Entrenamiento muscular del suelo pélvico en el tratamiento del prolapso de órganos pélvicos: un metaanálisis de ensayos controlados aleatorizados / Pelvic floor muscle training in the treatment of pelvic organ prolapse: A meta-analysis of randomized controlled trials

ANTECEDENTES: El objetivo fue evaluar el efecto general del entrenamiento muscular del suelo pélvico (EMSP) en pacientes con prolapso de órganos pélvicos (POP) con base en una selección de ensayos controlados aleatorizados (ECA). MÉTODOS: Se realizaron búsquedas en bases de datos, como PubMed, Cochrane y Embase, para identificar ECA elegibles en función de las palabras indexadas, actualizadas en diciembre del 2018. También buscamos en publicaciones relacionadas con el presente estudio. Los resultados principales se analizaron usando odds ratio (OR) y la diferencia media (DM), con un intervalo de confianza del 95% (IC del 95%). RESULTADOS: En este metaanálisis se incluyeron 15 ECA, con un total de 1.309 pacientes en el grupo de EMSP y un total de 1.275 pacientes en el grupo de control. Los resultados generales no mostraron diferencias significativas entre los 2grupos en la incidencia del aumento de 2 grados POP-Q (RR: 0,55, IC del 95%: 0,19-1,63), aumento de 1 grado POP-Q (RR: 1,04, IC del 95%: 0,69-1,57), ausencia de cambio de grado POP-Q (RR: 0,94, IC del 95%: 0,81-1,09), reducción de 2 grados POP-Q (RR: 1,72, IC del 95%: 0,79-3,76), ausencia de cambio en los síntomas reportada por las propias pacientes (RR: 0,70, IC del 95%: 0,45-1,09) y cambio a peor en los síntomas reportado por las propias pacientes (RR: 0,67, IC del 95%: 0,22-2,03). Además, la incidencia de la reducción de 1 grado POP-Q fue significativamente mayor en el grupo de EMSP que en el grupo de control (RR: 1,80, IC del 95%: 1,20-2,69) y el EMSP cambió significativamente los síntomas informados por las pacientes produciendo mejores resultados en comparación con el grupo de control (RR: 2,90, IC del 95%: 1,72-4,89). Sin embargo, después de la terapia, los resultados del grupo de EMSP disminuyeron frente al grupo de control en las siguientes pruebas: POP-SS (SMD: -0,24, IC del 95%: -0,71-0,22), POPDI-6 (SMD: -0,14, IC del 95%: -0,43-0,15), CRADI-8 (SMD: -0,03, IC del 95%: -0,16-0,11) y UDI-6 (SMD: -0,17, IC del 95%: -0,43-0,10), pero sin significación estadística. CONCLUSIÓN: El EMSP tuvo un mejor efecto en la reducción de 1 grado de POP-Q, con mejores resultados en los síntomas reportados por los pacientes, disminuyendo el puntaje POP-SS, POPDI-6, CRADI-8 y UDI-6 en las mujeres con POP versus el grupo de control. Sin embargo, se necesitan más ECA multicéntricos de alta calidad con un tamaño de muestra mayor para confirmar las presentes conclusiones

BACKGROUND: We aimed to assess the overall effect of pelvic muscle training (PFMT) on patients with pelvic organ prolapse (POP) based on eligible randomized controlled trials (RCT). METHODS: We searched the following databases, such as PubMed, Cochrane, and Embase, to identify eligible RCT based on the index words updated to December 2018. We also searched the publications related to the present study. Odds rations (OR), and mean difference (MD) along with 95% confidence interval (95% CI) were used to analyze the main outcomes. RESULTS: In this meta-analysis, 15 RCTs were included with a total of 1309 patients in the PFMT group and a total of 1275 patients in the control group. The overall results showed no significant difference in the incidence of add 2 POP-Q stages (RR: 0.55, 95%CI: 0.19-1.63), add 1 POP-Q stages (RR: 1.04, 95%CI: 0.69-1.57), no POP-Q stages change (RR: 0.94, 95%CI: 0.81-1.09), reduce 2 POP-Q stages (RR: 1.72, 95%CI: 0.79-3.76), self-reported same symptom change (RR: 0.70, 95%CI: 0.45-1.09), and self-reported worse symptom change (RR: 0.67, 95%CI: 0.22-2.03) between the 2groups. Besides, the incidence of reduce 1 POP-Q stages was significantly higher in the PFMT group than that of the control group (RR: 1.80, 95%CI: 1.20-2.69), and the PFMT significantly changed the self-reported symptoms with better outcomes when compared with the control group (RR: 2.90, 95%CI: 1.72-4.89). However, after the therapy, the PFMT group decreased the POP-SS (SMD: -0.24, 95%CI: -0.71-0.22), POPDI-6 (SMD: -0.14, 95%CI: -0.43-0.15), CRADI-8 (SMD: -0.03, 95%CI: -0.16-0.11), and UDI-6 (SMD: -0.17, 95%CI: -0.43-0.10) versus the control group, but without statistical significance. CONCLUSION: PMFT showed better effect in reducing 1 POP-Q stages, changing the self-reported symptoms with better outcomes, decreasing the score of POP-SS, POPDI-6, CRADI-8, and UDI-6 in women with POP versus the control group. However, more high-quality multicenter RCTs with a larger sample size are needed to confirm the present conclusions

MicroRNA-338-3p inhibits the progression of bladder cancer through regulating ETS1 expression.

