Neoadjuvant chemotherapy followed by surgery versus concurrent chemoradiotherapy in patients with stage IIB cervical squamous cell carcinoma: a retrospective cohort study.

PURPOSE: This study aims to compare treatment outcomes between neoadjuvant chemotherapy (NACT) followed by surgery and concurrent chemoradiotherapy (CCRT) in patients with stage IIB cervical squamous cell carcinoma (CSCC). MATERIALS AND METHODS: We conducted a retrospective cohort study involving patients with stage IIB CSCC treated at Guangxi Medical University Cancer Hospital between June 2012 and June 2019. We compared overall survival (OS), locoregional-free survival (LRFS), and distant metastasis-free survival (DMFS) between the NACT + surgery and CCRT groups. RESULTS: A total of 257 patients were enrolled: 165 underwent NACT + surgery and 92 received CCRT. Before propensity score matching, the NACT + surgery group exhibited lower 5-year OS (68.2% vs. 85.6%; hazard ratio [HR] = 2.50, 95% confidence interval [CI]: 1.26-4.96; P = 0.009), LRFS (85.2% vs. 96.9%; HR = 5.88, 95% CI: 1.33-25.94; P = 0.019), and DMFS (81.9% vs. 97.4%; HR = 6.65, 95% CI: 1.51-29.23; P = 0.012) compared to the CCRT group. After propensity score matching, OS, LRFS, and DMFS remained worse in the NACT + surgery group compared to the CCRT group. CONCLUSION: NACT followed by surgery is associated with decreased OS, LRFS, and DMFS compared to CCRT among patients with stage IIB CSCC.

Efficacy of treatment patterns based on concurrent chemoradiotherapy in patients with stage IIB cervical squamous cell carcinoma.

PURPOSE: To assess survival of treatment patterns based on concurrent chemoradiotherapy (CCRT) in patients with stage IIB cervical squamous cell carcinoma (CSCC). MATERIALS AND METHODS: Patients with stage IIB CSCC receiving CCRT were investigated from June 2012 to June 2019 in Guangxi Medical University Cancer Hospital. Baseline characteristics and treatment patterns were described. Survival between treatment patterns were compared using Kaplan-Meier methods. RESULTS: A total of 232 patients were included: 39.7% of patients received CCRT alone, 6.5% of patients received neoadjuvant chemotherapy (NACT) + CCRT, 45.6% of patients received CCRT + adjuvant chemotherapy (AC), and 8.2% of patients received NACT + CCRT + AC. CCRT + AC showed similar overall survival (OS; hazard ratio [HR] = 0.95, 95% confidence interval [CI]: 0.41-2.17; P = 0.894) and locoregional-free survival (LRFS; HR = 2.39, 95% CI: 0.45-12.63; P = 0.303) compared with CCRT. However, CCRT + AC had a worse distant metastasis-free survival (DMFS; HR = 5.39, 95% CI: 1.14-25.57; P = 0.034). After propensity score matching, CCRT + AC had comparable OS (HR = 0.89, 95% CI: 0.29-2.70; P = 0.833), LRFS (HR = 3.26, 95% CI: 0.30-35.38; P = 0.331), and DMFS (HR = 4.80, 95% CI: 0.55-42.26; P = 0.157) compared to CCRT. CONCLUSION: AC did not improve survival in patients with stage IIB CSCC receiving CCRT.

Three-dimensional printing of piezoelectric materials with designed anisotropy and directional response.

Piezoelectric coefficients are constrained by the intrinsic crystal structure of the constituent material. Here we describe design and manufacturing routes to previously inaccessible classes of piezoelectric materials that have arbitrary piezoelectric coefficient tensors. Our scheme is based on the manipulation of electric displacement maps from families of structural cell patterns. We implement our designs by additively manufacturing free-form, perovskite-based piezoelectric nanocomposites with complex three-dimensional architectures. The resulting voltage response of the activated piezoelectric metamaterials at a given mode can be selectively suppressed, reversed or enhanced with applied stress. Additionally, these electromechanical metamaterials achieve high specific piezoelectric constants and tailorable flexibility using only a fraction of their parent materials. This strategy may be applied to create the next generation of intelligent infrastructure, able to perform a variety of structural and functional tasks, including simultaneous impact absorption and monitoring, three-dimensional pressure mapping and directionality detection.

The efficacy and safety of neoadjuvant chemotherapy in the treatment of locally advanced cervical cancer: A randomized multicenter study.

