Targeting PAX8 sensitizes ovarian cancer cells to ferroptosis by inhibiting glutathione synthesis.

Ovarian cancer is a malignant tumor originating from the ovary, characterized by its high mortality rate and propensity for recurrence. In some patients, especially those with recurrent cancer, conventional treatments such as surgical resection or standard chemotherapy yield suboptimal results. Consequently, there is an urgent need for novel anti-cancer therapeutic strategies. Ferroptosis is a distinct form of cell death separate from apoptosis. Ferroptosis inducers have demonstrated promising potential in the treatment of ovarian cancer, with evidence indicating their ability to enhance ovarian cancer cell sensitivity to cisplatin. However, resistance of cancer cells to ferroptosis still remains an inevitable challenge. Here, we analyzed genome-scale CRISPR-Cas9 loss-of function screens and identified PAX8 as a ferroptosis resistance protein in ovarian cancer. We identified PAX8 as a susceptibility gene in GPX4-dependent ovarian cancer. Depletion of PAX8 rendered GPX4-dependent ovarian cancer cells significantly more sensitive to GPX4 inhibitors. Additionally, we found that PAX8 inhibited ferroptosis in ovarian cancer cells. Combined treatment with a PAX8 inhibitor and RSL3 suppressed ovarian cancer cell growth, induced ferroptosis, and was validated in a xenograft mouse model. Further exploration of the molecular mechanisms underlying PAX8 inhibition of ferroptosis mutations revealed upregulation of glutamate-cysteine ligase catalytic subunit (GCLC) expression. GCLC mediated the ferroptosis resistance induced by PAX8 in ovarian cancer. In conclusion, our study underscores the pivotal role of PAX8 as a therapeutic target in GPX4-dependent ovarian cancer. The combination of PAX8 inhibitors such as losartan and captopril with ferroptosis inducers represents a promising new approach for ovarian cancer therapy.

A Bistable Triboelectric Nanogenerator for Low-Grade Thermal Energy Harvesting and Solar Thermal Energy Conversion.

Converting ubiquitous ambient low-grade thermal energy into electricity is of great significance for tackling the fossil energy shortage and environmental crisis but poses a considerable challenge. Here, a novel thermal-driven triboelectric nanogenerator (TD-TENG) is developed, which utilizes a bimetallic beam with a bi-stable dynamic feature to induce continuous mechanical oscillations, and the mechanical motion is then converted into electric power using a contact-separation TENG. The thermal process inside the device is systematically investigated and effective thermal management is conducted accordingly. After optimization, the TD-TENG can produce a power density of 323.9 mW m-2 at 59.5 °C, obtaining the highest record of TENG-based thermal energy harvesters. Besides, the first prototype of TENG-based solar thermal harvester is successfully demonstrated, with a power density of 364.4 mW m-2 . Moreover, the TD-TENG can harvest and dissipate the heat at the same time, exhibiting great potential in over-heated electronics protection as well as architectural energy conservation. Most importantly, the operation temperature range of the TD-TENG is tunable by adjusting the bimetal parameters, allowing the device a wide and flexible working thermal gradient. These unique properties validate the TD-TENG is a simple, feasible, cost-effective, and high-efficient low-grade thermal energy harvester.

A Mutual Boosting Self-Excitation Hybrid Cell for Harvesting High Entropy Energy at 32% Efficiency.

Triboelectric nanogenerators (TENGs) and dielectric elastomer generators (DEGs) are potentially promising energy conversion technologies, but they still have limitations due to their own intrinsic characteristics, including the low energy output of TENGs caused by the air breakdown effect, and external polarization voltage requirement for DEGs, which severely limit their practical applications. Herein, coupling TENG with DEG is proposed to build a mutual beneficial self-excitation hybrid generator (named TDHG) for harvesting distributed and low-quality mechanical energy (high entropy energy). Experimental results demonstrate that the output charges of this TDHG are enhanced by fivefold of that of the conventional charge-excitation TENG, and continuous operation of DEG is also realized by simple mechanical triggering. More importantly, owing to the high peak power contributed by TENG and the long output pulse duration guaranteed by DEG, the TDHG realizes a much higher energy conversion efficiency of 32% in comparison to either the TENG (3.6%) or DEG (13.2%). This work proposes a new design concept for hybridized energy harvester toward highly efficient mechanical energy harvesting.

