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Growing clinical evidence shows that Qufeng Gutong Cataplasm may exert a significant analgesic effect. However, the pharmacological characteristics and mechanisms underlying this prescription are still unclear. In the current study, a "disease-syndrome-symptom-formula" association network analysis was performed to explore the pharmacological characteristics and mechanisms of Qufeng Gutong Cataplasm against osteoarthritis (OA), neuropathic pain (NP), chronic inflammatory pain (CIP) and myofascial pain syndrome (MPS) by integrating clinical phenomics data, transcriptomics data and biological interaction network mining. As a result, the three functional modules (Qufeng Sanhan-QFSHG, Shujin Huoxue-SJHXG and Xiaozhong Zhitong-XZZTG) enriched by the drug network targets were all related to the pharmacological effects of Qufeng Gutong Cataplasm, including dispersing cold and relieving pain, activating blood and relieving pain, reducing swelling and relieving pain. In addition, the main pharmacological effects of QFSHG and XZZTG were dispelling wind and dispersing cold and dehumidifying, promoting Qi and reducing swelling and relieving pain, respectively. In terms of reversing the imbalance of "immune-inflammation-vascular axis", the main pharmacological effects of SJHXG were regulating the liver and promoting Qi, activating blood circulation and removing stasis. Mechanically, the key network targets of Qufeng Gutong Cataplasm against OA, NP, CIP and MPS may play a therapeutic role in relieving hyperalgesia and paresthesia by reversing the "neuro-endocrine-immune" imbalance system during the occurrence and progression of diseases. In conclusion, our data indicate that Qufeng Gutong Cataplasm may relieve the pain and wind-cold-dampness arthralgia syndrome related symptoms by regulating the "neuro-endocrine-immune" system, neurological and endocrine disorders and reversing the imbalance of "immunity-inflammation". The relevant results may provide a network-based evidence for clinical positioning of Qufeng Gutong Cataplasm, and offer a direction for further clinical and experimental validation.
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The Baimai Ointment with the effect of relaxing sinew and activating collaterals demonstrates a definite effect on Baimai disease with pain, spasm, stiffness and other symptoms, while the pharmacodynamic characteristics and mechanism of this agent remain unclear. In this study, a rat model of chronic compression of L4 dorsal root ganglion(CCD) was established by lumbar disc herniation, and the efficacy and mechanism of Baimai Ointment in the treatment of CCD were preliminarily explored by behavioral tests, side effect evaluation, network analysis, antagonist and molecular biology verification. The pharmacodynamic experiment indicated that Baimai Ointment significantly improved the pain thresholds(mechanical pain, thermal pain, and cold pain) and gait behavior of CCD model rats without causing tolerance or obvious toxic and side effects. Baimai Ointment inhibited the second-phase nociceptive response of mice in the formalin test, increased the hot plate threshold of normal mice, and down-regulated the expression of inflammatory cytokines in the spinal cord. Network analysis showed that Baimai Ointment had synergistic effect in the treatment of CCD and was related to descending inhibition/facilitation system and neuroinflammation. Furthermore, behavioral tests, Western blot, and immunofluorescence assay revealed that the pain-relieving effect of Baimai Ointment on CCD may be related to the regulation of the interaction between neuroactive ligand and receptors(neuroligands) such as CHRNA7, ADRA2A, and ADRB2, and the down-regulation of the expression of NOS2/pERK/PI3K, the core regulatory element of HIF-1 signaling pathway in spinal microglia. The findings preliminarily reveal the mechanism of relaxing sinew and activating collaterals of Baimai Ointment in the treatment of Baimai disease, providing a reference for the rational drug use and further research of this agent.
