A retrospective study of ovarian tissue cryopreservation in female patients with hematological diseases for fertility preservation.

PURPOSES: To investigate the effect and safety of ovarian tissue cryopreservation (OTC) for fertility preservation in female patients with hematological diseases. METHODS: We designed a retrospective study. The clinical data of patients with hematological diseases undergoing OTC admitted to Peking University People's Hospital from April 2017 to January 2023 were analyzed and summarized. RESULTS: A total of 24 patients were included in the study, including 19 patients with malignant hematological diseases and 5 patients with non-malignant hematological diseases. The former included 14 patients with acute leukemia, 1 patient with chronic leukemia, and 4 patients with myelodysplastic syndrome, while the latter 5 patients were aplastic anemia (AA). 16 patients had received chemotherapy before OTC. The average age of 24 patients was 22.80 ± 6.81 years. The average anti-Mullerian hormone (AMH) was 1.97 ± 2.12 ng/mL, and the average follicle-stimulating hormone (FSH) was 7.01 ± 4.24 IU/L in examination before OTC. FSH was greater than 10.0 IU/L in 4 cases. The pre-OTC laboratory tests showed that the average white blood cell (WBC) count was (3.33 ± 1.35) × 109/L, the average hemoglobin was 91.42 ± 22.84 g/L, and the average platelet was (147.38 ± 114.46) × 109/L. After injection of recombinant human granulocyte colony-stimulating factor (rhG-CSF), blood transfusion, and iron supplementation in pre-OTC treatment, the average WBC count was (4.91 ± 3.07) × 109/L, the average hemoglobin was 98.67 ± 15.43 g/L, and the average platelet was (156.38 ± 103.22) × 109/L. Of the 24 patients, 22 underwent laparoscopic bilateral partial oophorectomy and oophoroplasty, and 2 underwent laparoscopic unilateral oophorectomy. The average duration of OTC was 59.54 ± 17.58 min, and the average blood loss was 32.1 ± 41.6 mL. The maximum blood loss was 200 mL. There was no significant difference in WBC count and hemoglobin concentration after OTC compared to pre-OTC period. Only the platelet count after OTC surgery was significantly different from that before surgery ([134.54 ± 80.84 vs. 156.38 ± 103.22] × 109/L, p < 0.05). None of the 24 patients had serious complications after OTC. 2 patients had mild infection symptoms, but both recovered well. 23 patients underwent hematopoietic stem cell transplantation (HSCT) after OTC. The median and interquartile range from OTC to the pretreatment of HSCT was 33 (57) days, and the median and interquartile range from OTC to HSCT was 41 (57) days. Seven of them began pretreatment of HSCT within 20 days and began HSCT within 30 days after OTC. All patients were followed up. Of the 23 patients who underwent HSCT after surgery, 22 presented with amenorrhea and 1 with scanty menstrual episodes. Seven patients underwent hormone replacement therapy (HRT) after HSCT. A patient with AA underwent ovarian tissue transplantation (OTT) 3 years after HSCT and resumed regular menstruation 6 months after OTT. CONCLUSIONS: Ovarian tissue cryopreservation has a promising future in fertility protection in patients with hematological diseases. However, patients with hematological malignancies often have received gonadotoxic therapy before OTC, which may be accompanied by myelosuppression while patients with non-malignant hematological diseases often present with severe hemocytopenia. So perioperative complete blood count of patients should be paid attention to. There was no significant difference in the WBC count and hemoglobin concentration in patients with hematological diseases before and after OTC surgery, and the platelet count decreased slightly within the normal range. Infection is the most common post-OTC complication, and HSCT pretreatment can be accepted as early as the 10th day after OTC. OTC has no adverse effects on patients with hematological diseases and does not delay HSCT treatment. For young patients with hematological diseases, OTC is an effective method of fertility preservation.

Metabolic syndrome score as an indicator in a predictive nomogram for lymph node metastasis in endometrial cancer.

BACKGROUND: Lymph node metastasis (LNM) is an important factor affecting endometrial cancer (EC) prognosis. Current controversy exists as to how to accurately assess the risk of lymphatic metastasis. Metabolic syndrome has been considered a risk factor for endometrial cancer, yet its effect on LNM remains elusive. We developed a nomogram integrating metabolic syndrome indicators with other crucial variables to predict lymph node metastasis in endometrial cancer. METHODS: This study is based on patients diagnosed with EC in Peking University People's Hospital between January 2004 and December 2020. A total of 1076 patients diagnosed with EC and who underwent staging surgery were divided into training and validation cohorts according to the ratio of 2:1. Univariate and multivariate logistic regression analyses were used to determine the significant predictive factors. RESULTS: The prediction nomogram included MSR, positive peritoneal cytology, lymph vascular space invasion, endometrioid histological type, tumor size > = 2 cm, myometrial invasion > = 50%, cervical stromal invasion, and tumor grade. In the training group, the area under the curve (AUC) of the nomogram and Mayo criteria were 0.85 (95% CI: 0.81-0.90) and 0.77 (95% CI: 0.77-0.83), respectively (P < 0.01). In the validation group (N = 359), the AUC was 0.87 (95% CI: 0.82-0.93) and 0.80 (95% CI: 0.74-0.87) for the nomogram and the Mayo criteria, respectively (P = 0.01). Calibration plots revealed the satisfactory performance of the nomogram. Decision curve analysis showed a positive net benefit of this nomogram, which indicated clinical value. CONCLUSION: This model may promote risk stratification and individualized treatment, thus improving the prognosis.

