Ginsenoside Rd inhibits apoptosis following spinal cord ischemia/reperfusion injury

Ginsenoside Rd has a clear neuroprotective effect against ischemic stroke. We aimed to verify the neuroprotective effect of ginsenoside Rd in spinal cord ischemia/reperfusion injury and explore its anti-apoptotic mechanisms. We established a spinal cord ischemia/reperfusion injury model in rats through the occlusion of the abdominal aorta below the level of the renal artery for 1 hour. Successfully established models were injected intraperitoneally with 6.25, 12.5, 25 or 50 mg/kg per day ginsenoside Rd. Spinal cord morphology was observed at 1, 3, 5 and 7 days after spinal cord ischemia/reperfusion injury. Intraperitoneal injection of ginsenoside Rd in ischemia/reperfusion injury rats not only improved hindlimb motor function and the morphology of motor neurons in the anterior horn of the spinal cord, but it also reduced neuronal apoptosis. The optimal dose of ginsenoside Rd was 25 mg/kg per day and the optimal time point was 5 days after ischemia/ reperfusion. Immunohistochemistry and western blot analysis showed ginsenoside Rd dose-de- pendently inhibited expression of pro-apoptotic Caspase 3 and down-regulated the expression of the apoptotic proteins ASK1 and JNK in the spinal cord of rats with spinal cord ischemia/reper- fusion injury. These findings indicate that ginsenoside Rd exerts neuroprotective effects against spinal cord ischemia/reperfusion injury and the underlying mechanisms are achieved through the inhibition of ASK1-JNK pathway and the down-regulation of Caspase 3 expression.

Incidence of human papilloma virus in esophageal squamous cell carcinoma in patients from the Lublin region

AIM:To assess the prevalence of human papilloma virus(HPV) in esophageal squamous cell carcinoma(ESCC) in the south-eastern region of Poland.METHODS:The study population consisted of 56 ESCC patients and 35 controls.The controls were patients referred to our department due to other nonesophageal and non-oncological disorders with no gross or microscopic esophageal pathology as confirmed by endoscopy and histopathology.In the ESCC patients,samples were taken from normal mucosa(56 mucosa samples) and from the tumor(56 tumor samples).Tissue samples from the controls were taken from normal mucosa of the middle esophagus(35 control samples).Quantitative determination of DNA was carried out using a spectrophotometric method.Genomic DNA was isolated using the QIAamp DNA Midi Kit.HPV infection was identified following PCR amplification of the HPV gene sequence,using primers MY09 and MY11 complementary to the genome sequence of at least 33 types of HPV.The sequencing results were computationally analyzed using the basic local alignment search tool database.RESULTS:In tumor samples,HPV DNA was identified in 28 of 56 patients(50%).High risk HPV phenotypes(16 or/and 18) were found in 5 of 56 patients(8.9%),low risk in 19 of 56 patients(33.9%) and other types of HPV(37,81,97,CP6108) in 4 of 56 patients(7.1%).In mucosa samples,HPV DNA was isolated in 21 of 56 patients(37.5%).High risk HPV DNA was confirmed in 3 of 56 patients(5.3%),low risk HPV DNA in 12 of 56 patients(21.4%),and other types of HPV in 6 of 56 patients(10.7%).In control samples,HPV DNA was identified in 4 of 35 patients(11.4%) with no high risk HPV.The occurrence of HPV in ESCC patients was significantly higher than in the controls [28 of 56(50%) vs 4 of 35(11.4%),P < 0.001].In esophageal cancer patients,both in tumor and mucosa samples,the predominant HPV phenotypes were low risk HPV,isolated 4 times more frequently than high risk phenotypes [19 of 56(33.9%) vs 5 of 56(8.9%),P < 0.001].A higher prevalence of HPV was identified in female patients(71.4% vs 46.9%).Accordingly,the high risk phenotypes were isolated more frequently in female patients and this difference reached statistical significance [3 of 7(42.9%) vs 2 of 49(4.1%),P < 0.05].Of the pathological characteristics,only an infiltrative pattern of macroscopic tumor type significantly correlated with the presence of HPV DNA in ESCC samples [20 of 27(74.1%) vs 8 of 29(27.6%) for ulcerative or protruding macroscopic type,P < 0.05].The occurrence of total HPV DNA and both HPV high or low risk phenotypes did not significantly differ with regard to particular grades of cellular differentiation,phases in depth of tumor infiltration,grades of nodal involvement and stages of tumor progression.CONCLUSION:Low risk HPV phenotypes could be one of the co-activators or/and co-carcinogens in complex,progressive,multifactorial and multistep esophageal carcinogenesis.