The dual role of KCNQ/M channels upon OGD or OGD/R insults in cultured cortical neurons of mice: Timing is crucial in targeting M-channels against ischemic injur ies.

KCNQ/M potassium channels play a vital role in neuronal excitability; however, it is required to explore their pharmacological modulation on N-Methyl- d-aspartic acid receptors (NMDARs)-mediated glutamatergic transmission of neurons upon ischemic insults. In the current study, both presynaptic glutamatergic release and activities of NMDARs were measured by NMDAR-induced miniature excitatory postsynaptic currents (mEPSCs) in cultured cortical neurons of C57 mice undergoing oxygen and glucose deprivation (OGD) or OGD/reperfusion (OGD/R). The KCNQ/M-channel opener, retigabine (RTG), suppressed the overactivation of postsynaptic NMDARs induced by OGD and then NO transient; RTG also decreased OGD-induced neuronal death measured with MTT assay, suggesting the beneficial role of KCNQ/M-channels for the neurons exposed to ischemic insults. However, when the neurons exposed to the subsequent reperfusion, KCNQ/M-channels played a differential role from its protective effect. OGD/R increased presynaptic glutamatergic release, which was further augmented by RTG or decreased by KCNQ/M-channel blocker, XE991. Reactive oxygen species (ROS) were produced partly in a NO-dependent manner. In addition, XE991 decreased neuronal injuries upon reperfusion measured with DCF and PI staining. Meanwhile, the addition of RTG upon OGD or XE991 upon reperfusion can reverse OGD or OGD/R-reduced mitochondrial membrane potential. Our present study indicates the dual role of KCNQ/M-channels in OGD and OGD/R, which will decide the fate of neurons. Provided that activation of KCNQ/M-channels has differential effects on neuronal injuries during OGD or OGD/R, we propose that therapy targeting KCNQ/M-channels may be effective for ischemic injuries but the proper timing is so crucial for the corresponding treatment.

[VisConnectome: an independent and graph-theory based software for visualizing the human brain connectome].

As a complex system, the topology of human's brain network has an important effect on further study of brain's structural and functional mechanism. Graph theory, a kind of sophisticated analytic strategies, is widely used for analyzing complex brain networks effectively and comparing difference of topological structure alteration in normal development and pathological condition. For the purpose of using this analysis methodology efficiently, it is necessary to develop graph-based visualization software. Thus, we developed VisConnectome, which displays analysis results of the brain network friendly and intuitively. It provides an original graphical user interface (GUI) including the tool window, tool bar and innovative double slider filter, brain region bar, runs in any Windows operating system and doesn't rely on any platform such as Matlab. When importing the user-defined script file that initializes the brain network, VisConnectome abstracts the brain network to the ball-and-stick model and render it. VisConnectome allows a series of visual operations, such as identifying nodes and connection, modifying properties of nodes and connection such as color and size with the color palette and size double slider, imaging the brain regions, filtering the brain network according to its size property in a specific domain as simplification and blending with the brain surface as a context of the brain network. Through experiment and analysis, we conclude that VisConnectome is an effective visualization software with high speed and quality, which helps researchers to visualize and compare the structural and functional brain networks flexibly.

cPKCγ-mediated down-regulation of UCHL1 alleviates ischaemic neuronal injuries by decreasing autophagy via ERK-mTOR pathway.