OBJECTIVE: This study sought to evaluate the toxicity and curative effect of irinotecan plus cisplatin neoadjuvant chemotherapy (NACT) for stage Ib2, IIa2, and IIb cervical cancer patients. METHODS: A total of 219 patients were randomly assigned to two groups: 109 patients were treated with 1-2 cycles of chemotherapy (NACT group), and 110 patients in the control group were treated directly with surgery (DS group). Patients in the NACT group were randomly assigned to two groups: 50 patients were treated with irinotecan plus cisplatin followed by surgery (IP group), and 59 patients were treated with paclitaxel plus cisplatin followed by surgery (TP group). Patients with pathological recurrence risk factors received post-operative radiotherapy. RESULTS: Survival analysis revealed no significant difference in disease-free survival (DFS) or overall survival (OS) between the NACT and DS groups. Analysis of clinicopathologic factors showed that the lymphovascular space invasion (LVSI) and deep stromal invasion rates were significantly lower in the NACT group. Grade 3/4 neutropenia and grade 3/4 diarrhea were both higher in the IP group than in the TP group. DFS and OS were similar in the IP and TP groups. Univariate analysis showed that LVSI was the only factor associated with DFS. CONCLUSION: NACT did not improve overall survival but did reduce the number of patients who received post-operative radiotherapy. NACT consisting of irinotecan plus cisplatin for cervical cancer showed similar efficacy and higher toxicity compared with the use of paclitaxel plus cisplatin, although the toxicity was tolerable.

[Comparison of the short-term and long-term outcomes after laparoscopic surgery for early-stage endometrial cancer].

OBJECTIVE: To evaluate the short- term and long- term outcomes after laparoscopic surgery compared with traditional laparotomy in patients with stage I-II endometrial cancer. METHODS: A retrospective study of population among 673 patientsfor early-stage endometrial cancer between Jan. 2007 and May 2014 was involved from 6 third-grade class-A communal hospitals in Guangxi. Three hundred and seventy-six cases were performed by laparoscopy, 297 cases by laparotomy. The t-test and χ(2) test was used to compare the short-term and long-term outcomes. The short-term outcomes including surgical related outcomes and operative complications, the long- term outcomes including quality of life (pelvic floor functions and sexual functions), survival analysis and recurrence. The International Consultation on Incontinence Questionnaire Female Lower Urinary Tract Sympotom (ICIQ- FLUTS) and the Female Sexual Function Index (FSFI) were used to assess pelvic floor function and sexual function. Survival rates were estimated by Kaplan-Meier analysis. The survival curves were compared by log-rank test. Cox regression analysis was used to select the risk factors for prognosis. RESULTS: (1) The short-term outcomes: There were significant difference in operative time [(258±71) vs (226±69) minutes], estimated blood loss [(343± 211) vs (491±411) ml], anus exhausting time [(2.3±0.9) vs (2.9±1.0) days], preserved days of installing catheter [(7 ± 5) vs (10±8) days], post- operative length of stay [(12 ± 7) vs (18 ± 12) days] between laparoscopic group andlaparotomy group (all P <0.05). While, there was no significant difference in lymph nodes yielded (21±8 vs 21±11; P>0.05),the intra-operative complications occurred [8.5%(32/376) vs 10.4%(31/297); P>0.05], and the post-operative complications [18.1% (68/376) vs 22.2% (66/297); P>0.05] between laparoscopic group and laparotomy group. However, the complications of vascular injury and the poor wound healing in laparoscopic group were respectively lower than those in laparotomy group [1.9%(7/376) vs 5.4% (16/297), P=0.003; and 0.3% (1/376) vs 4.7% (14/297), P<0.01]. (2) The long- term outcomes: There were no significant differences in overall survival (OS) and the degree of incontinence in ICIQ-FLUTS questionnaire between the two groups (all P >0.05). The sexual desire and sexual satisfaction scores dimension after 12 months of post- operative in FSFI questionnaire in the laparoscopic group were higher than those in laparotomy group (all P <0.05). However, there were no significant differences in sexual arousal, vaginal lubrication, orgasm and sexual pain dimension scores between the two groups (all P >0.05). The recurrence rate was 12.0%(45/376) in laparoscopic group and 14.5%(43/297) in laparotomy group (P= 0.269). The 5-year OS was 89.5% in the laparoscopic group and 87.2% in the open group (P >0.05) , and the 5-year free-progression survival rate was 87.9% in the laparoscopic group and 85.1% in the open group (P >0.05). (3) Prognostic factors in laparoscopic group: The univariate analysis shown that pathological type, surgical pathological staging, deep myometrial invasion, and retroperitoneal lymph node-positive were significantly affected prognosis in laparoscopic group (all P<0.01). The multivariate analyses showed that pathological type and surgical pathological stage were the independent prognostic factors (all P<0.01). CONCLUSIONS: Laparoscopy could reduce estimated blood loss, accelerate postoperative recovery and improve the quality of life after surgery compared to laparotomy, also ensure the same oncologically results as that by laparotomy. So, laparoscopic approach is a safe and effective treatment method for early- stage endometrial cancer.

