Development and clinical validation of a seven-gene signature based on tumor stem cell-related genes to predict ovarian cancer prognosis.

OBJECTIVE: Tumors are highly heterogeneous, and within their parenchyma, a small population of tumor-stem cells possessing differentiation potential, high oncogenicity, and self-renewal capabilities exists. These cells are pivotal in mediating tumor development, chemotherapy resistance, and recurrence. Ovarian cancer shares characteristics with tumor stem cells, making it imperative to investigate molecular markers associated with these cells. METHODS: Stem cell-related genes were collected, and molecular subtypes were established based on gene expression profiles from The Cancer Genome Atlas using the R package tool "ConsensusClusterPlus." Multi-gene prognostic markers were identified using LASSO regression analysis. Gene set enrichment analysis was employed to gain insights into the potential molecular mechanisms of these identified markers. The robustness of these prognostic markers was analyzed across different cohorts, and their clinical independence was determined through multivariate Cox analysis. A nomogram was constructed to assess the model's clinical applicability. Immunohistochemistry was performed to validate the expression of hub genes. RESULTS: Utilizing 49 tumor stem cell-related genes associated with prognosis, 362 ovarian cancer samples were divided into two distinct clusters, revealing significant prognostic disparities. A seven-gene signature (GALP, CACNA1C, COL16A1, PENK, C4BPA, PSMA2, and CXCL9), identified through LASSO regression, exhibited stability and robustness across various platforms. Multivariate Cox regression analysis confirmed the signature's independence in predicting survival in patients with ovarian cancer. Furthermore, a nomogram combining the gene signature demonstrated strong predictive abilities. Immunohistochemistry results indicated significantly elevated GALP, CACNA1C, COL16A1, PENK, C4BPA, PSMA2, and CXCL9 expression in cancer tissues. CONCLUSION: The seven-gene signature holds promise as a valuable tool for decision-making and prognosis prediction in patients with ovarian cancer.

Construction of Inorganic/Polymer Tandem Layer on Li Metal with Long-Term Stability by LiNO3 Concentration Gradient Electrolyte.

Metal electrode with long cycle life is decisive for the actual use of metal rechargeable batteries, while the dendrite growth and side reaction limit their cyclic stability. Herein, the construction of polymer and inorganic-rich SEI tandem layer structure on Li metal can be used for extraordinarily extending its cycle life is reported, which is generated by an in situ PVDF/LiF/LiNO3 (PLL) gel layer on the surface of Li metal with a chemically compatible ether solvent. The cycle life of Li//Li cells with the tandem layer structure is over 6000 h, six times longer than those with LiNO3 homogeneous electrolyte. It highlights the importance of LiNO3 concentration gradient electrolyte formed by the in situ PLL gel layer, in which highly concentrated LiNO3 is confined on the surface of Li metal to generate the uniform and inorganic-rich LiF/Li2 O/Li3 N layer on the bottom of PVDF/LiF with good mechanical strength, resulting in the dendrite free anode in cell cycling. The assembled Li//LiFePO4 and Li//NMC811 batteries show the capacity retention rate of 80.9% after 800 cycles and 82.3% after 500 cycles, respectively, much higher than those of references.

Cost-effectiveness analysis of digital therapeutics for home-based cardiac rehabilitation for patients with chronic heart failure: model development and data analysis.

BACKGROUND: In recent years, numerous guidelines and expert consensus have recommended the inclusion of digital technologies and products in cardiac rehabilitation. Digital therapeutics (DTx) is an evidence-based medicine that uses digital means for data collection and monitoring of indicators to control and optimize the treatment, management, and prevention of disease. OBJECTIVE: This study collected and reviewed real-world data and built a model using health economics assessment methods to analyze the potential cost-effectiveness of DTx applied to home-based cardiac rehabilitation for patients with chronic heart failure. From the perspective of medical and health decision-makers, the economic value of DTx is evaluated prospectively to provide the basis and reference for the application decision and promotion of DTx. METHODS: Markov models were constructed to simulate the outcomes of DTx for home-based cardiac rehabilitation (DT group) compared to conventional home-based cardiac rehabilitation (CH group) in patients with chronic heart failure. The model input parameters were clinical indicators and cost data. Outcome indicators were quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs). The robustness of the evaluation methods and results was tested using sensitivity analyses. Clinical indicators, cost data, and health utility values were obtained from real-world data, including clinical study data, published literature, and public website information. RESULTS: The Markov model simulated a time span of 10 years, with a cycle set at one month, for 120 cycles. The results showed that the per capita cost of the CH group was 38,442.11 CNY/year, with a QALY of 0.7196 per person per year. The per capita cost of the DT group was 42,300.26 CNY/year, with a QALY of 0.81687 per person per year. The ICER per person was 39,663.5 CNY/QALY each year, which was below the willingness-to-pay threshold of 85,698 CNY (China's GDP per capita in 2022). CONCLUSIONS: DTx for home-based cardiac rehabilitation is an extremely cost-effective rehabilitation option compared with conventional home-based cardiac rehabilitation. DTx for home-based cardiac rehabilitation is potentially valuable from the perspective of healthcare decision-makers.