Stroke is one of the leading causes of death in the world, but its underlying mechanisms remain unclear. Both conventional protein kinase C (cPKC)γ and ubiquitin C-terminal hydrolase L1 (UCHL1) are neuron-specific proteins. In the models of 1-hr middle cerebral artery occlusion (MCAO)/24-hr reperfusion in mice and 1-hr oxygen-glucose deprivation (OGD)/24-hr reoxygenation in cortical neurons, we found that cPKCγ gene knockout remarkably aggravated ischaemic injuries and simultaneously increased the levels of cleaved (Cl)-caspase-3 and LC3-I proteolysis product LC3-II, and the ratio of TUNEL-positive cells to total neurons. Moreover, cPKCγ gene knockout could increase UCHL1 protein expression via elevating its mRNA level regulated by the nuclear factor κB inhibitor alpha (IκB-α)/nuclear factor κB (NF-κB) pathway in cortical neurons. Both inhibitor and shRNA of UCHL1 significantly reduced the ratio of LC3-II/total LC3, which contributed to neuronal survival after ischaemic stroke, but did not alter the level of Cl-caspase-3. In addition, UCHL1 shRNA reversed the effect of cPKCγ on the phosphorylation levels of mTOR and ERK rather than that of AMPK and GSK-3ß. In conclusion, our results suggest that cPKCγ activation alleviates ischaemic injuries of mice and cortical neurons through inhibiting UCHL1 expression, which may negatively regulate autophagy through ERK-mTOR pathway.

Favorable factors for preserving bladder function after nerve-sparing radical hysterectomy: A protocol-based validation study.

OBJECTIVES: To investigate favorable factors of nerve-sparing radical hysterectomy (NSRH) for preserving the pelvic autonomic nerves and subsequent bladder function and to compare the safety between NSRH and conventional radical hysterectomy (CRH) for cervical cancer. METHODS: We recruited 87 consecutive patients with IB1-IIA cervical cancer who underwent NSRH, and reviewed the information of 81 patients who received CRH for historical comparisons. One gynaecologic oncologist performed all operations. RESULTS: IB1 disease was the only favorable factor for unilateral or bilateral preservation (adjusted OR, 0.245; 95% CI, 0.077-0.774), whereas IB1 disease and squamous cell carcinoma (SqCC) were favorable for bilateral preservation (adjusted ORs, 0.336 and 0.116; 95% CIs, 0.162-0.982 and 0.023-0.581). The median duration of postoperative catheterization (DPC) was different among bilateral, unilateral and failed preservation (median 6 vs 18 vs 90 days; P < 0.001). The median DPC was shorter in NSRH patients with stage IB1 disease or SqCC (7 vs 14 days; P < 0.05) despite no difference between NSRH and CRH in those with IB2-IIA disease or non-SqCC. Survival was not different between NSRH and CRH patients. CONCLUSIONS: IB1 disease and SqCC are favorable for preserving the pelvic autonomic nerves and subsequent bladder function without compromising survival outcomes in patients treated with NSRH.

Tat-collapsin response mediator protein 2 (CRMP2) increases the survival of neurons after NMDA excitotoxity by reducing the cleavage of CRMP2.

Collapsin response mediator protein 2 (CRMP2) is a brain-specific multifunctional adaptor protein involved in neuronal polarity and axonal guidance. Our previous results showed CRMP2 may be involved in the hypoxic preconditioning and ischemic injury, but the mechanism was not clear. This study explored whether CRMP2 was involved in NMDA-induced neural death, and the possible mechanism. Western blot analysis demonstrated that NMDA reduced the phosphorylation of CRMP2 and inspired the cleavage of CRMP2. Also, it was detected that NMDA treatment did not affect the phosphorylation of CRMP2 in early stage (<6 h). Over-expression of CRMP2 aggravated the NMDA-induced injury, suggesting the vital role of CRMP2 in excitotoxicity. Tat-CRMP2 was designed to provide the cleavage site of calpain. Thiazolyl blue tetrazolium bromide assay, Hoechst33342/Propidium Iodide staining and Western blot assay showed that Tat-CRMP2 pretreatment increased cell viability compared with the control group against NMDA exposure by decreasing the cleavage of CRMP2. In conclusion, these studies indicated that cleavage of CRMP2 plays an important role involved in the NMDA-induced injury. The cleavage of CRMP2 may be a promising target for excitatory amino acid-related ischemic and hypoxic injury.