Genetic polymorphisms of methylenetetrahydrofolate reductase (MTHFR) gene Ala222Val and susceptibility to ovary cancer: a systematic review and meta-analysis.

Many studies have reported the role of methylenetetrahydrofolate reductase (MTHFR) gene Ala222Val polymorphism with ovary cancer risk, but the results remained controversial. To derive a more precise estimation of the relationship, a meta-analysis was performed. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association between MTHFR Ala222Val polymorphism and ovary cancer risk. A total of 8 studies including 3,723 cases and 4,001 controls were also involved in this meta-analysis. When all the eligible studies were pooled into this meta-analysis, no significant association between ovary cancer risk and MTHFR Ala222Val polymorphism was found in all genetic models [codominant model: OR = 0.980, 95% CI = 0.756-1.270, P h = 0.088, P = 0.877; dominant model: OR = 1.022, 95% CI = 0.864-1.208, P h = 0.033, P = 0.803; recessive model: OR = 1.050, 95% CI = 0.803-1.373, P h = 0.032, P = 0.723; allele comparison model: OR = 1.028, 95% CI = 0.898-1.178, P h = 0.012, P = 0.685]. In the stratified analysis by ethnicity, no evidence of any associations of this polymorphism with ovary cancer was found in the Caucasian populations. Our meta-analysis supports that the MTHFR Ala222Val polymorphism is not contributed to the risk of ovary cancer from currently available evidence.

MiR-1246 promotes SiHa cervical cancer cell proliferation, invasion, and migration through suppression of its target gene thrombospondin 2.

PURPOSE: To investigate the effects of miR-1246 on proliferation, invasion, and migration in the human (CSCC) cell line SiHa. METHODS: SiHa cells were assigned into three groups: miR-1246 analog; miR-1246 antagonist; and control. The MTT, transwell, and wound healing assays were performed to evaluate the proliferation, invasion, and migration abilities of SiHa cells, respectively. Western blot was carried out to detect protein expression of thrombospondin-2 (THBS2) before and after transfection with miR-1246 analog, antagonist, or control. In addition, a THBS2 3'-UTR-containing dual luciferase plasmid was generated and co-transfected with miR-1246, the inhibitor, or non-specific miRNA, into SiHa cells to observe its effects on THBS2-driven luciferase enzyme activity. RESULTS: MTT, transwell, and wound healing assays revealed that proliferation, migration, and invasion were all significantly enhanced (P < 0.01) in SiHa cells transfected with miR-1246 analog, but were suppressed in those transfected with the miR-1246 antagonist. Western blot data showed that miR-1246 analog-transfected SiHa cells had significantly decreased THBS2 expression when compared with control-transfected cells (gray value = 6.28 ± 10.22 vs. 9.58 ± 17.58; P = 0.013) while those transfected with the miR-1246 antagonist had significantly increased THBS2 expression (gray value = 12.90 ± 19.81; P = 0.037). Moreover, SiHa cells co-transfected with miR-1246 and the THBS2 3'-UTR-containing plasmid exhibited decreased luciferase enzyme activity compared with the control. CONCLUSION: MiR-1246 induced CSCC SiHa cell proliferation, invasion and migration. Preliminary evidence suggests that miR-1246 might promote CSCC tumorigenesis and progression by the suppression of its target gene THBS2.

Comprehensive Analysis of angiogenesis associated genes and tumor microenvironment infiltration characterization in cervical cancer.

Background: Cervical cancer is among the most prevalent malignancies worldwide. This study explores the relationships between angiogenesis-related genes (ARGs) and immune infiltration, and assesses their implications for the prognosis and treatment of cervical cancer. Additionally, it develops a diagnostic model based on angiogenesis-related differentially expressed genes (ARDEGs). Methods: We systematically evaluated 15 ARDEGs using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Set Enrichment Analysis (GSEA), and Gene Set Variation Analysis (GSVA). Immune cell infiltration was assessed using a single-sample gene-set enrichment analysis (ssGSEA) algorithm. We then constructed a diagnostic model for ARDEGs using Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis and evaluated the diagnostic value of this model and the hub genes in predicting clinical outcomes and immunotherapy responses in cervical cancer. Results: A set of ARDEGs was identified from the Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and UCSC Xena database. We performed KEGG, GO, and GSEA analyses on these genes, revealing significant involvement in cell proliferation, differentiation, and apoptosis. The ARDEGs diagnostic model, constructed using LASSO regression analysis, showed high predictive accuracy in cervical cancer patients. We developed a reliable nomogram and decision curve analysis to evaluate the clinical utility of the ARDEG diagnostic model. The 15 ARDEGs in the model were associated with clinicopathological features, prognosis, and immune cell infiltration. Notably, ITGA5 expression and the abundance of immune cell infiltration (specifically mast cell activation) were highly correlated. Conclusion: This study identifies the prognostic characteristics of ARGs in cervical cancer patients, elucidating aspects of the tumor microenvironment. It enhances the predictive accuracy of immunotherapy outcomes and establishes new strategies for immunotherapeutic interventions.

