Using preoperative control nutritional status scores as prognostic factors for endometrial cancer.

Background: Previous investigations have reported that controlling nutritional (CONUT) status scores, incorporating total cholesterol (TC) and serum albumin (SA) values, and total lymphocyte (LY) counts, are reliable malignant tumor predictors. However, CONUT scores for predicting endometrial cancer (EC) remain unexplored. Objective: To evaluate preoperative CONUT scores as prognostic factors for postoperative EC. Methods: We retrospectively evaluated preoperative CONUT scores in 785 surgically resected EC patients at our hospital between June 2012 and May 2016. Using time-dependent receiver operating characteristic (ROC) analyses, patients were split into: 1) CONUT-high (CH) (≥1) and 2) CONUT-low (CL) (<1) groups. Relationships between CONUT scores and different clinicopathological, pathological differentiation, muscle layer infiltration depth, and prognosis factors were examined, and Cox regression analyses performed to assess prognostic values on overall survival (OS) rates. Results: We assigned 404 (51.5%) and 381 (58.5%) patients to CH and CL groups, respectively. In the CH group, body mass index (BMI), prognostic nutrition index (PNI), and LY/monocyte ratios (LMR) were decreased, however, neutrophil/LY (NLR) and platelet/LY ratios (PLR) were increased. Pathological differentiation analyses showed that G1 proportions were higher in the CL group, while G2 and G3 proportions were more prevalent in the CH group. Muscle layer infiltration depth in CL patients was < 50%, while that it was ≥50% in the CH group. No significant differences in OS rates were recorded between CH and CL groups over 60 months. However long-term survival (LTS) rates after 60 months in the CH group were significantly lower when compared with the CL group, and was more obvious in type II EC patients. Also, periuterine infiltration and preoperative CONUT scores were independent prognostic factors for OS rates as indicated by multi-factor analyses. Conclusion: CONUT scores not only facilitated the estimation of nutritional status, but were highly beneficial for predicting OS rates in patients with EC after curative resection. CONUT scores provided high predictive values for LTS rates over 60 months in these patients.

The safety of echo contrast-enhanced ultrasound in high-intensity focused ultrasound ablation for abdominal wall endometriosis: a retrospective study.

BACKGROUND: We aimed to investigate the efficacy and safety of echo contrast-enhanced ultrasound (CEUS) during high-intensity focused ultrasound (HIFU) ablation therapy for abdominal wall endometriosis (AWE). METHODS: A total of 67 patients with AWE were treated with HIFU ablation, and their demographic characteristics were retrospectively analysed. Blood perfusion of the focal lesion was assessed before the operation, during ablation and after the operation with the use of an ultrasound contrast agent, and the effect of the ultrasound contrast agent on treatment was assessed over a 1-year follow-up period. The degree of symptom relief and adverse effects were evaluated after HIFU ablation. RESULTS: Eighty-two lesions were ablated in 67 patients. CEUS showed that all lesions were successfully ablated with HIFU. The shrinkage ratio of the lesions significantly increased over the follow-up period. Intermittent pain disappeared at 1 month after the operation, and the patients' pain scores significantly decreased at the 1-year follow-up. The mean [± standard deviation (SD)] lesion volume was 7.64±8.95 cm3 on B-mode ultrasound. The post-HIFU non-perfused volume was 18.34±24.08 cm3, and the rate of massive changes on greyscale imaging was 96.16%±5.44% at 12 months. During the procedure, the main complications were a prickling sensation and tenderness in the treatment area and/or a transient "hot" sensation on the skin. After the procedure, there was no obvious discomfort except for pain. Two patients developed an approximately 1-cm area of skin that exhibited a waxy appearance. Seven patients had haematuria. No severe complications were observed. CONCLUSIONS: Ultrasound contrast agents are effective and safe for evaluating the effect of HIFU ablation on AWE, and this approach provides significant guidance and evaluation benefits for the use of HIFU treatment for AWE without obvious side effects.

Comparison of Laparoscopic Myomectomy with and without Uterine Artery Occlusion in Treatment of Symptomatic Multiple Myomas.

