Erratum: MicroRNA-449a Inhibits Tumor Metastasis through AKT/ERK1/2 Inactivation by Targeting Steroid Receptor Coactivator (SRC) in Endometrial Cancer: Erratum.

[This corrects the article DOI: 10.7150/jca.27748.].

[Research Advances of Immunotherapy for Follicular Lymphoma --Review].

Follicular lymphoma is an indolent malignant tumor originating from lymph nodes and lymphoid tissues, which may affect the patients' quality of survival due to the recurrence and progression. In recent years, with the deepening understand of the molecular biology and signaling pathways, many new targeted drugs for follicular lymphoma have been discovered, such as monoclonal antibodies, checkpoint inhibitors, epigenetic regulation related targeted therapies and signaling pathway inhibitors. In this review, the new progress of immunotherapy for follicular lymphoma is summarized briefly.

Biomechanical behaviour of implant prostheses and adjacent teeth according to bone quality: A finite element analysis.

The contribution of biomechanical factors in the formation of proximal contact loss has been observed, but there is little research on the mechanisms by which they contribute. Using finite element analysis, this study aimed to analyse the impact of bone quality on the biomechanical behaviour of a dentition consisting of implant prostheses and adjacent teeth. The occlusal load was applied on the implant/tooth crown. In the mesiodistal direction, the adjacent natural tooth mesially to the implant denture had the tendency for mesial movement, while the distal adjacent natural tooth had the tendency for distal movement. For the supporting bone around the mesial adjacent tooth, the maximum/minimum principal stress and strain values on the mesial side of the bone were higher than those on the distal side of the bone. Stress and strain values on the mesial side of the supporting bone around the distal adjacent tooth were lower than those on the distal side. With decreasing bone density, displacements of teeth and the implant denture, principal stresses and equivalent strains on tooth supporting bone increased. Studies on biomechanical behaviours of a tooth-implant dentition may provide a deeper understanding of implant-induced dental adaptive processes such as proximal contact loss.

[Clinical Significance of EBV-DNA Copy Number in EBV Positive Lymphoma Patients].

OBJECTIVE: To investigate the effect of EBV-DNA copy number on the prognosis of patients with EBV positive lymphoma. METHODS: Clinical data of 109 patients diagnosed as EBV positive lymphoma in Tianjin Medical University Cancer Institute and Hospital from January 2010 to January 2020 were enrolled and analyzed retrospectively. Kaplan-Meier analysis was used for survival analysis, Log-rank was used to compare the clinical characteristics between the patients in different groups, and Cox regression was used for multivariate analysis. RESULTS: Among the 109 patients with EBV-positive lymphoma, the medium age were 56 (range 15 to 83) years old. 29 patients at Ann Arbor stage I-II while 80 patients at stage III-IV. The average value of EBV-DNA was 1 023 510 IU/ml, 7 patients were higher than the average value, while 102 patients were lower. KM survival analysis showed that OS and PFS in patients with EBV-DNA above average level were shorter than those in patients with EBV-DNA below average level (OS: P=0.048, PFS: P=0.001), EBV-DNA copy number was a factor affecting the prognosis of patients. In addition, LDH level showed positive correlation with EBV-DNA copy number (r=0.650), which was also one of the factors affecting OS (P=0.053). CONCLUSION: EBV-DNA copy number and LDH level can influence the prognosis of EBV positive lymphoma patients. Therefore, detection of EBV-DNA copy number in peripheral blood is important for evaluate the prognosis the patients.

Identification of a TRIM32 from Penaeus monodon is involved in autophagy and innate immunity during white spot syndrome virus infection.

Many tripartite motif (TRIM) family proteins played an important role in regulating innate immune and autophagy pathway and were important for host defenses against viral pathogens. However, the role of TRIM proteins in autophagy and innate immunity during virus infection was seldom studied in crustaceans. In this study, a novel TRIM32 homolog was identified from Penaeus monodon (named PmTRIM32). PmTRIM32 was significantly upregulated by rapamycin stimulation and WSSV infection. RNA interference experiments showed that PmTRIM32 could restrict WSSV replication and lead P. monodon more resistance to WSSV challenge. Autophagy could be induced by WSSV or rapamycin challenge and has been proved to play a positive role in restricting WSSV replication in P. monodon. The autophagy activity induced by WSSV or rapamycin challenge could be obviously inhibited by silence of PmTRIM32 in P. monodon. Further studies revealed that PmTRIM32 positively regulated the expression of nuclear transcription factor (NF-κB) and it mediated antimicrobial peptides. Moreover, Pull-down and in vitro ubiquitination assay demonstrated that PmTRIM32 could interact with WSSV envelope protein and target it for ubiquitination in vitro. Collectively, this study demonstrated that PmTRIM32 restricted WSSV replication and was involved in positively regulating autophagy and NF-κB pathway during WSSV infection in P. monodon.

