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Objective: To compare the prognosis and perioperative situation of patients with stage Ⅱ endometrial cancer (EC) between radical hysterectomy/modified radical hysterectomy (RH/mRH) and simple hysterectomy (SH). Methods: A total of 47 patients diagnosed EC with stage Ⅱ [International Federation of Gynecology and Obstetrics (FIGO) 2009] by postoperative pathology, from January 2006 to January 2021 in Peking University People's Hospital, were analyzed retrospectively. The patients were (54.4±10.7) years old, and the median follow-up time was 65 months (ranged 9-138 months). They were divided into RH/mRH group (n=14) and SH group (n=33) according to the scope of operation. Then the prognosis of patients between the groups were compared, and the independent prognostic factors of stage Ⅱ EC were explored. Results: (1) The proportions of patients with hypertension in RH/mRH group and SH group were 2/14 and 45% (15/33), the amounts of intraoperative blood loss were (702±392) and (438±298) ml, and the incidence of postoperative complications were 7/14 and 15% (5/33), respectively. There were significant differences (all P<0.05). (2) The median follow-up time of RH/mRH group and SH group were 72 vs 62 months, respectively (P=0.515). According to Kaplan-Meier analysis and log-rank method, the results showed that there were no significant difference in 5-year progression-free survival (PFS) rate (94.3% vs 84.0%; P=0.501), and 5-year overall survival rate (92.3% vs 92.9%; P=0.957) between the two groups. Cox survival analysis indicated that age, pathological type, serum cancer antigen 125 (CA125), and estrogen receptor (ER) status were associated with 5-year PFS rate (all P<0.05). But the scope of hysterectomy (RH/mRH and SH) did not affect the 5-year PFS rate of stage Ⅱ EC patients (P=0.508). And level of serum CA125 and ER status were independent prognostic factors for 5-year PFS rate (all P<0.05). Conclusions: This study could not find any survival benefit from RH/mRH for stage Ⅱ EC, but increases the incidence of postoperative complications. Therefore, the necessity of extending the scope of hysterectomy is questionable.
Subject(s)
Female , Humans , Adult , Middle Aged , Aged , Disease-Free Survival , Retrospective Studies , Neoplasm Staging , Prognosis , Endometrial Neoplasms/pathology , Hysterectomy/methods , Postoperative Complications/epidemiology , Uterine Cervical Neoplasms/pathologyABSTRACT
Local anesthetic drugs are commonly used to block the conduction function of patient's nerves temporarily for anesthesia during surgery or to provide targeted analgesia after trauma. Compared with general anesthetics, local anesthetics makes less impact on the physiological status and alleviates pain complications in the presence of clear consciousness. However, its clinical application is still limited by its systemic toxicity, as well as toxicity to nerves and muscles, duration of action and lack of penetration. Nanotechnology can help it penetrate the physiological barrier, prolong the time of nerve block, and reduce toxic side effects. In addition, by building a light-responsive release system, local anesthetics can be released on demand, enhancing drug effectiveness and safety. However, in addition to the problems of poor consistency and high production costs, the system of light response release is still limited in application due to the limitation of the depth of penetration of the tissue. According to the current research progress, this paper briefly introduces and analyzes the main dosage forms, hoping to provide new ideas for the responsive release of local anesthetic drugs.