OBJECTIVE: Uterine artery occlusion (UAO) is a minimally invasive approach often used to treat symptomatic uterine myomas. This study aimed to compare the clinical effects of laparoscopic UAO (LUAO) in combination with laparoscopic myomectomy (LM) with LM alone to treat symptomatic multiple uterine myomas. METHODS: This was a prospective observational study. In total, 122 patients with symptomatic multiple uterine myomas underwent LUAO + LM or LM alone between April 2015 and October 2017. The surgical procedure time, blood loss, highest postoperative temperature, hospital length of stay, number of removed myomas, surgical complications, and recurrence rate of the two groups were compared. RESULTS: Mean blood loss was significantly lower in the LUAO + LM group compared with the LM group (177.97 ± 104.09 mL vs 258.10 ± 119.55 mL, p < 0.05). No significant difference in surgical procedure time, hospital length of stay, highest postoperative temperature, and surgical complications was found between the LUAO + LM group and LM group. The number of removed myomas was considerably higher in the LUAO + LM group than in the LM group (4[4-7] vs 3[3-5], p < 0.05). The recurrence rate in the LUAO + LM group was considerably lower than that in the LM group (6.2% vs 25.9%). CONCLUSION: LUAO in combination with LM was associated with higher surgical quality and lower recurrence of myomas compared with LM alone. LUAO in combination with LM is recommended for women with symptomatic multiple uterine myomas who wish to retain their uteruses.

Effects of different vaginal mould use approaches after vaginoplasty with artificial dermis in patients with Mayer-Rokitansky-Küster-Hauser syndrome.

OBJECTIVE: To assess the therapeutic effects of different vaginal mould use approaches after vaginoplasty in patients with Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome. METHODS: Patients with MRKH syndrome who underwent surgery from 2010 to 2015 in our hospital were retrospectively evaluated. Vaginoplasty was performed with artificial dermis, and vaginal moulds were used for 6 months postoperatively. The patients were divided into an intermittent group and continuous group according to the vaginal mould approach. RESULTS: Thirty-five patients were evaluated (intermittent group, 19 patients; continuous group, 16 patients). One month postoperatively, the mean vaginal length and width in the intermittent group were 9.26 ± 0.56 and 3.82 ± 0.25 cm, respectively, and those in the continuous group were 9.44 ± 0.51 and 3.86 ± 0.22 cm, respectively. Six months postoperatively, the mean vaginal length and width in the intermittent group were 8.94 ± 0.71 and 3.76 ± 0.26 cm, respectively, and those in the continuous group were 8.69 ± 0.48 and 3.65 ± 0.30 cm, respectively. The mean Female Sexual Function Index scores in the intermittent and continuous groups were 28.61 ± 0.71 and 28.4 80 ±0.79 respectively, after normal sexual life. CONCLUSION: Both intermittent and continuous use of postoperative vaginal moulds may be effective.

Retracted: Pleuromutilin Inhibits Proliferation and Migration of A2780 and Caov-3 Ovarian Carcinoma Cells and Growth of Mouse A2780 Tumor Xenografts by Down-Regulation of pFAK2.

Some cells or groups of cells in figures appear to be visible multiple times. Because the manuscript contains non-credible results this journal is retracting the above publication. Reference: Bo Zhang, Xiaoli Ma, Yuan Li, Sijing Li, Jiumei Cheng: Pleuromutilin Inhibits Proliferation and Migration of A2780 and Caov-3 Ovarian Carcinoma Cells and Growth of Mouse A2780 Tumor Xenografts by Down-Regulation of pFAK2. Med Sci Monit, 2020; 26: e920407. DOI: 10.12659/MSM.920704.

Comprehensive Identification of the Human Secretome as Potential Indicators in Treatment Outcome of HPV-Positive and -Negative Cervical Cancer Patients.