OBJECTIVE: MicroRNA-338-3p (miR-338-3p) was reported to influence the metastasis and development of several human cancers. However, in bladder cancer (BC), the special function of miR-338-3p remains unknown. Here, we aimed at exploring the miR-338-3p function in the progression of BC. PATIENTS AND METHODS: miR-338-3p and ETS1 expressions were examined by quantitative Real-time polymerase chain reaction (qRT-PCR) in BC samples. Following that, transwell assays for cell migration and invasion were performed. And MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay for cell proliferation was conducted as well. Western blot was employed to examine the epithelial-mesenchymal transition (EMT) marker expressions. Finally, the relationship between miR-338-3p and E26 transformation specific-1 (ETS1) was verified by luciferase reporter assay. RESULTS: The decreased miR-338-3p expression was examined in BC cells. Moreover, miR-338-3p upregulation repressed cell proliferation ability in BC. Next, miR-338-3p upregulation also depressed cell metastasis and EMT in BC cells. Furthermore, ETS1 was a direct target of miR-338-3p and inversely associated with its expression. And upregulation of ETS1 partially rescued the suppression of miR-338-3p for cell proliferation and metastasis in BC. CONCLUSIONS: Upregulation of miR-338-3p inhibited the proliferation, metastasis and EMT in BC by suppressing ETS, showing that miR-338-3p might block the development of BC through regulating ETS1 expression.

The expression of OCT4 and its clinical significance in laryngeal squamous carcinoma tissues.

OBJECTIVE: To investigate the expression of OCT4 and its clinical significance in laryngeal squamous carcinoma tissues. PATIENTS AND METHODS: Immunohistochemical staining was used to analyze the expression of OCT4 in 61 cases of laryngeal squamous carcinoma and 10 cases of the adjacent normal laryngeal tissues. RESULTS: The expression of OCT4 was not detected in normal laryngeal tissues, but could be detected in the nucleus of laryngeal carcinoma. The positive expression rates of OCT4 in well-moderately differentiated and poorly differentiated laryngeal squamous carcinoma tissues were 25.6% (11/43) and 66.7% (12/18) respectively, and there were significant differences (p < 0.01). The expression of the OCT4 protein was related to lymph node metastasis and TNM stage (p < 0.05), but not to gender, age and position of the tumor (p > 0.05). CONCLUSIONS: OCT4 is expressed in laryngeal squamous carcinoma tissues and is closely related to the cell differentiation of laryngeal carcinoma, lymph node metastasis and clinical stage.

Upregulation of miR-802 suppresses gastric cancer oncogenicity via targeting RAB23 expression.

OBJECTIVE: The aberrant expression of microRNAs (miRNAs) has been observed in various types of cancer. Recently, miR-802 was found to play important role in tumor progression. However, the function of miR-802 in gastric cancer (GC) remains unknown. The aim of the present study was to investigate biological effects and underlying mechanisms of miR-802 in GC. PATIENTS AND METHODS: Quantitative RT-PCR was performed to evaluate the expression level of miR-802 in GC tissues and cell lines. The in vitro cell proliferation was measured using the MTT method. Cell invasion and migration assays were performed using the transwell assay. The effects of miR-802 on tumor growth were examined using a GC xenograft model. Flow cytometry method was used to detect the effect of miR-802 in apoptosis of GC cells. Targets of miR-802 were predicted using bioinformatics and validated using luciferase reporter and Western blot analyses. RESULTS: The results showed that miR-802 was significantly down-regulated in GC tissues and cell lines. The enforced expression of miR-802 induced growth suppression and apoptosis of GC cells. Moreover, miR-802 overexpression suppressed the migration and invasion of GC cells. Bioinformatics analysis predicted that the RAB23 was a potential target gene of miR-802. The results of luciferase reporter assay demonstrated that miR-802 could directly target RAB23. Additionally, in vivo analysis, the xenograft mouse model also confirmed the suppressive effects of miR-802 on tumor growth. CONCLUSIONS: Our results are the first to demonstrate the tumor-suppressive role of miR-802 in GC. The identification of miR-802 and its novel target RAB23 will be valuable in developing therapeutic applications for GC.