Mechanisms of myocardial ischemic injury repair by bone marrow mesenchymal stem cell-derived miR-183-5P targeting FOXO1.

The homing rate of transplanted mesenchymal stem cells (BMSCs) after acute myocardial infarction (AMI) is generally low, with only 0%-6% of the number of transplanted stem cells distributed to the heart; therefore, this study will investigate the therapeutic effects and mechanisms of miR-183-5p-modified BMSCs cells on myocardial ischemia and hypoxia caused by AMI. In this experiment, After first establishing the BMSCs ischemic-hypoxic injury model, the rats were divided into healthy group, model group, BMSCs group and BMSCs+ miR-183-5P group, where the healthy group was taken to normal culture, the model group caused myocardial ischemic-hypoxic damage, the BMSCs group underwent BMSCs stem cell transplantation on the basis of the model group, and the BMSCs+ miR-183-5P group was group was cultured with BMSCs-derived miR-183-5P on the basis of the model group. Myocardial tissue sections of rats in each group were taken for HE staining and histopathological changes were observed by light microscopy. The proliferation, apoptosis and migration ability of the cells were detected by CCK-8 method, flow cytometry and Transwell transfer method. The target gene of miR-183-5P was predicted using bioinformatics software, and the binding of miR-183-5P to FOXO1 was investigated. The expression of FOXO1 was analysed using qRT-PCR and protein blotting techniques. The qRT-PCR results showed that the expression of miR-183-5P was higher in BMSCs of the BMSCs group and BMSCs+ miR-183-5P group compared with the model group, and the expression was highest in the BMSCs+ miR-183-5P group (P<0.05). The value-added ability and the migration capacity of BMSCs in the BMSCs group and BMSCs+ miR-183-5P group were increased compared with the model group, and the BMSCs+ miR-183-5P group BMSCs had the highest proliferation capacity and the migration capacity(P<0.05). In contrast, the apoptotic capacity of BMSCs was significantly reduced in the BMSCs group and BMSCs+ miR-183-5P group compared with the model group, and the apoptotic capacity of BMSCs was lowest in the BMSCs+ miR-183-5P group (P<0.05). The bioinformatics software RegRNA 2. 0 was used to predict that the specific target gene that may be regulated by miR-183-5P is FOXO1 and confirmed that miR-183-5P does indeed have a targeting relationship with the FOXO1 pathway. After upregulation of miR-183-5P expression, the expression of FOXO1 mRNA was higher in BMSCs of the BMSCs group and BMSCs+ miR-183-5P group compared with the model group, and the expression was highest in the BMSCs+ miR-183-5P group (P<0.05). The Western blotting showed that the expression of FOXO1 mRNA was higher in BMSCs of the BMSCs group and BMSCs+ miR-183-5P group compared with the model group, especially the expression was highest in the BMSCs+ miR-183-5P group (P<0.05). In conclusion, BMSCs-derived miR-183-5P can target and regulate FOXO1 to increase the proliferation and migration of BMSCs and reduce their apoptosis, and can also reduce myocardial tissue edema and inflammatory response by increasing the expression of FOXO1 mRNA, which can increase the survival rate of BMSCs and provide a clinical basis for BMSCs transplantation.

Formulated chitosan-sodium tripolyphosphate nanoparticles for co-encapsulation of ellagic acid and anti-inflammatory peptide: characterization, stability and anti-inflammatory activity.

BACKGROUND: Chitosan (CS) and tripolyphosphate (TPP) can be combined in the development of a material with synergistic properties and promising potential for the conservation of food products. In this study, ellagic acid (EA) and anti-inflammatory peptide (FPL)-loaded CS nanoparticles (FPL/EA NPs) were prepared using the ionic gelation method and optimal preparation conditions were obtained through a single factor design. RESULTS: The synthesized nanoparticles (NPs) were characterized using a scanning electron microscope (SEM), Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and differential scanning calorimetry (DSC). Nanoparticles were spherical, with an average size of 308.33 ± 4.61 nm, a polydispersity index (PDI) of 0.254, a zeta potential of +31.7 ± 0.08 mV, and a high encapsulation capacity (22.16 ± 0.79%). An in vitro release study showed that EA/FPL had a sustainable release from FPL/EA NPs. The stability of the FPL/EA NPs was evaluated for 90 days at 0, 25, and 37 °C. Significant anti-inflammatory activity of FPL/EA NPs was verified by nitric oxide (NO) and tumor necrosis factor-α (TNF-α) reduction. CONCLUSION: These characteristics support the use of CS nanoparticles to encapsulate EA and FPL and improve their bioactivity in food products. © 2023 Society of Chemical Industry.