Material Classification and Aging Time Prediction of Structural Metals Using Laser-Induced Breakdown Spectroscopy Combined with Probabilistic Neural Network.

In this paper, laser-induced breakdown spectroscopy (LIBS) combined with a probabilistic neural network (PNN) was applied to classify engineering structural metal samples (valve stem, welding material, and base metal). Additionally, utilizing data from the plasma emission spectrum generated by laser ablation of samples with different aging times, an aging time prediction model based on a firefly optimized probabilistic neural network (FA-PNN) was established, which can effectively evaluate the service performance of structural materials. The problem of insufficient features obtained by principal component analysis (PCA) for predicting the aging time of materials is addressed by the proposal of a time-frequency feature extraction method based on short-time Fourier transform (STFT). The classification accuracy (ACC) of time-frequency features and principal component features was compared under PNN. The results indicate that, in comparison to the PCA feature extraction approach, the time-frequency feature extraction method based on STFT demonstrates higher accuracy in predicting the time of aging materials. Then, the relationship between classification accuracy (ACC) and settings of PNN was discussed. The ACC of the PNN model for both the material classification test set and the aging time test set achieved 100% with Firefly (FA) optimization algorithms. This result was also compared with the ACC of ANN, KNN, PLS-DA, and SIMCA for the aging time test set (95%, 87.5%, 85%, and 62.5%, respectively). The experimental results demonstrated that the classification model using LIBS combined with FA-PNN could realize better classification accuracy.

Establishment and Optimization of Molecular Cytogenetic Techniques (45S rDNA-FISH, GISH, and Fiber-FISH) in Kiwifruit (Actinidia Lindl.).

The kiwifruit (Actinidia chinensis) has long been regarded as "the king of fruits" for its nutritional importance. However, the molecular cytogenetics of kiwifruit has long been hampered because of the large number of basic chromosome (x = 29), the inherent small size and highly similar morphology of metaphase chromosomes. Fluorescence in situ hybridization (FISH) is an indispensable molecular cytogenetic technique widely used in many plant species. Herein, the effects of post-hybridization washing temperature on FISH, blocking DNA concentration on genomic in situ hybridization (GISH), extraction method on nuclei isolation and the incubation time on the DNA fiber quality in kiwifruit were evaluated. The post-hybridization washing in 2 × saline sodium citrate (SSC) solution for 3 × 5 min at 37°C ensured high stringency and distinct specific FISH signals in kiwifruit somatic chromosomes. The use of 50 × blocking DNA provided an efficient and reliable means of discriminating between chromosomes derived from in the hybrids of A. chinensis var. chinensis (2n = 2x = 58) × A. eriantha (2n = 2x = 58), and inferring the participation of parental genitors. The chopping method established in the present study were found to be very suitable for preparation of leaf nuclei in kiwifruit. A high-quality linear DNA fiber was achieved by an incubation of 20 min. The physical size of 45S rDNA signals was approximately 0.35-0.40 µm revealed by the highly reproducible fiber-FISH procedures established and optimized in this study. The molecular cytogenetic techniques (45S rDNA-FISH, GISH, and high-resolution fiber-FISH) for kiwifruit was for the first time established and optimized in the present study, which is the foundation for the future genomic and evolutionary studies and provides chromosomal characterization for kiwifruit breeding programs.

Accurate identification and surgical correction of type IIb uterine malformation using synchronized hysteroscopy and laparoscopy.