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Objective: To investigate the relationships between molecular types of the cancer genome atlas (TCGA) of patients with endometrial carcinoma (EC) and lymph node metastasis and other clinicopathological features. Methods: The clinical pathological information of 295 patients with EC who underwent initial inpatient surgical treatment and accepted the detection of the molecular types of TCGA with next-generation sequencing technology at Peking University People's Hospital were collected during April 2016 and May 2022. The TCGA molecular typing of EC was divided into four types: POLE-ultramutated (15 cases), high microsatellite instability (MSI-H; 50 cases), copy-number low (CNL; 175 cases), and copy-number high (CNH; 55 cases). The differences of clinical pathological features among different molecular types and the risk factors of lymph node metastasis were analyzed retrospectively. Results: Among 295 patients with EC, the average age was (56.9±0.6) years. (1) There was a statistically significant difference in lymph node metastasis (0, 8.0%, 10.3% and 25.5%) among the four molecular types (χ2=12.524, P=0.006). There were significant differences in age, stage, pathological type, grade (only endometrioid carcinoma), myometrium invasion, lymphatic vascular space infiltration, and estrogen receptor among the EC patients of four molecular types (all P<0.05). Among them, while in the patients with CNH type, the pathological grade was G3, the pathological type was non-endometrioid carcinoma, and the proportion of myographic infiltration depth ≥1/2 were higher (all P<0.05). (2) Univariate analysis suggested that pathological type, grade, myometrium infiltration depth, cervical interstitial infiltration, lymphatic vascular space infiltration, and progesterone receptor were all factors which significantly influence lymph node metastasis (all P<0.01); multivariate analysis suggested that the lymphatic vascular space infiltration was an independent risk factor for lymph node metastasis (OR=5.884, 95%CI: 1.633-21.211; P=0.007). (3) The factors related to lymph node metastasis were different in patients with different molecular types. In the patients with MSI-H, the non-endometrioid carcinoma of pathological type was independent risk factor for lymph node metastasis (OR=29.010, 95%CI: 2.067-407.173; P=0.012). In the patients with CNL, myometrium infiltration depth≥1/2 (OR=4.995, 95%CI: 1.225-20.376; P=0.025), lymphatic vascular space infiltration (OR=14.577, 95%CI: 3.603-58.968; P<0.001) were the independent risk factors for lymph node metastasis. While in the CNH type patients pathological type of non-endometrioid carcinoma (OR=7.451, 95%CI: 1.127-49.281; P=0.037), cervical interstitial infiltration (OR=22.938, 95%CI: 1.207-436.012; P=0.037), lymphatic vascular space infiltration (OR=9.404, 95%CI: 1.609-54.969; P=0.013), were the independent risk factors for lymph node metastasis. Conclusions: POLE-ultramutated EC patients have the lowest risk of lymph node metastasis, and CNH patients have the highest risk of lymph node metastasis. The risk factors of lymph node metastasis of different molecular types are different. According to preoperative pathological and imaging data, lymph node metastasis is more likely to occur in patients with non-endometrioid carcinoma in MSI-H and CNH type patients, and lymph node metastasis is more likely to occur in patients with myometrium infiltration depth ≥1/2 in CNL type patients.
Subject(s)
Female , Humans , Middle Aged , Carcinoma, Endometrioid/pathology , Endometrial Neoplasms/pathology , Lymph Node Excision , Lymph Nodes/pathology , Lymphatic Metastasis/pathology , Neoplasm Staging , Retrospective Studies , Risk Factors , Risk Assessment , Molecular TypingABSTRACT
Objective: To explore the effects of preoperative hysteroscopic guided biopsy and segmental diagnosis and curettage on the risk of abdominal dissemination and prognosis of non-endometrioid carcinoma. Methods: The clinical and pathological data of 97 patients who underwent surgical treatment and were pathologically confirmed as non-endometrioid carcinoma (including serous carcinoma, clear cell carcinoma, mixed adenocarcinoma, and undifferentiated carcinoma, etc.) from October 2008 to December 2021 in Peking University People's Hospital, were collected for retrospective analysis. According to preoperative diagnostic methods, they were divided into hysteroscopic group (n=44) and non-hysteroscopic group (n=53). The impact of hysteroscopy examination on peritoneal cytology and prognosis was analyzed. Results: (1) There were no statistical differences in age, body mass index, tumor size, pathological characteristics, and treatment methods between the hysteroscopic group and the non-hysteroscopic group (all P>0.05), but the proportion of stage Ⅰ-Ⅱ patients in the hysteroscopic group was significantly higher than that in the non-hysteroscopic group [68% (30/44) vs 47% (25/53); χ2=4.32, P=0.038]. (2) Among 97 patients, 25 (26%, 25/97) of them were cytologically positive for ascites. The hysteroscopic group had a lower positive rate of peritoneal cytology than that in the non-hysteroscopy group, which was significantly different [11% (5/44) vs 38% (20/53); χ2=8.74, P=0.003]. Stratification according to surgical and pathological stages showed that the positive rate of peritoneal cytology in the hysteroscopic group (3%, 1/30) was lower than that in the non-hysteroscopic group (12%, 3/25) in the 55 patients with stage Ⅰ-Ⅱ, and that in the hysteroscopic group (4/14) was also lower than that in the non-hysteroscopic group (61%, 17/28) in the 42 patients with stage Ⅲ-Ⅳ. There were no significant differences (all P>0.05). (3) The 5-year disease-free survival (DFS) rate of the hysteroscopic group and the non-hysteroscopic group were respectively 72.7% and 60.4%, and there was no significant difference between the two groups (P=0.186). After stratification according to staging, the 5-year DFS rate were respectively 90.0% and 72.0% (P=0.051) between the hysteroscopic and non-hysteroscopic groups of patients in stage Ⅰ-Ⅱ, and 35.7% and 50.0% (P=0.218) between the hysteroscopic and non-hysteroscopic groups of patients in stage Ⅲ-Ⅳ, in which there were not statistically significant differences. The 5-year overall survival (OS) rate were respectively 86.4% and 81.1% between the hysteroscopic group and the non-hysteroscopic group, with no significant difference between the two groups (P=0.388). The 5-year OS rate were respectively 93.3% and 96.0% in the hysteroscopic group and non-hysteroscopic group for patients with stage Ⅰ-Ⅱ(P=0.872), and 71.4% and 67.9% in the hysteroscopic group and non-hysteroscopic group in patients with stage Ⅲ-Ⅳ (P=0.999), with no statistical significance. Conclusions: Diagnostic hysteroscopy do not increase the rate of positive peritoneal cytology result at the time of surgery in this cohort, and no significant correlation between preoperative hysteroscopy examination and poor prognosis of non-endometrioid carcinoma is observed. Therefore, preoperative hysteroscopic guided biopsy and segmental diagnosis and curettage in non-endometrioid carcinoma maybe safe.