De novo domestication: a new way for crop design and breeding.

The impending global climate change presents significant challenges to agricultural production. It is imperative to find approaches to ensure sustained growth in food production while reducing agricultural input, in order to meet the needs of worldwide people for nutritious food supply. One of the effective strategies to address this challenge is still the development of new crop varieties with high yield, stable yield, environmental friendliness and rich nutrition. The creation of new crop cultivars depends largely on the expansion of genetic resources and the innovation of breeding techniques. De novo domestication is an innovative breeding strategy for developing new crop varieties. It involves utilizing undomesticated or semi-domesticated plants with desirable traits as founder species for breeding. The process involves rapid domestication of wild plants through the redesign of agronomic traits and the introduction of domestication genes to meet diverse human needs. In this review, we overview the history of crop domestication and genetic improvement, clarify the necessity of enriching crop diversity, and emphasize the significance of wild plants' genetic diversity in expanding the scope for crop redesign. Breeding strategy innovation is the key to accelerate crop breeding. We also discuss the feasibility and prospects of rapid developing new crops through de novo domestication.

Contribution of NADPH oxidase to the retention of UVR-induced DNA damage by arsenic.

Arsenic is a naturally occurring element present in food, soil and water and human exposure is associated with increased cancer risk. Arsenic inhibits DNA repair at low, non-cytotoxic concentrations and amplifies the mutagenic and carcinogenic impact of other DNA-damaging agents, such as ultraviolet radiation (UVR). Arsenic exposure leads to oxidation of zinc coordinating cysteine residues, zinc loss and decreased activity of the DNA repair protein poly(ADP)ribose polymerase (PARP)-1. Because arsenic stimulates NADPH oxidase (NOX) activity leading to generation of reactive oxygen species (ROS), the goal of this study was to investigate the role of NOX in arsenic-induced inhibition of PARP activity and retention of DNA damage. NOX involvement in the arsenic response was assessed in vitro and in vivo. Keratinocytes were treated with or without arsenite, solar-simulated UVR, NOX inhibitors and/or isoform specific NOX siRNA. Knockdown or inhibition of NOX decreased arsenite-induced ROS, PARP-1 oxidation and DNA damage retention, while restoring arsenite inhibition of PARP-1 activity. The NOX2 isoform was determined to be the major contributor to arsenite-induced ROS generation and DNA damage retention. In vivo DNA damage was measured by immunohistochemical staining and analysis of dorsal epidermis sections from C57BI/6 and p91phox knockout (NOX2-/-) mice. There was no significant difference in solar-simulated UVR DNA damage as detected by percent PH2AX positive cells within NOX2-/- mice versus control. In contrast, arsenite-dependent retention of UVR-induced DNA damage was markedly reduced. Altogether, the in vitro and in vivo findings indicate that NOX is involved in arsenic enhancement of UVR-induced DNA damage.

Prediction of postpartum hemorrhage in pregnant women with immune thrombocytopenia: Development and validation of the MONITOR model in a nationwide multicenter study.

Globally, postpartum hemorrhage (PPH) is the leading cause of maternal death. Women with immune thrombocytopenia (ITP) are at increased risk of developing PPH. Early identification of PPH helps to prevent adverse outcomes, but is underused because clinicians do not have a tool to predict PPH for women with ITP. We therefore conducted a nationwide multicenter retrospective study to develop and validate a prediction model of PPH in patients with ITP. We included 432 pregnant women (677 pregnancies) with primary ITP from 18 academic tertiary centers in China from January 2008 to August 2018. A total of 157 (23.2%) pregnancies experienced PPH. The derivation cohort included 450 pregnancies. For the validation cohort, we included 117 pregnancies in the temporal validation cohort and 110 pregnancies in the geographical validation cohort. We assessed 25 clinical parameters as candidate predictors and used multivariable logistic regression to develop our prediction model. The final model included seven variables and was named MONITOR (maternal complication, WHO bleeding score, antepartum platelet transfusion, placental abnormalities, platelet count, previous uterine surgery, and primiparity). We established an easy-to-use risk heatmap and risk score of PPH based on the seven risk factors. We externally validated this model using both a temporal validation cohort and a geographical validation cohort. The MONITOR model had an AUC of 0.868 (95% CI 0.828-0.909) in internal validation, 0.869 (95% CI 0.802-0.937) in the temporal validation, and 0.811 (95% CI 0.713-0.908) in the geographical validation. Calibration plots demonstrated good agreement between MONITOR-predicted probability and actual observation in both internal validation and external validation. Therefore, we developed and validated a very accurate prediction model for PPH. We hope that the model will contribute to more precise clinical care, decreased adverse outcomes, and better health care resource allocation.