OBJECTIVE: To introduce an effective approach for accurate identification and treatment of type IIb uterine malformation using synchronized hysteroscopy and laparoscopy. DESIGN: Step-by-step video explanation of the surgical procedure with still pictures and surgical video clips to demonstrate the detailed technique. The patient provided written informed consent for video and data collection for research purposes. The study was approved by the local ethics committee of Shengjing Hospital of China Medical University. SETTING: Academic medical center. PATIENT(S): A 32-year-old young woman diagnosed with a right unicornuate uterus with a left rudimentary horn, with a 2-year history of dysmenorrhea. INTERVENTION(S): First, the patient was diagnosed with a unicornuate uterus with a rudimentary horn using ultrasonography and magnetic resonance imaging before the surgery. During surgery, synchronized hysteroscopy and laparoscopy coupled with a light test was performed to make a definite identification of the type IIb uterine malformation. During treatment of the type IIb uterine malformation, there were two key steps: resected the rudimentary horn and reserved more myometrial tissue to reduce the risk of uterine rupture in a subsequent pregnancy; and corrected the uterus to prevent future uterine prolapse. For the suture technique, suturing during resection was performed instead of suturing after complete resection to reduce the intraoperative bleeding as much as possible. Furthermore, tubal catheterization and hydrotubation under hysteroscopy monitoring were performed. MAIN OUTCOME MEASURE(S): Value and feasibility of synchronized hysteroscopic and laparoscopic identification and treatment of the type IIb uterine malformation. RESULT(S): The total operation time was 89 minutes. The postoperative pathological findings revealed that the endometrium was found in the rudimentary horn. No dysmenorrhea was found during follow-up. At 26 months after the operation, the patient became pregnant naturally. Cesarean section was performed at 36 weeks + 2 days owing to premature rupture of the membranes. CONCLUSION(S): For the accurate identification and management of a type IIb uterine malformation, synchronized hysteroscopy and laparoscopy is an effective and feasible method.

LINC01116 promotes proliferation and migration of endometrial stromal cells by targeting FOXP1 via sponging miR-9-5p in endometriosis.

Endometriosis is a common multi-factorial gynaecological disease. Recent studies have revealed that long non-coding RNAs (lncRNAs) are involved in the pathogenesis of endometriosis. In the present study, the expression profiles of lncRNAs in 6 pairs of endometriosis ectopic endometrium (ecEM) and eutopic endometrium (euEM) tissues were analysed by RNA sequencing. From the profiles, LINC01116 was found to be up-regulated in ecEM tissues compared to euEM tissues and was verified by quantitative real-time PCR (qRT-PCR). Then, functional experiments demonstrated that LINC01116 promoted the proliferation and migration of ectopic primary endometrial stromal cells (ESCs), while miR-9-5p exerted the opposite effects. Dual-luciferase reporter assays verified that LINC01116 directly sponged miR-9-5p and relieved the suppression of its target, Forkhead box protein P1 (FOXP1). Rescue experiments further demonstrated that LINC01116 could promote proliferation and migration of ESCs by targeting FOXP1 via sponging miR-9-5p. Overall, our study illuminates that LINC01116 promotes the progression of endometriosis through the miR-9-5p/FOXP1 axis. This finding provides a novel therapeutic target for patients with endometriosis.

An effective method using laparoscopy in treatment of upper vaginal leiomyoma.

OBJECTIVE: To introduce an effective approach using laparoscopy in the treatment of upper vaginal leiomyoma. DESIGN: Step-by-step video explanation of the surgical procedure with still pictures and surgical video clips to demonstrate the detailed technique, approved by the Shengjing Hospital of China Medical University. SETTING: Hospital. PATIENT(S): A 34-year-old woman diagnosed with 5-cm upper vaginal leiomyoma, who had sexual discomfort for 5 years. INTERVENTION(S): Using laparoscopy in the treatment of upper vaginal leiomyoma consists of five steps: first lysing the pelvic adhesion; exploring the pelvic cavity and locating the vaginal leiomyoma through gynecologic examination by the assistant; recognizing the position between leiomyoma and ureter and carefully dissociating ureter while avoiding injury; completely enucleating and resecting the vaginal leiomyoma using laparoscopy; and exploring the ureter, rectum, and uterine artery to make sure there was no injury. MAIN OUTCOME MEASURE(S): Value and feasibility of using laparoscopy in treatment of upper vaginal leiomyoma. RESULT(S): The vaginal leiomyoma was removed successfully using laparoscopic operation and the operative time was 95 minutes. In the follow-up period, the patient did not report any symptoms, and she became pregnant at the time of the 20th month after operation and underwent a vaginal delivery at full-term. CONCLUSION(S): For upper vaginal leiomyoma treatment, laparoscopic operation could present a clear visual field to avoid injury of bladder, ureter, rectum, and uterine artery. Laparoscopic operation is safe and feasible in treatment of upper vaginal leiomyoma.

miR-96-5p regulated TGF-ß/SMAD signaling pathway and suppressed endometrial cell viability and migration via targeting TGFBR1.