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Ratas , Ratones , Animales , Dolor Crónico/metabolismo , Ratas Sprague-Dawley , Ganglios Espinales/metabolismo , Ligandos , Transducción de Señal , Hiperalgesia/metabolismo , Medicamentos Herbarios ChinosRESUMEN
Drug repositioning provides new clinical indications for existing drugs. The imbalance between body's "immune-inflammation" regulation is one of the important factors in the occurrence and development of diabetic nephropathy (DN). Chinese patent medicine Kunxian capsule is clinically used for treating rheumatoid arthritis with satisfying immune-modulatory and anti-inflammatory actions. Notably, accumulating clinical evidence based on small cohorts had shown that Kunxian capsule may be used to treat DN. But the underlying pharmacological mechanisms remain unclear. Therefore, this study integrated "drug target-disease gene-biological pathway-function module" multi-level associated network analysis, and in vivo and in vitro experiments, to verify the pharmacological effects of Kunxian capsules in DN and to elucidate its molecular mechanisms. The experimental protocol was reviewed by the Laboratory Animal Welfare and Ethics Committee of China Academy of Chinese Medical Sciences, and it complies with the relevant regulations on laboratory animal welfare and ethics. As a result, the network analysis showed that the candidate targets of Kunxian capsule against DN were significantly involved into various functional modules which were related to modulation of immune-inflammation system, basement membrane lesion, abnormal hemorheology, energy metabolism and hormone metabolism, and the number of targets enriched by PI3K/AKT/NF-κB pathway is the largest. In addition, both in vivo and in vitro experiments demonstrated that Kunxian capsule by gavage effectively reduced blood glucose, improved insulin resistance, reduced blood lipid, inhibited renal extracellular matrix protein production and renal inflammation, improved renal function and pathological damages, and inhibited the activity of PI3K/AKT/NF-κB/TNF-α/IL-1β pathway in diabetic nephropathy rats. Collectively, these findings suggest the therapeutic potentials of Kunxian capsule to alleviate DN by regulating the imbalance of immune-inflammation system.
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Objective:To explore the mechanism and compatibility characteristics of Baimai ointment （BMO） in the treatment of white vein disease from the network perspective based on system theory， so as to provide biological basis for its clinical application. Method:The chemical components and the corresponding candidate target spectra of BMO were obtained from The Encyclopedia of Traditional Chinese Medicine （ETCM） and Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine （TCMIP）. According to the clinicopathological characteristics of white vein disease， focusing on four diseases/symptoms including neuropathic pain， inflammatory pain， chronic pain and lumbar disc herniation root neuralgia， the gene sets related to white vein disease were collected in Human Phenotype Ontology （HPO）， DisGeNET and other databases， then the interaction network of the targets of active components in BMO-gene sets related to white vein disease was constructed. On this basis， the hub network nodes were selected and enriched for exploring the mechanism of four functional groups of BMO in the treatment of white vein disease such as Huoxue Tongluo group （Curcumae Longae Rhizoma， Moschus， Tronae）， Xingqi Zhitong group （Myristicae Semen， Nardostachyos Radix et Rhizoma， Acori Calami Rhizoma）， Wenjing Sanhan Tongluo group （Zingiberis Rhizoma， Zanthoxyli Pericarpium， Caraway） and Jianpi Wenshen Qianggu group （Actinolite， Glycyrrhizae Radix et Rhizoma）. Result:The enriched pathways of the four functional groups in BMO were mainly distributed in three modules of nervous system function， inflammation-immune system regulation and body energy metabolism， and each module was connected by common target genes especially had its own focus. Among them， the regulation of nervous system function in Huoxue Tongluo group and Xingqi Zhitong group could be summarized as Huoxue Buqi and Xingshen Kaiqiao. Xingqi Zhitong group and Jianpi Wenshen Qianggu group were mainly used to promote the operation of Qi， promote blood metaplasia， enhance immunity and maintain the regulation of inflammation-immune system. Jianpi Wenshen Qianggu group and Wenjing Sanhan Tongluo group mainly regulated body energy metabolism by invigorating the spleen and supplementing Qi as well as warm-heat medicine. The whole formula focused on the multi-dimensional and multi-level mechanism of BMO in the intervention of white vein disease. Each functional group emphasized its respective characteristics in nervous system function， inflammation-immune regulation， and body energy metabolism. Two types of networks analysis models complemented and verified each other. Conclusion:BMO plays a role in the treatment of white vein disease mainly by regulating the function of nervous system， maintaining the balance of inflammation-immune system and interfering with energy metabolism. The relevant research results can provide reference for the in-depth exploration of the mechanism of BMO， and help to guide the clinical rational use of this preparation.