BACKGROUND: The aim of this work was to explore the novel and promising biomarkers for the diagnosis and prognosis of cervical cancer patients. METHODS: The secretome of primary cervical tissues was extracted and then determined by the LC-MS/MS assay. The level of screened targets was confirmed using the RT-PCR and ELISA in cervical cancer tissue samples. The median expression level of certain targets was used as a cutoff value to divide the patients into 2 groups, and then the patients were followed up. The predictive abilities of the targets on the prognosis were further studied. RESULTS: LC-MS/MS, together with bioinformatic analysis, demonstrated that totally 95 targets were dysregulated in cervical cancer. Among them, ECM2, KLK6, and MASP1 were increased in cervical cancer in a stage-dependent manner, whereas FGA was negatively associated with the stage of cervical cancers. Overall survival (OS) and disease-free survival (DFS) rates were significantly decreased in the KLK6 high group, whereas little difference was found between the high and low groups of other 3 cases. Univariate analysis of the 5-year OS and DFS revealed a significantly worse outcome for patients with KLK6 high tumors. In multivariate analysis, KLK6 remained a highly significant prognostic marker for OS and DFS. Combined survival analysis of KLK6 expression and the HPV infection revealed that KLK6highHPV(-) predicted the most poor OS rate and the KLK6lowHPV(+) group showed the best prognosis. CONCLUSION: Through the secretome analysis, we identified a series of secreted proteins differentially expressed in the clinical cancer, among which KLK6 has the potential to become a promising biomarker for the diagnosis and prognosis of cervical cancer patients.

Prospective Evaluation of the Accuracy of A Training Program in Image Recognition by Narrow-Band Imaging Guided Hysteroscopy of Endometrial Neoplasms.

INTRODUCTION: Narrow-band imaging (NBI) hysteroscopy by experienced hysteroscopists (EH) is useful for diagnosing endometrial neoplasms. OBJECTIVE: We investigated whether the diagnostic reliability of NBI could be improved by specific professional training. METHODS: Three levels of trainees who were Surgeons at our hospital were selected. Level I: 6 trainees had no prior hysteroscopic experience; level II: 6 trainees had experience with <100 cases; and level III: 6 trainees had <500 cases. The two-hour training program for white light hysteroscopy (WLH) and NBI included information on the classifications of diseases of the uterine cavity and on the features of diagnostic images. Images from 529 patients were evaluated independently by trainees with 3 levels of before and after training, and by EH. Trainees and EHs had to analyze and arrive at a hysteroscopic diagnosis for each image that was compared to the pathological diagnosis for diagnostic accuracy. RESULTS: After training, all levels achieved higher diagnostic accuracy with NBI than was seen with WLH. Level III trainees achieved diagnostic accuracy and kappa values for NBI that were equivalent to those of EH. CONCLUSIONS: Training can increase the diagnostic skill of all trainees using NBI, especially for trainees with prior hysteroscopic experience.

Pleuromutilin Inhibits Proliferation and Migration of A2780 and Caov-3 Ovarian Carcinoma Cells and Growth of Mouse A2780 Tumor Xenografts by Down-Regulation of pFAK2.

BACKGROUND Pleuromutilin is a natural tricyclic, derived from the fungus, Pleurotus mutilus. This study aimed to investigate the effects of pleuromutilin on migration and proliferation of A2780 and Caov-3 human ovarian carcinoma cells and the growth of A2780 tumor xenografts in mice and the molecular mechanisms involved. MATERIAL AND METHODS A2780 and Caov-3 human ovarian carcinoma cells were cultured with and without 40, 160, and 200 µM of pleuromutilin. The Edu fluorescence assay, the wound-healing assay, and Matrigel were used to measure A2780 and Caov-3 cell proliferation, migration, invasion, and adhesion in vitro, respectively. Western blot measured protein levels of FAK, p-FAK, MMP-2, and MMP-9. A2780 cells were injected subcutaneously into mice to determine the effects of pleuromutilin on the growth of tumor xenografts. RESULTS Pleuromutilin significantly reduced A2780 and Caov-3 cell proliferation at 48 h in a dose-dependent manner (P<0.05), and at 200 µM, pleuromutilin reduced cell proliferation by 21.43% and 23.65%, respectively. Treatment of A2780 cells with pleuromutilin significantly reduced cell migration, invasion, and adhesion and the expression of p-FAK, MMP-2, and MMP-9 compared with untreated controls. In the mouse tumor xenograft model, treatment with pleuromutilin significantly reduced tumor size compared with the untreated group and inhibited tumor metastasis to the intestine, spleen, and peritoneal cavity. CONCLUSIONS In A2780 and Caov-3 human ovarian carcinoma cells, pleuromutilin inhibited cell proliferation, migration, invasion, and adhesion in a dose-dependent manner, and reduced tumor growth and metastases in a mouse A2780 cell tumor xenograft model.

[Diagnose and treatment of post-cesarean section scar diverticulum by hysteroscopy combined ultrasonography and laparoscopy].