Subject(s)
Female , Pregnancy , Humans , Endometrial Neoplasms/pathology , Retrospective Studies , Hysteroscopy/methods , Cell Biology , Prognosis , Carcinoma , Neoplasm StagingABSTRACT
Objective: To compare the efficacy between percutaneous coronary intervention (PCI) and conservative medication treatment in chronic total occlusions (CTO) patients. Methods: It was a meta-analysis.Articles on drug therapy and PCI for complete coronary artery occlusion were retrieved from Pubmed, Embase and Web of Science databases. The search time was from the database construction to May 10, 2020, and the following search criteria were used for the search "chronic total occlusion" "percutaneous coronary intervention" and "medical therapy". References from searched literatures were also searched to identify more eligible studies. Randomized controlled trials (RCT) and cohort studies comparing efficacy of PCI versus oral medication as well as medication as initial therapy option for CTO patients with single or multiple lesions were included. The primary endpoints included all-cause death, cardiac death, recurrent myocardial infarction, re-revascularization, major adverse cardiac events (MACE) and stroke. Data were analyzed with ReviewManager5.3.0 software. Pooled effect size RR and 95%CI were calculated by randomization effect model. Heterogeneity was evaluated by I2. Bege test was used to evaluate publication bias. Subgroup analyses were performed for RCT and cohort studies. Results: A total of 1 079 articles were retrieved and 16 studies (RCT=4, cohort study=12) were included with 12 223 patients. Fourteen publications (RCT=4, cohort study=10) reported all-cause death post PCI and/or drug therapy. Results showed that risk of all-cause death was significantly lower in PCI group than in drug therapy group (RR=0.45,95%CI 0.39-0.53,P<0.001);subgroup analysis showed that risk of all-cause death was significantly lower in PCI group than in drug therapy group from cohort studies (RR=0.44,95%CI 0.38-0.52,P<0.001),but comparable in RCT (P=0.27). Thirteen studies (RCT=3, cohort study=10) reported cardiac death post PCI and/or drug therapy. Results showed that risk of cardiac death was significantly lower in PCI group than in drug therapy group (RR=0.44,95%CI 0.35-0.55,P<0.001);subgroup analysis showed that risk of cardiac death was significantly lower in PCI group than in drug therapy group in cohort studies (RR=0.43,95%CI 0.34-0.54,P<0.001),but not in RCT (P=0.25). Fourteen publications (RCT=4, cohort study=10) reported recurrent myocardial infarction post PCI and/or drug therapy. Results showed that risk of recurrent myocardial infarction was significantly lower in PCI group than in drug therapy group (RR=0.62,95%CI 0.44-0.88,P=0.007);subgroup analysis showed that risk of recurrent myocardial infarction was significantly lower in PCI group than in drug therapy group from cohort studies (RR=0.56,95%CI 0.40-0.78,P=0.000 5),but comparable in RCT (P=0.17). Fourteen publications (RCT=4, cohort study=10) reported re-revascularization post PCI and/or drug therapy. Results showed that risk of re-revascularization was comparable between PCI group and drug therapy group (P=0.91);subgroup analysis showed that risk of re-revascularization was comparable between PCI group and drug therapy group both in cohort study and RCT (P=0.60 and 0.41, respectively). Eleven publications (RCT=3, cohort study=8) reported MACE post PCI and/or drug therapy. Results showed that risk of MACE was significantly lower in PCI group than in drug therapy group (RR=0.74,95%CI 0.59-0.93,P=0.03);subgroup analysis showed that risk of MACE was significantly lower in PCI group than in drug therapy group in cohort studies (RR=0.72,95%CI 0.56-0.93,P=0.01), but not in RCT (P=0.8). Six publications (RCT=2, cohort study=4) reported stroke post PCI and/or drug therapy. Results showed that risk of stroke was comparable between PCI and drug therapy groups (RR=0.62,95%CI 0.32-1.20, P=0.15);subgroup analysis showed that risk of stroke was comparable between PCI and drug therapy groups both in cohort studies and RCT (P=0.48 and 0.32, respectively). Conclusion: Compared with oral drug therapy, PCI may have better efficacy for CTO patients based on results from this cohort study.