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Purpose To analyze the expression and prognostic value of metastasis-associated protein 2 (MTA2) in epithelial ovarian carcinoma. Methods The expression of MTA2 protein was examined in 91 paraffin-embedded specimens by immunohistochemical SP method, and in fresh specimens by Western blot, and then combined with follow-up data for prognosis analysis. Results There was an increasing tendency in positive rate of MTA 2 expression from benign ovarian cysts (17.5％) to epithelial ovarian cancers (78.43％), and there were significant difference (χ2=33.328, P<0.001). The expression of the MTA2 was significantly correlated to FIGO stage and lymph node metastasis (both P<0.05). The relative expression of MTA2 in benign ovarian cysts and epithelial ovarian cancers was 0.58±0.05, and 1.22±0.10, respectively, and the difference was statistically significant (t=-22.274, P<0.001). The survival curve of patients with MTA2 (+) differed from the survival curve of patients with MTA2 (-) and the difference was statistically significant (χ2=10.203, P<0.05). The multiple factor analysis revealed that the expression of MTA2, FIGO stage and lymph node metastasis were independent prognostic factors for clinical outcome of epithelial ovarian cancer. Conclusion MTA2 may be involved in the progression and metastasis of epithelial ovarian cancer as an oncogene. Overexpression of the marker indicates poor prognosis of patients.
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Increasing evidence suggests that epigenetic dysfunction may influence the stability of normal pregnancy.The ten-eleven translocation (TET) family and 5-hydroxymethylcytosine (5-hmC) were found to be linked with epigenetic reprogramming.The present study aimed to examine the expression of the TET family and 5-hmC in the villi of human embryos and compared their expression between normal pregnancy and early pregnancy loss (EPL).Embryonic villi were collected from normal pregnant women (control) experiencing medical abortion and from EPL patients at gestation ages of 6,7 and 8 weeks.The mRNAs of TET family were analysed using quantitative polymerase chain reaction (qPCR),and TET proteins using Western blotting and immunohistochemical analysis.The MethylFlashTM Kit was used to quantify the absolute amount of 5-methylcytosine (5-mC) and 5-hmC.Our results showed that the expression of the TETs and 5-hmC in the normal villus decreased with increasing gestational age.Immunohistochemistry revealed that the TET proteins were expressed in the cytoplasm of trophoblasts and their expression was the highest in the 6-week tissue samples,which was consistent with the qPCR and Western blot results.The expression of TET1,TET2,and TET3 was lower in the villi in EPL group than in normal pregnancy group (P＜0.05 for all).It was concluded that the TET family and 5-hmC are critical in epigenetic reprogramming of human embryo.The findings also suggest that a deficiency of TETs in the villus might be associated with human EPL.
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Increasing evidence suggests that epigenetic dysfunction may influence the stability of normal pregnancy.The ten-eleven translocation (TET) family and 5-hydroxymethylcytosine (5-hmC) were found to be linked with epigenetic reprogramming.The present study aimed to examine the expression of the TET family and 5-hmC in the villi of human embryos and compared their expression between normal pregnancy and early pregnancy loss (EPL).Embryonic villi were collected from normal pregnant women (control) experiencing medical abortion and from EPL patients at gestation ages of 6,7 and 8 weeks.The mRNAs of TET family were analysed using quantitative polymerase chain reaction (qPCR),and TET proteins using Western blotting and immunohistochemical analysis.The MethylFlashTM Kit was used to quantify the absolute amount of 5-methylcytosine (5-mC) and 5-hmC.Our results showed that the expression of the TETs and 5-hmC in the normal villus decreased with increasing gestational age.Immunohistochemistry revealed that the TET proteins were expressed in the cytoplasm of trophoblasts and their expression was the highest in the 6-week tissue samples,which was consistent with the qPCR and Western blot results.The expression of TET1,TET2,and TET3 was lower in the villi in EPL group than in normal pregnancy group (P＜0.05 for all).It was concluded that the TET family and 5-hmC are critical in epigenetic reprogramming of human embryo.The findings also suggest that a deficiency of TETs in the villus might be associated with human EPL.