OBJECTIVE: To investigate the application of hysteroscopy combined ultrasonography and laparoscopy in the diagnose and treatment of post-cesarean section scar diverticulum (PCSD). METHODS: From March 2011 to February 2013, 27 patients with PCSD were diagnosed and treated in Beijing Obstetrics and Gynecology Hospital. All patients were diagnosed by hysteroscopy and ultrasonography. Treatment protocols were decided by the thickness of the diverticulum. The clinical data of all patients were analysed fully. RESULTS: (1) All patients were diagnosed by hysteroscopy combined ultrasound, of which only 17 cases were diagnosed by preoperative ultrasound, the coincidence rate was 63% (17/27). (2) The thickness of diverticulum was measured by hysteroscopy combined ultrasound. Thickness of less than 3 mm in 19 cases, were treated by hysteroscopy combined with laparoscopy diverticulectomy repair; no less than 3 mm in 8 cases, were used hysteroscopy diverticulum incision. (3) The effective rate was 7/8 after hysteroscopy, and which was 16/19 after laparoscopy combined with hysteroscopy surgery. There was no difference in the treatment effect (P=0.663). The ineffective rate was 1/8 after hysteroscopy, and which was 3/19 after laparoscopy combined with hysteroscopy surgery. The size of the PCSD was smaller and the thickness of diverticulum was thicker than preoperation in the later one, which has no difference in the former one. CONCLUSIONS: (1) Hysteroscopy combined ultrasound is an accurate method for the diagnose of PCSD. (2) According to the thickness of the diverticulum operation method is choosed, which is beneficial to reduce the trauma, and relieve symptoms. (3) Diverticulum poor positioning and incomplete resection are the main causes of postoperative recurrence of the diverticulum.

[Study of ultrastructural features of myocytes in uterine junctional zone].

OBJECTIVE: To study the ultrastructural features of myocytes in uterine junctional zone (JZ). METHODS: From August 2010 to August 2013, there were 16 pre-menopause patients who suffered from cervical neoplasm to be performed hysterectomy. Samples of JZ and outer myometrium (OM) of hysterectomy specimens were collected. There were 8 specimens from the proliferative-phase and 8 specimens from the secretory-phase of endometrium. Ultrastructural features of JZ and OM were examined by using transmission electron microscopy and the related indices of myocytes were compared by using Student's t test. RESULTS: At JZ, there were more cytoplasmic process in the myocytes. The myocytes of JZ exhibited significant difference compared with those of OM. Firstly, the contractile structural components, such as the dense patches, dense bodies and the myofilaments were less abundant. In contrast, the perinuclear cell organelles were more distinct. The mitochondria, endoplasmic reticulum and Golgi apparatus were more prominent, denoting active protein synthesis. Secondly, the mean diameter of cell and nuclei demonstrated cyclic change. In proliferative phase of endometrium, the cell diameters of JZ and OM were (4.70±0.52) and (4.69±1.20)µm, respectively, which there were no significant difference (P = 0.987). While in secretory phase, the cell diameters of JZ and OM were (3.75±0.36)and (4.92±0.51)µm, which there were significant difference (P = 0.006). In proliferative phase, the nuclei diameters of JZ and OM were (3.24±0.41) and (2.90±0.62)µm, and in secretory phase, the nuclei diameters of JZ and OM were (2.44±0.27) and (2.92±0.44)µm. There were no significantly different in both phases (P = 0.374, P = 0.097). The diameters of cell and nuclei had cyclical changes (P < 0.05). However, the cyclical changes were absent in OM (P > 0.05). Thirdly, the myofilaments/cytoplasm ratio of JZ in proliferative and secretory phases were 0.27±0.04 and 0.34±0.03, which were significantly less than those of OM in respective phases (0.49±0.03 and 0.±0.03; P = 0.000, P = 0.000). The myofilaments/cytoplasm ratio exhibited cyclical changes in JZ (P = 0.029), but in OM, the cyclical changes were absent (P = 0.083). CONCLUSIONS: Compared with OM, ultrastructures associated with synthetic organelles are prominent, whereas the contractile organelles are reduced. And there are the cyclical changes in ultrastructural characteristics. The ultrastructural features of JZ are the basis of its physiology.

The impact of preoperative gonadotropin-releasing hormone agonist treatment on women with uterine fibroids: a meta-analysis.