宫颈上皮内瘤变的保守治疗——局部切除术

Objective: The purpose of this study was to evaluate a conservative cold-knife section technique for treatment of cervical intraepithelial neoplasia (CIN). This procedure can be adapted to patient age, preservation of childbearing potential and extent of dysplasia. Design: Prospective study. Setting: Gynecological Oncology Department in French Public Hospital. Population: A total of 460 women treated for CIN between 1985 and 1999 were included. Methods: A conservative cold-knife cervical section followed by blanket suture reconstruction was used in all cases. Main outcome measures: Immediate operative results, recurrence and reproductive function were assessed. Results: The mean length of the cervical specimen was 11.4 mm (range, 4-22 mm). Mean specimen thickness was strongly correlated with age: 10.6 ± 4.1 mm in women < 40 years versus 12.1 in women >40 years; p < 0.001. Complete excision was achieved in 395 cases (85.8% ). Post-operative bleeding was observed in 5 cases (1.1% ). The mean duration of follow-up was 62 months (range, 12.3-156.5 months). Recurrences developed in 26 patients (6.6% ) including CIN 1 in 9 cases, CIN 2 in 9 and CIN 3 in 8. No patient developed carcinoma. The actuarial risk of recurrence was 2.4% (± S.D., 0.9) at 24 months and 7.8% (± S.D., 1.9) at 60 months. A total of 52 pregnancies were observed in 39 patients. No case of de novo infertility was reported post-operatively. Amenorrhea was noted in 1 patient (0.1% ) and dysmenorrhea in 1 patient (0.1% ). Conclusions: This conservative cold-knife section technique is effective for treatment of CIN with low morbidity and little adverse effect on childbearing potential. Exposure of the squamo columnar junction (SCJ) greatly facilitates follow-up.

Gynecological malignancies and hormonal therapies: Clinical management and recommendations

Every year in the world a large number of women receive a diagnosis of gynecological cancer and undergo a therapy such as surgery, chemotherapy and radiotherapy to the pelvic region. A large portion of these patients are already in menopause, but for younger patients therapies are responsible of early menopause. The physical and psychological symptoms due to iatrogenic menopause significantly reduce the quality of life; however hormone replacement therapy(HRT) has a high efficacy in reducing menopausal symptoms. The prescription of HRT in patients with story of gynecological cancer is debated because its safety has not been completely proven. The main criticism is based on the theory that the hormone replacement could stimulate growth of residual cancer cells increasing the risk of recurrence.

Changes of the F-wave in the acute phase of permanent spinal cord ischaemic injury predict spinal cord function in animal models of rabbits

Objective:to explore the changes of the F-wave in the posterior tibial nerve of rabbits after different levels of lumbar spinal cord ischaemic injury and its correlation with motor function and the extent of lumbar spinal cord pathological damage.Methods:thirty New Zealand rabbits were randomly divided into 6 groups.The control group(n=5)was used to exclude the influence of anaesthesia and surgery on the F-wave.Different levels of lumbar arteries were ligated in the five experimental groups(n=5).The F-wave was recorded to observe the changes in the acute phase of spinal cord ischaemia.The correlation between the changes of the F-wave in the acute reversible phase and the motor function of the spinal cord was analysed.Motor functions were assessed after surgery and 2 d after vascular ligation.The specimens were taken 2 d after ligation for histopathologic observation.Results:the results for the control group indicated that anaesthesia and surgery did not affect the F-wave results.There was no statistically significant difference in the F-wave amplitudes and latency before and after ligation in the 1 and 2 level ligation groups.The F-wave changed immediately after ligation in the 3,4 and 5 ligation groups.The latency of the F-wave gradually extended,the amplitude of the F-wave gradually reduced.The amplitude variations of the F-wave were positively correlated with the motor function 2 d after ligation,there was a statistically significant difference.With the increase in the number of vascular ligation,the degree of destruction of the motor neurons in the anterior horn of the spinal cord in the pathological specimens increased.Conclusion:the F-waves in the posterior tibial nerve of rabbits were found to be sensitive to the lumbar spinal cord ischaemic injury and specific to predict motor function.

