Mitophagy in fibrotic diseases: molecular mechanisms and therapeutic applications.

Mitophagy is a highly precise process of selective autophagy, primarily aimed at eliminating excess or damaged mitochondria to maintain the stability of both mitochondrial and cellular homeostasis. In recent years, with in-depth research into the association between mitophagy and fibrotic diseases, it has been discovered that this process may interact with crucial cellular biological processes such as oxidative stress, inflammatory responses, cellular dynamics regulation, and energy metabolism, thereby influencing the occurrence and progression of fibrotic diseases. Consequently, modulating mitophagy holds promise as a therapeutic approach for fibrosis. Currently, various methods have been identified to regulate mitophagy to prevent fibrosis, categorized into three types: natural drug therapy, biological therapy, and physical therapy. This review comprehensively summarizes the current understanding of the mechanisms of mitophagy, delves into its biological roles in fibrotic diseases, and introduces mitophagy modulators effective in fibrosis, aiming to provide new targets and theoretical basis for the investigation of fibrosis-related mechanisms and disease prevention.

CA-125 elimination rate constant K (KELIM) as a promising predictor of complete cytoreduction after neoadjuvant chemotherapy in advanced ovarian cancer patients: a retrospective study from two Chinese hospitals.

BACKGROUND: The modeled CA-125 elimination constant K (KELIM) is a potential marker of tumor chemosensitivity in ovarian cancer patients treated with neoadjuvant chemotherapy (NACT) before interval surgery. The objective of this study was to externally validate the KELIM (rate of elimination of CA-125) score in patients with high-grade serous ovarian cancer (HGSC) undergoing NACT and explore its relation to the completeness of IDS and survival. METHODS: The study was based on a retrospective cohort of 133 patients treated for advanced HGSC, International Federation of Gynecology and Obstetrics (FIGO) stages III-IV, with neoadjuvant chemotherapy, folllowed by interval surgery, in two centres in China. CA-125 concentrations at baseline and during neoadjuvant chemotherapy were collected. We used standardized (std) KELIM for subsequent analysis. Clinicopathologic parameters were collected, and Kaplan‒Meier survival analyses were performed for PFS and OS. RESULTS: KELIM was an independent predictor of the probability of complete surgery and survival in our cohort. The median std KELIM score of patients with complete surgery was significantly higher than that of patients with incomplete IDS (1.20 vs. 0.71, P < 0.001). Multivariate analysis showed that a std KELIM score ≥0.925 was an independent predictive factor for achieving complete resection (OR = 5.480; 95% CI, 2.409-12.466, P < 0.001) and better PFS (HR = 0.544; 95% CI: 0.349-0.849, P = 0.007) and OS (HR = 0.484; 95% CI: 0.251-0.930, P = 0.030). CONCLUSIONS: The tumor-primary tumor chemosensitivity, assessed by the modeled CA-125 KELIM, calculated during NACT, is a major parameter to consider for decision-making regarding IDS attempts and predicting patient survival.

The role of epithelial cells in fibrosis: Mechanisms and treatment.

Fibrosis is a pathological process that affects multiple organs and is considered one of the major causes of morbidity and mortality in multiple diseases, resulting in an enormous disease burden. Current studies have focused on fibroblasts and myofibroblasts, which directly lead to imbalance in generation and degradation of extracellular matrix (ECM). In recent years, an increasing number of studies have focused on the role of epithelial cells in fibrosis. In some cases, epithelial cells are first exposed to external physicochemical stimuli that may directly drive collagen accumulation in the mesenchyme. In other cases, the source of stimulation is mainly immune cells and some cytokines, and epithelial cells are similarly altered in the process. In this review, we will focus on the multiple dynamic alterations involved in epithelial cells after injury and during fibrogenesis, discuss the association among them, and summarize some therapies targeting changed epithelial cells. Especially, epithelial mesenchymal transition (EMT) is the key central step, which is closely linked to other biological behaviors. Meanwhile, we think studies on disruption of epithelial barrier, epithelial cell death and altered basal stem cell populations and stemness in fibrosis are not appreciated. We believe that therapies targeted epithelial cells can prevent the progress of fibrosis, but not reverse it. The epithelial cell targeting therapies will provide a wonderful preventive and delaying action.

Human dispersals out of Africa via the Levant.

