Integrin αV mediated activation of myofibroblast via mechanoparacrine of transforming growth factor ß1 in promoting fibrous scar formation after myocardial infarction.

BACKGROUND: Myocardial infarction (MI) dramatically changes the mechanical stress, which is intensified by the fibrotic remodeling. Integrins, especially the αV subunit, mediate mechanical signal and mechanoparacrine of transforming growth factor ß1 (TGF-ß1) in various organ fibrosis by activating CFs into myofibroblasts (MFBs). We investigated a possible role of integrin αV mediated mechanoparacrine of TGF-ß1 in MFBs activation for fibrous reparation in mice with MI. METHODS: Heart samples from MI, sham, or MI plus cilengitide (14 mg/kg, specific integrin αV inhibitor) treated mice, underwent functional and morphological assessments by echocardiography, and histochemistry on 7, 14 and 28 days post-surgery. The mechanical and ultrastructural changes of the fibrous scar were further evaluated by atomic mechanics microscope (AFM), immunofluorescence, second harmonic generation (SHG) imaging, polarized light and scanning electron microscope, respectively. Hydroxyproline assay was used for total collagen content, and western blot for protein expression profile examination. Fibroblast bioactivities, including cell shape, number, Smad2/3 signal and expression of extracellular matrix (ECM) related proteins, were further evaluated by microscopic observation and immunofluorescence in polyacrylamide (PA) hydrogel with adjustable stiffness, which was re-explored in fibroblast cultured on stiff matrix after silencing of integrin αV. The content of total and free TGF-ß1 was tested by enzyme-linked immunosorbent assay (ELISA) in both infarcted tissue and cell samples. RESULT: Increased stiffness with heterogeneity synchronized with integrin αV and alpha smooth muscle actin (α-SMA) positive MFBs accumulation in those less mature fibrous areas. Cilengitide abruptly reduced collagen content and disrupted collagen alignment, which also decreased TGF-ß1 bioavailability, Smad2/3 phosphorylation, and α-SMA expression in the fibrous area. Accordingly, fibroblast on stiff but not soft matrix exhibited obvious MFB phenotype, as evidenced by enlarged cell, hyperproliferation, well-developed α-SMA fibers, and elevated ECM related proteins, while silencing of integrin αV almost abolished this switch via attenuating paracrine of TGF-ß1 and nuclear translocation of Smad2/3. CONCLUSION: This study illustrated that increased tissue stiffness activates CFs into MFBs by integrin αV mediated mechanoparacrine of TGF-ß1, especially in immature scar area, which ultimately promotes fibrous scar maturation.

Predictors of Infused Distending Fluid Volume in Hysteroscopic Myomectomy.

Background and Objectives: The use of a bipolar resectoscope has become popular due to the lower risk of hyponatremia. However, gynecologists might overlook the risk of water intoxication. Water intoxication is associated with the infusion of distending fluid. We were interested in the prediction of the infused distending fluid volume in the era of bipolar hysteroscopy. Thus, the aim of this study was to identify the predictors of the infused distending fluid volume for hysteroscopic myomectomy. Materials and Methods: All consecutive women who underwent monopolar (n = 45) or bipolar (n = 137) hysteroscopic myomectomy were reviewed. Results: Myoma diameter (cm, coefficient = 680 mL, 95% confidence interval (CI) = 334-1025 mL, p <0.001) and bipolar hysteroscopy (coefficient = 1629 mL, 95% CI = 507-2752 mL, p = 0.005) were independent predictors of infused distending fluid volume. A myoma diameter ≥4.0 cm was the optimal cutoff value to predict the presence of >5000 mL of infused distending fluid. One woman in the bipolar group developed life-threatening water intoxication. Conclusions: Myoma diameter is associated with an increase in infused distending fluid volume, especially for myomas ≥4 cm. Meticulous monitoring of the infused distension fluid volume is still crucial to avoid fluid overload during bipolar hysteroscopic myomectomy.

Stachydrine Protects Against Pressure Overload-Induced Cardiac Hypertrophy by Suppressing Autophagy.

