Background:Treatment selection for very elderly patients with endometrial cancer (EC) is frequently constrained by multimorbidity and frailty, increasing the risk of undertreatment and compromised outcomes. With the incorporation of molecular profiling into clinical practice, a subset of ECs has been recognized to exhibit homologous recombination deficiency (HRD), providing a rationale for the use of poly(ADP-ribose) polymerase (PARP) inhibitors. However, evidence for PARP inhibitor maintenance in EC remains limited, particularly in nonagenarians. Case Description:A 92-year-old woman at first-time diagnosis of International Federation of Gynecology and Obstetrics (FIGO) stage IVB uterine serous carcinoma (USC) harboring a somatic BRCA2 mutation received initial treatment consisting of suboptimal cytoreductive surgery followed by first-line carboplatin monotherapy, achieving a partial response (PR). Given the moderate renal impairment of the patient and her advanced age with anticipated vulnerability to treatment-related adverse events (TRAEs), maintenance olaparib was initiated at a reduced dose (150 mg twice daily) rather than the standard 300 mg twice daily. Under olaparib maintenance, the patient achieved a durable PR by serial imaging that has been maintained for 40 months until the latest follow-up (March 2026, 46 months after initial diagnosis), with serum cancer antigen 125 (CA-125) levels remaining consistently low and stable. The treatment was well tolerated; TRAEs were grade 1 or lower and were manageable with supportive care. Conclusions:This case illustrates that reduced-dose olaparib maintenance may be feasible and well-tolerated in very elderly patients with advanced, BRCA-mutated USC. It also highlights the potential clinical value of molecular profiling to enable individualized treatment strategies in this high-risk population.

Women with placenta previa (PP) typically present with severe hemorrhaging during cesarean section (CS). Nevertheless, the hemostatic efficacy of the current suture technique remains to be optimized. This study was conducted to evaluate the efficacy of reconstructing the lower uterine segment by wave compression suture (WCS) in women with PP who have underwent CS. The cohort study included 123 women who received WCS as the first uterine suture technique between 2016 and 2020 at the West China Second University Hospital of Sichuan University. The hemostatic effect of WCS was evaluated in accordance with the type of PP and the intraoperative circumstances. A total of 72 (58.5%) women were successfully achieved hemostasis without the need for further intervention. In 51 (41.5%) cases, additional procedures were required, namely uterine artery ligation, cervical hanging maneuver, and Bakri tamponade. Seventy-nine cases exhibiting thin anterior walls and lower uterine atony following placental dissection; of these, 72 (91.1%) achieved hemostasis through WCS. No woman required a subsequent laparotomy or hysterectomy. No complications were identified as being attributable to the WCS following surgery. Among the 5 women who subsequently became pregnant, no intrauterine adhesions or abnormal uterine morphologies were caused by WCS. No ectopic or cesarean scar pregnancies occurred. WCS represents an efficient technique for women presenting with thin anterior walls and uterine atony of the lower uterine segment, in conjunction with PP.

Advancements in diagnostic and therapeutic standards have substantially enhanced the survival of patients with malignant tumors. Nevertheless, the quest for effective strategies to address resistant or recurrent advanced tumors remains a critical and unwavering objective. Bispecific antibodies (BsAbs) unleashed a new era of anti-tumor treatment by simultaneously binding to two distinct targets, thereby enhancing specificity, minimizing off-target toxicities, and synergistically modulating anti-tumor immunity and the tumor microenvironment. Compared with the combination of two monoclonal antibodies, BsAbs represent the physical integration of dual specificities, demonstrating superior binding efficacy, reducing the risk of drug resistance, and enabling unique biological functions such as bridging tumor cells and T cells to achieve precise cytotoxicity. However, limitations such as off-target toxicities, drug resistance and immune-related adverse effects require carefully evaluation and further optimization. Further studies are necessary to explore the potential of combining BsAbs with other anti-tumor strategies, balancing the efficacy and safety, optimizing the outpatient-based administration workflow. By tracking the research advancements of recently approved BsAbs and BsAb candidates in clinical trials, it is evident that BsAbs holds significant promise as a novel and transformative option for improving survival outcomes for patients.