Comprehensive analysis of autophagy associated genes and immune infiltrates in cervical cancer.

Objectives: Cervical cancer (CC) is the most common gynecological malignant tumor and the fourth leading cause of cancer-related death in women. The progression of CC is significantly affected by autophagy. Our objective was to use bioinformatics analysis to explore the expression, prognostic significance, and immune infiltration of autophagy-related genes in CC. Materials and Methods: We identified a set of autophagy-related differentially expressed genes (ARDEGs) from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. ARDEGs were further validated by The Human Protein Atlas (HPA), GSE52903, and GSE39001 dataset. Hub genes were found by the STRING network and Cytoscape. We performed Gene Set Enrichment Analysis (GSEA), Gene ontology analysis (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and immune infiltration analysis to further understand the functions of the hub genes. Kaplan-Meier (K-M) and receiver operating characteristic (ROC) were used to check the hub genes. Results: A total of 10 up-regulated (CXCR4, BAX, SPHK1, EIF2AK2, TBK1, TNFSF10, ITGB4, CDKN2A, IL24, and BIRC5) and 19 down-regulated (PINK1, ATG16L2, ATG4D, IKBKE, MLST8, MAPK3, ERBB2, ULK3, TP53INP2, MTMR14, BNIP3, FOS, CCL2, FAS, CAPNS1, HSPB8, PTK6, FKBP1B , and DNAJB1) ARDEGs were identified. The ARDEGs were enriched in cell growth, apoptosis, human papillomavirus infection, and cytokine-mediated. Then, we found that low expression of MAPK3 was associated with poor prognosis in CC patients and was significantly enriched in immune pathways. In addition, the expression of MAPK3 was significantly positively correlated with the infiltration levels of macrophages, B cells, mast cell activation, and cancer-associated fibroblasts. Furthermore, MAPK3 was positively correlated with LGALS9, and negatively correlated with CTLA4 and CD40. Conclusion: Our results show that MAPK3 can be used as a new prognostic biomarker to predict the prognosis of patients with CC.

Learning curve of ovarian cystectomy by vaginal natural orifice transluminal endoscopic surgery: a cumulative sum analysis.

Purpose: To identify the learning curve in ovarian cystectomy by vaginal natural orifice transluminal endoscopic surgery. Methods: Data consist of consecutively ordered patients who underwent ovarian cystectomy via vaginal natural orifice transluminal endoscopic surgery between May 2020 and June 2023. The learning curve of ovarian cystectomy via vaginal natural orifice transluminal endoscopic surgery was measured in terms of the operating time adjusted by multivariate linear regression. A cumulative sum analysis was performed to establish the learning curve. Patients' characteristics and surgical outcomes were compared based on the inflection points of this curve. Results: The learning curve was divided into two unique phases: phase 1 (1-26 patients), and phase 2 (27-40 patients). The expected operating time in phase 2 was shorter than in phase 1 (86.4 ± 11.2 min vs. 102.0 ± 22.7 min, p = 0.021). The time to first postoperative flatus was shorter in phase 2 compared with phase 1 (14.6 ± 6.5 h vs. 20.6 ± 6.3 h, respectively, p = 0.008). No significant differences were observed in terms of patient's age, BMI, tumor size, parity, bilateral ovarian tumor, pathological diagnoses, estimated blood loss, postoperative pain score, or perioperative complications between the two phases. Conclusion: Proficiency in ovarian cystectomy by vaginal natural orifice transluminal endoscopic surgery was achieved after 26 surgeries based on cumulative sum analysis. These findings may provide insight for structured training programs of ovarian cystectomy via vaginal natural orifice transluminal endoscopic surgery.

Initial experience of ureteric visualization using methylene blue during laparoscopy for gynecological surgery.