We previously performed high throughput RNA-seq in paired eutopic and ectopic endometrial specimen of endometriosis patients, and validated the results by qRT-PCR in endometriosis endometrial tissues. MiR-96-5p was significantly downregulated in ectopic endometrial tissues compared to eutopic tissues. In order to identify the role of miR-96-5p in endometriosis and endometrial cells, and investigate the underlying mechanisms, the Ishikawa and End1/E6E7 cell lines were transfected with miR-96-5p mimics, miR-96-5p inhibitors or TGFBR1 siRNA. The expression of TGF-ß/SMAD signaling pathway components and epithelial-mesenchymal transition (EMT) markers were examined by qRT-PCR and western blot, and cell viability and migration were determined by CCK-8, transwell and wound healing assays, respectively. We discovered miR-96-5p to be significantly downregulated while TGFBR1 was distinctly up-regulated in endometriosis. Overexpression of miR-96-5p inhibited endometrial cells viability and migration, while inhibition of miR-96-5p had opposite effect. Furthermore, we confirmed TGFBR1 was a direct target of miR-96-5p. Overexpression of miR-96-5p could block the TGF-ß/SMAD signaling pathway via targeting TGFBR1 and reverse the TGF-ß1 induced EMT in endometrial cell lines. In conclusion, we demonstrated that miR-96-5p interacted with TGF-ß/SMAD signaling pathway and blocked the TGF-ß1 induced EMT in endometrial cells via directly targeting TGFBR1.

The role of miR-34c-5p/Notch in epithelial-mesenchymal transition (EMT) in endometriosis.

Endometriosis, a common benign gynecological disease, has the growth characteristics of malignant tumors, however, the pathogenesis of this disease remains unclear. It is well known that micro ribonucleic acids (miRNAs) are involved in epithelial-mesenchymal transition (EMT), associated with the development of endometriosis. This study investigated the role of a specific miRNA, miR-34c-5p, in endometriosis. High-throughput sequencing (HTS) showed that miR-34c-5p expression was reduced in ectopic endometrium (ecEM) in patients from Northeast Asia with ovarian endometriosis. A wound healing assay and a transwell invasion assay showed that miR-34c-5p inhibits the invasion and migration of Ishikawa and End1/E6E7 endocervical cells. Dual luciferase gene reporter assays revealed that miR-34c-5p specifically targets Notch1 3 'UTR, and Western blot analyses showed that miR-34c-5p promotes E-cadherin expression but inhibits Notch1, N-cadherin and vimentin expression in Ishikawa and End1/E6E7 cell lines. These results were reversed following knockdown of miR-34c-5p. Using quantitative real time reverse transcriptase polymerase chain reaction (qRT-PCR) and western blot analyses, there was a significant reduction in the expression of Notch1 in ecEM compared with eutopic endometrium (euEM). The results of this study indicate that miR-34c-5p inhibits the progression of EMT and cell invasion and migration by targeting the Notch signaling pathway, specifically, Notch1. The findings of this study provide unique insights into the development of EMT in endometriosis and novel, potential therapeutic targets.

Laparoscopic myomectomy using self-made retrieval bag to contain tissue extraction.