Subject(s)
Humans , Conservative Treatment/adverse effects , Death , Myocardial Infarction/complications , Percutaneous Coronary Intervention/methods , Stroke , Treatment OutcomeABSTRACT
BACKGROUND@#After radical hysterectomy for cervical cancer, the most common complication is lower urinary tract symptoms. Post-operatively, bladder capacity can alter bladder function for a prolonged period. This study aimed to identify factors affecting bladder storage function.@*METHODS@#A multicenter, retrospective cohort study was conducted. Information of patients with stages IA2 to IIB cervical cancer with urodynamic study results were retrospectively collected from nine hospitals between June 2013 and June 2018 according to the inclusion criteria. Demographic, surgical, and oncological data were collected. The univariate and multivariate logistic regression was used to identify clinical factors associated with bladder storage function.@*RESULTS@#Two hundred and three patients with cervical cancer had urodynamic testing post-operatively. Ninety-five (46.8%) patients were diagnosed with stress urinary incontinence (SUI). The incidence of low bladder compliance (LBC) was 23.2%. Twenty-seven (13.3%) patients showed detrusor overactivity (DO). Fifty-seven patients (28.1%) presented with a decreased maximum cystometric capacity (DMCC). The probability of composite bladder storage dysfunction was 68.0%. Multivariate analysis confirmed that laparoscopy represents a protective factor for SUI with an odds ratio of 0.498 (P = 0.034). Patients who underwent a nerve-sparing procedure were less odds to experience SUI (P = 0.014). A significant positive correlation between LBC and DO was observed (P < 0.001). A greater length of the resected vagina and chemoradiotherapy were common risk factors for LBC and DO, while radiotherapy exerted a stronger effect than chemotherapy. Additionally, patients who received chemoradiotherapy frequently developed a DMCC. The follow-up time was not correlated with bladder storage function.@*CONCLUSION@#A nerve-sparing procedure without longer resected vagina is recommended for protecting the bladder storage function.
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Objective: To investigate the protective role of alprostadil on aortic dissection. Methods: 26 C57BL6 male mice were divided into control group (normal drinking water, n=13) and model group (1 g·kg-1·d-1 BAPN via drinking water, n=13). On day 14, mRNA expression of inflammatory-related genes as well as EP receptor families were detected by RT-PCR (n=6 each) and EP4 protein levels were determined by Western blot (n=7 each). Another 88 mice were divided into 3 groups: control group (n=22), model group (n=33) and treatment group (n=33). The mice in model group and treatment group were applied with BAPN (1 g·kg-1·d-1) via drinking water. The mice in treatment group received additional intraperitoneal injection with alprostadil (80 μg·kg-1·d-1) for 28 days. The mice in the control and model group received equal volume intraperitoneal injection with 0.9% saline respectively. The body weight and systolic blood pressure, the mortality and morbidity were monitored from the beginning until the designed end of the study. On day 28, the mice were sacrificed and aorta were fixed, embedded and sliced, followed by staining with HE and Victoria Blue. The distribution of EP4 was determined by immunohistochemistry in control (n=6) and model group (n=6). Furthermore, the concentration of PGE1 were tested among model (n=3) and treatment group (n=4). EP4 protein expression was determined in model group (n=7) and treatment group (n=6). Results: On day 14, mRNA expression level of MCP-1 ((2.74±1.55) vs. (1.00±0.49),<0.05) and MMP2((1.38±0.42) vs. (1.00±0.27), P<0.05) was significantly upregulated in model group compared with control group. Protein expression of EP4 receptor also increased in aorta in model group compared with control group (1.48±0.51 vs. 1.00±0.19, P<0.05). In the dissection area, the EP4 expression was also enriched compared with non-dissection area, particularly in endothelial cells and inflammatory cells on day 28. BAPN applied in drinking water (model and treatment groups) successfully induced the aortic dissection in mice, some mice died of the rupture. The