Viscosity sensitive endoplasmic reticulum fluorescent probes based on oxazolopyridinium.

A series of viscosity sensitive fluorescent probes 1a-e were synthesized by linking coumarin and oxazolopyridinium via dimethylene in this paper. The viscosity test of probes 1a-e indicated that the fluorescence intensity of the probes enhanced significantly with the increase of viscosity of the system (0.89-865 cP), and exhibited a nearly OFF-ON response to viscosity at 648 nm, 650 nm and 650 nm, respectively. In addition, cells still had a high survival rate after co-culturing with probes 1a-e for 12 h (94-98%). Meanwhile, the laser confocal experiment showed that the variation of the carbon chain length in the oxazolopyridinium could affect the subcellular region of the localization of the probes in cells. When the length of the carbon chain in oxazolopyridinium was between n-C7H15 and n-C12H23, probes 1b-d had the ability to target the endoplasmic reticulum in the cells. Moreover, probes 1b-d showed no significant change in fluorescence intensity after 35 min of continuous laser confocal irradiation, indicating that they had excellent anti-photobleaching properties.

[Research Progression of Subcutaneous Panniculitis-like T-Cell Lymphoma--Review].

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a very rare cutaneous malignant lymphoma derived from cytotoxic T cells that mainly involves subcutaneous adipose tissue rather than epidermis and dermis. It usually occurs in young and middle-aged population, and the etiology is currently unclear. Clinically, SPTCL is characterized by subcutaneous plaques, nodules, and skin ulcers with swell and ache, mainly presenting in limbs and trunk. SPTCL has been restricted to cases that express α/ß phenotype, whereas cases with γ/δ phenotype are categorized to cutaneous γ/δ+ T cell lymphoma by WHO-EORTC classification. The standard treatment for SPTCL is not definite with a relatively good prognosis. The recent research progression of SPTCL is summarized in this review.

Prevalence and Influencing Factors on Fatigue of First-line Nurses Combating with COVID-19 in China: A Descriptive Cross-Sectional Study.

Nurses' work-related fatigue has been recognized as a threat to nurse health and patient safety. The aim of this study was to assess the prevalence of fatigue among first-line nurses combating with COVID-19 in Wuhan, China, and to analyze its influencing factors on fatigue. A multi-center, descriptive, cross-sectional design with a convenience sample was used. The statistical population consisted of the first-line nurses in 7 tertiary general hospitals from March 3, 2020 to March 10, 2020 in Wuhan of China. A total of 2667 samples from 2768 contacted participants completed the investgation, with a response rate of 96.35%. Social-demographic questionnaire, work-related questionnaire, Fatigue Scale-14, Generalized Anxiety Disorder-7, Patient Health Questionnaire-9, and Chinese Perceived Stress Scale were used to conduct online survey. The descriptive statistic of nurses' social-demographic characteristics was conducted, and the related variables of work, anxiety, depression, perceived stress and fatigue were analyzed by t-tests, nonparametric test and Pearson's correlation analysis. The significant factors which resulted in nurses' fatigue were further analyzed by multiple linear regression analysis. The median score for the first-line nurses' fatigue in Wuhan was 4 (2, 8). The median score of physical and mental fatigue of them was 3 (1, 6) and 1 (0, 3) respectively. According to the scoring criteria, 35.06% nurses (n=935) of all participants were in the fatigue status, their median score of fatigue was 10 (8, 11), and the median score of physical and mental fatigue of them was 7 (5, 8) and 3 (2, 4) respectively. Multiple linear regression analysis revealed the participants in the risk groups of anxiety, depression and perceived stress had higher scores on physical and mental fatigue and the statistically significant positive correlation was observed between the variables and nurses' fatigue, the frequency of exercise and nurses' fatigue had a statistically significant negative correlation, and average daily working hours had a significantly positive correlation with nurses' fatigue, and the frequency of weekly night shift had a low positive correlation with nurses' fatigue (P<0.01). There was a moderate level of fatigue among the first-line nurses fighting against COVID-19 pandemic in Wuhan, China. Government and health authorities need to formulate and take effective intervention strategies according to the relevant risk factors, and undertake preventive measures aimed at reducing health hazards due to increased work-related fatigue among first-line nurses, and to enhance their health status and provide a safe occupational environment worldwide. Promoting both medical and nursing safety while combating with the pandemic currently is warranted.