BACKGROUND: Autophagy is required for the maintenance of cardiomyocyte homeostasis. However, excessive autophagy plays a maladaptive role in pressure overload-induced heart failure. To identify mechanisms by which Stachydrine inhibits pressure overload-induced cardiac hypertrophy, we determined inhibitory activities against activation of NADPH oxidase, reactive oxygen species(ROS) production and excessive activation of autophagy. METHODS: Stachydrine was administered intragastrically to Wistar rats after Transverse aortic constriction(TAC) and H9c2 cells were treated with Stachydrine after Angiotension II stimulation. The activation of NADPH oxidase2 required the membrane translocation of p47phox and p67phox. Cell membrane fraction was isolated by ultracentrifuge in sucrose. The expression of p67phox, p47phox, gp91phox subunit in the cell membrane were determined by western blot. The combination of p67phox and gp91 phox subunit was detected by immunofluorescence staining. The expression of phosphorylated p47phox subunit was determined by western blot. The intracellular ROS were measured with DCF-DA fluoresence. The autophagic flux was measured by recording the fluorescence emission of the fusion protein mRFP-GFP-LC3 by dynamic live-cell imaging. Reuslts: We report here that stachydrine, a major constituent of Leonurus heterophyllus Sweet, inhibited AngII-induced excessive autophagy within H9c2 cells. Stachydrine blocked the over phosphorylation of the p47phox subunit, decreased the translocation of p47phox and p67phox to the membrane, inhibited the activity of NOX2, and reduced the generation of ROS. We also demonstrated that stachydrine ameliorated TAC-induced cardiac hypertrophy, dysfunction and excessive autophagy in vivo. CONCLUSIONS: Our study highlights the importance of regulating NOX2 when autophagy is obviously activated. By inhibiting NOX2, Stachydrine inhibits ROS production, thus exerting a remarkable activity of inhibiting hypertrophy, which could have considerable effect on clinical practice.

Intraperitoneal Chemotherapy without Bevacizumab versus Intravenous Chemotherapy with Bevacizumab as the Frontline Adjuvant Therapy in Advanced Ovarian Cancer.

Objectives: To compare the clinical outcomes of intravenous carboplatin/paclitaxel chemotherapy plus bevacizumab versus intraperitoneal cisplatin/paclitaxel chemotherapy without bevacizumab as the frontline treatment in women with advanced ovarian, fallopian tube and primary peritoneal cancer. Methods: Between November 2012 and January 2024, medical records of all consecutive women with stage II~IV cancer treated with either frontline adjuvant intraperitoneal cisplatin/paclitaxel without bevacizumab (IP group), intravenous carboplatin/paclitaxel without bevacizumab (IV group) or intravenous carboplatin/paclitaxel with bevacizumab (IVB group) at a tertiary referral center were reviewed. Results: A total of 143 women (IP group, n = 57; IVB group, n = 23; IV group, n = 63) were reviewed. The IP group had greater progression-free survival compared to the IVB group (49.1 months, 95% confidence interval [CI] = 27.8 months to infinity, versus 11.9 months, 95% CI = 11.2 to 16.2 months; adjusted hazard ratio [HR] = 0.45, 95% CI = 0.24 to 0.87, p = 0.017). Additionally, the IP group also had a higher overall survival compared to the IVB group (not reached, 95% CI = 55.6 months to infinity, versus 38.9 months, 95% CI = 21.9 months to infinity; adjusted HR = 0.34, 95% CI = 0.15 to 0.79, p = 0.012). Conclusions: Intraperitoneal cisplatin/paclitaxel chemotherapy without bevacizumab seems to offer a survival advantage when compared with intravenous carboplatin/paclitaxel with bevacizumab in the frontline treatment of women with advanced ovarian cancer.

Comparison of clinical outcomes in women with surgically treated early primary cervical cancer: Lymphadenectomy versus sentinel lymph node biopsy.