elastic fibers were fractured, and the infiltrated immune cells were visible in dissected tissue. False lumen was formed. There was no dissection and death in the control group. Compared with control group, the morbidity and mortality rates were significantly increased in the model group (60.6%, 20/33, 30.3%, 10/33) and the treatment group (72.7%, 24/33, 24.2%, 8/33). The mortality and morbidity rates were similar between model and treatment groups. There is no difference in terms of SBP among three groups (P>0.05). Further study showed that after alprostadil injection, the blood concentration of PGE1 was increased in treatment group ((0.540±0.041 vs. 0.436±0.012)μmol/L, P<0.05). Besides, the EP4 receptor expression was downregulated in the treatment group compared to model group (0.60±0.30 vs. 1.00±0.20, P<0.05). Conclusion: EP4 expression is upregulated in BAPN induced aortic dissection mouse model. No protective effects are observed post alprostadil treatment in this model probably due to the reduced expression of EP4.
Subject(s)
Animals , Male , Mice , Alprostadil , Aminopropionitrile , Aortic Dissection , Disease Models, Animal , Endothelial CellsABSTRACT
Background@#Fusion genes may play an important role in tumorigenesis, prognosis, and drug resistance; however, studies on fusion genes in endometrial cancer (EC) are rare. This study aimed to identify new fusion genes and to explore their clinical significance in EC.@*Methods@#A total of 28 patients diagnosed with EC were enrolled in this study. RNA sequencing was used to obtain entire genomes and transcriptomes. STAR-comparison and STAR-fusion prediction were applied to predict the fusion genes. Chi-square tests and Student t tests were used to verify the clinical significance with SPSS 13.0 software.@*Results@#New fusion genes were found, and the number of fusion genes varied from 3 to 110 among all patients with EC. The type of fusion genes varied and included messenger RNA (mRNA)-mRNA, long non-coding RNA (lncRNA)-lncRNA, and lncRNA-mRNA. There were six fusion genes with high fusion rates, namely, RP11–123O10.4–GRIP1, RP11–444D3.1–SOX5, RP11– 680G10.1–GSE1, NRIP1–AF127936.7, RP11–96H19.1–RP11–446N19.1, and DPH7–PTP4A3. Further studies showed that these fusion genes are related to stage, grade, and recurrence, in which NRIP1–AF127936.7 and DPH7–PTP4A3 were found only in stage III patients with EC. DPH7–PTP4A3 was found in grades 2 and 3, and recurrent patients with EC.@*Conclusion@#Fusion genes play an essential role in EC. Six genes that are overexpressed with high fusion rates are identified. NRIP1– AF127936.7 and DPH7–PTP4A3 might be related to stage, and DPH7–PTP4A3 be related to grade and recurrence.
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BACKGROUND@#Fusion genes may play an important role in tumorigenesis, prognosis, and drug resistance; however, studies on fusion genes in endometrial cancer (EC) are rare. This study aimed to identify new fusion genes and to explore their clinical significance in EC.@*METHODS@#A total of 28 patients diagnosed with EC were enrolled in this study. RNA sequencing was used to obtain entire genomes and transcriptomes. STAR-comparison and STAR-fusion prediction were applied to predict the fusion genes. Chi-square tests and Student t tests were used to verify the clinical significance with SPSS 13.0 software.@*RESULTS@#New fusion genes were found, and the number of fusion genes varied from 3 to 110 among all patients with EC. The type of fusion genes varied and included messenger RNA (mRNA)-mRNA, long non-coding RNA (lncRNA)-lncRNA, and lncRNA-mRNA. There were six fusion genes with high fusion rates, namely, RP11-123O10.4-GRIP1, RP11-444D3.1-SOX5, RP11-680G10.1-GSE1, NRIP1-AF127936.7, RP11-96H19.1-RP11-446N19.1, and DPH7-PTP4A3. Further studies showed that these fusion genes are related to stage, grade, and recurrence, in which NRIP1-AF127936.7 and DPH7-PTP4A3 were found only in stage III patients with EC. DPH7-PTP4A3 was found in grades 2 and 3, and recurrent patients with EC.@*CONCLUSION@#Fusion genes play an essential role in EC. Six genes that are overexpressed with high fusion rates are identified. NRIP1-AF127936.7 and DPH7-PTP4A3 might be related to stage, and DPH7-PTP4A3 be related to grade and recurrence.