A Dual-Functional Triboelectric Nanogenerator Based on the Comprehensive Integration and Synergetic Utilization of Triboelectrification, Electrostatic Induction, and Electrostatic Discharge to Achieve Alternating Current/Direct Current Convertible Outputs.

Traditional alternating current (AC) and direct current (DC) triboelectric nanogenerators (TENGs), which are implemented via the pairwise coupling of triboelectrification, electrostatic induction, and electrostatic discharge, have been widely explored in various fields. In this work, the comprehensive integration and synergetic utilization of triboelectrification, electrostatic induction, and electrostatic discharge in a single device for the first time is realized, achieving a dual-functional TENG (DF-TENG) to produce an AC/DC convertible output. Distinguishing from the conventional TENGs, the coupling of triboelectrification and electrostatic discharge enables charge circulation between the dielectric tribo-layers, while electrostatic induction realizes charge transfer in the external circuit. This novel energy conversion mechanism has been proven to be applicable to a variety of materials, including polymers, fabrics, and semiconductors. The output mode of the DF-TENG can be tuned by adjusting the slider motion state, and its constant output current and power density can reach 1.51 mA m-2 Hz-1 and 398 mW m-2 Hz-1 , respectively, which are the highest records reported for constant DC-TENGs to date. This work not only provides a paradigm shift to achieve AC/DC convertible output, but it also exhibits high potential for extending the TENG design philosophy.

The suppression of cervical cancer ferroptosis by macrophages: The attenuation of ALOX15 in cancer cells by macrophages-derived exosomes.

Induction of cancer cell ferroptosis has been proposed as a potential treatment in several cancer types. Tumor-associated macrophages (TAMs) play a key role in promoting tumor malignant progression and therapy resistance. However, the roles and mechanisms of TAMs in regulating tumor ferroptosis is still unexplored and remains enigmatic. This study shows ferroptosis inducers has shown therapeutic outcomes in cervical cancer in vitro and in vivo. TAMs have been found to suppress cervical cancer cells ferroptosis. Mechanistically, macrophage-derived miRNA-660-5p packaged into exosomes are transported into cancer cells. In cancer cells, miRNA-660-5p attenuates ALOX15 expression to inhibit ferroptosis. Moreover, the upregulation of miRNA-660-5p in macrophages depends on autocrine IL4/IL13-activated STAT6 pathway. Importantly, in clinical cervical cancer cases, ALOX15 is negatively associated with macrophages infiltration, which also raises the possibility that macrophages reduce ALOX15 levels in cervical cancer. Moreover, both univariate and multivariate Cox analyses show ALOX15 expression is independent prognostic factor and positively associated with good prognosis in cervical cancer. Altogether, this study reveals the potential utility of targeting TAMs in ferroptosis-based treatment and ALOX15 as prognosis indicators for cervical cancer.

Association between tennis training experience and executive function in children aged 8-12.

Cognitively engaging activities have been shown to facilitate the improvement of executive functions in children. However, a limited number of studies have investigated whether the relationship between dose parameters of physical activities and executive functions, and heterogeneity exists. In the present study, we aim to explore the association between tennis training experience and executive functions in children. Sixty children between the ages of 8 and 12 were recruited in this study and were allocated to the short-term (ST) group (<12 months, n = 30) and the long-term (LT) group (more than 12 months, n = 30). The abilities of inhibitory control, cognitive flexibility, and working memory were measured by the Stop-signal task, Switching task, and N-back task, respectively. There was no significant group difference in either the accuracy or reaction time of the Stop-signal task. No significant difference between the groups' accuracy in the Switching task was observed. However, the LT group presented a shorter reaction time than the ST group (731.69 ± 149.23 ms vs. 857.15 ± 157.99 ms, P < 0.01) in the Switching task. Additionally, training experience was positively associated with the reaction time of the Switching task. As for the N-back task, in comparison with the LT group, the ST group showed a longer reaction time (711.37 ± 168.14 ms vs. 164.75 ± 635.88 ms, P < 0.05). Moreover, training experience was also positively associated with the reaction time of the N-back task. But there was no significant group difference in the accuracy of the N-back task. In conclusion, children trained for over 1 year have better performance in cognitive flexibility and working memory than those trained in <1 year; thus, tennis experience is positively associated with executive functions.