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We report a case of in vitro fertilization and embryo transfer (IVF?ET) with oocyte donation in a woman with premature ovarian insufficiency (POI) complicated by systemic lupus erythematosus (SLE) during pregnancy. The patient had a diagnosis of POI 4 years earlier and 11 weeks after successful pregnancy by IVF?ET with oocyte donation in 2003, she presented with facial edema, and further examinations confirmed the diagnosis of lupus nephritis. She received treatment with prednisone to control the activity of SLE and aspirin and low?molecular?weight heparin to improve placental blood flow with close monitoring of gravida and fetus throughout pregnancy. The condition of the patient remained unstable during pregnancy, and liver damage and placental circulation disorder occurred in late gestational weeks with suspected intrauterine growth retardation (IUGR) of the fetus. For maternal and fetal safety, the patient received elective caesarean section and delivered a premature boy at 31 weeks of gestation. She subsequently received further medications for SLE and showed good recovery of the immunological parameters and absence of SLE symptoms during the follow?up for 14 years, indicating a clinical cure of SLE. Her son shows normal growth and development. Based on the experience with this case and literature review, we believe that immunological factor is an important cause of POI and thus recommend full immunological examinations in cases of idiopathic POI.
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<p><b>OBJECTIVE</b>To investigate the changes of pulmonary function and fractional exhaled nitric oxide (FeNO) in the standardized treatment of bronchial asthma in children.</p><p><b>METHODS</b>A total of 254 children who were newly diagnosed with acute exacerbation of bronchial asthma were selected as asthma group, and they were divided into two subgroups: asthma with concurrent rhinitis and asthma without concurrent rhinitis. All patients received the standardized management and treatment for one year. The pulmonary function parameters included forced expiratory volume in one second (FEV1), peak expiratory flow (PEF), maximal mid-expiratory flow (MMEF), and mid-expiratory flow at 25%, 50%, and 75% of vital capacity (MEF25, MEF50, and MEF75). The FeNO levels were measured before treatment and at 3, 6, 9, and 12 months after treatment. Another 62 healthy children were selected as the control group, and the pulmonary function and FeNO levels were measured only once.</p><p><b>RESULTS</b>During one year of standardized treatment, FEV1, PEF, MMEF, MEF25, MEF50, and MEF75 gradually increased, and FeNO levels gradually decreased (P<0.05). Indicators of large airway function, such as FEV1 and PEF, almost returned to normal after 6 months of treatment; indicators of small airway function, such as MMEF, MEF25, MEF50, and MEF75 almost returned to normal after 9 months of treatment; there were no significant differences in the above indices between the asthma group and the control group after one year of treatment (P>0.05). However, the asthma group had a significantly higher FeNO levels than the control group after one year of treatment (P<0.05). The asthmatic patients with concurrent rhinitis had significantly higher FeNO levels than those without concurrent rhinitis before treatment and 3 months after treatment (P<0.05). Before treatment, there was a significant negative correlation between FeNO levels and pulmonary function parameters (P<0.05).</p><p><b>CONCLUSIONS</b>With the standardized treatment of bronchial asthma in children, pulmonary function parameters gradually increase and FeNO levels gradually decrease. The recovery of large airway function occurs earlier than the recovery of small airway function. Furthermore, the effect of rhinitis on airway responsiveness should be noted.</p>
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Niño , Femenino , Humanos , Masculino , Asma , Terapéutica , Pruebas Respiratorias , Volumen Espiratorio Forzado , Pulmón , Flujo Espiratorio Medio Máximo , Óxido Nítrico , RinitisRESUMEN
The effects of pituitary suppression with one-third depot of long-acting gonadotropin-releasing hormone (GnRH) agonist in GnRH agonist long protocol for in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) were investigated. A retrospective cohort study was performed on 3186 cycles undergoing IVF/ICSI with GnRH agonist long protocol in a university-affiliated infertility center. The pituitary was suppressed with depot triptorelin of 1.25 mg or 1.875 mg. There was no significant difference in live birth rate between 1.25 mg triptorelin group and 1.875 mg triptorelin group (41.2% vs. 43.7%). The mean luteinizing hormone (LH) level on follicle-stimulating hormone (FSH) starting day was significantly higher in 1.25 mg triptorelin group. The mean LH level on the day of human chorionic gonadotrophin (hCG) administration was slightly but statistically higher in 1.25 mg triptorelin group. There was no significant difference in the total FSH dose between the two groups. The number of retrieved oocytes was slightly but statistically less in 1.25 mg triptorelin group than in 1.875 mg triptorelin group (12.90±5.82 vs. 13.52±6.97). There was no significant difference in clinical pregnancy rate between the two groups (50.5% vs. 54.5%). It was suggested that one-third depot triptorelin can achieve satisfactory pituitary suppression and produce good live birth rates in a long protocol for IVF/ICSI.