Cost-effectiveness of paclitaxel, doxorubicin, cyclophosphamide and trastuzumab versus docetaxel, cisplatin and trastuzumab in new adjuvant therapy of breast cancer in china.

BACKGROUND: Breast cancer is the most common cancer among women in China. Amplification of the Human epidermal growth factor receptor type 2 (HER2) gene is present and overexpressed in 18-20% of breast cancers and historically has been associated with inferior disease-related outcomes. There has been increasing interest in de-escalation of therapy for low-risk disease. This study analyzes the cost-effectiveness of Doxorubicin/ Cyclophosphamide/ Paclitaxel/ Trastuzumab (AC-TH) and Docetaxel/Carboplatin/Trastuzumab(TCH) from payer perspective over a 5 year time horizon. METHODS: A half-cycle corrected Markov model was built to simulate the process of breast cancer events and death occurred in both AC-TH and TCH armed patients. Cost data came from studies based on a Chinese hospital. One-way sensitivity analyses as well as second-order Monte Carlo and probabilistic sensitivity analyses were performed.The transition probabilities and utilities were extracted from published literature, and deterministic sensitivity analyses were conducted. RESULTS: We identified 41 breast cancer patients at Hangzhou First People's Hospital, among whom 15 (60%) had a partial response for AC-TH treatment and 13 (81.25%) had a partial response for TCH treatment.No cardiac toxicity was observed. Hematologic grade 3 or 4 toxicities were observed in 1 of 28 patients.Nonhematologic grade 3 or 4 toxicities with a reverse pattern were observed in 6 of 29 patients. The mean QALY gain per patient compared with TCH was 0.25 with AC-TH, while the incremental costs were $US13,142. The incremental cost-effectiveness ratio (ICER) of AC-TH versus TCH was $US 52,565 per QALY gained. CONCLUSIONS: This study concluded that TCH neoadjuvant chemotherapy was feasible and active in HER2-overexpressing breast cancer patients in terms of the pathological complete response, complete response, and partial response rates and manageable toxicities.

Synovial and pulmonary dysfunctions are induced by crosstalk of Smad and Erk pathways in an arthritis model.

In the current experiment, the effects of transforming growth factor (TGF)-ß1/Smad and ERK pathway crosstalk on synovial and pulmonary systems during rheumatoid arthritis have been investigated. For this purpose, rats were divided into normal control (NC) and model control (MC) groups. In the MC group, 0.1 ml Freund's complete adjuvant was injected intradermally into the right hind paw, and the resulting inflammation represented a rheumatoid arthritis model. Joint swelling and changes in lung functions were observed in arthritic rats. Synovial and lung were observed by light and electron microscopies. Enzyme-linked immunosorbent assays were used to detect TGF-ß1, interleukin (IL)-1ß, IL-4, IL-10, interferon-γ (IFN-γ), connective tissue growth factor (CTGF), and fibroblast growth factor (FGF). PCR, immunohistochemistry, and immunoblotting were used to detect changes in Smad and ERK pathways of synovial and lung tissues. Compared with the NC group, toe swelling was elevated in the MC group. Pulmonary functions FEV1, FEF50, FEF75, MMF, and PEF were decreased (P< 0.01). Serum cytokines IL-1ß, IL-4, TGF-ß1, and CTGF were increased, while IFN-γ, IL-10, Th1/Th2 cell ratio, and FGF were decreased (P< 0.01 or P< 0.05). Expression of TGF-ß1 and Smad2/3/4 mRNAs and TGF-ß1, TßRI, TßRII, Smad2/3, p-Smad2/3, and Smad4 proteins in the synovial membrane and lung tissue were increased, and expression of Smad7 mRNA and protein was decreased (P<0.01) or P<0.05). Expression of ERK2 mRNA and p-ERK1/2 protein was increased in the synovial membrane and lung tissue, and expression of ERK1/2 mRNAs and ERK1/2 and p-ERK1/2 proteins was increased in lung tissue (P< 0.01 or P< 0.05). Correlation analysis showed that FEV1 was negatively correlated with TGF-ß1 mRNA and protein in arthritic rats, FEF25 was negatively correlated with Smad4 protein, and FEF50 was negatively correlated with the TßRII protein, and FEF75, TGF-ß1 and Smad3 mRNAs. There was a negative correlation between Smad2/3 protein and a negative correlation between PEF and TGF-ß1 protein (P< 0.05). FEF50 and MMF were positively correlated with Smad7 mRNA (P< 0.05). FEV1 was negatively correlated with ERK2 mRNA, and FEF25 was negatively correlated with p-ERK1/2 protein. FEF75 and MMF were negatively correlated with ERK1/2 and p-ERK1/2, respectively (P< 0.05). ERK1 mRNA was positively correlated with Smad3 mRNA and TßRII protein, ERK2 mRNA was positively correlated with p-Smad2/3, and ERK1/2 protein was positively correlated with Smad2 mRNA, Smad4 protein, p-ERK1/2 protein, Smad4 mRNA, and p-Smad2/3 protein (P< 0.05). p-ERK1/2 protein was negatively correlated with Smad7 protein (P< 0.05). It is concluded that arthritic rats have synovial and systemic pulmonary damage. Smad and ERK pathway crosstalk leads to systemic lesions. Smad and ERK pathways are gradually activated by phosphorylation under the induction of the TGF-ß1 promoter, and then participate in transcriptional activities, leading to the increase in synovial inflammation of arthritis, pulmonary lesions, and decreases in lung functions.