Anti-Overturning Fully Symmetrical Triboelectric Nanogenerator Based on an Elliptic Cylindrical Structure for All-Weather Blue Energy Harvesting.

Triboelectric nanogenerators (TENGs) have shown promising potential for large-scale blue energy harvesting. However, the lack of reasonable designs has largely hindered TENG from harvesting energy from both rough and tranquil seas. Herein, a fully symmetrical triboelectric nanogenerator based on an elliptical cylindrical structure (EC-TENG) is proposed for all-weather blue energy harvesting. The novel elliptical cylindrical shell provides a unique self-stability, high sensitivity to wave triggering, and most importantly, an anti-overturning capability for the EC-TENG. Moreover, benefiting from its internal symmetrical design, the EC-TENG can produce energy normally, even if it was overturned under a rude oscillation in the rough seas, which distinguishes this work from previous reported TENGs. The working mechanism and output performance are systematically studied. The as-fabricated EC-TENG is capable of lighting 400 light-emitting diodes and driving small electronics. More than that, an automatic monitoring system powered by the EC-TENG can also monitor the water level in real-time and provide an alarm if necessary. This work presents an innovative and reliable approach toward all-weather wave energy harvesting in actual marine environments.

Downregulation of mitochondrial pyruvate carrier 2 aggravates neuronal injury in the cortex following cerebral ischemia in rat.

Cerebral ischemia is one of the most common disabling and lethal diseases worldwide, but its underlying mechanisms remain unclear. Mitochondrial pyruvate carrier 2 (MPC2), a subunit of MPC complex, plays pivotal roles in coordinating glycolytic and mitochondrial activities. In the present study, the expression of MPC2 was significantly reduced in the ischemic cerebral cortex of rats at 24 h after bilateral internal carotid artery occlusion (BICAO), and in the cortical neurons after 1 h oxygen-glucose deprivation (OGD)/24 h reoxygenation treatment. After MPC2 gene knockdown, the number and expression of neurons were remarkably decreased in the ischemic cerebral cortex of BICAO rats and OGD-treated neurons. UK5099 significantly reduced the number, expression and viability of OGD-treated neurons, and resulted in a significant decrease in length of neurite. Using RNA-sequencing (RNA-seq) technique, we further identified MPC2-related differential genes in the ischemic cerebral cortex of BICAO rats. In conclusion, our results suggested that the decrease in MPC2 expression aggravated ischemic injury, and MPC2-related genes might be a novel therapeutic target for cerebral ischemia.

cPKCγ Deficiency Exacerbates Autophagy Impairment and Hyperphosphorylated Tau Buildup through the AMPK/mTOR Pathway in Mice with Type 1 Diabetes Mellitus.

Type 1 diabetes mellitus (T1DM)-induced cognitive dysfunction is common, but its underlying mechanisms are still poorly understood. In this study, we found that knockout of conventional protein kinase C (cPKC)γ significantly increased the phosphorylation of Tau at Ser214 and neurofibrillary tangles, but did not affect the activities of GSK-3ß and PP2A in the hippocampal neurons of T1DM mice. cPKCγ deficiency significantly decreased the level of autophagy in the hippocampal neurons of T1DM mice. Activation of autophagy greatly alleviated the cognitive impairment induced by cPKCγ deficiency in T1DM mice. Moreover, cPKCγ deficiency reduced the AMPK phosphorylation levels and increased the phosphorylation levels of mTOR in vivo and in vitro. The high glucose-induced Tau phosphorylation at Ser214 was further increased by the autophagy inhibitor and was significantly decreased by an mTOR inhibitor. In conclusion, these results indicated that cPKCγ promotes autophagy through the AMPK/mTOR signaling pathway, thus reducing the level of phosphorylated Tau at Ser214 and neurofibrillary tangles.