Homo sapiens dispersed from Africa into Eurasia multiple times in the Middle and Late Pleistocene. The route, across northeastern Africa into the Levant, is a viable terrestrial corridor, as the present harsh southern Levant would probably have been savannahs and grasslands during the last interglaciation. Here, we document wetland sediments with luminescence ages falling in the last interglaciation in the southern Levant, showing protracted phases of moisture availability. Wetland sediments in Wadi Gharandal containing Levallois artifacts yielded an age of 84 ka. Our findings support the growing consensus for a well-watered Jordan Rift Valley that funneled migrants into western Asia and northern Arabia.

Highly Enhanced Mechanical, Thermal, and Crystallization Performance of PLA/PBS Composite by Glass Fiber Coupling Agent Modification.

To improve the toughness and heat resistance of polylactic acid (PLA), polybutylene succinate (PBS) was sufficiently blended with PLA as the base matrix, and the glass fiber (GF) that was modified with 3-aminopropyltriethoxysilane (KF-GF) was added as the reinforcement. The results demonstrated a noteworthy boost in both mechanical and heat resistance properties when employing KH-GF, in comparison to pristine GF. When the content of KH-GF reached 20%, the tensile, flexural, and IZOD impact strength of the composites were 65.53 MPa, 83.43 MPa, and 7.45 kJ/m2, respectively, which were improved by 123%, 107%, and 189% compared to the base matrix, respectively. This enhancement was primarily attributed to the stronger interfacial adhesion between KH-GF and the PLA/PBS matrix. Furthermore, the Vicat softening temperature of the composites reached 128.7 °C, which was a result of increased crystallinity. In summary, the incorporation of KH-GF into PLA/PBS composites resulted in notable enhancements in their mechanical properties, crystallinity, and thermal characteristics. The high performance KH-GF-reinforced PLA/PBS composite showed a broad application potential in the field of biodegradable packaging, biodegradable textiles, and biodegradable plastic bags.

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Necroptosis is one of the regulated cell death, which involves receptor interacting protein kinase (RIPK) 1/RIPK3/mixed lineage kinase domain like protein (MLKL) signaling pathway. Among them, MLKL is the final execution of necroptosis. The formation of RIPK1/RIPK3/MLKL necrosome induces the phosphorylated MLKL, and the activated MLKL penetrates into the membrane bilayer to form membrane pores, which damages the integrity of the membrane and leads to cell death. In addition to participating in necroptosis, MLKL is also closely related to other cell death, such as NETosis, pyroptosis, and autophagy. Therefore, MLKL is involved in the pathological processes of various diseases related to abnormal cell death pathways (such as cardiovascular diseases, neurodegenerative diseases and cancer), and may be a therapeutic target of multiple diseases. Understanding the role of MLKL in different cell death can lay a foundation for seeking various MLKL-related disease targets, and also guide the development and application of MLKL inhibitors.

Multiple remote C(sp3)-H functionalizations of aliphatic ketones via bimetallic Cu-Pd catalyzed successive dehydrogenation.

The dehydrogenation-triggered multiple C(sp3)-H functionalizations at remote positions γ, δ or ε, ζ to carbonyl groups of aliphatic ketones with aryl/alkenyl carboxylic acids as coupling partners have been achieved using a bimetallic Cu-Pd catalyst system. This reaction allows access to alkenylated isocoumarins and their derivatives in generally good yields with high functional group tolerance. The identification of bimetallic Cu-Pd synergistic catalysis for efficient successive dehydrogenation of aliphatic ketones, which overcomes the long-standing challenge posed by the successive dehydrogenation desaturation of terminally unsubstituted alkyl chains in aliphatic ketones, is essential to achieving this bimetallic Cu-Pd catalyzed dehydrogenation coupling reaction.

Optimized ACE2 decoys neutralize antibody-resistant SARS-CoV-2 variants through functional receptor mimicry and treat infection in vivo.

As severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) evolves to escape natural antibodies, it also loses sensitivity to therapeutic antibody drugs. By contrast, evolution selects for binding to ACE2, the cell-surface receptor required for SARS-CoV-2 infection. Consistent with this, we find that an ACE2 decoy neutralizes antibody-resistant variants, including Omicron, with no loss in potency. To identify design features necessary for in vivo activity, we compare several enzymatically inactive, Fc effector-silenced ACE2-Fc decoys. Inclusion of the ACE2 collectrin-like domain not only improves affinity for the S protein but also unexpectedly extends serum half-life and is necessary to reduce disease severity and viral titer in Syrian hamsters. Fc effector function is not required. The activity of ACE2 decoy receptors is due, in part, to their ability to trigger an irreversible structural change in the viral S protein. Our studies provide a new understanding of how ACE2 decoys function and support their development as therapeutics to treat ACE2-dependent coronaviruses.