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Adulto , Femenino , Humanos , Embarazo , Regulación hacia Abajo , Fertilización In Vitro , Métodos , Hormona Folículo Estimulante , Sangre , Nacimiento Vivo , Hormona Luteinizante , Sangre , Hipófisis , Secreciones Corporales , Inyecciones de Esperma Intracitoplasmáticas , Métodos , Pamoato de Triptorelina , Farmacología , Usos TerapéuticosRESUMEN
<p><b>OBJECTIVE</b>To investigate the clinical outcomes in vitro fertilization or intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) in women aged over 40 years.</p><p><b>METHODS</b>We retrospectively analyzed 1050 non-donor IVF/ICSI-ET cycles performed from January, 2007 to December, 2015 in women at the age 40 years or above, including 393 women at 40 years of age, 266 at 41 years, 158 at 42 years, 107 at 43 years, 64 at 44 years, and 65 at 45-51 years. The clinical characteristics and outcomes of the women in different age groups were compared and analyzed. The pregnancy outcome of different ovarian stimulation protocols and different numbers of embryo transferred were also compared.</p><p><b>RESULTS</b>Oocyte retrieval was achieved in 1032 treatment cycles. Of the 750 embryo transfer cycles, the clinical pregnancy rate was 17.7% (113/750), and the live birth rate was 8.5% (64/750). The clinical pregnancy rate in the 5 age groups was 23.4%, 21.0%, 13.1%, 9.2%, 5.6% and 0%, and the implantation rate was 11.2%, 10.2%, 6.3%, 5.1%, 2.3% and 0%, respectively; the early spontaneous abortion rate was 31.0%, 35.9%, 42.9%, 42.9% and 100%, and the live birth rate was 11.9%, 11.8%, 2.8% and 3.9%. The clinical pregnancy rates of long protocol, short prorocol, GnRHa antagonist protocol, and ovulation induction protocol were 23.6%, 10.2%, 13.3%, and 2.3%, respectively. In the 750 transfer cycles, the clinical pregnancy rate was 3.8% with single embryo transfer, 12.6% with double embryos transfer, and 23.0% with 3 embryos transfer.</p><p><b>CONCLUSION</b>In women aged 40 years or above, the clinical pregnancy rate decreased significantly with age, and the live birth rate was extremely low in women aged beyond 44 years. Assisted reproductive technique is recommended for women aged 40 years and above even when no identifiable causes of sterility are present. For women aged above 44 years of age, oocyte donation may be a better option.</p>
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<p><b>OBJECTIVE</b>To analyze the incidence, management, and outcomes of monozygotic twin (MZT) pregnancy conceived by assisted reproductive techniques (ART).</p><p><b>METHODS</b>A retrospective analysis was performed of clinical pregnancies after in vitro fertilization and embryo transfer (IVF-ET) and introcytoplasmic sperm injection and embryo transfer (ICSI-ET) from January, 2010 to June 2015 at our center. We investigated the incidence, managements and outcomes of 94 MZT pregnancies. Comparison of the pregnancy outcomes was made between the expectantly managed MZT pregnancies, dizygotic twin (DZT) pregnancies, monozygotic (MZ)-triplet pregnancies with selective embryo reduction (SER) to 2 fetuses and 1 fetus, and non-MZ triplet pregnancies with SER to 2 fetuses.</p><p><b>RESULTS</b>Ninety-four MZT pregnancies occurred in the total of 6257 clinical pregnancy cycles with an incidence of 1.5%. No significant difference was found in the incidence of MZT pregnancies between IVF and ICSI cycles or between fresh and thawed cycles (P>0.05). Of the 94 MZT pregnancies, 45 were MZT pregnancy cycles, 43 were MZ-triplet pregnancy cycles, 3 were MZ-quadruplet pregnancy cycles and 3 were ectopic pregnancies. The expectantly managed MZT was associated with a significantly greater rate of miscarriage and malformation and a lower rate of live birth and term birth (P<0.05) in comparison with DZT pregnancy cycles that did not undergo SER. Similar outcomes were found between MZ-triplet pregnancies with SER to 2 fetuses and MZ-triplet pregnancies with SER to 1 fetus (P>0.05), and between MZ-triplets with SER to 2 fetuses and non-MZ triplet pregnancies with SER to 2 fetuses (P>0.05).</p><p><b>CONCLUSION</b>ART is associated with a much higher incidence of MZT pregnancies than spontaneous conception. MZT pregnancies are at high risk of adverse outcomes, and reduction of MZT in multiple pregnancies may help to improve the outcomes.</p>
