)and its implication.Methods Fifty-four patients with BPH were divided into two groups:the obstructive DM stability and instability groups;and 15 men with bladder tumor who underwent operation in the same period were enrolled in the control group.The bFGF mRNA level in DM was measured by reverse transcription and polymerase chain reaction(RT-PCR)and the bFGF protein level was measured by immunohistochemical staining method.Results The bFGF-mRNA expression level of bladder smooth muscle cells was significantly lower in the control group than that in the obstructive DM stability and instability groups(all P＜0.05),but there was no significant difference between the obstructive DM stability and instability groups(P＞0.05). Conclusions The expression level of bFGF mRNA in bladder DM is elevated in BOO due to BPH,but there is little or no correlation between the increased expression of bFGF mRNA and detrusor muscle instability.