Lipoxin A4 mitigates experimental autoimmune myocarditis by regulating inflammatory response, NF-κB and PI3K/Akt signaling pathway in mice.

OBJECTIVE: Myocarditis, an acute inflammation disease of the heart, is a potentially lethal disease and can lead to sudden death. This study aims to investigate the therapeutic effect of lipoxin A4 (LXA4) on experimental autoimmune myocarditis (EAM) and to explore the underlying mechanism. MATERIALS AND METHODS: EAM was induced in BALB/c mice by injection of porcine cardiac myosin and LAX4 at doses of 10 or 50 µg/kg was administrated from day 1 to 21. The severity of myocarditis was evaluated by detection of heart weight/body weight (HW/BW) ratio and histopathological examination of the heart. Cardiac function and heart structure were assessed by echocardiography. Serum levels of Th1 and Th2 cytokines were determined by ELISA. Protein expression was detected by Western blot analysis. RESULTS: The results demonstrated that LXA4 mitigated the severity of myocarditis by decreasing HW/BW ratio and reducing infiltration of inflammatory cells. Echocardiographic analysis indicated that cardiac function of LXA4-treated rats was significantly improved compared with non-treated group. LXA4 treatment significantly increased the levels of Th1 cytokines (TNF-α and IL-6) and decreased Th2 cytokines (IL-4 and IL-10). Furthermore, LXA4 administration effectively inhibited NF-κB nuclear translocation and deactivated PI3K/Akt pathway. CONCLUSIONS: LXA4 has a protective effect against EAM by reducing the inflammatory response and inhibiting NF-κB and PI3K/Akt signaling pathway.

Diagnostic and prognostic significance of E-cadherin and Ki-67 expression in non-small cell lung cancer patients.

OBJECTIVE: To elucidate the relationship between E-cadherin (E-cad) and Ki-67, and to determine their clinical significance in non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: A total of 68 NSCLC paraffin embedded tissue specimens and tumor-adjacent normal tissue specimens were collected. The expression of E-cad and Ki-67 was examined by immunohistochemistry and the relationships between the expression of these two markers were evaluated. The clinicopathological features were correlated with the expression of E-cad and Ki-67 to check whether these proteins have any association and if exist an association whether E-cad and Ki-67 can be used in diagnosis and prognosis of NSCLSC. RESULTS: E-cad was expressed in all the normal tissues but Ki-67 expressed in only 5.8% of normal tissues. Ki-67 and E-cad expression were observed in 61.8% and 25% of NSCLC tissues respectively. Correlation analysis revealed an inverse association between the expression of E-cad and Ki-67 (r = 0.524, p = 0.000). The clinicopathological features such as tumor differentiation, TNM stage, lymph node metastasis and pleural invasion were all significantly associated with E-cad and Ki-67 expression (p < 0.05). CONCLUSIONS: E-cad and Ki-67 together play a key role in the development, invasion and metastasis of NSCLC and combined detection of them serve as a potential marker for clinical diagnosis in addition to exploiting them as a therapeutic target.

Relationship between CD4+CD25+ Treg and expression of HIF-1α and Ki-67 in NSCLC patients.

OBJECTIVE: To investigate the relationship between the CD4+CD25+ Treg cell proportion in the peripheral blood and the clinicopathologic features of non-small cell lung cancer (NSCLC) patients and hypoxia-inducible factor-1α (HIF-1α), Ki-67 expression. PATIENTS AND METHODS: Flow cytometry was used to measure the CD4+CD25+ Treg cell level in peripheral blood and immunohistochemical staining used to detect the expression of HIF-1α and Ki-67 protein in cancer tissue of each of 50 NSCLC patients. RESULTS: The level of CD4+CD25+ Treg cell in peripheral blood was related to pathologic grades (t = 3.265, p = 0.006) and clinical stage (t = 4.417, p = 0. 001) of NSCLC instead of to patient's gender and pathologic type of tumor (p > 0.05). The level of CD4+CD25+ Treg cell was positively correlated with the expression of HIF-1α (r = 0.711, p = 0.003) and Ki-67 (r = 0.517, p = 0.04), respectively. CONCLUSIONS: CD4+CD25+ Treg cell can be used as a predictor of immune status and prognosis of NSCLC patients and the levels of HIF-1α and Ki-67 protein expression may relate to inhibition of immune cells.

Establishing a new electrical conduction pathway by anastomosis of the right auricle and right ventricle assisted by mesenchymal stem cells in a canine model.