China is implementing the national nutrition plan of action.

With the transformation of Chinese economic and social structure, the social determinants of nutrition have undergone significant changes, which have a great influence on the dietary patterns and nutrition status of its population. The transition in the structure of nutrition intake in China can be characterized by a rapid trend in food accessibility, affordability, and diversity. However, challenges, such as the triple burden of malnutrition (undernourishment, micronutrient deficiencies, and obesity), still seriously threaten the population's health. To approach the targets for the "Healthy China 2030," the General Office of the State Council of the People's Republic of China issued the National Nutrition Plan of Action (2017-2030), which specifies multi-sectoral transdisciplinary measures to improve population nutrition status. In our study, we recognized the role of the National Nutrition Plan of China in responding to the call for the Sustainable Development Goals (SDGs). Under the global- and country-level targets, this paper presented six primary intervention measures specified in the National Nutrition Plan of Action in China, highlighting the importance of collaborative actions for participants in all sectors.

The research progress of Chikungunya fever.

Chikungunya fever, an acute infectious disease caused by Chikungunya virus (CHIKV), is transmitted by Aedes aegypti mosquitoes, with fever, rash, and joint pain as the main features. 1952, the first outbreak of Chikungunya fever was in Tanzania, Africa, and the virus was isolated in 1953. The epidemic has expanded from Africa to South Asia, the Indian Ocean islands and the Americas, and is now present in more than 100 countries and territories worldwide, causing approximately 1 million infections worldwide each year. In addition, fatal cases have been reported, making CHIKV a relevant public health disease. The evolution of the virus, globalization, and climate change may have contributed to the spread of CHIKV. 2005-2006 saw the most severe outbreak on Reunion Island, affecting nearly 35% of the population. Since 2005, cases of Chikungunya fever have spread mainly in tropical and subtropical regions, eventually reaching the Americas through the Caribbean island. Today, CHIKV is widely spread worldwide and is a global public health problem. In addition, the lack of a preventive vaccine and approved antiviral treatment makes CHIKV a major global health threat. In this review, we discuss the current knowledge on the pathogenesis of CHIKV, focusing on the atypical disease manifestations. We also provide an updated review of the current development of CHIKV vaccines. Overall, these aspects represent some of the most recent advances in our understanding of CHIKV pathogenesis and also provide important insights into the current development of CHIKV and potential CHIKV vaccines for current development and clinical trials.

FLT3L Release by Natural Killer Cells Enhances Response to Radioimmunotherapy in Preclinical Models of HNSCC.

PURPOSE: Natural killer (NK) cells are type I innate lymphoid cells that are known for their role in killing virally infected cells or cancer cells through direct cytotoxicity. In addition to direct tumor cell killing, NK cells are known to play fundamental roles in the tumor microenvironment through secretion of key cytokines, such as FMS-like tyrosine kinase 3 ligand (FLT3L). Although radiotherapy is the mainstay treatment in most cancers, the role of radiotherapy on NK cells is not well characterized. EXPERIMENTAL DESIGN: This study combines radiation, immunotherapies, genetic mouse models, and antibody depletion experiments to identify the role of NK cells in overcoming resistance to radiotherapy in orthotopic models of head and neck squamous cell carcinoma. RESULTS: We have found that NK cells are a crucial component in the development of an antitumor response, as depleting them removes efficacy of the previously successful combination treatment of radiotherapy, anti-CD25, and anti-CD137. However, in the absence of NK cells, the effect can be rescued through treatment with FLT3L. But neither radiotherapy with FLT3L therapy alone nor radiotherapy with anti-NKG2A yields any meaningful tumor growth delay. We also identify a role for IL2 in activating NK cells to secrete FLT3L. This activity, we show, is mediated through CD122, the intermediate affinity IL2 receptor, and can be targeted with anti-CD25 therapy. CONCLUSIONS: These findings highlight the complexity of using radio-immunotherapies to activate NK cells within the tumor microenvironment, and the importance of NK cells in activating dendritic cells for increased tumor surveillance.