BACKGROUND: The primary objective of this study was to elucidate the impact of sentinel lymph node (SLN) mapping and biopsy techniques on the clinical outcomes of women with early primary cervical cancer. METHODS: All consecutive women with clinically determined stage I-IIA cervical cancer who underwent lymph node assessment with either SLN mapping or conventional pelvic/para-aortic lymphadenectomy were reviewed. RESULTS: Women in the SLN group (n=33) had fewer total dissected pelvic nodes (8.3±5.9 versus 17.4±7.7, p<0.001), less intraoperative blood loss (513±332mL versus 1228±1170mL, p<0.001), a shorter length of hospital stay (7.1±2.4 versus 10.2±6.1 days, p=0.004) and a trend toward a lower incidence of lymphocysts (3% versus 14%, p=0.090) than women in the conventional lymphadenectomy group (n=74). The rates of recurrence-free survival (3-year: 87.6% vs. 82.9%) and overall survival (3-year: 100% vs. 91.0%) did not differ between the SLN group and the conventional lymphadenectomy group (p=0.846 and p=0.254, respectively). CONCLUSION: SLN biopsy does not seem to be associated with an inferior survival outcome compared with conventional lymphadenectomy in women with early primary cervical cancer. In addition, it is associated with less blood loss and a shorter length of hospital stay.

The effect of illness perception on psychosocial adjustment of patients with breast cancer and their spouses: actor-partner independence model.

OBJECTIVE: With the increase in the prevalence rate and improvements in the survival of breast cancer patients, there is a growing interest in understanding the level of psychosocial adjustment in these patients. The study aimed to describe the illness perception and psychosocial adjustment levels of both breast cancer patients and their spouses, to use the Actor-Partner Interdependence Model (APIM) to clarify the actor-partner relationships between spouses, and to explore the impact of illness perception on psychosocial adjustment to the disease within the joint actions of both spouses. METHODS: A total of 216 female patients with breast cancer and their spouses participated in the study. They were selected from two tertiary hospitals in Guangdong Province, China from October 2022 to May 2023 using a convenience sampling method. The participants were assessed using the Brief Illness Perception Questionnaire and the Psychosocial Adjustment to Illness Scale to examine the relationship between illness perception and psychosocial adjustment. AMOS24.0 was used to test and analyze the actor-partner interdependence model. RESULTS: The illness perception score (57.75 ± 10.91) was slightly higher than that of the spouse (57.10 ± 11.00), and the psychosocial adjustment score (64.67 ± 6.33) was slightly lower than that of the spouse (64.76 ± 7.49). The results of the actor-partner interdependence model indicated that there was a couple partner between breast cancer patients and their spouses: the spouse's illness perception significantly affected the patient's psychosocial adjustment (ß = 0.095, p = 0.015); the patient's illness perception also significantly affected the spouse's psychosocial adjustment (ß = 0.106, p = 0.033). Among them, the patient's psychosocial adjustment was found to be related to the patient's illness comprehensibility or coherence of illness (ß = 0.433, p = 0.009), the spouse's emotional illness representation (ß = 0.218, p = 0.037), and the spouse's illness comprehensibility or coherence of illness (ß = 0.416, p = 0.007), while the spouse's psychosocial adjustment was only related to the spouse's illness comprehensibility or coherence of illness (ß = 0.528, p = 0.007). CONCLUSIONS: The psychosocial adjustment of breast cancer patients is affected by both their own and spouse's illness perception. Therefore, in the future, the healthcare staff can implement early psychological interventions for patients diagnosed with breast cancer and their spouses as a unit to promote the psychosocial adjustment of them.

Feasibility and Safety of Intraoperative Radiotherapy with Low Energy X-ray Photon Therapy for Recurrent Gynecological Cancer: A Case Series.

OBJECTIVES: To evaluate the feasibility and safety of low energy X-ray photon intraoperative radiotherapy (IORT) as an adjuvant therapy for recurrent gynecological cancer. METHODS: Medical records of all recurrence gynecological cancer patients who underwent IORT were reviewed. RESULTS: Between January 2018 and December 2021, five women (including cervical cancer (n = 2), endometrial cancer (n = 2), and uterine leiomyosarcoma (n = 1)), who underwent IORT and surgical resection for recurrent gynecologic cancer were reviewed. A median dose of 15.62 Gy (range, 12 to 20 Gy) was used for IORT. Repeated IORT and surgical resection was performed in two women. Three women experienced local recurrence, and three women died during follow-up. The 1-year local control rate was 60%. The 2-year overall survival rate was 30%. There was no Clavien-Dindo classification grade III-V complication. CONCLUSION: IORT using low energy X-ray photon therapy seems to be feasible and safe as an adjuvant therapy in women who underwent salvage surgery for recurrent gynecologic cancer. However, large-scale prospective studies are needed to confirm our findings and evaluate its efficacy.