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Aim To demonstrate that bigelovii E,one of the triterpenoid compounds isolated from Salicornia bigelovii Torr. ,induced apoptosis and inhibited prolif-eration of human breast cancer cells MCF-7. Methods MTT and Clonogenic were used to detect the anti-proliferative effect of bigelovii E on human tumor cells. Hoechst 33258 staining was used to observe the chan-ges of cell morphology in the treatment with bigelovii E. The effect of bigelovii E on cell apoptosis,cell mi-tochondrial membrane potential and the ROS level was analyzed by flow cytometry. The expression of mito-chondrial apoptotic pathway and its regulated proteins were analyzed by Western blot. Results Bigelovii E was most sensitive to MCF-7;bigelovii E had lower toxicity to normal cells HLF1;bigelovii E inhibited the colony formation of breast cancer MCF-7;the apoptosis pattern induced by bigelovii E was detected by Hoechst 33258;Western blot showed that bigelovii E could down-regulate the phosphorylation of mTOR,p70S6K and 4-EBP,up-regulate the expression of Bcl-xl and Mcl-1 proteins,promote the mitochondrial apoptosis pathway,reduce the mitochondrial membrane poten-tial,and induce ROS,leading to mitochondrial func-tion damage,and ultimately inducing apoptosis. Con-clusion Bigelovii E regulates mitochondrial apoptosis pathway through mTOR pathway,induces apoptosis and has a good anti-tumor effect.
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The (anaphylactoid) hypersensibility mechanism of ″imprinting templates″ characteristics of traditional Chinese medicine (TCM) injection supramolecules was clarified to lay the foundation to build safety evaluation method. Based on the previous publication on special impact of Chinese medicine theories on supramolcular chemistry, combined with the natural origination of (anaphylactoid) hypersensitized special rules as well as the sensitization phenomenon of cordate houttuynia injection, the impact of the structure characteristics of ″imprinting templates″ in TCM injection supramolecules on its (anaphylactoid) hypersensibility was clarified. In Chinese medicine injections, the supramolecular structures can independently be generated, showing overall apparent (anaphylactoid) hypersensibility nature, and their structure characteristics were dependent on the strength. In addition, (anaphylactoid) hypersensitive critical supramolecular structure was present. When it was administrated by ″injection″, it's structure was not easy to be destroyed, often showing apparent immunogenicity, whereas if it was administrated by ″oral″, the structure would be destroyed by the gastrointestinal tract, showing weaker or no apparent immunogenicity. Therefore, there are differences in (anaphylactoid) hypersensibility between ″injection″ and ″oral″ administration of TCM. TCM injections would produce the supramolecules between ″molecular society″ by independent reaction of supramolecular ″imprinting template″ (chemical determinants), showing apparent immune process of recognition, copying, and storage. Single molecule is a special example for this. The screening of anaphylactoid (sensitinogen) includes the single ingredients and their forming supramolecules for TCM injection. This is the unique feature for safety evaluation of Chinese medicine injection.