Basketball training frequency is associated with executive functions in boys aged 6 to 8 years.

This study investigates the relationship between the frequency of basketball training and executive functions (inhibitory control, working memory, and cognitive flexibility) in boys aged 6 to 8. A total of 40 boys recruited from a local after-school basketball training club were divided into a low-frequency group (once a week) and a high-frequency group (at least twice a week). An additional 20 age-matched boys recruited from a local elementary school were considered as the control group (no training experience). All subjects conducted the Stop-signal task, the N-back task, and the switching task at rest. The mean reaction time and accuracy data obtained from each task were used in statistical analysis. There was no significant group difference in either the accuracy or reaction time of inhibitory control. Meanwhile, no significant difference was found in the reaction time of working memory across groups. However, the high-frequency group exhibited significantly higher accuracy (93.00 ± 4.31%) with regard to working memory than the low-frequency group (85.4 ± 6.04%, P < 0.001) and the control group (83.73 ± 7.70%, P < 0.001), respectively. A positive correlation was also found between the accuracy of working memory and groups. Furthermore, in comparison with the control group, the high-frequency group exhibited significantly higher cognitive flexibility accuracy (91.93 ± 7.40% vs. 85.70 ± 9.75%, P = 0.004) and shorter reaction time (934.24 ± 213.02 ms vs. 1,122.06 ± 299.14 ms, P < 0.001). There was also a positive correlation between the accuracy of cognitive flexibility and groups. These findings suggest that regular basketball training, especially with higher frequency, is beneficial to working memory and cognitive flexibilityin boys aged 6 to 8.

The proteomic characterization of the peritumor microenvironment in human hepatocellular carcinoma.

The tumor microenvironment (TME) was usually studied in tumor tissue and in relation to only tumor progression, with little involved in occurrence, recurrence and metastasis of tumor. Thus, a new concept "peritumor microenvironment (PME)" was proposed in the proteomic characterization of peritumor liver tissues in human hepatocellular carcinoma (HCC). The PME for occurrence (PME-O) and progression (PME-P) were almost totally different at proteome composition and function. Proteins for occurrence and progression rarely overlapped and crossed. Immunity played a central role in PME-O, whereas inflammation, angiogenesis and metabolism were critical in PME-P. Proteome profiling identified three PME subtypes with different features of HCC. Thymidine phosphorylase (TYMP) was validated as an antiangiogenic target in an orthotopic HCC mouse model. Overall, the proteomic characterization of the PME revealed that the entire processes of HCC occurrence and progression differ substantially. These findings could enable advances in cancer biology, diagnostics and therapeutics.

[Brain mechanisms of male sexual function].

In this paper, we reviewed the brain imaging studies of male sexual function in recent years from three aspects: the brain mechanism of normal sexual function, the brain mechanism of sexual dysfunction, and the mechanism of drug therapy for sexual dysfunction. Studies show that the development stages of male sexual activities, such as the excitement phase, plateau phase and orgasm phase, are controlled by different neural networks. The mesodiencephalic transition zone may play an important role in the start up of male ejaculation. There are significant differences between sexual dysfunction males and normal males in activation patterns of the brain in sexual arousal. The medial orbitofrontal cortex and inferior frontal gyrus in the abnormal activation pattern are correlated with sexual dysfunction males in sexual arousal. Serum testosterone and morphine are commonly used drugs for male sexual dysfunction, whose mechanisms are to alter the activating levels of the medial orbitofrontal cortex, insula, claustrum and inferior temporal gyrus.

The Risk Stratification for Cervical Cancer and Precursors of Domestic HPV Testing With HPV 16/18 Genotyping in Women With NILM Cytology in CentralChina: A Cohort Study.