Experimental Study on Danggui Shaoyao San Improving Renal Fibrosis by Promoting Autophagy.

Renal fibrosis could lead to chronic kidney disease (CKD) developing into the end-stage with its pathological manifestation is the deposition of extracellular matrix (ECM). Danggui Shaoyao San (DSS) is one of the widely used herbal formulas in ancient China, which has been proven to have efficacy in the treatment of CKD. The experiment employed TGF-ß1 to stimulate the NRK-52E cells to establish a renal fibrosis model. With rapamycin (RAPA) used as the positive control, we detected the expression of fibronectin (FN), caspase-3, and autophagy-related proteins in the NRK-52E cells treated with DSS by Western blot and immunofluorescence assay. In order to further verify autophagy-promoting effects of DSS, we adopted 3-MA to inhibit autophagy. The experiment has found that DSS can lower the protein levels of FN and caspase-3 in the NRK-52E cells induced by TGF-ß1. After TGF-ß1 stimulation, the expression of LC3 II/I and Beclin 1 has decreased, and the protein levels of mTOR and p62 have increased. Consistent with rapamycin, DSS has significantly reduced these effects of TGF-ß1. It has also been found that DSS can increase the expression of LC3 II/I and Beclin 1 proteins and can reduce the level of mTOR in cells treated with 3-MA, suggesting that DSS can promote autophagy. In conclusion, DSS has been proved to reduce the apoptosis and fibrosis of NRK-52E cells induced by TGF-ß1, which may be achieved by promoting autophagy.

Fatal rectovaginal fistula in post-radiotherapy locally advanced cervical cancer patients.

OBJECTIVE: To present the detailed history of three cervical cancer patients with rectovaginal fistula, who had undergone radiotherapy. CASES REPORT: A 74-year-old patient with end-stage renal disease undergoing hemodialysis had radiotherapy for her advanced cervical cancer. Colonoscopic biopsy showed radiation sigmoid colitis and ulcers. Laparotomy revealed colon perforation and rectovaginal fistula. The second case is a 54-year-old cervical cancer patient, who had received concurrent chemoradiation therapy and further systemic therapy with cisplatin, paclitaxel, and bevacizumab. She suffered from bloody stool and abdominal pain. Rectovaginal fistula was found during exploratory laparotomy. The third case is a 35-year-old cervical cancer patient, who had received concurrent chemoradiation therapy. Systemic therapy was then prescribed with platinum, paclitaxel, and bevacizumab for her lung metastasis, and a rectovaginal fistula was found later. All three patients did not survive later. CONCLUSIONS: Fatal rectovaginal fistula may occur in post-radiation advanced cervical cancer patients. Unnecessary colonoscopic biopsy may cause significant sequelae. In patients with high risk for rectovaginal fistulas, chemotherapy without adding bevacizumab might be suggested in patients with low risk of poor response to chemotherapy. In addition, three-dimensional conformal radiation therapy or intensity-modulated radiation therapy should be used for patients with high risk for fistulas.

Predictors for the Recurrence of Clinically Uterine-Confined Endometrial Cancer and the Role of Cytokeratin Immunohistochemistry Stain in the Era of Sentinel Lymph Node Mapping.

BACKGROUND: The primary objective of this study was to elucidate the predictors for cancer recurrence in women with clinically uterine-confined endometrial cancer in the era of sentinel lymph node (SLN) mapping. METHODS: All consecutive women with clinically determined uterine-confined endometrial cancer who had lymph node assessment by either SLN mapping or traditional pelvic lymphadenectomy were reviewed. RESULTS: Women in the SLN mapping group had lower total dissected pelvic nodes, lower incidence of para-aortic lymph node dissection, less intraoperative blood loss and lower complication rates, but a longer operation time compared to the traditional lymphadenectomy group. Para-aortic lymph node metastasis (hazard ratio = 7.60, p = 0.03) was the sole independent predictor for recurrence-free survival. In addition, the utilization of cytokeratin immunohistochemistry stain detected more lymph node metastases (adjusted odds ratio = 3.04, p = 0.03). Recurrence-free survival did not differ between SLN mapping and traditional lymphadenectomy groups (p = 0.24). CONCLUSIONS: Para-aortic lymph node metastasis is an important predictor of cancer recurrence. Women with negative hematoxylin and eosin stain should undergo cytokeratin immunohistochemistry stain to increase the detection rate of positive lymph node metastasis. Besides, the probabilities of recurrence seem to be similar between SLN mapping and traditional lymphadenectomy groups in women with clinically uterine-confined endometrial cancer.