AIM: The objectives of this study were to evaluate the efficacy of gonadotropin-releasing hormone agonist (GnRHa) treatment before surgery for women with uterine fibroids and to explore potential factors predicting the pooled effect sizes. METHODS: A meta-analysis was performed from published randomized controlled trials using the random effects model. The efficacy of preoperative treatment with GnRHa was investigated according to volume measurements of fibroid tumors, postoperative complications, myoma recurrence, and changes in fertility. Metaregression and subgroup analysis were used to identify potential predictors of the effect sizes. RESULTS: A total of 26 studies were selected for the meta-analysis. Preoperative GnRHa therapy for women with uterine fibroids was associated with a smaller preoperative volume of fibroid tumors, increased hemoglobin and hematocrit levels, reductions in preoperative pelvic symptoms and the vertical incision rate, and a higher proportion of patients undergoing a vaginal procedure. No differences were observed in postoperative complications, myoma recurrence, and changes in fertility in the GnRHa-treated patients compared with patients treated with placebo or alternative clinical agents. The metaregression suggested that age, the duration of GnRHa treatment, the type of control group, and the type of surgery were important predictors of the efficacy of preoperative GnRHa treatment. CONCLUSIONS: Preoperative GnRHa treatment for women with uterine fibroids reduces preoperative fibroid size and increases hemoglobin and hematocrit levels. Gonadotropin-releasing hormone agonist pretreatment reduces preoperative pelvic symptoms and the rate of vertical incision and results in a higher chance of patients to receive a vaginal procedure, without significant difference in postoperative complications when comparing with other preoperative treatments. The patients' age, duration of GnRHa treatment, agents selected as control, and types of surgical procedures serve as predictors of the efficacy of preoperative GnRHa treatment.

Hysteroscopic and laparoscopic management of uterine defects on previous cesarean delivery scars.

OBJECTIVE: To examine the treatment of previous cesarean delivery scar defect after cesarean delivery and the feasibility of laparoscopic uterine repair or hysteroscopic scar excision. STUDY DESIGN: A retrospective clinical study that took place from June 2009 to March 2013 and included 41 women who had previously had cesarean deliveries. RESULTS: Seventeen women underwent a laparoscopic approach for the repair of scar diverticula, and 24 women underwent a hysteroscopic resection of fibrotic tissue overhanging underneath the diverticula. Most women remained free of symptoms over a 3- to 16-month follow-up and 6 women became pregnant without pregnancy complications. CONCLUSION: Women with a history of cesarean delivery combined with irregular perimenstrual bleeding should undergo combined hysteroscopy and ultrasound examination to detect latent scar defects. In diagnosed cases, in those who desired future pregnancies and had a residual myometrial thickness of <3.5 mm or a defect that accounted for ≥50% of the anterior uterine wall, laparoscopic surgical repair was performed with good postoperative anatomic outcomes. Women with residual myometrial thickness of ≥3.5 mm or a defect that accounted for <50% of the anterior uterine wall were treated with hysteroscopic surgery and had a relief of symptoms.

Treatment options to terminate persistent cesarean scar pregnancy.

AIMS: Persistent Cesarean scar pregnancy (PCSP) is a rare and special type of Cesarean scar pregnancy (CSP) which is resistant to conservative treatment. The treatment option is challenging. We report a case series to provide indications for further treatment. METHODS: Ten women diagnosed as having a PCSP, seeking better treatment because of primary treatment failure, were admitted to a gynecologic minimally invasive center. Ultrasound combined with office hysteroscopy was used for preoperative evaluation, and then a further surgical strategy was selected. Clinical data were retrospectively studied. RESULTS: Among ten PCSP patients, 4 were type I and 6 were type II. In the 4 type I cases, 2 were treated by laparoscopy and the other 2 by hysteroscopy; to stop bleeding in 1 of them, the uterine artery was occluded laparoscopically. All type II cases were successfully treated by laparoscopic excision. The mean operating time was 61.5 min. The mean blood loss was 83.5 ml. No complications occurred except one intraoperative hemorrage. CONCLUSIONS: Experience from this case series indicates that an individualized surgical plan based on a full preoperative evaluation provides useful information for choosing a suitable treatment for PCSP. Endoscopically guided surgical excision with experienced hands may be considered the most useful treatment.