OBJECTIVE: To introduce an effective approach using a self-made retrieval bag during laparoscopic myomectomy to contain tissue extraction. DESIGN: Step-by-step video explanation of the surgical procedure with still pictures and surgical video clips to demonstrate the detailed technique, approved by the Shengjing Hospital of China Medical University. SETTING: University hospital. PATIENT(S): A 32-year-old woman diagnosed with a uterine myoma (diameter, 6 cm). She had endured 5 years of intermittent lower abdominal pain and 2 years of infertility. INTERVENTION(S): A self-made retrieval bag during laparoscopic myomectomy was used (consists of four steps) to contain tissue extraction. 1. Self-made retrieval bag using a sterile medical bag. 2. Inspect the pelvic cavity, evaluate and determine the location and number of myomas. 3. Resect the myoma. 4. Morcellate the myoma into pieces inside the retrieval bag using laparoscopic power morcellation. MAIN OUTCOME MEASURE(S): Value and feasibility of using a self-made retrieval bag in laparoscopic myomectomy. RESULT(S): The myoma was successfully and completely resected by laparoscopy using a self-made retrieval bag to contain tissue extraction. Operative time was 93 minutes. In the follow-up period, the patient did not report any symptom of iatrogenic parasitic myoma. The woman had a pregnancy at month 26 after operation and underwent a cesarean section. This resulted in a full-term baby. CONCLUSION(S): Our surgical approach demonstrated a number of noteworthy advantages. The use of retrieval bag to contain tissue extraction during laparoscopic morcellation can avoid the risk of iatrogenic parasitic myoma. The retrieval bag is self-made using a sterile packing bag, which is cost free and also reduces operative expenses.

Dose-response relation between dietary inflammatory index and human cancer risk: evidence from 44 epidemiologic studies involving 1,082,092 participants.

Background: A newly developed dietary inflammatory index (DII) to evaluate the inflammatory potential of diets was published recently. Many studies have investigated the link between diet-related inflammation and human cancer risk, but the results remain controversial. Objective: We sought to determine the dose-response relation between DII and human cancer risk based on published epidemiologic literature. Design: To summarize evidence, we performed a dose-response meta-analysis to investigate the association between DII and cancer incidence. We systematically searched PubMed, Embase, Web of Science, and the Cochrane library up to 5 November 2017. After data extraction, pooled RRs were calculated and dose-response analyses were performed using a restricted cubic spline model with 4 knots. Subgroup analyses, sensitivity analyses, and tests for publication bias were also performed. Results: In all, 44 high-quality studies with 1,082,092 participants were included. The results showed that an elevated DII (continuous-RR: 1.13; 95% CI: 1.09, 1.16; category DIIhighest vs lowest-RR: 1.58; 95% CI: 1.45, 1.72) independently indicated higher cancer risk except for lung cancer and Australian studies. A linear dose-response relation between DII and overall cancer risk was found, with an 8.3% increase in the risk of cancer per DII score. The pooled RR of DII and cancer risk was 1.86 (95% CI: 1.63, 2.13) from 30 case-control studies but was lower in 14 prospective cohorts (RR: 1.29; 95% CI: 1.19, 1.40). The sensitivity analysis and Egger's test supported the main results. Conclusions: Our analysis indicated that higher DII is significantly correlated with cancer risk. More prospective studies with large sample sizes, involving more ethnic groups and different cancer types, are required in the future. This review was registered with PROSPERO as CRD42017077075.

Effect of the BRCA1-SIRT1-EGFR axis on cisplatin sensitivity in ovarian cancer.

There is accumulating evidence that breast cancer 1 (BRCA1), sirtuin 1 (SIRT1), and epidermal growth factor receptor (EGFR) help to modulate cisplatin cytotoxicity. The role of dynamic crosstalk among BRCA1, SIRT1, and EGFR in cisplatin sensitivity remains largely unknown. We found that BRCA1, SIRT1, and EGFR levels were increased in cisplatin-resistant ovarian cancers compared with those in cisplatin-sensitive ovarian cancers. Hypomethylation in the BRCA1 promoter was associated with BRCA1 activation, significantly elevated SIRT1 levels, decreased nicotinamide adenine dinucleotide (NAD)-mediated SIRT1 activity, and decreased EGFR levels. Treatment with 5 and 10 µg/ml cisplatin induced a gradual increase in BRCA1 and SIRT1 levels and a gradual decrease in NAD levels and NAD-mediated SIRT1 activity, whereas EGFR levels were increased or decreased by treatment with 5 or 10 µg/ml cisplatin, respectively. The overexpression of SIRT1 or the enhancement of SIRT1 activity synergistically enhanced the BRCA1-mediated effects on EGFR transcription. In contrast, the knockdown of SIRT1 or the inhibition of SIRT1 activity inhibited the BRCA1-mediated effects on EGFR transcription. BRCA1 regulates EGFR through a BRCA1-mediated balance between SIRT1 expression and activity. Those results improve our understanding of the basic molecular mechanism underlying BRCA1-related cisplatin resistance in ovarian cancer.