Factors affecting clinical outcomes in women with non-gastric gastrointestinal stromal tumors.

OBJECTIVE: The clinical presentation of non-gastric GISTs might mimic adnexal cancer, and non-gastric GIST might be managed and treated by gynecologists. Knowledge of the clinical outcomes of women with non-gastric gastrointestinal stromal tumors (GISTs) is important. Our aim is to elucidate the factors affecting the clinical outcomes of women with non-gastric GISTs. MATERIALS AND METHODS: Between January 2000 and October 2019, all consecutive women with non-gastric GISTs who underwent surgery in a tertiary referral center were reviewed. RESULTS: Twenty-six women were reviewed. Eight (31%) women experienced recurrence. The probabilities of recurrence-free survival (RFS) at 60 and 120 months were 65.2% and 55.9%, respectively. The probabilities of overall survival (OS) at 60 and 120 months were 71.1% and 63.9%, respectively. Cancer stage was the only independent predictor of RFS (hazard ratio = 6.00, p = 0.007) and OS (hazard ratio = 3.88, p = 0.04). However, excluding cancer stage, metastasis (hazard ratio = 8.74) was the only independent predictor of RFS, and tumor size (hazard ratio = 1.20) and metastasis (hazard ratio = 6.03) were independent predictors of OS. Tumor size ≥13.9 cm was the optimum cut-off value to predict death and had an area under the receiver operating characteristic curve of 0.75 (95% confidence interval = 0.53 to 0.98). Among the above 5 women with non-gastric GISTs admitted to the Gynecology Department, optimal debulking surgery was performed in two women, and small bowel resection was performed in three women; and all five women remained alive without disease. CONCLUSION: Non-gastric GISTs may mimic gynecologic tumors. Metastasis was an independent predictor of PFS. In addition, metastasis and large tumor size (especially ≥13.9 cm) were independent predictors of OS in women with non-gastric GISTs.

Trans-cinnamaldehyde suppresses microtubule detyrosination and alleviates cardiac hypertrophy.

BACKGROUND: Trans-cinnamaldehyde (TCA) is a main compound of Cinnamomum cassia, used in traditional Chinese medicine to treat many ailments. Increasing evidence has demonstrated the therapeutic effects of TCA in cardiovascular diseases. PURPOSE: The present study aimed to determine whether TCA exerts antihypertrophic effects in vitro and in vivo and to elucidate the underlying mechanisms of these effects. METHODS: Neonatal rat cardiac myocytes (NRCMs) and adult mouse cardiac myocytes (AMCMs) were treated with 50 µΜ phenylephrine (PE) for 48 h. Tubulin detyrosination, store-operated Ca2+ entry (SOCE), stromal interaction molecule-1 (STIM1)/Orai1 translocation, and calcineurin/nuclear factor of activated T-cells (NFAT) signaling pathways were analyzed in NRCMs. Meanwhile, tubulin detyrosination, junctophilin-2, T-tubule distribution pattern, Ca2+ handling, and sarcomere shortening were observed in AMCMs. Male C57BL/6 mice were stimulated with PE (70 mg/kg per day) with or without TCA treatment for 2 weeks. Cardiac hypertrophy and tubulin detyrosination were also assessed. RESULTS: TCA was confirmed to alleviate cardiac hypertrophy induced by PE stimulation in vitro and in vivo. PE-induced cardiac hypertrophy was associated with excessive tubulin detyrosination and overexpression of vasohibin 1 (VASH1) and small vasohibin binding protein (SVBP), two key proteins responsible for tubulin detyrosination. These effects were largely blocked by TCA administration. PE treatment also enhanced SOCE with massive translocation of STIM1 and Orai1, Ca2+ mishandling, reduced sarcomere shortening, junctophilin-2, and T-tubule redistribution, all of which were significantly ameliorated by TCA administration. CONCLUSION: Our study indicated that the therapeutic effects of TCA against cardiac hypertrophy may be associated with its ability to reduce tubulin detyrosination.