[Clinical practice guideline for Tripterygium Glycosides/Tripterygium wilfordii Tablets in treatment of rheumatoid arthritis].

Tripterygium wilfordii Hook.f.(TwHF) is one of the most effective traditional Chinese herbal medicines against rheumatoid arthritis. As the representative agents of TwHF, Tripterygium Glycoside Tablets(TGT) and Tripterygium wilfordii Tablets(TWT) were included as Class A drugs in the 2019 edition of Medicine Catalogue for National Basic Medical Insurance, Injury Insurance and Maternity Insurance, and TGT was also included in 2018 edition of National Essential Drug List and 2015 edition of Chinese Pharmacopoeia. However, it is difficult to grasp the specific clinical applications of TGT and TWT. Side effects occur from time to time. The curative effect is uneven in patients. And the package inserts of TGT and TWT are not described in details. In order to standardize the clinical application of Tripterygium wilfordii preparations, 38 authoritative units and 48 well-known experts in rheumatoid immunology clinical department, drug supervision and management, pharmacy and evidence-based medicine research fields jointly developed Tripterygium Glycoside Tablets and Tripterygium wilfordii Tablets Medication Guide for reference in clinical application, teaching and scientific research. The guideline followed the "evidence-based, consensus-assisted and experience-based" principles to form "recommendations" for the evidence supported ones, and form "consensus suggestions" for those without evidence support by using nominal group method. In this way, the medication recommendations on function, usage and dosage, drug combinations, precautions, efficacy, safety and other aspects of TGT and TWT can be provided. The application of this Guide will help to avoid or reduce the adverse reactions of T. wilfordii preparations, enhance the efficacy and reduce the cost of medicine, with certain demonstration and promotion values to improve the rational use level of traditional Chinese medicine.

[Editorial explanation for Clinical practice guideline for Tripterygium Glycosides/Tripterygium wilfordii Tablets in treatment of rheumatoid arthritis].

Clinical practice guideline for Tripterygium Glycosides/Tripterygium wilfordii Tablets in the treatment of rheumatoid arthritis(T/CACM 1337-2020) was approved on June, 2020 by the Standardization Office of Chinese Association of Chinese Medicine. Our group developed this guideline for the clinical application of Tripterygium Glycosides/Tripterygium wilfordii Tablets according to the manual for the clinical experts consensus of Chinese patent medicine from January, 2018, when this project was approved by Chinese Association of Chinese Medicine. In this article, the detailed information on our compilation process was provided, in order to facilitate the understanding and the application of the guideline, as well as provide reference for the development of clinical practice guideline for other Chinese patent medicine.

Germline mutations in 40 cancer susceptibility genes among Chinese patients with high hereditary risk breast cancer.

Multigene panel testing of breast cancer predisposition genes have been extensively conducted in Europe and America, which is relatively rare in Asia however. In this study, we assessed the frequency of germline mutations in 40 cancer predisposition genes, including BRCA1 and BRCA2, among a large cohort of Chinese patients with high hereditary risk of BC. From 2015 to 2016, consecutive BC patients from 26 centers of China with high hereditary risk were recruited (n = 937). Clinical information was collected and next-generation sequencing (NGS) was performed using blood samples of participants to identify germline mutations. In total, we acquired 223 patients with putative germline mutations, including 159 in BRCA1/2, 61 in 15 other BC susceptibility genes and 3 in both BRCA1/2 and non-BRCA1/2 gene. Major mutant non-BRCA1/2 genes were TP53 (n = 18), PALB2 (n = 11), CHEK2 (n = 6), ATM (n = 6) and BARD1 (n = 5). No factors predicted pathologic mutations in non-BRCA1/2 genes when treated as a whole. TP53 mutations were associated with HER-2 positive BC and younger age at diagnosis; and CHEK2 and PALB2 mutations were enriched in patients with luminal BC. Among high hereditary risk Chinese BC patients, 23.8% contained germline mutations, including 6.8% in non-BRCA1/2 genes. TP53 and PALB2 had a relatively high mutation rate (1.9 and 1.2%). Although no factors predicted for detrimental mutations in non-BRCA1/2 genes, some clinical features were associated with mutations of several particular genes.