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<p><b>OBJECTIVE</b>To investigate the mechanism of new bone formation in the distraction osteogenesis (DO) for correction of cleft palate (CP) in rhesus.</p><p><b>METHODS</b>CP was created by operation in 23 rhesus. The CP was corrected with DO in 21 animals as experimental group. The distraction rate was 0.8 mm per day, two times a day. The bone fragments were fixed after cleft closure, every 3 animals were sacrificed to get specimen after 1, 2, 4, 6, 8, 12, 24 weeks of fixation. 6 days before sacrifice, tetracycline was administrated for labeling (30 mg/kg).</p><p><b>RESULTS</b>The hard and soft tissue def of fixation. At the same time, the bone volume and calcification between the distraction gap increased. The cleft in the control group could not b ect was successfully closed with DO by intramembrane osteogenesis. The new formed bone was remodeling and became maturation during the period e corrected spontaneously.</p><p><b>CONCLUSIONS</b>The DO can successfully correct both the soft and hard tissue defect in CP by intramembrane osteogenesis. The fixation is important for remodeling and maturation of the new formed bone.</p>
Subject(s)
Animals , Biomarkers , Cleft Palate , Pathology , General Surgery , Macaca , Osteogenesis, Distraction , Palate, Hard , Pathology , Palate, Soft , PathologyABSTRACT
<p><b>OBJECTIVE</b>To study the expression and distribution of bone morphogenetic protein (BMP) in newly formed bone by distraction osteogenesis (DO), and to explore the mechanism of the DO bone formation and remodeling.</p><p><b>METHODS</b>The cleft palate (CP) experimental animal models (23 Rhesus monkeys) were established surgically. In experimental group (21 Rhesus monkeys), the palatal defects were corrected by means of DO at the rhythm of 0.4 mm twice per day. The specimens were retrieved under euthanasia at 1, 2, 4, 6, 8, 12, 24 weeks intervals respectively in retention period. BMP immunohistochemical study was then performed. The blank control and experimental group (each of 2 animals) were set for comparison study.</p><p><b>RESULTS</b>The immunohistochemical study showed that BMP existed mainly in cytoplasma of osteoblasts, during the process of new bone formation. In early stage of 1 or 2 weeks, abundant osteoblasts aggregating on surfaces of the new bone trabeculae with positive DAB dye were observed. Through 4 to 6 weeks, the proliferative osteoblasts with very strong positive DAB dye indicating BMP expression were recorded. From 8 to 12 weeks, the expression of BMP and quantity of osteoblasts decreased gradually while more matured new bone structures were observed.</p><p><b>CONCLUSION</b>During the whole retention period, the expression of BMP showed a tendency from weak to strong and then to final cessation, this indicated a process of formation, remodeling and maturation of osteogenesis.</p>
Subject(s)
Animals , Bone Morphogenetic Proteins , Metabolism , Cleft Palate , Metabolism , General Surgery , Macaca mulatta , Osteogenesis, DistractionABSTRACT
<p><b>OBJECTIVE</b>To study the ultrastructure and Ca/P element spectrometry of distraction osteogenesis (DO) for reconstruction of cleft palate (CP), so as to explore the osteogenesis and remodeling of new bone in situ.</p><p><b>METHODS</b>23 rhesus macaques were operated to establish animal models of CP. 2 monkeys didn't received DO as controls. The other 21 monkeys in experimental group underwent DO to correct both bony and soft tissue defects in palate. The distraction was performed at a rate of 0.8 mm/d, twice a day until the cleft was closed. After fixation for 1, 2, 4, 6, 8, 12, 24 weeks, every 3 animals were sacrificed to get the specimens at the distraction gap. The scanning electron microscopic study and Ca, P elements spectrometric analysis were adopted. There were also two unoperated animals as sham group.</p><p><b>RESULTS</b>After fixation for 1-2 weeks, the distraction gap was full of collagen fibers oriented along vector of distraction. Few trabeculae was seen at the margin area. After fixation for 4-6 weeks, active osteogenesis was presented with new formed bone trabeculae and abundant cellular component. After fixation for 8-12 weeks, the new formed bone became mature and couldn't distinguish from the normal bone. 24 weeks later, the bone between the distraction gap had a similar structure to the normal bone. Elements spectrometric analysis results indicated that in early stage of osteogenesis, the P and S peaks were relatively high while the Ca peak was much lower. During the late stage, the S peak was obviously decreased, and Ca/P ratio increased to normal level as in the empty control group.</p><p><b>CONCLUSIONS</b>The CP can be corrected by DO. The new bone between the distraction gap is formed and remodeled through intramembraneous osteogenesis.</p>
Subject(s)
Animals , Female , Male , Cleft Palate , Metabolism , Pathology , General Surgery , Disease Models, Animal , Macaca mulatta , Microscopy, Electron, Scanning , Osteogenesis , Osteogenesis, Distraction , Methods , Palate , General SurgeryABSTRACT