Stachydrine hydrochloride ameliorates cardiac hypertrophy through CaMKII/HDAC4/MEF2C signal pathway.

Stachydrine hydrochloride (Sta), an activated alkaloid, is isolated from traditional Chinese medicine Yimucao. In previous studies, the cardioprotective effects of Sta were found in our laboratory. However, the underling mechanisms of Sta is not fully elucidated. The aim of this study was to provide a detailed account of the anti-hypertrophic effects of Sta on transcriptional regulation. In vivo, C57BL/6J mice were subjected to transverse aortic constriction (TAC) and were orally treated with Sta. Morphological assessments, echocardiographic parameters, histological analyses and immunofluorescence were used to evaluate cardiac hypertrophy. In vitro, cardiomyocytes were stimulated by phenylephrine (PE), and cell surface and hypertrophy markers were tested by immunofluorescence and real-time polymerase chain reaction (RT-PCR). Moreover, western blotting, RT-PCR and luciferase reporter genes were used to assess the expression of proteins, mRNA and the activity of the CaMKII/HDAC4/MEF2C signal pathway in vivo and in vitro. We found that Sta blocked cardiac hypertrophy induced by pressure overload. We also demonstrated that Sta inhibited nuclear export or promoted nuclear import of HDAC4 through regulation of p-CaMKII, and it further improved the repression of MEF2C. Taken together, our findings demonstrated that Sta ameliorates cardiac hypertrophy through CaMKII/HDAC4/MEF2C signal pathway.

Robotic or laparoscopic treatment of cesarean scar defects or cesarean scar pregnancies with a uterine sound guidance.

OBJECTIVE: To evaluate the feasibility and effectiveness of robotic/laparoscopic repair of cesarean scar defects or cesarean scar pregnancies with a uterine sound. MATERIALS AND METHODS: All consecutive women with cesarean scar defects or cesarean scar pregnancies who underwent robotic/laparoscopic repair with a bent uterine sound guidance were reviewed. Subjective changes in symptoms and objective changes in the depth and width of cesarean scar defects after surgery were reviewed. RESULTS: A total of 20 women underwent robotic (n = 3) or conventional laparoscopic (n = 17) repair of cesarean scar defects, which included postmenstrual vaginal bleeding associated with cesarean scar defects (n = 15), cesarean scar pregnancies (n = 3), accumulated pus in the cesarean scar defect (n = 1) and an incomplete abortion incarcerated in the cesarean scar defect (n = 1). Bladder perforation occurred in one woman during robotic adhesiolysis. All women with cesarean scar defects (n = 15) reported an improvement in postmenstrual vaginal bleeding after surgery. Follow-up sonography showed a decrease in the depth and width of the cesarean scar defect and an increase in the residual myometrial thickness. CONCLUSION: Robotic or laparoscopic repair with a uterine sound guidance seems to be a feasible and effective method in the treatment of cesarean scar defect or cesarean scar pregnancy.

Disastrous delayed postpartum hemorrhage after 3 days of Shenghua decoction treatment.

Taiwanese women frequently receive Shenghua decoction treatment for uterus involution. However, prolonged Shenghua decoction treatment can be detrimental. Herein, we report the case of a woman with disastrous postpartum hemorrhage after prolonged Shenghua decoction treatment. A 36-year-old woman underwent scheduled cesarean delivery due to cephalopelvic disproportion. On the 8th postpartum day, she started taking Shenghua decoction twice per day. Massive vaginal bleeding was noted after 3 days of Shenghua decoction treatment. Emergency hysterectomy was performed due to severe hypotension and refractory postpartum hemorrhage. Despite being rare, disastrous delayed postpartum hemorrhage could occur after 3 days of Shenghua decoction treatment. Further research might be needed to clarify the relationship between prolonged Shenghua decoction treatment and delayed postpartum hemorrhage.

Predictors of Survival in Women with High-Risk Endometrial Cancer and Comparisons of Sandwich versus Concurrent Adjuvant Chemotherapy and Radiotherapy.