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The effects of pituitary suppression with one-third depot of long-acting gonadotropin-releasing hormone (GnRH) agonist in GnRH agonist long protocol for in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) were investigated. A retrospective cohort study was performed on 3186 cycles undergoing IVF/ICSI with GnRH agonist long protocol in a university-affiliated infertility center. The pituitary was suppressed with depot triptorelin of 1.25 mg or 1.875 mg. There was no significant difference in live birth rate between 1.25 mg triptorelin group and 1.875 mg triptorelin group (41.2% vs. 43.7%). The mean luteinizing hormone (LH) level on follicle-stimulating hormone (FSH) starting day was significantly higher in 1.25 mg triptorelin group. The mean LH level on the day of human chorionic gonadotrophin (hCG) administration was slightly but statistically higher in 1.25 mg triptorelin group. There was no significant difference in the total FSH dose between the two groups. The number of retrieved oocytes was slightly but statistically less in 1.25 mg triptorelin group than in 1.875 mg triptorelin group (12.90±5.82 vs. 13.52±6.97). There was no significant difference in clinical pregnancy rate between the two groups (50.5% vs. 54.5%). It was suggested that one-third depot triptorelin can achieve satisfactory pituitary suppression and produce good live birth rates in a long protocol for IVF/ICSI.
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<p><b>OBJECTIVE</b>To explore the developmental potential of embryos at different developmental days and provide evidence for blastocyst culture of non-top quality cleavage stage embryos in frozen-thawed embryo transfer (FET) cycles.</p><p><b>METHODS</b>The clinical data of 687 FET cycles were retrospectively analyzed. According to the embryo freezing time, the patients were divided into day 5 (D5) blastocyst group (n=87), day 6 (D6) blastocyst group (n=111) and day 3 cleavage-stage embryo (D3) group (n=489) with hormone replacement cycles or natural cycles for endometrial preparation. The clinical pregnancy rates, miscarriage rates, and implantation rates were compared between the 3 groups.</p><p><b>RESULTS</b>The clinical pregnancy rate, miscarriage rate and implantation rate per transfer were 58.6%, 9.8%, and 42.9% in D5 group, 32.4%, 19.4%, and 23.3% in D6 group, and 44.9%, 16.4%, and 26.9% in D3 group, respectively. The clinical pregnancy rate and implantation rate were significantly higher in D5 group than in the other two groups (P<0.05).</p><p><b>CONCLUSION</b>The D5 blastocysts derived from non-top quality D3 embryos after cryopreservation can have better clinical outcomes than those derived from D3 cleavage-stage embryos and D6 blastocysts, and are therefore a better option than D3 cleavage-stage embryos in FET cycles.</p>
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Femenino , Humanos , Embarazo , Aborto Espontáneo , Blastocisto , Fase de Segmentación del Huevo , Criopreservación , Implantación del Embrión , Transferencia de Embrión , Índice de Embarazo , Estudios RetrospectivosRESUMEN
Objective: To investigate the effect of rapamycin (RAPA) on expression of nestin in osteosarcoma MG63 cells, and to explore its possible mechanism. Methods: The relative proliferation rate of MG63 cells treated with RAPA was determined by MTT assay. The expression levels of nestin mRNA and protein in MG63 cells were determined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting, respectively. The MG63 cells were pre-treated with extracellular signal-regulated kinase (ERK) inhibitor U0126, protein kinase B (PKB, Akt) inhibitor wortmannin, glycogen synthase kinase-3β (GSK-3β) inhibitor lithium chloride (LiCl) or transient transfection of small interfering RNA (siRNA) targeting GSK-3β and protein kinase A (PKA) inhibitor H89, and then treated with RAPA. The effects of the activities of ERK, Akt, GSK-3β and PKA on the expression of nestin induced by RAPA were examined by Western blotting. The effects of RAPA treatment on the activities of Akt and Gsk-3β [the ratio of phospho-Akt (p-Akt) to Akt and the ratio of p-Gsk-3β to Gsk-3β] were detected by Western blotting. Results: RAPA had no effect on relative proliferation rate of MG63 cells. The protein expression levels of nestin in MG63 cells treated with RAPA (100 nmol/L) for 48 h was 1.93 folds as high as that of the control group (P < 0.05). The mRNA expression levels of nestin in MG63 cells treated with RAPA (100 nmol/L) for 24 and 48 h were 1.89 and 1.84 folds as high as those of the control group, respectively (both P < 0.05). Akt inhibitor wortmannin promote the upregulation of nestin expression induced by RAPA, while GSK-3β inhibitor LiCl or GSK-3β-siRNA inhibited the upregulation of nestin expression induced by RAPA through interfering the expression of GSK-3β. U0126 and H89 did not have significant effect on nestin expression. The ratios of p-Akt to Akt were decreased by 21% and 63% after treatment with RAPA for 24 and 48 h, respectively; while the ratios of p-GSK-3β to GSK-3β were decreased by 26% and 42%, respectively. Conclusion: RAPA increases the expression of nestin in MG63 cells by inhibiting the activity of Akt and increasing the activity of GSK-3β.