Objectives: Iatrogenic ureteral injury is a severe surgical complication, with a highest incidence of 1.5% in gynecological surgeries. The purpose of this report is to document our initial experience with using methylene blue (MB) to label the ureter in gynecological laparoscopic surgeries and to explore its effectiveness and safety. This is also a novel description of simultaneously visualizing ureteral MB fluorescence and sentinel lymph nodes (SLN's) Indocyanine Green (ICG) fluorescence using the same camera. Methods: This study included patients undergoing gynecological laparoscopic surgeries, with the same surgeon performing all cases. During the early stages of each surgery, rapid intravenous infusion of MB was administered. For cases requiring SLN imaging, we also injected ICG solution into the cervix. Assessment of the included cases was conducted both intraoperatively and postoperatively. The group that had MB fluorescence (Group A) was compared to a control group that did not have it (Group B). Results: A total of 25 patients (Group A) received MB during surgery, demonstrating 45 ureters clearly, with an imaging success rate of 90%. Continuous and clearer fluorescence imaging was achieved in cases with ureteral hydronephrosis. In most patients, ureteral fluorescence was visible 15-20 min after intravenous infusion of MB, and 64% still exhibited fluorescence at the end of the surgery. In patients who had both ICG and MB, dual fluorescence imaging was achieved clearly. Among the included cases, there were no iatrogenic ureteral injuries (0%), which we observed to be lower than in patients who did not receive MB (1.3%). The rate of adverse events was similar in both groups. Conclusion: Using MB fluorescence is an effective and safe method of visualizing the ureters during gynecological surgeries, and can diminish iatrogenic ureteral injury without increased associated adverse events. It therefore may offer promising prospects for clinical application.

Rapid inverse design of metamaterials based on prescribed mechanical behavior through machine learning.

Designing and printing metamaterials with customizable architectures enables the realization of unprecedented mechanical behaviors that transcend those of their constituent materials. These behaviors are recorded in the form of response curves, with stress-strain curves describing their quasi-static footprint. However, existing inverse design approaches are yet matured to capture the full desired behaviors due to challenges stemmed from multiple design objectives, nonlinear behavior, and process-dependent manufacturing errors. Here, we report a rapid inverse design methodology, leveraging generative machine learning and desktop additive manufacturing, which enables the creation of nearly all possible uniaxial compressive stress‒strain curve cases while accounting for process-dependent errors from printing. Results show that mechanical behavior with full tailorability can be achieved with nearly 90% fidelity between target and experimentally measured results. Our approach represents a starting point to inverse design materials that meet prescribed yet complex behaviors and potentially bypasses iterative design-manufacturing cycles.

Downregulation of ITIH3 contributes to cisplatin-based chemotherapy resistance in ovarian carcinoma via the Bcl-2 mediated anti-apoptosis signaling pathway.

Platinum resistance of ovarian cancer is one of the primary factors of poor prognosis and inter-α-trypsin inhibitor heavy chain 3 (ITIH3) is a potential DDP resistance-associated gene. The present study assessed protein expression levels of ITIH3 in human ovarian cancer and evaluated the relationship between its expression and platinum-resistance in patients. Furthermore, the effect of ITIH3 on cisplatin (DDP)-resistant ovarian cancer cells and the underlying molecular mechanism were evaluated. Tissue microarrays of ovarian cancer samples were used to assess the association between ITIH3 protein expression levels and drug resistance and the prognosis of ovarian cancer. ITIH3 RNA interference (RNAi) ovarian cancer cell lines were constructed and expression levels of anti- and pro-apoptotic proteins of the Bcl-2 associated pathway, including Bcl-2, Bcl-xL, Mcl-1, Bak, Bim, Bax, caspase 3 and poly ADP-ribose polymerase (PARP), were assessed following DDP treatment. The Bcl-2 inhibitor ABT-737 was used to rescue DDP-resistance induced by loss of ITIH3 in vitro. Finally, a subcutaneous xenograft tumor model was used to evaluate the effect of multiple DDP injections on expression levels of apoptosis-related proteins like Bcl-2, Bcl-xL, Bak, caspase 3 and PARP. The results of tissue microarray immunohistochemistry revealed that decreased ITIH3 protein expression levels were associated with a shorter overall survival for patients with ovarian cancer. The results of Cell Counting Kit-8 assay showed that the half-maximal inhibitory concentration and resistance index of DDP in SKOV3-ITIH3 and OVCAR3-ITIH3 RNAi cells were significantly higher than in control groups. Following DDP treatment, the results of western blotting revealed that expression levels of anti-apoptotic proteins of the Bcl-2 family significantly increased in SKOV3-ITIH3 and OVCAR3-ITIH3 RNAi cells. Pro-apoptotic protein expression was not significantly changed following DDP treatment, whereas cleaved caspase 3, caspase 3 and cleaved (C-PARP) were markedly downregulated. The Bcl-2 inhibitor ABT-737 was demonstrated to reverse increased DDP resistance induced by ITIH3 expression in flow cytometric and western blotting analysis. In the subcutaneous murine xenograft model, an increased number of DDP injections yielded a decrease in phosphorylated Bcl-2, cleaved caspase 3, caspase 3 and C-PARP protein expression levels in the SKOV3-ITIH3 RNAi group tested by western blotting. To the best of our knowledge, this is the first study to demonstrate that ITIH3 could be a vital molecule involved in chemosensitivity via regulation of the Bcl-2 family-mediated apoptotic pathway. Lower protein expression levels of ITIH3 were significantly associated with platinum resistance and poor prognosis in ovarian cancer. ITIH3 may predict cisplatin-resistance in ovarian cancer.