OBJECTIVES:To compare the effects of different adjuvant treatments for different pathological types of early-stage cervical cancer post-surgery. MATERIALS AND METHODS:Patients with International Federation of Gynecology and Obstetrics (FIGO) stages I-II squamous cell carcinoma (SCC), adenocarcinoma (ADC), and adenosquamous carcinoma (ASC) who underwent hysterectomy and postoperative radiotherapy (RT) from 2004 to 2015 in the surveillance, epidemiology, and end results program database were analyzed. The clinicopathological characteristics and survival rates were compared. RESULTS:A total of 5444 cases were included. ADC had the highest 5-year overall survival (OS) and cervical carcinoma-specific survival (CCSS) rates, followed by SCC and ASC. No significant difference in prognosis was noted among the three histological subtypes when treated with chemoradiation therapy (CRT). However, the survival benefit for ASC was significantly lower than that for SCC (hazard ratio [HR], 1.625; 95% confidence interval [CI], 1.024-2.579; P = 0.039) when treated with RT alone. The prognosis of FIGO stage I patients was significantly better with RT than with CRT (HR, 0.766; 95% CI, 0.622-0.943; P = 0.012). No significant differences in CCSS were observed between patients (stages I and II) treated with external beam RT (EBRT) and EBRT + intracavity brachytherapy. CONCLUSION:No significant differences in OS and CCSS were observed among the three histological subtypes. The prognosis of ASC patients who received CRT was better than that of those who received RT alone. Patients with stage I tumors could obtain better survival with RT alone. The addition of brachytherapy to EBRT yielded no benefits across the three histological subtypes.

Backgroud: Neurological disorders are common in preterm (PT) born individuals. Diffusion tensor imaging (DTI) studies using tract-based spatial statistics (TBSS) effectively detect microstructural white matter (WM) abnormalities in the brain. We conducted this systematic review to integrate the findings of TBSS studies to determine the most consistent WM alterations in PT born individuals. Methods: PubMed, Embase, Web of Science and Science Direct were searched. DTI studies using TBSS in PT born individuals were screened up to October 2022. The systematic review included studies reporting alterations in FA values for the entire brain in a stereotactic space, with three coordinates (x, y, z), according to the seed-based d mapping method. Results: The search strategy identified seventeen studies that fulfilled our inclusion criteria, with a total of 911 PT-born individuals and 563 matched controls were analysed. Of the seventeen studies, eight were dedicated to 650 adults, five to 411 children and four to 413 infants. Ten studies recruited 812 individuals born very prematurely (GA <29 weeks), six studies recruited 386 moderately premature individuals (GA = 29-32 weeks) and one study recruited 276 individuals born late prematurely (GA >32 weeks). This meta-analysis of six studies including 388 individuals highlighted four brain regions in which fractional anisotropy (FA) was lower in PT group than in people born at term. The quantitative meta-analysis found that the most robust WM alterations were located in the corpus callosum (CC), the bilateral thalamus and the left superior longitudinal fasciculus (SLF) II. Significant changes in FA reflect WM abnormalities in PT born individuals from infant to young adulthood. Conclusions: Significant changes in FA reflect WM abnormalities in individuals born PT from infancy to young adulthood. The abnormal development of the CC, bilateral thalamus and left SLF may play a vital role in the neurodevelopment of PT individuals.

The key role of structural cells in immune modulation has been revealed with the advent of single-cell multiomics, but the underlying mechanism remains poorly understood. Here, we revealed that the transcriptional activation of interferon regulatory factor 1 (IRF1) in response to ionizing radiation, cytotoxic chemicals and SARS-CoV-2 viral infection determines the fate of structural cells and regulates communication between structural and immune cells. Radiation-induced leakage of mtDNA initiates the nuclear translocation of IRF1, enabling it to regulate the transcription of inflammation- and cell death-related genes. Novel posttranslational modification (PTM) sites in the nuclear localization sequence (NLS) of IRF1 were identified. Functional analysis revealed that mutation of the acetylation site and the phosphorylation sites in the NLS blocked the transcriptional activation of IRF1 and reduced cell death in response to ionizing radiation. Mechanistically, reciprocal regulation between the single-stranded DNA sensors SSBP1 and IRF1, which restrains radiation-induced and STING/p300-mediated PTMs of IRF1, was revealed. In addition, genetic deletion or pharmacological inhibition of IRF1 tempered radiation-induced inflammatory cell death, and radiation mitigators also suppressed SARS-CoV-2 NSP-10-mediated activation of IRF1. Thus, we revealed a novel cytoplasm-oriented mechanism of IRF1 activation in structural cells that promotes inflammation and highlighted the potential effectiveness of IRF1 inhibitors against immune disorders.