Background: to elucidate the predictors of progression-free survival (PFS) and overall survival (OS) in high-risk endometrial cancer patients. Methods: the medical records of all consecutivewomen with high-risk endometrial cancer were reviewed. Results: among 92 high-risk endometrial cancer patients, 30 women experienced recurrence, and 21 women died. The 5-year PFS and OS probabilities were 65.3% and 75.9%, respectively. Multivariable Cox regression revealed that body mass index (hazard ratio (HR) = 1.11), paraaortic lymph node metastasis (HR = 11.11), lymphovascular space invasion (HR = 5.61), and sandwich chemoradiotherapy (HR = 0.15) were independently predictors of PFS. Body mass index (HR = 1.31), paraaortic lymph node metastasis (HR = 32.74), non-endometrioid cell type (HR = 11.31), and sandwich chemoradiotherapy (HR = 0.07) were independently predictors of OS. Among 51 women who underwent sandwich (n = 35) or concurrent (n = 16) chemoradiotherapy, the use of sandwich chemoradiotherapy were associated with better PFS (adjusted HR = 0.26, 95% CI = 0.08-0.87, p = 0.03) and OS (adjusted HR = 0.11, 95% CI = 0.02-0.71, p = 0.02) compared with concurrent chemoradiotherapy. Conclusion: compared with concurrent chemoradiotherapy, sandwich chemoradiotherapy was associated with better PFS and OS in high-risk endometrial cancer patients. In addition, high body mass index, paraaortic lymph node metastasis, and non-endometrioid cell type were also predictors of poor OS in high-risk endometrial cancer patients.

Comparisons of Clinical Outcomes in Women with Advanced Ovarian Cancer Treated with Frontline Intraperitoneal versus Dose-Dense Platinum/Paclitaxel Chemotherapy without Bevacizumab.

Background: We aimed to compare the clinical outcomes between intraperitoneal chemotherapy and dose-dense chemotherapy for the frontline treatment of advanced ovarian, fallopian tube and primary peritoneal cancer in women not receiving bevacizumab. Methods: All consecutive women with stage II~IV cancer treated with either frontline intraperitoneal or dose-dense platinum/paclitaxel chemotherapy and not receiving bevacizumab between March 2006 and June 2019 were reviewed. Results: A total of 50 women (intraperitoneal group, n = 22; dose-dense group, n = 28) were reviewed. Median progression-free survival (32.6 months versus 14.2 months; adjusted hazard ratio = 0.38; 95% CI = 0.16 to 0.90, p = 0.03) and overall survival (not reached versus 30.7 months; adjusted hazard ratio = 0.23, 95% CI = 0.07 to 0.79, p = 0.02) were significantly higher in the intraperitoneal group than in the dose-dense group. A multivariable Cox proportional-hazards model also indicated that the number of frontline chemotherapy cycles (adjusted hazard ratio = 0.66, 95% CI 0.47 to 0.94, p = 0.02) was a predictor of better overall survival. Nausea/vomiting and nephrotoxicity occurred more frequently in the intraperitoneal group (p = 0.02 and <0.0001, respectively). Conclusions: Intraperitoneal chemotherapy seems to be superior in progression free survival and overall survival to dose-dense chemotherapy in the frontline treatment of women with optimally resected advanced ovarian, fallopian tube or primary peritoneal cancer and not receiving bevacizumab.

Stachydrine hydrochloride alleviates pressure overload-induced heart failure and calcium mishandling on mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine Leonurus japonicus Houtt. has a long history in the treatment of cardiovascular diseases. Stachydrine hydrochloride, the main bioactive ingredient extracted from Leonurus japonicus Houtt., has been shown to have cardioprotective effects. However, the underlying mechanisms of stachydrine hydrochloride haven't been comprehensively studied so far. AIM OF THE STUDY: The aim of this study was to investigate the protective role of stachydrine hydrochloride in heart failure and elucidate its possible mechanisms of action. MATERIALS AND METHODS: In vivo, transverse aorta constriction was carried out in C57BL/6J mice, and thereafter, 7.2 mg/kg telmisartan (a selective AT1R antagonist as positive control) and 12 mg/kg stachydrine hydrochloride was administered daily intragastrically for 4 weeks. Cardiac function was evaluated by assessing morphological changes as well as echocardiographic and haemodynamic parameters. In vitro, neonatal rat cardiomyocytes or adult mice cardiomyocytes were treated with stachydrine hydrochloride and challenged with phenylephrine (α-AR agonist). Ventricular myocytes were isolated from the hearts of C57BL/6J mice by Langendorff crossflow perfusion system. Intracellular calcium was measured by an ion imaging system. The length and movement of sarcomere were traced to evaluate the systolic and diastolic function of single myocardial cells. RESULTS: Stachydrine hydrochloride improved the cardiac function and calcium transient amplitudes, and inhibited the SR leakage and the amount of sparks in cardiac myocytes isolated from TAC mice. We also demonstrated that stachydrine hydrochloride could ameliorated phenylephrine-induced enhance in sarcomere contraction, calcium transients and calcium sparks. Moreover, our data shown that stachydrine hydrochloride blocked the hyper-phosphorylation of CaMKII, RyR2, PLN, and prevented the disassociation of FKBP12.6 from RyR2. CONCLUSION: Our results suggest that stachydrine hydrochloride exerts beneficial therapeutic effects against heart failure. These cardioprotective effects may be associated with the regulation of calcium handling by stachydrine hydrochloride through inhibiting the hyper-phosphorylation of CaMKII.