The risk and latency evaluation of secondary primary malignancies of cervical cancer patients who received radiotherapy: A study based on the SEER database.

Objectives: To study the risk factors for the onset of secondary primary malignancies (SPM) and the latency between SPM and cervical cancer after radiotherapy. Methods: We selected patients with cervical cancer who underwent radiotherapy between 2000 and 2019 from the Surveillance, Epidemiology, and End Results (SEER) database. And the data of patients with cervical cancer who underwent radiotherapy in Guangxi Medical University Cancer Hospital during January 1,1997 to December 31,2016 were collected and analyzed. The factors associated with SPM onset and latency were then estimated by nomograms based on logistic regression and a complete risk model. Dynamic risk plots were performed by Poisson regression. Results: A total of 32,313 cases of cervical cancer who underwent radiotherapy were downloaded from the SEER database; of these, 19,439 cases had a complete dataset and were included in the final analysis. In total, 561 cases suffered from SPM; the remaining 18,878 did not. And a total of 1486 cases of cervical cancer who underwent radiotherapy from Guangxi Medical University Cancer Hospital were analyzed, 27 cases caught SPM and the rest of 1459 cases did not. Patients with SPM were older than those without SPM(p=0.000); significant associations were also identified between SPM and white race(p=0.000), localized stage (p=0.000), squamous carcinoma (SCC)(p=0.003), surgery(p=0.000), and combination radiotherapy (p=0.026). A logistic regression nomogram showed that older age (HR:1.015, 95%CI:1.009-1.021, p=0.000), localized stage (HR:4.056, 95%CI: 2.625-6.269, p=0.000) and regional stage (HR: 3.181, 95%CI:2.094-4.834, p=0.000), white (HR: 1.722, 95%CI:1.145-2.590, p=0.000) and black race (HR: 1.889, 95%CI:1.327-2.689, p=0.000), and the receipt of surgery (HR: 1.381, 95%CI:1.151-1.657, p=0.000) were all independent risk factors for the onset of SPM. The largest proportion of cases involved SPM in the female reproductive system. A dynamic risk plot showed that age, race, stage, and surgery had impacts on the latency of SPM onset. A competing risk regression analysis nomogram showed that age (HR: 1.564, 95%CI: 1.272-1.920, p=0.000), surgery (HR: 1.415, 95%CI: 1.140-1.760, p=0.002), localized stage (HR: 8.035, 95%CI: 4.502-14.340, p=0.000) and regional stage (HR: 4.904, 95%CI: 2.790-8.620, p=0.000), and black race (HR: 1.786, 95%CI: 1.161-2.750, p=0.008) all had significant impacts on the cumulative incidence and latency of SPM. Conclusions: Advanced age, the receipt of surgery, earlier stages, and white and black race were identified as risk factors for SPM onset and influenced latency in patients with cervical cancer after radiotherapy.

A Novel Pyroptosis-Related Prognostic Signature for Cervical Squamous Cell Carcinoma.

PURPOSE: Pyroptosis has vital roles in tumorigenesis and cancer development; however, its relationship with cervical squamous cell cancer (CSCC) remains unexplored. In this study, we aimed to develop a CSCC prediction signature related to pyroptosis. PATIENTS AND METHODS: Consensus clustering analysis was conducted to detect pyroptosis-related subclusters for CSCC. Next, differentially expressed genes (DEGs) between subclusters were identified. Univariate, least absolute shrinkage and selection operator, and stepwise multivariate Cox regression analyses were applied to establish a prognostic model and a nomogram drawn. Additionally, functional enrichment analysis, tumor mutation burden, and immune characteristics associated with this signature were investigated. RESULTS: We constructed a seven-gene signature that functions as an independent predictor of prognosis in CSCC using data from The Cancer Genome Atlas. Patients with CSCC were divided into two groups based on median risk score, and patients in the low-risk group had significantly longer survival time than those in the high-risk group. Our findings were validated using Gene Expression Omnibus cohort data. We also established a nomogram, to expand the clinical applicability of our findings. The seven gene signature was associated with various molecular pathways, tumor mutation status, and immune microenvironment. CONCLUSION: The pyroptosis-related risk signature consisting of seven genes developed here represents a potential robust biomarker for predicting prognosis and immunotherapy response in patients with CSCC.