AbstractBackgroundNumerous observational studies have investigated the potential link between hypertensive disorders of pregnancy (HDPs) and the subsequent risks of gynecologic tumors, yet the findings have been inconsistent. In this study, we utilized Mendelian randomization (MR) approach to assess the influence of HDPs on the future risks of ovarian, cervical, endometrial, and breast cancer and uterine fibroids, controlling for confounding factors.MethodsThe genome‐wide association studies (GWAS) summary data relevant to HDPs was obtained from the FinnGen databases (10,736 cases and 136,325 controls). Gynecologic tumor outcomes were extracted from the IEU Open GWAS project and UK Biobank (47,690 cases and 1, 092,073 controls). The inverse variance weighted (IVW) approach was selected as the principal method for MR analysis, supplemented by MR‐Egger, weighted median, weighted model, simple model methods, MR pleiotropy residual sum and outlier (MR‐PRESSO) test, and leave‐one‐out method. Multivariate MR (MVMR) analysis was conducted after adjusting systolic blood pressure (SBP), body mass index (BMI) and type 2 diabetes mellitus (T2DM).ResultsOur univariate MR analysis (UVMR) results revealed no significant relationship between HDPs and the risks of ovarian cancer (odds ratio [OR] = 0.924, p = 0.360), cervical cancer (OR = 1.230, p = 0.738), endometrial cancer (OR = 1.006, p = 0.949), uterine fibroids (OR = 1.155, p = 0.158), and breast cancer (OR = 0.792, p = 0.241) by IVW test. Similar results were observed in gestational hypertension and preeclampsia/eclampsia. Additionally, our study detected neither heterogeneity nor pleiotropy. MVMR analysis also provided no evidence of a causal association between HDPs and common gynecologic tumors after adjusting SBP, BMI, and T2DM.ConclusionWe discovered no causal relationship between HDPs and ovarian, cervical, endometrial, breast cancer, and uterine fibroids in European populations. However, present analysis did not explore the effect of HDPs on the subtypes of gynecologic tumors across varied ethnic populations, which may require additional research.