OBJECTIVE: To evaluate the clinical performance and utility for risk stratification of DH3 HPV assay in women (≥30 years) with NILM cytology. METHODS: A prospective cohort was established in Central China between November 8 to December 14, 2016 which consisted of 2180 women aging 30-64 years with NILM cytology. At baseline, all women were screened using DH3 HPV assay. HPV 16/18 positive women would be assigned to colposcopy and biopsied if necessary. Then, hr-HPV positive women without CIN2+ lesions would be followed up by cytology every 12 months for two years. In the 3rd year of follow up, all women that were not biopsy proven CIN2+ would be called back and screened by cytology again. In follow-up period, women with ASC-US and above were referred to colposcopy and biopsied if clinically indicated. CIN2+ was the primary endpoint in analysis. The clinical performance and utility for risk stratification of DH3 HPV assay were assessed by SPSS 22.0 and SAS 9.4. RESULTS: Of 2180 qualified women, the prevalence of hr-HPV was 8.5% (185/2180), 45(2.1%) were HPV 16/18 positive. The clinical performance for HPV16/18 was 91.7% for sensitivity, 98.4% for specificity, respectively against CIN2+ detection at baseline. In four years of study, the corresponding rates of HPV 16/18 were 51.5% and 98.7%, respectively. The cumulative absolute risk for the development of CIN2+ was as high as 37.8% for HPV 16/18 positive women, followed by hr-HPV positive (14.6%), other hr-HPV positive (11.0%) and HPV negative (0.3%) in three years. The relative risk was 125.6 and 3.4 for HPV 16/18 positive group when compared with HPV negative and other hr-HPV positive group, respectively. CONCLUSIONS: DH3 HPV assay demonstrated excellent clinical performance against CIN2+ detection in cervical cancer screening and utility of risk stratification by genotyping to promote scientific management of women with NILM cytology.

Laterally Extended Endopelvic Resection Versus Chemo or Targeted Therapy Alone for Pelvic Sidewall Recurrence of Cervical Cancer.

BACKGROUND: Laterally extended endopelvic resection (LEER) has been introduced for treatment of pelvic sidewall recurrence of cervical cancer (PSRCC), which occurs in only 8% of patients with relapsed cervical cancer. LEER can only be performed by a proficient surgeon due to the high risk of surgical morbidity and mortality, but there is no evidence as to whether LEER is may be more effective than chemo or targeted therapy alone for PSRCC. Thus, we aimed to compare the efficacy and safety between LEER and chemo or targeted therapy alone for treatment of PSRCC. METHODS: We prospectively recruited patients with PSRCC who underwent LEER between December 2016 and December 2019. Moreover, we retrospectively collected data on patients with PSRCC who received chemo or targeted therapy alone between January 2000 and December 2019. We compared treatment-free interval (TFI), progression-free survival (PFS), treatment-free survival (TFS), overall survival (OS), tumor response, neurologic disturbance of the low extremities, and pelvic pain severity in the different patient groups. RESULTS: Among 1295 patients with cervical cancer, we included 28 (2.2%) and 31 (2.4%) in the prospective and retrospective cohorts, respectively. When we subdivided all patients into two groups based on the median value of prior TFI (PTFI, 9.2 months), LEER improved TFI, PFS, TRS and OS compared to chemo or targeted therapy alone (median, 2.8 vs. 0.9; 7.4 vs. 4.1; 30.1 vs. 16.9 months; P ≤ 0.05) in patients with PTFI < 9.2 months despite no difference in survival in those with PTFI ≥ 9.2 months, suggesting that LEER may lead to better TFI, PFS, TRS and OS in patients with PTFI < 9.2 months (adjusted hazard ratios, 0.28, 0.27, 0.44 and 0.37; 95% confidence intervals, 0.12-0.68, 0.11-0.66, 0.18-0.83 and 0.15-0.88). Furthermore, LEER markedly reduced the number of morphine milligram equivalents necessary to reduce pelvic pain when compared with chemo or targeted therapy alone. CONCLUSION: Compared to chemo or targeted therapy alone, LEER improved survival in patients with PSRCC and PTFI < 9.2 months, and it was effective at controlling the pelvic pain associated with PSRCC. TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT02986568.

Corrigendum: Identification of BRCA1:c.5470_5477del as a Founder Mutation in Chinese Ovarian Cancer Patients.

[This corrects the article DOI: 10.3389/fonc.2021.655709.].