Perineural Invasion Should Be Regarded as an Intermediate-Risk Factor for Recurrence in Surgically Treated Cervical Cancer: A Propensity Score Matching Study.

BACKGROUND: Perineural invasion (PNI) is considered as a poor prognostic factor in cervical cancer, but there has been no postoperative adjuvant therapy for it, because whether it belongs to high- or intermediate-risk factors has not been determined, this study intends to provide evidences to solve this problem. METHODS: We conducted a retrospective analysis of cervical cancer patients who underwent radical surgery and be reported PNI from January 2012 to June 2017 at the Sun Yat-sen University Cancer Center. After 1 : 1 propensity score matching (PSM), a group of patients without PNI was matched according to the clinical pathological features. Postoperative pathological parameters and prognosis were evaluated between the PNI and the matched groups. RESULTS: 1836 patients were screened, of which 162 (8.8%) diagnosed as stages IB1 to IIB reported PNI. Comparing to the matched group, more PNI (+) patients had deep outer cervix stromal invasion, cervical tunica adventitia invasion, positive lymph nodes, and positive margins. Among patients without high-risk factors, PNI (+) patients had worse 3-year overall survival (90.8% vs. 98.1%, P = 0.02), PNI (+) patients with single intermediate-risk factor and PNI (-) patients who meet with SEDLIS criteria had similar progress free survival (P = 0.63) and overall survival (P = 0.63), even similar survival curves. CONCLUSION: PNI is related to a worse overall survival among cervical cancer patients without high-risk factors and play the role as an intermediate-risk factor.

miR-129 Attenuates Myocardial Ischemia Reperfusion Injury by Regulating the Expression of PTEN in Rats.

PTEN/AKT signaling plays pivotal role in myocardial ischemia reperfusion injury (MIRI), and miRNAs are involved in the regulation of AKT signaling. This study was designed to investigate the interaction between miR-129 and PTEN in MIRI. A MIRI rat model and a hypoxia reoxygenation (H/R) H9C2 cell model were constructed to simulate myocardial infarction clinically. TTC staining, creatine kinase (CK) activity, TUNEL/Hoechst double staining, Hoechst staining and flow cytometer were used for evaluating myocardial infarction or cell apoptosis. miR-129 mimic transfection experiment and luciferase reporter gene assay were conducted for investigating the function of miR-129 and the interaction between miR-129 and PTEN, respectively. Real-time PCR and western blotting were performed to analyze the gene expression. Compared to the control, MIRI rats presented obvious myocardial infarction, higher CK activity, increased expression of caspase-3 and PTEN, decreased expression of miR-129, and insufficient AKT phosphorylation. Consistently, H/R significantly increased the apoptosis of H9C2 cells, concomitant with the downregulation of miR-129, upregulation of PTEN and caspase-3, and insufficient phosphorylation of AKT, while miR-129 mimic obviously inhibited the expression of PTEN and caspase-3, increased the AKT phosphorylation, and decreased the cell apoptosis. Additionally, miR-129 mimic obviously decreased the relative luciferase activity in H9C2 cells. To our best knowledge, this study firstly found that the low expression of miR-129 accelerates the myocardial cell apoptosis by directly targeting 3'UTR of PTEN. miR-129 is an important biomarker for MIRI, as well as a potential therapy target.

Exercise hormone irisin is a critical regulator of cognitive function.

Identifying secreted mediators that drive the cognitive benefits of exercise holds great promise for the treatment of cognitive decline in ageing or Alzheimer's disease (AD). Here, we show that irisin, the cleaved and circulating form of the exercise-induced membrane protein FNDC5, is sufficient to confer the benefits of exercise on cognitive function. Genetic deletion of Fndc5/irisin (global Fndc5 knock-out (KO) mice; F5KO) impairs cognitive function in exercise, ageing and AD. Diminished pattern separation in F5KO mice can be rescued by delivering irisin directly into the dentate gyrus, suggesting that irisin is the active moiety. In F5KO mice, adult-born neurons in the dentate gyrus are morphologically, transcriptionally and functionally abnormal. Importantly, elevation of circulating irisin levels by peripheral delivery of irisin via adeno-associated viral overexpression in the liver results in enrichment of central irisin and is sufficient to improve both the cognitive deficit and neuropathology in AD mouse models. Irisin is a crucial regulator of the cognitive benefits of exercise and is a potential therapeutic agent for treating cognitive disorders including AD.