Radical Vaginal Hysterectomy and Trachelectomy in Early-Stage Cervical Cancer

Objective: To communicate a minimally invasive technique for surgical handling of early-stage cervical cancer and its results. Methods: 110 patients with cervical cancer in stages IA2 and IB1, all of them operated in a period of 5 years in both hospitals, are presented. Laparoscopic systemic pelvic lymphadenectomy with radical vaginal hysterectomy or radical vaginal trachelectomy was performed to patients, with the exception of those patients who had compromised nodes detected in contemporary biopsy. Results: Between April 2008 and May 2013, 110 patients were submitted to this technique. 15 patients had their surgery aborted: 13 presented positive nodes for carcinoma in contemporary biopsy and 2 had extensive cervical compromise when performing radical vaginal hysterectomy or trachelectomy. Analysis of the remaining 95 cases shows an average age of 43.9 years (26 - 61), all of them had given birth before, 23 (21%) of them through C-section. BMI averaged 30.5 and 31 (28.2%) had cone surgery performed previously. Average duration of surgery was of 220 minutes. Postoperative hospitalization averaged 3.1 days. Bleeding volume was estimated at 125 cc and one patient required blood transfusion. En 25 patients’ uterine annexes were kept and all of them were suspended by means of laparoscopy. On average, 25.4 pelvic nodes were obtained. Complications 13.6% with eight patients suffered bladder injury, two had rectovaginal fistula, 3 patients requires surgical repair of ureteral obstruction, two patients present thromboembolic disease. The disease-free and overall survivals are consistent with reports in the literature. Conclusion: We believe that handling patients with this technique is possible and has the advantages of vaginal and laparoscopic surgery with minimal complications.

Platelet RNA enables accurate detection of ovarian cancer:an intercontinental,biomarker identification study

Platelets are reprogrammed by cancer via a process called education,which favors cancer development.The transcriptional profile of tumor-educated platelets(TEPs)is skewed and therefore practicable for cancer detection.This intercontinental,hospital-based,diagnostic study included 761 treatment-naive inpatients with histologically confirmed adnexal masses and 167 healthy controls from nine medical centers(China,n=3;Netherlands,n=5;Poland,n=1)between September 2016 and May 2019.The main outcomes were the performance of TEPs and their combination with CA125 in two Chinese(VC1 and VC2)and the European(VC3)validation cohorts collectively and independently.Exploratory outcome was the value of TEPs in public pan-cancer platelet transcriptome datasets.The AUCs for TEPs in the combined validation cohort,VC1,VC2,and VC3 were 0.918(95%CI 0.889-0.948),0.923(0.855-0.990),0.918(0.872-0.963),and 0.887(0.813-0.960),respectively.Combination of TEPs and CA125 demonstrated an AUC of 0.922(0.889-0.955)in the combined validation cohort;0.955(0.912-0.997)in VC1;0.939(0.901-0.977)in VC2;0.917(0.824-1.000)in VC3.For subgroup analysis,TEPs exhibited an AUC of o.858,0.859,and 0.920 to detect early-stage,borderline,non-epithelial diseases and 0.899 to discriminate ovarian cancer from endometriosis.TEPs had robustness,compatibility,and universality for preop.erative diagnosis of ovarian cancer since it withstood validations in populations of different ethnicities,heterogeneous histoiogical subtypes,and early-stage ovarian cancer.However,these observations warrant prospective validations in a larger population beforeclinicalutilities.