[Clinical analysis of conversion from gynecological laparoscopic surgery to laparotomy].

OBJECTIVE: To discuss the causes and clinical significance of conversion to laparotomy during laparoscopic surgery. METHOD: Three thousand two hundred and three cases who underwent laparoscopic surgery during the past five years were analyzed retrospectively. RESULTS: Three thousand one hundred and eighty cases underwent laparoscopic surgery, in which 23 cases were converted to laparotomy due to factors including severe pelvic adhesions (6 cases), complex disease with difficulties in laparoscopy (7 cases), massive haemorrhage (3 cases), bladder trauma (1 case), gastric trauma (1 case), intestinal trauma (1 case), as well as unexpected malignant genitalia neoplasm (4 cases). CONCLUSION: The major causes for the conversion to laparotomy during gynecology laparoscopic surgery are severe pelvic adhesion and complex disease with difficulties in laparoscopy. Careful evaluation before surgery and conversion to laparotomy at the right moment can decrease the complication.

[Analysis on the complications of hysteroscopic surgeries].

OBJECTIVE: To investigate the causations, management and prevention methods on the complications of hysteroscopic procedures. METHODS: Retrospective analysis of 36 cases with hysteroscopic complication, focusing on their characteristics and clinical management as well as prevention methods during the ten years from 1993 to 2004. RESULTS: Among 36 cases, 11 cases with uterine perforation and incomplete perforation, which happened during the complicated procedures, were treated by both laparoscopy and laparotomy. Five cases with heavy bleeding were encountered because of the deeply injury to the uterine wall and Foley catheter was inserted into uterine cavity and it stopped the bleeding successfully except in one case done by hysterectomy. Three cases with fluid overload syndrome were cured by using diuretic agent and saline infusion. There is no serious consequence in one case with air embolism due to prompt diagnosis and treatment. Four cases with postablation-sterilization syndrome were treated effectively by performing hysterectomy plus single or bilateral salpingectomy, dilating cervical canal as well as resecting adhesions. Twelve cases with adhesion inside uterine cavity followed hysteroscopy were also treated by dilating cervical canal, underwent adhesionlysis and hysterectomy. CONCLUSIONS: The potential factors causing complications of hysteroscopy include complicated procedures inside uterine cavity, higher pressure of irrigation, deep injury of endometrium as well as incomplete removal of endometrium during hysteroscopic operations. It is the necessary measures to reduce the complications by performing laparoscopy or B ultrasound monitoring simultaneously, standardizing the procedure and strengthening postoperation management.

[Analysis of the efficiency of transcervical resection of endometrium for treating dysfunctional uterine bleeding and factors reducing the efficiency of the operation].

OBJECTIVE: To investigate the efficiency and factors related to the recurrence of transcervical resection of endometrium (TCRE) in treating women with dysfunctional uterine bleeding (DUB). METHODS: Two hundred and twenty women with DUB were selected for TCRE. Specimens from removed endometrium were obtained during the procedures and their menstruation and menorrhagia after the operations were followed up. We also studied the uterine specimens obtained from the recurrent cases undergoing hysterectomies. The specimens were stained by hematoxylin-eosin and immuno-histochemistry respectively to evaluate the depth of removed myometrium and the histopathologic changes in relapsed cases. RESULTS: The follow up period after operation was 24 to 114 months. (1) Overall effective rate was 94.5%, in which amenorrhea rate was 25.9%, menstruation reduction rate was 68.6%. (2) The effective rate of corrective anemia was 97.3% and the satisfaction rate for the operation was 92.3%. (3) Thirty-eight cases required subsequent treatment as a result of recurrence, of which 10 cases underwent hysterectomy and 3 cases underwent repeat TCRE and 25 cases were given medicine treatment. (4) The average depth of myometrium in removed endometrium strip was 2.12 approximately 3.26 mm. (5) Endometrium regrowth was seen in the resected uterine specimens from relapsed cases and adenomyosis was also found in the intra-uterine wall in some cases. CONCLUSIONS: (1) TCRE is a safe and effective alternative treatment for DUB. (2) The main factor reducing the efficiency is either incomplete removal of endometrium or adenomyosis. (3) Standardizing the procedures and strengthening postoperative management are essential requirements for improving the efficiency of TCRE.