Curative efficacy of low frequency electrical stimulation in preventing urinary retention after cervical cancer operation.

BACKGROUND: To evaluate the clinical significance of low-frequency electrical stimulation in preventing urinary retention after radical hysterectomy. METHODS: A total of 91 women with stage IA2-IB2 cervical cancer, who were treated with radical hysterectomy and lymphadenectomy from January 2009 to December 2012, were enrolled into this study and were randomly divided into two groups: trail group (48 cases) and control group (43 cases). Traditional bladder function training and low-frequency electrical stimulation were conducted in the trail group, while patients in the control group were only treated by traditional bladder training. The general condition, rate of urinary retention, and muscle strength grades of pelvic floor muscle in the perioperative period were compared between these two groups. RESULTS: The incidence of postoperative urinary retention in the electrical stimulation group was 10.41%, significantly lower than that in the control group (44.18%), and the difference was statistically significant (P < 0.01). The duration of postoperative fever and use of antibiotics were almost the same between these two groups. Eleven days after surgery, the difference in grades of the pelvic floor muscle between these two groups was not statistically significant. However, 14 days after the operation, grades of the pelvic floor muscle were significantly higher in the trail group than in the control group, and the difference was statistically significant (P < 0.01). In addition, although there was no significant difference between the two groups with different parameters (P = 0.782), the incidence of urinary retention was lower in the endorphins analgesia program group than in the neuromuscular repair program group (9.09% < 11.54%). CONCLUSION: Low-frequency electrical stimulation is more effective than conventional intervention in preventing urinary retention after radical hysterectomy. It also intensifies the recovery of pelvic muscle strength.

Morphological Changes of Collagen Fibers in Myocardium of Rats under Different Exercise Loads Based on Three-Dimensional Simulation Technique.

In order to improve the visual analysis ability of the morphological changes of rat liulimyocardial collagen fibers under different exercise loads, a method of extracting the morphological changes of collagen fibers in rat myocardium under different exercise loads based on three-dimensional simulation technique is proposed. The three-dimensional morphological characteristics of the collagen fibers in the original rat myocardium are made by CT scanning technique. Like information collection, a gradient decomposition method is used to filter the three-dimensional morphological features of rat myocardial collagen fibers. The edge contour features of the three-dimensional morphological features of rat myocardial collagen fibers under different motion loads are extracted. The threshold segmentation method is used to carry out the rat myocardial glue under different exercise loads. The segmentation of the regional pixel feature block of the three-dimensional morphological features of the original fiber is segmented into a block vector with high resolution, and the regional reconstruction of the three-dimensional morphological features of the rat myocardial collagen fibers under different motion loads is carried out to realize the high resolution identification and classification of the 3D morphological features of the rat myocardial collagen fibers. The simulation results show that the three-dimensional simulation of the morphological changes of rat myocardial collagen fibers under different exercise loads is better, and the accuracy of feature extraction is higher.

Effect of transcutaneous electrical stimulation treatment on lower urinary tract symptoms after class III radical hysterectomy in cervical cancer patients: study protocol for a multicentre, randomized controlled trial.

BACKGROUND: Class III radical hysterectomy (RH III)_plus pelvic lymphadenectomy is the standard surgery for early stage cervical cancer (CC) patients, the 5 year survival rate is about 90%, but pelvic floor disorders especially bladder dysfunction are common due to damaged vessels and nerve fibers following surgery. Transcutaneous electrical stimulation (TENS) treatment has been used to treat bladder disorders for many years, but its effect on cervical cancer patients, the best treatment time point and stimulated protocol, had never been assessed. The aim of this study is to investigate the efficacy of TENS treatment on lower urinary tract symptoms (LUTS) after RH III in CC patients. METHODS/DESIGN: The study will be conducted as a clinical, multicentre, randomised controlled trial with balanced randomisation (1:1). The planned sample size is 208 participants (at 1:1 ratio, 104 subjects in each group). At 5-7 days after RH III, patients are screened according to operative and pathological findings. Enrolled participants are randomised into an intervention group (TENS plus conventional clinical care) or control group (conventional clinical care), with stratification by menopausal status (menopause vs. non-menopause) and surgical modality (laparoscopic RH or abdominal RH). Participants in both groups will be followed up at 14 days, 21 days, 28 days, 3 months, 6 months, 12 months, 18 months and 24 months after surgery. The primary endpoint is improvement rate of urination function which is defined as recovery (residual urine ≤50 ml) or improvement (residual urine 50-100 ml). Secondary endpoints include urodynamic parameter, urinary incontinence, anorectal function, pelvic function, quality of life (QOL), disease-free survival and adverse events. Primary endpoint analyses will be carried out by Cochran-Mantel-Haenszel tests taking into center effect. DISCUSSION: To our knowledge this is the first trial to investigate the effect of TENS treatment on bladder function recovery after RH III among CC patients. This study will provide new information on TENS efficacy for bladder function recovery. Once confirmed, it may help to provide a new, non-invisive treatment for those postoperative CC patients with poor pelvic function, which would help improve their quality of life. TRIAL REGISTRATION: The study is registered to Clinical Trials.gov ( NCT02492542 ) on June 25, 2015.