Objective:Female fertility gradually decreases with the increase in women's age. The underlying reasons include the decline in the quantity and quality of oocytes. Oocyte aging is an important manifestation of the decline in oocyte quality, including in vivo oocyte aging before ovulation and in vitro oocyte aging after ovulation. Currently, few studies have been done to examine oocyte aging, and the relevant molecular mechanisms are not fully understood. Therefore, we used zebrafish as a model to investigate oocyte aging. Three different age ranges of female zebrafish were selected to mate with male zebrafish of the best breeding age. In this way, we studied the effects of maternal age-related oocyte aging on fertility and investigated the potential molecular mechanisms behind maternal age-related fertility decline. Methods:Eight female zebrafish aged between 158 and 195 d were randomly selected for the 6-month age group (180±12) d, 8 female zebrafish aged between 330 and 395 d were randomly selected for the 12-month age group (360±22) d, and 8 female zebrafish aged between 502 and 583 d were randomly selected for the 18-month age group (540±26) d. Male zebrafish of (180±29) d were randomly selected from zebrafish aged between 158 and 195 d and mated with female zebrafish in each group. Each mating experiment included 1 female zebrafish and 1 male zebrafish. Zebrafish embryos produced by the mating experiments were collected and counted. The embryos at 4 hours post-fertilization were observed under the microscope, the total number of embryos and the number of unfertilized embryos were counted, and the fertilization rate was calculated accordingly. The numbers of malformed embryos and dead embryos were counted 24 hours after fertilization, and the rates of embryo malformation and mortality were calculated accordingly. The primary outcome measure was the embryo fertilization rate, and the secondary outcome measures were the number of embryos per spawn (the total number of embryos laid within 1.5 hours after the beginning of mating and reproduction of the zebrafish), embryo mortality, and embryo malformation rate. The outcome measures of each group were compared. The blastocyst embryos of female zebrafish from each group born after mating with male zebrafish in their best breeding period were collected for transcriptomics analysis. Fresh oocytes of female zebrafish in each group were collected for transcriptomics analysis to explore the potential molecular mechanisms of maternal age-related fertility decline. Results:Compared with that of the 6-month group (94.9%±3.6%), the embryo fertilization rate of the 12-month group (92.3%±4.2%) showed no significant difference, but that of the 18-month group (86.8%±5.5%) decreased significantly (P<0.01). In addition, the fertilization rate in the 18-month group was significantly lower than that in the 12-month group (P<0.05). Compared with that of the 6-month group, the embryo mortality of the female zebrafish in the 12-month group and that in the 18-month group were significantly higher than that in the 6-month group (P<0.000 1, P<0.001). There was no significant difference in the number of embryos per spawn or in the embryo malformation rate among the three groups. The results of the transcriptomics analysis of blastocyst embryos showed that some genes, including dusp5, bdnf, ppip5k2, dgkg, aldh3a2a, acsl1a, hal, mao, etc, were differentially expressed in the 12-month group or the 18-month group compared with their expression levels in the 6-month group. According to the KEGG enrichment analysis, these differentially expressed genes (DEGs) were significantly enriched in the MAPK signaling pathway, the phosphatidylinositol signaling system, and the fatty acid degradation and histidine metabolism pathway (P<0.05). The analysis of the expression trends of the genes expressed differentially among the three groups (the 6-month group, the 12-month group, and the 18-month group in turn) showed that the gene expression trends of fancc, fancg, fancb, and telo2, which were involved in Fanconi anemia pathway, were statistically significant (P<0.05). In the results of oocyte transcriptomics analysis, the genes that were differentially expressed in the 12-month group or the 18-month group compared with the 6-month group were mainly enriched in cell adhesion molecules and the protein digestion and absorption pathway (P<0.05). The results of the trends of gene expression in the zebrafish oocytes of the three groups (the 6-month group, the 12-month group, and the 18-month group in turn) showed that three kinds of gene expression trends of declining fertility with growing maternal age had significant differences (P<0.05). Further analysis of the three significantly differential expression trends showed 51 DEGs related to mitochondria and 5 DEGs related to telomere maintenance and DNA repair, including tomm40, mpc2, nbn, tti1, etc. Conclusion:With the increase in the maternal age of the zebrafish, the embryo fertilization rate decreased significantly and the embryo mortality increased significantly. In addition, with the increase in the maternal age of the zebrafish, the expression of mitochondria and telomere-related genes, such as tomm40, mpc2, nbn, and tti1, in female zebrafish oocytes decreased gradually. Maternal age may be a factor contributing to the decrease in oocyte fertilization ability and the increase in early embryo mortality. Maternal age-related oocyte aging affects the fertility and embryo development of the offspring.

Background: Complete uterine rupture can lead to serious adverse maternal and child outcomes. Uterine rupture is rare, and it can occur in an intact uterus. Methods: We identified patients with intact uterus who encountered uterine rupture between 2010 and 2020 from the medical records of 10 hospitals in Sichuan Province. Results: In total, 37 cases of uterine rupture in intact uteri were identified. Eight ruptures (8/37, 21.6%) occurred before spontaneous labor, 11 ruptures (11/37, 29.7%) occurred during spontaneous labor, and 18 ruptures (18/37, 48.6%) occurred during induced labor. The clinical manifestations of the patients were abdominal pain in 20 cases (20/37, 54.1%), vaginal bleeding in three cases (3/37, 8.1%), and abdominal pain and vaginal bleeding in eight cases (8/37, 21.6%). The rate of hysterectomy/death was significantly higher in patients with more than three previous vaginal deliveries (p = 0.005). In addition, the rate of hysterectomy/death in the spontaneous labor group was significantly higher than that in the induced labor group (p = 0.011). The fetal survival rate in patients with uterine rupture at the uterine horn was significantly higher than that in patients with uterine rupture at the lower uterine segment (p = 0.007). Conclusions: Uterine rupture in an intact uterus was associated with a high hysterectomy rate and high fetal/neonatal mortality rate. For pregnant women with sudden abdominal pain and abnormal fetal heart rate, we should be alert to the possibility of uterine rupture. Induction and augmentation of labor need to be performed with caution to avoid this potential obstetric emergency.