Development and External Validation of a Novel Model for Predicting Postsurgical Recurrence and Overall Survival After Cytoreductive R0 Resection of Epithelial Ovarian Cancer.

Purpose: Treatment of epithelial ovarian cancer is evolving towards personalization and precision, which require patient-specific estimates of overall survival (OS) and progression-free survival (PFS). Patients and Methods: Medical records of 1173 patients who underwent debulking surgery in our center were comprehensively reviewed and randomly allocated into a derivation cohort of 879 patients and an internal validation cohort of 294 patients. Five hundred and seventy-seven patients from the other three cancer centers served as the external validation cohort. A novel nomogram model for PFS and OS was constructed based on independent predictors identified by multivariable Cox regression analysis. The predictive accuracy and discriminative ability of the model were measured using Harrell's concordance index (C-index) and calibration curve. Results: The C-index values were 0.82 (95% CI: 0.76-0.88) and 0.84 (95% CI: 0.78-0.90) for the PFS and OS models, respectively, substantially higher than those obtained with the FIGO staging system and most nomograms reported for use in epithelial ovarian cancer. The nomogram score could clearly classify the patients into subgroups with different risks of recurrence or postoperative mortality. The online versions of our nomograms are available at https://eocnomogram.shinyapps.io/eocpfs/ and https://eocnomogram.shinyapps.io/eocos/. Conclusion: A externally validated nomogram predicting OS and PFS in patients after R0 reduction surgery was established using a propensity score matching model. This nomogram may be useful in estimating individual recurrence risk and guiding personalized surveillance programs for patients after surgery, and it could potentially aid clinical decision-making or stratification for clinical trials.

Design and printing of proprioceptive three-dimensional architected robotic metamaterials.

Advances in additive manufacturing techniques have enabled the creation of stimuli-responsive materials with designed three-dimensional (3D) architectures. Unlike biological systems in which functions such as sensing, actuation, and control are closely integrated, few architected materials have comparable system complexity. We report a design and manufacturing route to create a class of robotic metamaterials capable of motion with multiple degrees of freedom, amplification of strain in a prescribed direction in response to an electric field (and vice versa), and thus, programmed motions with self-sensing and feedback control. These robotic metamaterials consist of networks of piezoelectric, conductive, and structural elements interwoven into a designed 3D lattice. The resulting architected materials function as proprioceptive microrobots that actively sense and move.

Fuzuloparib Maintenance Therapy in Patients With Platinum-Sensitive, Recurrent Ovarian Carcinoma (FZOCUS-2): A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase III Trial.

PURPOSE: This phase III trial aimed to explore the efficacy and safety of fuzuloparib (formerly fluzoparib) versus placebo as a maintenance treatment after response to second- or later-line platinum-based chemotherapy in patients with high-grade, platinum-sensitive, recurrent ovarian cancer. PATIENTS AND METHODS: Patients with platinum-sensitive, recurrent ovarian cancer previously treated with at least two platinum-based regimens were assigned (2:1) to receive fuzuloparib (150 mg, twice daily) or matching placebo for 28-day cycles. The primary end points were progression-free survival (PFS) assessed by blinded independent review committee (BIRC) in the overall population and PFS by BIRC in the subpopulation with germline BRCA 1/2 mutation. RESULTS: Between April 30, 2019, and January 10, 2020, 252 patients were randomly assigned to the fuzuloparib (n = 167) or placebo (n = 85). As of July 1, 2020, the median PFS per BIRC assessment in the overall population was significantly improved with fuzuloparib treatment (hazard ratio [HR], 0.25; 95% CI, 0.17 to 0.36; one-sided P < .0001) compared with that with placebo. The HR derived from a prespecified subgroup analysis showed a consistent trend of benefit in patients with germline BRCA 1/2 mutations (HR, 0.14; 95% CI, 0.07 to 0.28) or in those without mutations (HR, 0.46; 95% CI, 0.29 to 0.74). The most common grade ≥ 3 treatment-emergent adverse events reported in the fuzuloparib group were anemia (25.1%), decreased platelet count (16.8%), and decreased neutrophil count (12.6%). Only one patient (0.6%) discontinued fuzuloparib because of treatment-related toxicity (concurrent decreased white blood cell count and neutrophil count). CONCLUSION: Fuzuloparib as maintenance therapy achieved a statistically significant and clinically meaningful improvement in PFS for patients with platinum-sensitive, recurrent ovarian cancer versus placebo, regardless of germline BRCA 1/2 mutation, and showed a manageable safety profile.