Ca2+ channel subunit α 1D promotes proliferation and migration of endometrial cancer cells mediated by 17ß-estradiol via the G protein-coupled estrogen receptor.

Calcium and calcium channels are closely related to the estrogen-induced nongenomic effect of endometrial carcinoma, but the specific role of calcium channels is unknown. This study aimed to explore the expression and the biologic effect of the L-type calcium channel in endometrial carcinoma cells and to clarify the molecular mechanism of the relationship between L-type calcium channels and estrogen. The immunohistochemical results showed that Ca(2+) channel subunit α 1D (Cav1.3) expression was high in atypical hyperplasia (1.90 ± 0.35) and endometrial carcinoma tissues (2.05 ± 0.82) but weak (0.80 ± 0.15) in benign endometrial tissues (P < 0.05). Treatment with 17ß-estradiol rapidly increased Cav1.3 expression in a dose- and time-dependent manner, and 100 nM cell-impermeable ß-estradiol-6-(O-carboxymethyl)oxime:bovine serum albumin also promoted Cav1.3 expression. Transfection with small interfering RNA against G protein-coupled estrogen receptor (GPER) suppressed estrogen-induced up-regulation of Cav1.3 compared with control cells and markedly reduced the estrogen-induced phosphorylation of ERK1/2 and CREB. Knocking down the Cav1.3 significantly suppressed estrogen-stimulated Ca(2+) influx, cell proliferation, and migration in endometrial cancer cells. Taken together, Cav1.3 was overexpressed in atypical hyperplasia and endometrial carcinoma, and the estrogen-induced phosphorylation of downstream molecular ERK1/2 and CREB is the result of activation of the GPER pathway. L-type channel Cav1.3 is required for estrogen-stimulated Ca(2+) influx and contributes broadly to the development of endometrial cancer. The Cav1.3 channel may be a new target for endometrial carcinoma treatment.

Outcomes of fertility and pregnancy in patients with early-stage cervical cancer after undergoing neoadjuvant chemotherapy.

OBJECTIVE: To explore the outcomes of oncology, fertility, and pregnancy in patients after undergoing neoadjuvant chemotherapy (NACT) followed by fertility-sparing operations with cervical cancer, and its value in clinical treatment. MATERIALS AND METHODS: A total of 11 patients from seven hospitals in Beijing with cervical cancer since August 2009 to December 2011, who had undergone fertility- sparing treatments were recruited in this study. RESULTS: Among the 11 patients, there were nine cases of squamous cell carcinoma, two cases of adenocarcinoma, one case in Stage IA2, and ten cases in Stage IB1 (FIGO, 2009). All of the 11 patients were treated with NACT of one to two cycles before the operations, and then they underwent radical trachelectomy (RT) + retroperitoneal lymphadenectomy. Eleven patients had completed the follow-up (100%) and the mean follow-up was 24.4 months. The outcomes of the oncology and pregnancy are as follows: no patient recurred after fertility-sparing treatments; in seven patients seeking pregnancy after the treatments, three pregnancies occurred in two women. CONCLUSIONS: NACT+RT, as a fertility-sparing treatment for young women with bulky early-stage cervical cancer and its outcomes in fertility and pregnancy are satisfactory, however its safety needs to be studied further.

[Role of S100A4 in the epithelial-mesenchymal transition of esophageal squamous cell carcinoma and its molecular mechanism].