Is Routine Gastroscopy/Colonoscopy Reasonable in Patients With Suspected Ovarian Cancer: A Retrospective Study.

OBJECTIVE: To evaluate the value of routine preoperative gastroscopy/colonoscopy in patients with suspected ovarian cancer for differential diagnosis and judgment of bowel resection. METHODS: All women diagnosed with suspected ovarian cancer who underwent gastroscopy/colonoscopy before surgery in our center were retrospectively identified. Gastroscopy/colonoscopy results and clinical pathology, imaging, and surgical findings were analyzed. RESULTS: 389 patients were included. Among them, 40 (including 13 gastric and 9 colonic malignancy) were ovarian metastasis. Compared with imaging, gastrointestinal endoscopy showed no statistical advantage in the specificity and sensitivity (99.4% vs. 99.7%, P=1.0; 55.0% vs. 45.2%, P=0.057; respectively). All patients with gastric/colonic cancer metastasize except for one had indicative imaging or tumor marker abnormalities. Three patients with colonic cancer metastases underwent optimal surgery and alive with no recurrence, the other 19 patients experienced palliative chemotherapy. There is no significant difference in the sensitivity of colonoscopy and imaging in predicting intestinal incision (61.5% vs. 43.8%, P=0.804), whereas the latter had higher specificity (87.8% vs. 74.3%, P=0.001). CONCLUSIONS: For patients with suspected ovarian cancer, the incidence of gastrointestinal metastases is low, routine gastroscopy/colonoscopy before treatment is less efficient. Gastroscopy/colonoscopy has limited power to predict the need for gastrointestinal resection before ovarian cancer surgery.

Combination of ponatinib with deferoxamine synergistically mitigates ischemic heart injury via simultaneous prevention of necroptosis and ferroptosis.

Necroptosis, ferroptosis and cyclophilin D (Cyp D)-dependent necrosis contribute to myocardial ischemia/reperfusion (I/R) injury, and ponatinib, deferoxamine and cyclosporine are reported to inhibit necroptosis, ferroptosis and Cyp D-dependent necrosis, respectively. This study aims to explore whether the any two combination between ponatinib, deferoxamine and cyclosporine exerts a better cardioprotective effect on I/R injury than single medicine does. The H9c2 cells were subjected to 10 h of hypoxia (H) plus 4 h of reoxygenation (R) to establish H/R injury model. The effects of any two combination between ponatinib, deferoxamine and cyclosporine on H/R injury were examined. On this basis, a I/R injury model in rat hearts was established to focus on the effect of ponatinib, deferoxamine and their combination on myocardial I/R injury and the underlying mechanisms. In H/R-treated H9c2 cells, all three medicines can attenuate H/R injury (decrease in LDH release and necrosis percent). However, only the combination of ponatinib with deferoxamine exerted synergistic effect on reducing H/R injury, showing simultaneous suppression of necroptosis and ferroptosis. Expectedly, administration of ponatinib or deferoxamine either before or after ischemia could suppress necroptosis or ferroptosis in the I/R-treated rat hearts as they did in vitro, concomitant with a decrease in myocardial infarct size and creatine kinase release, and the combination therapy is more efficient than single medication. Based on these observations, we conclude that the combination of ponatinib with deferoxamine reduces myocardial I/R injury via simultaneous inhibition of necroptosis and ferroptosis.

Long-term outcomes of individualized management after sentinel lymph-node biopsy for vulvar cancer.