Abstract This study used structural magnetic resonance imaging to analyze changes in the gray matter volume (GMV) of preterm‐born (PTB) and term‐born (TB) children to help elucidate the influence of magnesium sulfate treatment on the nervous system development. A total of 51 subjects were recruited, including 28 PTB and 23 TB children. The intelligence scale and MRI scan were completed at the corrected age of 10 to 16 years. A whole‐brain voxel‐wise analysis tested the main effect of the status (PTB without magnesium, PTB with magnesium, and TB) using a factorial design in SPM8. The mean volumes of the regions that showed significant group effects on the GMV after the FDR correction were extracted in the common space for each subject. Verbal and full‐scale intelligence quotient scores were significantly lower for PTB children without magnesium than for TB children; however, the scores of PTB children with magnesium and TB children were almost identical. Compared with TB children, PTB children had significantly reduced left straight gyrus and left inferior frontal gyrus GMVs; however, the volumes of PTB children with magnesium were closer to those of TB children. Changes in the GMV of the left inferior frontal gyrus were significantly correlated with full‐scale and verbal intelligence quotient scores, whereas the lower gestational age at the time of mgsou4 treatment led to a larger GMV of the left inferior frontal gyrus. Brain structural abnormalities could exist in PTB children. The GMVs of the left straight gyrus and left inferior frontal gyrus were significantly reduced in these children. The influence of magnesium sulfate treatment was not significant, but the cognitive levels of these children were significantly increased and almost identical to those of TB children. Initiation of magnesium sulfate treatment during gestation is negatively correlated with the left inferior frontal gyrus GMV.

Human skin is daily exposed to oxidative stresses in the environment such as physical stimulation, chemical pollutants and pathogenic microorganisms, which are likely to cause skin diseases. As important post-translational modifications, protein ubiquitination and deubiquitination play crucial roles in maintaining cellular homeostasis by the proteolytic removal of oxidized proteins. We have previously reported that the expression of ubiquitin-specific protease 47 (USP47), a kind of deubiquitinating enzymes (DUBs), was signifi-cantly elevated in response to oxidative stress. However, the role of USP47 in cutaneous oxidative injury remains unclear. Usp47 wild-type (Usp47(+/+)) mice and Usp47 knockout (Usp47(-/-)) mice were used to establish two animal models of oxidative skin damage: (1) radiation-and (2) imiquimod (IMQ)-induced skin injury. Loss of Usp47 consistently aggravated mouse skin damage in vivo. Subsequently, we screened 63 upregulated and 170 downregulated proteins between the skin tissues of wild-type and Usp47(-/-)mice after 35 Gy electron beam radiation using proteomic analysis. Among the dysregulated proteins, nicotinamide nucleotide transhydrogenase (NNT), which has been reported as a significant regulator of oxidative stress and redox homeostasis, was further investigated in detail. Results showed that NNT was regulated by USP47 through direct ubiquitination mediated degradation and involved in the pathogenesis of cutaneous oxidative injury. Knockdown of NNT expression dramatically limited the energy production ability, with elevated mitochondrial reactive oxygen species (ROS) accumulation and increased mitochondrial membrane potential in irradiated HaCaT cells. Taken together, our present findings illustrate the critical role of USP47 in oxidative skin damage by modulating NNT degradation and mitochondrial homeostasis.

目的 比较不同铅门设置对宫颈癌术后容积旋转调强放疗(Volumetric Intensity Modulated Arc Therapy,VMAT)计划的剂量学影响.方法 选取14例已执行的宫颈癌术后VMAT计划的患者为研究对象,在Eclipse 15.5计划系统中对铅门设置3种情况:固定铅门一侧,另一侧分别设置2、3、4 cm,射野参数、剂量限值等优化条件不变,重新优化通量和计算剂量得到3种计划:Planl(2 cm)、Plan2(3 cm)、Plan3(4 cm).采用方差分析模型比较3种计划的靶区和危及器官剂量学参数以及机器跳数.结果 3种计划靶区的Dmean和D50％、危及器官直肠的Dmax、左侧股骨头的Dmax和V40比较差异具有统计学意义(P＜0.05),Planl计划组的机器跳数高于其他计划组(P＜0.05),3种计划中其余参数的差异无统计学意义(P＞0.05).结论 3种铅门固定方案均满足临床要求,铅门较大的计划组Plan2和Plan3的机器跳数更少,可以提高治疗效率及机器执行率,但对于危及器官的保护略弱于铅门较小的Planl组.