OBJECTIVE: To explore the role of S100A4 in the epithelial-mesenchymal transition (EMT) in esophageal squamous cell carcinoma and its possible molecular mechanism. METHODS: Three chemically synthesized S100A4 siRNA sequences were transiently transfected into esophageal carcinoma EC9706 cells. EC9706 cells transfected with negative siRNA, lipofectamine 2000, and vacant EC9706 cells were used as control. Fluorescence quantitative RT-PCR and Western blot were used to detect the inhibition rate of S100A4 siRNA. S100A4 siRNA2 with the best inhibition rate was chosen to transiently transfect into EC9706 cells under the same conditions. The EC9706 cells transfected with negative siRNA, lipofectamine 2000 and vacant EC9706 cells were also used as control. Fluorescence quantitative RT-PCR and Western blot were used to detect the mRNA and protein expressions of E-cadherin, vimentin and snail. The morphology of EC9706 cells was observed under an inverted microscope. Boyden chamber and scratch test were used to detect the invasion and migration ability of EC9706 cells, and CCK8 assay was used to detect the proliferation ability of EC9706 cells. EC9706 cells transfected with S100A4 siRNA2 were further transfected with snail eukaryotic expression vector. The EC9706 cells transfected with S100A4 siRNA, EC9706 cells transfected with snail eukaryotic expression vector and vacant EC9706 cells were used as control. The above indexes of all the groups were observed, too. RESULTS: The S100A4 mRNA and protein expression levels of the S100A4 siRNA2 group were 0.417 ± 0.041 and 0.337 ± 0.039, the transmembrane cell number was 61.608 ± 8.937, the scratch healing distance was (0.216 ± 0.064) mm, the A value was 0.623 ± 0.084, the E-cadherin mRNA and protein levels were 0.619 ± 0.032 and 0.495 ± 0.034, the vimentin mRNA and protein levels were 0.514 ± 0.032 and 0.427 ± 0.028, the snail mRNA and protein levels were 0.573 ± 0.029 and 0.429 ± 0.041. These data were significantly different with the liposome group, the negative control group and the blank group (P < 0.05 for all). After the S100A4 siRNA2 treatment for 24 h, the appearance of EC9706 cells changed to epithelial cell morphology. The transmembrane cell number and the scratch healing distance of the S100A4 siRNA2+snail eukaryotic expression vector group were (69.382 ± 9.666) cells and (0.274 ± 0.029) mm, the A value was 0.823 ± 0.101, the snail mRNA and protein levels were 0.704 ± 0.037 and 0.625 ± 0.031, the vimentin mRNA and protein levels were 0.712 ± 0.046 and 0.609 ± 0.038, and these data were significantly higher than those of the Sl00A4 siRNA2 group (P < 0.05 for all). The E-cadherin mRNA and protein levels of the S100A4 siRNA2+eukaryotic expression vector group were 0.437 ± 0.038 and 0.381 ± 0.031, significantly lower than those of the S100A4 siRNA2 group (P < 0.05 for all). However, snail had no effect on the morphology of EC9706 cells. CONCLUSIONS: S100A4 may be involved in the EMT process of esophageal squamous-cell carcinoma by regulating the expression of snail and then plays a role in the invasion and metastasis of esophageal carcinoma.

[Nongenomic effects of estrogen on extracellular signal-regulated kinases through initiating transient calcium flux in endometrial cancer].

OBJECTIVE: To study the mechanism on extracellular signal-regulate kinases (ERK) signal transduction by calcium influx initiated by combination of estrogen with calcium channels or estrogen receptor in endometrial cancer cell Ishikawa. METHODS: Confocal test was used to determine the relative calcium mobilization by stimulation of estrodiol together with and without the inhibition of ICI182780 and nifedipine. Western-blotting was used to detect the protein expression of phosphorylated ERK1/2 (P-ERK1/2) in the same condition. RESULTS: The transient calcium flux initiated by 17ß-estrodiol (E2) and a membrane-impermeable conjugate of estrogen and bovine serum albumin (E2-BSA), and the calcium mobilization could be inhibited by ICI182780 and nifedipine in 1 min. In Ishikawa cells, phosphorylation of ERK1/2 was stimulated by E2, and the phosphorylation could not be inhibited by E2 after the combination with ICI182780 in 5 min and in 30 min. The phosphorylation also could not be inhibited by E2-BSA after the combination with nifedipine in 5 min, but in 30 min the phosphorylation was decreased. The phosphorylation of ERK by E2-BSA was decreased by the combination with nifedipine in 30 min. CONCLUSION: The transient calcium flux initiated by estrogen has an effect on the activation of ERK signal pathway in endometrial carcinoma cells.

Elevator block brake structural optimization design based on an approximate model.

An Aquila optimizer-back propagation (AO-BP) neural network was used to establish an approximate model of the relationship between the design variables and the optimization objective to improve elevator block brake capabilities and achieve a lightweight brake design. Subsequently, the constraint conditions and objective functions were determined. Moreover, the multi-objective genetic algorithm optimized the structural block brake design. Finally, the effectiveness of the optimization results was verified using simulation experiments. The results demonstrate that the maximum temperature of the optimized brake wheel during emergency braking was 222.09°C, which is 36.71°C lower than that of 258.8°C before optimization, with a change rate of 14.2%. The maximum equivalent stress after optimization was 246.89 MPa, 28.87 MPa lower than that of 275.66 MPa before optimization, with a change rate of 10.5%. In addition, the brake wheel mass was reduced from 58.85 kg to 52.40 kg, and the thermal fatigue life at the maximum equivalent stress increased from 64 times before optimization to 94 times after optimization.