A preliminary evaluation of VEGF-A, VEGFR1 and VEGFR2 in patients with well-controlled type 2 diabetes mellitus

Objective： Decompensated chronic hyperglycemia often leads to late microvascular complications such as retinopathy, diabetic foot syndrome, and diabetic kidney disease. The aim of this study was to determine the concentration of vascular endothelial growth factor A （VEGF-A） and its receptors in patients with well-controlled diabetes. Methods： The study was conducted on 31 patients with well-controlled type 2 diabetes without microor macroangiopathy. Thirty healthy volunteers were enrolled in a control group. Serum concentrations of VEGF-A, VEGF receptors 1 and 2 （VEGFR1 and VEGFR2）, fasting glucose, and lipid profiles were measured, and the plasma concentration of glycated hemoglobin （HbAlc） was determined. Results： No significant differences were observed between the concentration of VEGF-A, VEGFR1 or VEGFR2 in the subject group and that in the control group. Positive correlations were noted between the levels of VEGF-A, VEGFR2, and triglyceride, and there was a negative correlation between the levels of VEGFR2 and high-density lipoprotein （HDL）-cholesterel in the study group. Conclusions： The concentrations of VEGF-A and its receptors 1 and 2 in patients with well-controlled diabetes are comparable to those of healthy individuals, which may indicate that appropriate control of glucose levels delays the occurrence of vascular complications. A negative correlation between VEGFR2 and HDL-cholesterol levels, and positive correlations between VEGF-A, VEGFR2, and triglyceride levels, suggest that lipid abnormalities occurring in diabetes may be involved in the modulation of angiogenesis.

Assessment of ghrelin and leptin receptor levels in postmenopausal women who received oral or transdermal menopausal hormonal therapy

Objective： In postmenopausal women, an increased leptin concentration and reduced levels of ghrelin and adiponectin were observed. The aim of this study was to evaluate the concentrations of the active form of ghrelin, total ghrelin, leptin receptor, lipoprotein（a） （Lp（a））, and plasminogen activator inhibitor type 1 （PAl-l） in postmenopausal women who received oral or transdermal menopausal hormonal therapy （MHT）. Methods： The study involved 76 healthy women： 46 women aged from 44 to 58 years who received oral （26） or transdermal （20） MHT; the control group consisted of 30 women aged from 44 to 54 years who did not receive MHT. The plasma concentrations of total ghrelin, the active form of ghrelin, Lp（a）, and PAI-I：Ag were measured by enzyme-linked immunosorbent assay （ELISA）. The concentration of the leptin receptor was measured by enzyme immunometric assay （EIA）. Results： We observed a significantly higher concentration o~ total ghrelin and the active form of ghrelin in women who received transdermal MHT in comparison with those who took oral MHT. We also found a significantly lower concentration of total ghrelin in women who received oral MHT compared with the control group. A higher concentration of PAl-1 ：Ag was found in the group of women who took transdermal MHT in comparison with those who took oral MHT and with the control group. The differences were statistically significant. Additionally, we found a significant negative correlation between the concentrations of total ghrelin and PAl-1 ：Ag and a positive correlation between the concentrations of total ghrelin and leptin receptor in women who received transdermal MHT. Conclusions： The study showed that women who used transdermal MHT had higher levels of total ghrelin than women who took oral MHT. This indicates a beneficial effect of the transdermal route of MHT. However, transdermal therapy was associated with adverse effects with regard to the observed higher levels of PAl-1 ：Ag, which in turn, can lead to a reduction in fibrinolytic activity.

Environmental exposure to cadmium but not lead is associated with decreased semen quality parameters:quality regionalism of sperm properties

Environmental factors may negatively contribute to a progressive worsening of semen quality,and differences in semen quality may result from different environmental exposures(regional differences)or lifestyle differences.Heavy metals are factors with a confirmed negative influence on male fertility.Among them,lead and cadmium are commonly found in human surroundings.Thus,we analyzed semen parameters(according to the World Health Organization 2010 recommendations)and semen lead and cadmium concentrations in 188 men from two different regions in Poland,a typical agricultural area and an industrial area,in couples that had been diagnosed with infertility.The assays were performed using flameless electrothermal atomic absorption spectrometry.In the statistical analysis,regional comparisons and then taxonomic comparisons based on three parameters(age,semen concentration,and sperm morphology)were applied.We showed that more cadmium than lead accumulated in semen,a higher cadmium concentration was observed in semen obtained from men from the agricultural region,and better semen quality and lower cadmium concentrations were found in the semen of men from the industrial,more polluted region.We thus showed an existing regionalism in the sperm quality properties.However,semen parameters such as morphology and progressive and nonprogressive motility followed the same trends,regardless of the patient’s age,region,or class.We could conclude that the environment has a minor impact on sperm morphology and progressive and nonprogressive motility and that other existing factors could have an indirect influence on semen quality.