BACKGROUND: The management for patients with vulvar cancer after sentinel lymph-node biopsy (SLNB) remains controversial. The aim of this study was to investigate the long-term outcomes of individualized management after SLNB for early stage vulvar cancer. METHODS: The medical records of patients with vulvar cancer treated by surgery involving SLNB between 2004 and 2019 were retrospectively reviewed. During this period, the inguinofemoral lymphadenectomy (IL) were performed with individualized strategy, while the postoperative intensity-modulated radiotherapy was planned with a consistent policy. RESULTS: We identified 138 patients with at least one sentinel node detected, of whom 64 underwent further IL while 74 had SLNB only. Nodal metastases (pN+) were confirmed in 22 patients with IL and 16 without. Radiotherapy was scheduled with the dose of 60-70 Gy for all pN+ patients and finally completed in 15 with IL and 15 without. The median follow-up time was 56 months (6-156 months). Recurrence was observed in 24 patients, of whom 10 were pN- at primary treatment. The 3-year overall survival (OS) was 97.2, 95.2, 68.3, and 71.8%; 3-year disease-free survival (DFS) was 94.5, 91.4, 60.2, and 59.2%, respectively, for patients with pN- and IL, pN- and SLNB, pN+ and IL, and pN+ and SLNB. Neither OS nor DFS showed significant difference between SLNB and IL in pN- (P = 0.564 for OS, P = 0.423 for DFS), or pN + patients (P = 0.920 for OS, P = 0.862 for DFS). CONCLUSIONS: With appropriate adjuvant radiotherapy, SLNB alone provided similar long-term survival compared with IL for both patients with and without sentinel node metastasis.

A coma-free super-high resolution optical spectrometer using 44 high dispersion sub-gratings.

Unlike the single grating Czerny-Turner configuration spectrometers, a super-high spectral resolution optical spectrometer with zero coma aberration is first experimentally demonstrated by using a compound integrated diffraction grating module consisting of 44 high dispersion sub-gratings and a two-dimensional backside-illuminated charge-coupled device array photodetector. The demonstrated super-high resolution spectrometer gives 0.005 nm (5 pm) spectral resolution in ultra-violet range and 0.01 nm spectral resolution in the visible range, as well as a uniform efficiency of diffraction in a broad 200 nm to 1000 nm wavelength region. Our new zero-off-axis spectrometer configuration has the unique merit that enables it to be used for a wide range of spectral sensing and measurement applications.

Effectiveness of Sequential Chemoradiation vs Concurrent Chemoradiation or Radiation Alone in Adjuvant Treatment After Hysterectomy for Cervical Cancer: The STARS Phase 3 Randomized Clinical Trial.

IMPORTANCE: There is no current consensus on the role of chemotherapy in addition to radiation for postoperative adjuvant treatment of patients with early-stage cervical cancer with adverse pathological factors. OBJECTIVE: To evaluate the clinical benefits of sequential chemoradiation (SCRT) and concurrent chemoradiation (CCRT) compared with radiation alone (RT) as a postoperative adjuvant treatment in early-stage cervical cancer. DESIGN, SETTING, AND PARTICIPANTS: After radical hysterectomy at 1 of 8 participating hospitals in China, patients with FIGO (International Federation of Gynecology and Obstetrics) stage IB to IIA cervical cancer with adverse pathological factors were randomized 1:1:1 to receive adjuvant RT, CCRT, or SCRT. Data were collected from February 2008 to December 2018. INTERVENTIONS: Patients received adjuvant RT (total dose, 45-50 Gy), CCRT (weekly cisplatin, 30-40 mg/m2), or SCRT (cisplatin, 60-75 mg/m2, plus paclitaxel, 135-175 mg/m2) in a 21-day cycle, given 2 cycles before and 2 cycles after radiotherapy, respectively. MAIN OUTCOMES AND MEASURES: The primary end point was the rate of disease-free survival (DFS) at 3 years. RESULTS: A total of 1048 women (median [range] age, 48 [23-65] years) were included in the analysis (350 in the RT group, 345 in the CCRT group, and 353 in the SCRT group). Baseline demographic and disease characteristics were balanced among the treatment groups except that the rate of lymph node involvement was lowest in the RT group (18.3%). In the intention-to-treat population, SCRT was associated with a higher rate of DFS than RT (3-year rate, 90.0% vs 82.0%; hazard ratio [HR], 0.52; 95% CI, 0.35-0.76) and CCRT (90.0% vs 85.0%; HR, 0.65; 95% CI, 0.44-0.96). Treatment with SCRT also decreased cancer death risk compared with RT (5-year rate, 92.0% vs 88.0%; HR, 0.58; 95% CI, 0.35-0.95) after adjustment for lymph node involvement. However, neither DFS nor cancer death risk was different among patients treated with CCRT or RT. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, conducted in a postoperative adjuvant treatment setting, SCRT, rather than CCRT, resulted in a higher DFS and lower risk of cancer death than RT among women with early-stage cervical cancer. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00806117.