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This study examined the misdiagnosis and delayed diagnosis factors for ectopic pregnancy (EP) and heterotopic pregnancy (HP) after in vitro fertilization and embryo transfer (IVF-ET) in an attempt to reduce the diagnostic error. Clinical data of patients who underwent IVF-ET treatment and had clinical pregnancy from 12463 cycles were retrospectively analyzed. Their findings of serum β-hCG test and transvaginal ultrasonography were also obtained during follow-up. These patients were divided into two groups according to the diagnosis accuracy of EP/HP: early diagnosis and misdiagnosis/delayed diagnosis. The results showed that the incidence of EP and HP was 3.8% (125/3286) and 0.8% (27/3286) respectively for IVF/ICSI-ET cycle, and 3.8% (55/1431) and 0.7% (10/1431) respectively for frozen- thawed embryo transfer (FET) cycle. Ruptured EP occurred in 28 patients due to initial misdiagnosis or delayed diagnosis. Related factors fell in 3 categories: (1) clinician factors: misunderstanding of patients' medical history, insufficient training in ultrasonography and unawareness of EP and HP; (2) patient factors: noncompliance with medical orders and lack of communication with clinicians; (3) complicated conditions of EP: atypical symptoms, delayed elevation of serum β-hCG level, early rupture of cornual EP, asymptomatic in early gestation and pregnancy of unknown location. All the factors were interwoven, contributing to the occurrence of EP and HP. It was concluded that complicated conditions are more likely to affect the diagnosis accuracy of EP/HP after IVF-ET. Transvaginal ultrasonography should be performed at 5 weeks of gestation. Intensive follow-up including repeated ultrasonography and serial serum β-hCG tests should be performed in patients with a suspicious diagnosis at admission.
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This study examined the misdiagnosis and delayed diagnosis factors for ectopic pregnancy (EP) and heterotopic pregnancy (HP) after in vitro fertilization and embryo transfer (IVF-ET) in an attempt to reduce the diagnostic error. Clinical data of patients who underwent IVF-ET treatment and had clinical pregnancy from 12463 cycles were retrospectively analyzed. Their findings of serum β-hCG test and transvaginal ultrasonography were also obtained during follow-up. These patients were divided into two groups according to the diagnosis accuracy of EP/HP: early diagnosis and misdiagnosis/delayed diagnosis. The results showed that the incidence of EP and HP was 3.8% (125/3286) and 0.8% (27/3286) respectively for IVF/ICSI-ET cycle, and 3.8% (55/1431) and 0.7% (10/1431) respectively for frozen- thawed embryo transfer (FET) cycle. Ruptured EP occurred in 28 patients due to initial misdiagnosis or delayed diagnosis. Related factors fell in 3 categories: (1) clinician factors: misunderstanding of patients' medical history, insufficient training in ultrasonography and unawareness of EP and HP; (2) patient factors: noncompliance with medical orders and lack of communication with clinicians; (3) complicated conditions of EP: atypical symptoms, delayed elevation of serum β-hCG level, early rupture of cornual EP, asymptomatic in early gestation and pregnancy of unknown location. All the factors were interwoven, contributing to the occurrence of EP and HP. It was concluded that complicated conditions are more likely to affect the diagnosis accuracy of EP/HP after IVF-ET. Transvaginal ultrasonography should be performed at 5 weeks of gestation. Intensive follow-up including repeated ultrasonography and serial serum β-hCG tests should be performed in patients with a suspicious diagnosis at admission.