<p><b>OBJECTIVE</b>To study the mechanism of new bone formation and remodeling of distraction osteogenesis (DO) by analysis of the expression of osteopontin (OPN) and osteocalcin (OC).</p><p><b>METHODS</b>Rhesus were operated to reconstruct the animal model of cleft palate (CP). The CP was closed by DO in experimental group(n = 21). After consolidation of 1, 2, 4, 6, 8, 12, 24 weeks, every 3 animals were killed to collect the specimens, respectively. The OPN and OC and their mRNA were detected quantitatively by Real-time RT-PCR and ELISA, respectively. The animals in control group (n = 2) and sham group (n = 2) were used as control.</p><p><b>RESULTS</b>The mRNA expression of OPN increased since 2nd week of consolidation and reached the peak at 4th week (7.59 +/- 0.37). The mRNA expression of OC was up-regulated since 4th week, and reach the peak at 6th week (7.94 +/- 0.31). Then they decreased to about the level in sham group at 24th week (P > 0.05). The OPN and OC were highly expressed during 4 to 6 weeks of consolidation. During 8 to 12 weeks, they decreased like their mRNA expression.</p><p><b>CONCLUSION</b>The intramembraneous new bone formation after DO can reconstruct the bone defect of CP. The new formed bone can be remodeled to be quite normal bone tissue.</p>
Subject(s)
Animals , Cleft Palate , Metabolism , General Surgery , Macaca mulatta , Osteocalcin , Metabolism , Osteogenesis, Distraction , Osteopontin , MetabolismABSTRACT
<p><b>OBJECTIVE</b>To investigate the osteogenesis mechanism by analysis of the expression of insulin-like growth factor-I (IGF-1) and alkaline phosphatase (ALP) in the reconstruction of cleft palate (CP) with distraction osteogenesis (DO) in rhesus.</p><p><b>METHODS</b>The CP animal models were established surgically. 21 rhesus in experimental group underwent DO to close the soft and bony defect, followed by consolidations. Every 3 animals were killed and the specimen were taken out after consolidation of 1, 2, 4, 6, 8, 12, 24 weeks. The mRNA of IGF-1 and ALP were detected with Real-time RT-PCR technique. The expression of IGF-1 and ALP was quantitatively analyzed by ELISA. The results were compared with those in control and sham groups (each of 2 animals), respectively.</p><p><b>RESULTS</b>Since consolidation, the mRNA of IGF-1 and ALP increased significantly at one week and reached the peak at two weeks, but decrease to control level after 12 weeks of consolidation. The expression of IGF-1 also increased to peak level after two weeks of consolidation. The expression of ALT increased significantly since consolidation and reach the peak value after six weeks. They all decreased to nearly control level after 8-12 weeks.</p><p><b>CONCLUSIONS</b>The palate cleft can be successfully closed with new formed bone after DO. The mechanism of bone consolidation is intramembranous bone formation.</p>
Subject(s)
Animals , Alkaline Phosphatase , Metabolism , Bone Regeneration , Cleft Palate , Metabolism , General Surgery , Insulin-Like Growth Factor I , Metabolism , Macaca , Osteogenesis, Distraction , Postoperative PeriodABSTRACT
Objective To analyze if there are membrane estrogen receptors(ER)in endometrial carcinoma and if there is some relationship between membrane ER and nuclear ER.Methods The cell membrane and total cell ER?and ER?expressions of high and moderate differentiation endometrial carcinoma cells(Ishikawa and HEC-1A cells)were analyzed.Intermittent immunofluorescence dyeing and fluorescent microscopy were carried out with the ceils treated with polyformaldehyde and Triton X-100. Intermittent immunofluorescence dyeing and flow cytometry were carried out with the live cells and the cells treated with Triton X-100 respectively.Results There were fluorescences on the membrane of the Ishikawa and HEC-1A cells which were treated with polyformaldehyde.When the cells were treated with Triton X- 100,the fluorescences were also seen inside the cells.The fluorescence intensity of ER?and ER?in Ishikawa cell membrane(1.09?0.21,1.27?0.33)was stronger than the control,but there were no significant differences(P>0.05).When treated with Triton X-100,the total cell fluorescence intensity of ER?and ER?in Ishikawa cell(4.21?0.34,4.69?1.96)was stronger than the membrane(P<0.05). The ER?and ER?fluorescence intensity of HEC-1A cell membrane(1.58?0.13,1.49?0.04)were stronger than the control(P<0.05).The fluorescence intensity of ER?and ER?of the HEC-1A cell (2.34?0.33,2.52?0.15)was stronger than the membrane also(P<0.05).The membrane ER?fluorescence intensity of Ishikawa was lower than HEC-1A(P=0.028).But the total cell ER?fluorescence intensity of Ishikawa was higher than HEC-1A(P=0.002).Conclusions There are membrane ER on endometrial carcinoma cells Ishikawa and HEC-1A.The membrane ER must have some similarity to the nuclear receptor.There is no direct correlation between the quantity of the membrane ER and nuclear ER.