BACKGROUND: Electronic pacemakers are the primary treatment of complete atrioventricular (AV) block, but their use is associated with many complications. The aim of the present study was to create an alternative treatment for these patients. MATERIALS AND METHODS: Mesenchymal stem cells (MSCs) isolated from the bone marrow of a 3-month-old dog were cultured in vitro. The MSCs were labeled with 4', 6-diamidino-2-phenylindole (DAPI) before transplantation. We anastomosed the right auricle and right ventricle in 24 dogs, and transplanted labelled MSCs into the anastomotic area of 8 dog hearts. Using immunostaining we assessed survival and differentiation of the implanted cells at 8 weeks posttransplantation. Electrocardiography confirmed the secondary electrical conduction pathway. RESULTS: The ventricular current was captured by the electronic pacemaker in 21 dogs. Compared with the control group (surgery alone), pacemaker stimulus current was significantly less in the MSC group (surgery+MSCs). CONCLUSIONS: Anastomosis of the right auricle and right ventricle assisted by MSCs may be a new treatment for patients with complete AV block in the future.

Low expression of Mel-18 predicts poor prognosis in patients with breast cancer.

BACKGROUND: Our previous study suggested that melanoma nuclear protein 18 (Mel-18) acted as a tumor suppressor in human breast cancer. This study was designed to investigate the clinical and prognostic significance of Mel-18 in breast cancer patients. PATIENTS AND METHODS: Mel-18 was detected by immunohistochemistry in paraffin-embedded tissues from 287 breast cancer patients, of which 287 were from primary cancer sites, 63 from matched adjacent noncancerous sites, and 35 from metastatic lymph nodes. Differences in Mel-18 expression and clinical characteristics were compared by χ² test. Prognostic outcomes correlated with Mel-18 were examined using Kaplan-Meier analysis and Cox proportional hazards model. RESULTS: The decreased Mel-18 expression is incremental depending upon the magnitude of cancer progression (P < 0.001). Mel-18 was conversely correlated with the pathological classifications (P < 0.001 for T, N, and M classifications, respectively), clinical staging (P < 0.001), and progesterone receptor (P = 0.030). Furthermore, patients with higher level of Mel-18 showed prolonged overall survivals (P < 0.001). The diminished Mel-18 expression may be a risk factor for the patients' survival (P < 0.001). CONCLUSIONS: Lower Mel-18 expression is correlated with advanced clinicopathologic classifications and a poor overall survival in breast cancer patients. These findings suggest that Mel-18 may serve as a useful marker in prognostic evaluation for patients.

Silencing Livin gene expression to inhibit proliferation and enhance chemosensitivity in tumor cells.

Livin, a novel member of the human inhibitors of apoptosis protein (IAP) family, plays an important role in tumor progression and occurrence by inhibiting cell apoptosis. It is selectively expressed in the most common human neoplasms and appears to be involved in tumor cell resistance to chemotherapeutic agents. To investigate its possibility as a therapeutic target for human malignancies, we established two genetically different stable tumor cell lines (LoVo and SPCA-1) and RNA interference (RNAi) technique was employed to downregulate Livin expression in two human tumor cell lines. The specific downregulation of Livin expression in tumor cell lines significantly inhibited in vitro cell proliferation and in vivo tumorigenicity. Furthermore, Livin knockdown led to cell arrest in the G(1)/G(0) phase of cell cycle, eventual apoptosis and chemosensitivity enhancement in tumor cells. All these results indicate that RNAi-mediated downregulation of Livin expression can lead to potent antitumor activity and chemosensitizing effects in human cancers.

Prognostic factors for ovarian metastases from primary gastric cancer.

The purpose of this study was to analyze prognostic factors for ovarian metastases from primary gastric cancer, helping establish optimal strategy in ameliorating survival for this entity. Clinical data of 68 consecutive patients histologically diagnosed with ovarian metastases from primary gastric cancer were accrued from 1096 cases with female gastric cancer. Metachronous surgery was performed on 36 patients and 32 received synchronous surgery. There were 14 patients treated with surgery alone and 54 with combined modality therapy. After the median follow-up time of 9.1 months, the median survival time (MST) of 12.4 months was observed for all patients. Patients treated with synchronous surgery tended to have an inferior survival compared with those treated with metachronous surgery (MST: 10.9 vs 14.3 months; P = 0.100). Combined modality showed a significantly better MST compared with surgery alone (13.6 vs 7.9 months; P = 0.004). Chemotherapy cycles (more than four or less than or equal to four) were found to have an impact on survival (MST: 14.3 vs 9.4 months; P = 0.031). Peritoneal metastases, lymphovascular involvement, and unilateral ovarian metastasectomy were independent unfavorable prognostic factors. Combined modality therapy as primary therapy resulted in good outcome, and more aggressive chemotherapy (more than four cycles) was accompanied by an improvement in survival. Innovative systemic treatments need to be explored in treatment of peritoneal metastases and lymphovascular involvement. Bilateral oophorectomy was considered when ovarian metastases were histologically diagnosed.