Predictors of Lymphoceles in Women Who Underwent Laparotomic Retroperitoneal Lymph Node Dissection for Early Gynecologic Cancer: A Retrospective Cohort Study.

Background: Lymphoceles could represent a detrimental complication after retroperitoneal lymph node dissection. Our aim was to elucidate predictors of lymphoceles. Methods: Between 2011 and 2017, medical records of consecutive women who underwent laparotomic retroperitoneal lymph node dissection for FIGO stage I or II gynecologic cancer were reviewed. Results: A total of 204 women, including those with lymphoceles (n = 31) and symptomatic lymphoceles (n = 7), were reviewed. According to multivariable analysis, parity (odds ratio = 0.59, p = 0.003), adjuvant pelvic radiotherapy (odds ratio = 2.60, p = 0.039), and peritoneal nonclosure without pelvic drainage (odds ratio = 2.31, p = 0.048) were predictors of lymphoceles. In addition, parity (odds ratio = 0.73, p = 0.03), hypertension (odds ratio = 2.62, p = 0.02), and peritoneal partial closure with pelvic drainage (odds ratio = 0.27, p = 0.02) were predictors of complications. Conclusion: Low parity, adjuvant pelvic radiotherapy, and peritoneal nonclosure without pelvic drainage were associated with increased lymphocele formation. In addition, a lower complication rate was found in the peritoneal partial closure with pelvic drainage group; thus, peritoneal partial closure with pelvic drainage might be suggested for women who undergo laparotomic retroperitoneal lymph node dissection.

Danggui Shaoyao San Ameliorates Renal Fibrosis via Regulation of Hypoxia and Autophagy.

Danggui Shaoyao San (DSS), a traditional Chinese medicinal prescription, was widely used to reinforce earth to activate collaterals in ancient times. Recently, many clinical studies found that DSS had a renoprotection. In this study, we evaluated the effect of DSS on unilateral ureteral obstruction- (UUO-) induced renal fibrosis in rats and investigated the mechanisms underlying the effect. Sprague Dawley (SD) rats were randomized to UUO or Sham operation. After 1 day, the rats that underwent UUO were randomized to treatment for four experimental groups (n=10 each group): Sham, UUO only, UUO+ benazepril (Bena), and UUO+DSS. After 4 weeks, we demonstrated that DSS significantly suppressed UUO-induced renal hypertrophy by gravimetric. In addition, DSS obviously prevented UUO-induced disorder in renal structure and renal function by HE and biochemistry test. We also found that DSS abrogated UUO-induced renal fibrosis by Masson's staining and collagen volume fraction (CVF) analysis; this is consistent with the western blot analysis that showed DSS abrogated the UUO-induced enhanced TGF-ß1 and weakened BMP-7. Compared with the UUO only group, rats treated with DSS exhibited significant increase in vascular density, followed by decrease in hypoxia and HIF-1α protein level through western blot and immunofluorescence analysis. Furthermore, we also determined proteins of autophagy and DSS enhanced autophagy to prevent the damage-induced by UUO. Taken together, our findings demonstrated that DSS had a renoprotection effect in ameliorating renal fibrosis possibly via attenuating tissue hypoxia and regulating autophagy.