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Adulto , Femenino , Humanos , Embarazo , Gonadotropina Coriónica Humana de Subunidad beta , Sangre , Diagnóstico Tardío , Errores Diagnósticos , Transferencia de Embrión , Fertilización In Vitro , Estudios de Seguimiento , Embarazo Ectópico , Diagnóstico , Embarazo Heterotópico , Diagnóstico , Estudios Retrospectivos , Factores de Tiempo , Ultrasonografía , MétodosRESUMEN
This study explored the cumulative live birth rate after three ovarian stimulation in vitro fertilization (IVF) cycles for poor ovarian responders according to the Bologna criteria. In this retrospective cohort study, 479 poor ovarian responders according to the Bologna criteria in the first ovarian stimulation IVF cycle between July 2006 and January 2012 in our IVF centre were included. The cumulative live birth rate was calculated by optimistic and pessimistic methods. The cumulative live birth rate after three ovarian stimulation IVF cycles for poor ovarian responders according to the Bologna criteria was 12.7%-20.5%. The three-cycle cumulative live birth rate was 18.5%-24.5%, 13.2%-27.4% and 8.6%-14.9% for poor responders aged ≤35 years, 36-39 years and ≥40 years, respectively. In conclusion, poor responders according to the Bologna criteria can receive an acceptable cumulative live birth rate after three ovarian stimulation IVF cycles, especially poor responders aged <40 years.
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This study explored the cumulative live birth rate after three ovarian stimulation in vitro fertilization (IVF) cycles for poor ovarian responders according to the Bologna criteria. In this retrospective cohort study, 479 poor ovarian responders according to the Bologna criteria in the first ovarian stimulation IVF cycle between July 2006 and January 2012 in our IVF centre were included. The cumulative live birth rate was calculated by optimistic and pessimistic methods. The cumulative live birth rate after three ovarian stimulation IVF cycles for poor ovarian responders according to the Bologna criteria was 12.7%-20.5%. The three-cycle cumulative live birth rate was 18.5%-24.5%, 13.2%-27.4% and 8.6%-14.9% for poor responders aged ≤35 years, 36-39 years and ≥40 years, respectively. In conclusion, poor responders according to the Bologna criteria can receive an acceptable cumulative live birth rate after three ovarian stimulation IVF cycles, especially poor responders aged <40 years.
Asunto(s)
Adulto , Femenino , Humanos , Persona de Mediana Edad , Embarazo , Adulto Joven , China , Epidemiología , Fertilización In Vitro , Infertilidad Femenina , Epidemiología , Terapéutica , Nacimiento Vivo , Epidemiología , Inducción de la Ovulación , Resultado del TratamientoRESUMEN
This study was aimed to investigate the expression of cdx2 gene in pediatric patients with acute leukemia and its clinical implication. The bone marrow and peripheral blood were collected from 33 newly diagnosed pediatric patients with acute leukemia, the cdx2 gene expression in each AL subtypes and normal controls was detected by RT-PCR, the relationship between cdx2 expression and response to treatment was observed. The results showed that the expression of cdx2 was positive in 25 out of 30 AL cases (83.3%), to be exact, in 20 of 21 ALL cases (95.2%) and in 5 of 9 AML cases (55.6%), which showed statistical difference (p < 0.05). The cdx2 mRNA could be detected also in 1 of 3 CML cases. However, no expression of cdx2 was observed in all normal control which revealed significant difference between patient group and normal control group. 21 AL patients with cdx2 positive expression (17 ALL and 4 AML patients) and 4 AL patients with cxd2 negative expression (1 ALL and 3 AML patients) all reached complete remission (CR) after treatment, which showed no correlation with CR rate. 8 patients with positive cdx2 expression were followed up. As a result, the cdx2 positive expression at initial diagnosis of patients remained positive at reaching CR, but it gradually turned to negative along with prolonging of CR, while the cdx2 negative expression at initial diagnosis of patients remained negative at CR in bone marrow level. It is concluded that cdx2 positive expression is observed in the majority of pediatric AL patients, even positive rate in ALL patients is higher than that in AML patients, while the cdx2 expression also can be observed in CML patients. The cdx2 positive expression is not related to the CR rate in AL patients.