目的 分析和比较宫颈癌术后容积旋转调强放射治疗(Volumetric Intensity-Modulated Arc Therapy,VMAT)中光子剂量算法(Acuros External Beam Algorithm,AXB)和各向异性分析算法(Anisotropic Analytical Algorithm,AAA)的剂量学差异.方法 选取24例宫颈癌术后患者,分别在Eclipse 15.5治疗计划系统上采用AXB算法和AAA算法设计VMAT计划,并生成相应的EPID验证计划,比较靶区及危及器官的剂量学参数.结果 两种算法计算所得靶区的D2％、D5％、D98％及Dmax均有显著统计学差异(P<0.05),其中AAA算法中的最大剂量为(48.1±17.2)Gy,AXB算法中的最大剂量为(48.7±28.7)Gy,两种算法PTV的适形度指数有显著统计学差异(P=0.047);危及器官的骨(髂骨和骶骨)、左股骨头和右股骨头的Dmean差异均有显著统计学差异(P<0.05).除Dmin、D95％、D98％和小肠的V25外,其余参考指标AAA算法结果均低于AXB算法;两种算法的验证计划无统计学差异(P>0.05).结论 AXB算法与AAA算法在宫颈癌VMAT中虽然存在一定的剂量学差异,但均符合剂量学和临床要求,且在验证通过率方面差异无统计学意义,两种算法都可以应用于临床治疗.

Purpose To determine the differences in supraclavicular lymph node metastasis between esophageal cancer (EC) and nasopharyngeal cancer (NPC) and explore the feasibility of differential supraclavicular clinical target volume (CTV) contouring between these two diseases based on the involvement of different fascial spaces. Materials and methods One hundred patients with supraclavicular nodes positive for EC or NPC were enrolled, and their pre-treatment images were reviewed. The distribution patterns of nodes between the two diseases were compared in the context of node levels defined by the 2017 Japanese Esophageal Society and 2013 International Consensus on Cervical Lymph Node Level Classification. Grouping supraclavicular nodes based on sub-compartments formed by the cervical fascia was discussed, and the feasibility of differential CTV contouring based on the differences in the involvement of these sub-compartments between EC and NPC was explored. Results The 2013 Consensus on cervical node levels and 2017 Japanese Esophageal Society node station could not practically guide supraclavicular CTV contouring. We divided the supraclavicular space into six sub-compartments: the para-esophageal space (PES), carotid sheath space (CSS), sub-thyroid pre-trachea space (STPTS), pre-vascular space (PVS), and vascular lateral space (VLS) I and II. EC mainly spread to the PES, STPTS, CSS, and VLS I, whereas NPC tended to spread to the CSS, VLS I, and VLS II. These combinations of sub-compartments may help constitute the supraclavicular CTVs for EC and NPC. Conclusions The fascia anatomy-based sub-compartments sufficiently distinguished metastasis to the supraclavicular space between EC and NPC, thus facilitating differential CTV contouring between these two diseases.

BACKGROUND:Radiation facilities and radioactive materials have been widely used in military, industry, medicine, science and nuclear facilities, which has significantly increased the potential of large-scale, uncontrolled exposure to radiation. The skin is one of the radiosensitive organ systems and radiation-induced skin injury remains a serious concern after ionizing radiation exposure. Our previous report indicates the involvement of the peroxisome proliferator-activated receptor pathway in the response of skin tissues to ionizing radiation. PPARα is a member of the PPAR nuclear hormone receptor superfamily, which can be activated by fibrate ligands. However, the protection of fenofibrate against ionizing radiation in skin keratinocytes and fibroblasts has not been described.METHODS:The PPARα mRNA levels in irradiated and nonirradiated skin tissues of rats were determined by real-time assay. The expression of PPARα, and FABP4 were evaluated by western blot and IHC assay. The cell proliferation was detected by colony formation. The γH2AX foci and ROS levels in irradiated WS1 cells with FABP4 overexpression than in control cells were performed by Immunofluorescence assay.RESULTS:We found that PPARα expression was lower in the irradiated skin tissues of mouse, rat, monkey, and human patients than in their nonirradiated counterparts. PPARα fenofibrate significantly decreased radiation-induced ROS and apoptosis in a dose-dependent manner in human keratinocyte HaCaT and skin fibroblast WS1 cells. Moreover, fenofibrate significantly decreased radiation-induced ROS and malondialdehyde (MDA) levels in electron beam irradiated skin tissues of rats. Mechanistically, the proximal promoter of fatty acid binding protein 4 (FABP4) harbored three binding sites of PPARα and fenofibrate stimulated the transcription of FABP4 in skin cells. FABP4 overexpression decreased radiation-induced ROS and γH2AX foci. FABP4 inhibitor BMS309403 abrogated the ROS-eliminating activity as well as the lipid-accumulating role of fenofibrate, indicating that FABP4 mediates the radioprotective role of fenofibrate. In addition, FABP4 overexpression significantly decreased radiation-induced oxidative damage in vivo.CONCLUSIONS:These results confirm that fenofibrate attenuated radiation-induced oxidative damage to the skin by stimulating FABP4.