[Clinicopathologic analysis of small cell neuroendocrine carcinoma of the cervix].

OBJECTIVE: To analyse the clinico-pathologic characteristics, diagnosis, therapy and prognostic of small cell neuroendocrine carcinoma of the cervix (SCNCC). METHODS: The clinic-pathological features of 12 patients with SCNCC treated in Tumor Hospital of Guangxi Medical University, admitted during March 2006 to July 2010, were analyzed retrospectively. RESULTS: Of 12 patients, the mean age was 38.7 years (rang 28 - 57 years), 6 had stages Ib1-IIa, 6 had stages IIb-IV. Among 8 patients (Ib1-IIIb) underwent surgery, 4 of them received neoadjuvant chemotherapy, 8 of them received adjuvant chemotherapy and(or) radiotherapy. All had greater than one-half stromal invasion, 4 patients had positive pelvic lymph nodes metastases. The positive ratio of the chromogranin (CgA), synaptophysin, neuronspecific enolase (NSE), cytokeratins (CK), CD(56) tested by immunohistochemical staining were 8/12, 9/10, 4/4, 4/4, 4/4, respectively. Median follow-up period was 3 months (1 - 22 months). Among 8 patients underwent surgery, 2 patients developed lung metastases, 1 patient developed liver and lung metastases, 1 patient developed liver metastases concurrently with bone metastases, disease-free survival (DFS) were 3 months (Ib2 with positive lymph nodes), 4.6 months (IIa), 7 months (Ib1), 17 months (Ib2); 2 patient died (8.5 and 11.3 months, respectively) after surgery; 4 patients are alive and show no evidence of disease. Among 4 patients untreated, 1 patients received concurrent chemoradiation and are alive for 10.1 months. Two patient untreated (IIIb, IV) died after 0.6 and 1.3 months final diagnosis, respectively. One patient was lost follow-up. CONCLUSIONS: SCNCC is a highly malignant tumor with rare morbility, propensity for distant spread and dismal prognosis. Final diagnosis of SCNCC depends on pathomorphology and immunohistochemical analysis. Combined therapeutic modalities may in favor of survival in some patients.

[Impact on survival and quality of life of laparoscopic radical hysterectomy and pelvic lymphadenectomy to patients with early-stage cervical cancer].

OBJECTIVE: To compare intraoperative, pathologic, postoperative outcomes and quality of life of laparoscopic radical hysterectomy and pelvic lymphadenectomy (LRH + LPL) with abdominal radical hysterectomy and pelvic lymphadenectomy (ARH + APL) for patients with early-stage cervical cancer. METHODS: The consecutive cases with International Federation of Gynecology and Obstetrics (FIGO) stages Ia2-IIa cervical cancer who underwent surgery from Jan. 1, 2002 to Jan. 1, 2011 were documented, including 85 patients underwent LRH + LPL, and 85 patients underwent ARH + APL as control group. The clinical data of intraoperative, pathologic, postoperative outcomes and quality of life were compared between two groups. Survival data were estimated using Kaplan-Meier survival curves and compared with the log-rank test. Cox proportional hazards model was used for multivariate analysis. RESULTS: All but 2 surgical procedures were completed laparoscopically because of right common iliac vein vessel injuries. Mean operative time, it was longer for LRH + LPL than that for ARH + APL [(242 ± 74) minutes vs. (190 ± 61) minutes, P = 0.000]. Mean recovery time of intestines function was less for LRH + LPL than that for ARH + APL [(45 ± 7) hours vs. (63 ± 11) hours, P = 0.000]. Mean estimated blood loss was less for LRH + LPL than that for ARH + APL [(367 ± 252) ml vs. (460 ± 220) ml, P = 0.006]. Mean recovery time of urinary function was less that for LRH + LPL than that for ARH + APL [(19 ± 4) days vs. (21 ± 4) days, P = 0.000]. There were no significant difference in numbers of the pelvic lymph nodes resected, the extent of parametrial tissue, vaginal cuff, negative margins obtained and complications. The median follow-up was 32 months (range 4 to 105 months), there was no significant difference in the recurrence rate (7% vs. 5%, P = 0.540) and mortality rate (7% vs. 5%, P = 0.540), 5 years disease-free survival (90% vs. 94%, P = 0.812), 5 years over survival (90% vs. 95%, P = 0.532). There were not significant difference in quality of life between ARH + APL group and LRH + LPL group (P > 0.05). Only lympho-vascular space invasion was an independent prognostic factor by multivariate analysis (P = 0.016). CONCLUSIONS: For early-stage cervical cancer, LRH + LPL has similar outcomes compared with ARH + APL. Laparoscopic treatment by experienced surgeons should be an ideal alternative.