目的:比较在收敛模式打开(ON)和关闭(OFF)时设计宫颈癌术后容积旋转调强放疗(volumetric modulated arc thrapy,VMAT)计划的剂量学差异.方法:选取20例宫颈癌术后患者,在Eclipse 15.5计划系统上,保证其余设计参数一致,分别采用收敛模式ON和OFF设计VMAT计划,并生成相应的电子射野影像系统(electronic portal imaging device,EPID)验证计划.比较2种收敛模式下计划靶区(planning target volume,PTV)和危及器官的剂量学参数、优化时间以及EPID验证计划的γ通过率.采用SPSS 24.0软件进行统计学分析.结果:2种收敛模式下PTV的Dmax具有统计学差异(P=0.004),其中ON模式的Dmax为(48.3±0.3)Gy,OFF模式的Dmax为(48.6±0.4)Gy;PTV的均匀性指数(homogeneity index,HI)有统计学差异(P=0.017),其中ON模式优于OFF模式;危及器官的所有剂量学参数均没有统计学差异(P>0.05);2种收敛模式下优化时间具有统计学差异(P=0.000),其中OFF模式优于ON模式;2种收敛模式下EPID验证计划γ通过率无统计学差异(P>0.05).结论:2种收敛模式的宫颈癌VMAT计划虽然存在一定的剂量学差异,但均符合剂量学和临床要求,可将其应用于临床,以指导宫颈癌术后患者VMAT计划设计.

PurposeTo observe the hemostatic efficacy of reconstructing the lower uterine segment by wave compression sutures (WCSs) in patients with placenta previa who underwent cesarean section (CS).MethodsRetrospective analysis the medical records with placenta previa underwent WCS at the West China Second University Hospital of Sichuan University.One-hundred-and-twenty-three women who received WCSs as the first uterine suture technique from January 1, 2016, to December 31, 2020, were included in this study. The hemostatic effect of WCS was compared according to the type of placenta previa and the intraoperative situation. All patients were followed up after CS.ResultsThe hemostatic effect during CS and postpartum hemorrhage were observed. Seventy-two (58.5%) patients successfully achieved hemostasis without further intervention. Fifty-one (41.5%) cases required additional uterine artery ligation (UAL), cervical hanging maneuver (CHM), and Bakri tamponade. Seventy-nine cases exhibited thin anterior walls and lower uterine atony after placental dissection; of these, 72 (91.1%) obtained hemostasis by WCS. No patient required repeat laparotomy or hysterectomy. There were no complications attributable to the WCS following surgery. Among the five patients who had a second pregnancy, no intrauterine adhesions or abnormal uterine morphologies were caused by WCS. No ectopic or incision pregnancies occurred.ConclusionsReconstruction of the lower uterine segment by WCS is a suitable technique for patients with thin anterior walls and uterine atony of the lower uterine segment along with placenta previa. WCS is easy to perform, effective, and safe.

PURPOSE:This work assessed local and systemic alternations of the tumor immune microenvironment during concurrent chemoradiation therapy (CCRT) of local advanced cervical cancer to estimate the optimal timing for immune therapy in relation to CCRT.METHODS AND MATERIALS:In this single-center prospective clinical trial, 55 patients with stage IIA through IVA cervical cancer were enrolled between December 2016 and November 2017. The median follow-up was 32.1 months. All patients received cisplatin concurrently with external beam radiation therapy combined with high-dose-rate brachytherapy. Tumor tissues and peripheral blood mononuclear cells (PBMCs) were collected before, during and after CCRT. We analyzed the changes in lymphocyte subpopulations, programmed death-1 (PD-1) and programmed cell death ligand 1 (PD-L1) expression, and the T cell receptor (TCR) repertoire that occurred throughout CCRT.RESULTS:The frequencies of CD4+ and PD-1+ T cells in PBMCs decreased after the start of CCRT, whereas that of inhibitory regulatory T cells increased. In the tumor tissues, CCRT decreased the numbers of CD4+ and CD8+ T cells and reduced the median percentage of positive cells expressing PD-L1 from 78.1% to 49.8%. As indicated by the numbers of unique clones, the TCRs of PBMCs exhibited greater diversity before CCRT than after CCRT. Greater TCR diversity in PBMCs before CCRT was associated with superior 30-month progression-free survival (hazard ratio [HR], 0.12; 95% confidence interval [CI], 0.04-0.39; P = .001) and overall survival (HR, 0.17; 95% CI, 0.04-0.68; P = .004).CONCLUSIONS:CCRT for cervical cancer altered the tumor immune microenvironment by reducing CD4+ and CD8+ T lymphocyte populations, PD-1/PD-L1 expression, and TCR diversity. Higher TCR diversity in PBMCs before CCRT resulted in better survival and prognosis, indicating that CCRT might inhibit immune activation. Our results suggest that it might be more effective to administer immune checkpoint inhibitors before CCRT of cervical cancer rather than during or after CCRT.

Cervical cancer is a common malignant tumor in women; most cervical cancer patients are premenopausal. Ovarian resection or preservation remains controversial. The purpose of this study was to discover the risk factors for ovarian metastasis in women with stage I-II cervical cancer. A total of 3292 women with cervical carcinoma who had undergone radical hysterectomy, with pelvic lymphadenectomy and bilateral oophorectomy or wedge resection of ovaries, were included in this multicenter retrospective study. We analyzed patients’ demographics, International Federation of Obstetrics and Gynecology stage, and histopathologic records to determine clinicopathologic risk factors of ovarian metastasis. Of the patients, 115 (3.49%) were confirmed to have ovarian metastasis. The ovarian metastasis rate was 2% (56/2794) for squamous cell carcinoma and 11.8% (59/498) for nonsquamous cell carcinoma. The risk factors independently associated with ovarian metastasis were histologic type (odds ratio [OR] 8.76, 95% CI 2.09-19.24), lymph node metastasis (OR 2.57, 95% CI 1.76-4.89), lymphovascular space invasion (OR 2.82, 95% CI 1.98-4.24), and corpus invasion (OR 6.34, 95% CI 2.37-11.42). The histologic type, lymph node metastasis, lymphovascular space invasion, and corpus invasion were independently associated with ovarian metastasis. Histologic type and corpus invasion were the most important risk factors. Therefore, we suggest that corpus invasion might be a strong contraindication for preservation of the ovaries.

Introduction Cervical cancer is a common malignant tumor in women; most cervical cancer patients are premenopausal. Ovarian resection or preservation remains controversial. The purpose of this study was to discover the risk factors for ovarian metastasis in women with stage I-II cervical cancer. Material and methods A total of 3292 women with cervical carcinoma who had undergone radical hysterectomy, with pelvic lymphadenectomy and bilateral oophorectomy or wedge resection of ovaries, were included in this multicenter retrospective study. We analyzed patients' demographics, International Federation of Obstetrics and Gynecology stage, and histopathologic records to determine clinicopathologic risk factors of ovarian metastasis. Results Of the patients, 115 (3.49%) were confirmed to have ovarian metastasis. The ovarian metastasis rate was 2% (56/2794) for squamous cell carcinoma and 11.8% (59/498) for nonsquamous cell carcinoma. The risk factors independently associated with ovarian metastasis were histologic type (odds ratio [OR] 8.76, 95% CI 2.09-19.24), lymph node metastasis (OR 2.57, 95% CI 1.76-4.89), lymphovascular space invasion (OR 2.82, 95% CI 1.98-4.24), and corpus invasion (OR 6.34, 95% CI 2.37-11.42). Conclusions The histologic type, lymph node metastasis, lymphovascular space invasion, and corpus invasion were independently associated with ovarian metastasis. Histologic type and corpus invasion were the most important risk factors. Therefore, we suggest that corpus invasion might be a strong contraindication for preservation of the ovaries.