[Research on the relationship between ABO blood type and oral and maxillofacial malignancy in Chongqing area].

PURPOSE: To explore the relationship between ABO blood type and oral and maxillofacial malignancy in Chongqing area. METHODS: A total of 1054 patients with oral and maxillofacial malignant tumors diagnosed in the Stomatological Hospital of Chongqing Medical University in the past five years were selected as the research subjects, and the blood types of the healthy people were examined as the control group. SPSS 22.0 software package and Chi-square test were used to verify the correlation between the groups. The OR values of oral and maxillofacial malignancy of different blood types were compared among patients of three major cancers (squamous cell carcinoma, adenoid cystic carcinoma, mucoepidermoid carcinoma), so as to judge the relative risk of oral and maxillofacial malignant tumors of each blood type. RESULTS: The distribution of blood type in oral and maxillofacial malignancy patients was as follows: O(4.2%)>A(32.8%)>B(24.6%)>AB(8.4%), there was no significant difference in blood types between the patients and the controls. Patients with blood type O were easier to develop mucoepidermoid carcinoma compared with patients with other blood types (P<0.05, OR=2.09, 95%CI=1.04~4.17). In addition, the distribution of blood type of patients with mucoepidermoid carcinoma was significantly different from the control group. Males with blood type O were different from males with other blood types, which were more susceptible to adenoid cystic carcinoma and mucoepidermoid carcinoma (P<0.05, OR=3.06/3.06, 95%CI=1.31~7.12). CONCLUSIONS: There is certain relationship between the occurrence of oral and maxillofacial malignancy and ABO blood type in Chongqing area. The population of O blood type is easier to develop mucoepidermoid carcinoma while males with O blood type are more likely to develop adenoid cystic carcinoma and mucoepidermoid carcinoma.

The fluorescent markers based on oxazolopyridine unit for imaging organelles.

Bioactive oxazolopyridine unit was used in the synthesis of fluorescent markers for specific organelles in this paper. The compounds 1a-c are linked with double bond between oxazolopyridine ring and photogenic precursors (3a-c). Compound 1a showed higher fluorescence yield (0.86 in THF), compounds 1b-c showed larger stokes shifts in DMSO. In lipid vesicles environment, they also showed good optical properties. In addition, the three compounds are biomarkers with lower cytotoxicity. Among them, compound 1a based on oxazolopyridine and coumarin unit is a dual targetable fluorescent marker for mitochondria and lipid droplets; while the other two compounds 1b-c are only biomarkers for lipid droplets.

Suppressive effect of microRNA-449a on the NDRG1/PTEN/AKT axis regulates endometrial cancer growth and metastasis.

Database screening indicated that microRNAs (miRNAs) are involved in pathogenesis of endometrial cancer. Among these miRNAs, miR-449a might be involved in tumorigenesis and lower expression of miR-449a was associated with poor prognosis. However, the role of miR-449a and its underlying molecular mechanism in endometrial cancer (EC) has not been investigated. In this study, our analysis found that miR-449a expression is inversely correlated with the stage of EC. Downregulation of miR-449a was correlated with tumor progression and poor prognosis in the EC patients. Results of functional analyses revealed that overexpression of miR-449a in human EC cells alleviated cell proliferation, invasion and metastasis. Conversely, loss of miR-449a in EC cancer cells facilitated all these cellular activities. Moreover, we identified N-myc downstream-regulated gene 1 (NDRG1) as a direct and functional target gene of miR-449a in EC cells, and the expression of NDRG1 in 87 EC specimens were inversely correlated with that of miR-449a. Additionally, further studies show that the down-regulation of NDRG1 expression inhibited proliferation and metastasis of EC cells through the PTEN/AKT pathway. Therefore, these results suggest that miR-449a suppresses the growth and metastasis of EC by directly targeting the NDRG1 gene and that the activation of miR-449a may represent an effective therapeutic strategy in EC.

Cortical morphologic changes in recent-onset, drug-naïve idiopathic generalized epilepsy.

PURPOSE: Only a few studies have investigated the brain morphology abnormalities in structural MRI in patients with drug-naïve idiopathic generalized epilepsy (IGE) and mainly focused on brain volume changes. In the present study, we aimed to investigate the changes in three morphologic measurement differences including cortical thickness, cortical volume, and surface area using FreeSurfer in a pediatric cohort of recent-onset, drug-naïve IGE. METHODS: Forty-five recent-onset, drug-naïve patients diagnosed with IGE and 32 demographically matched healthy controls were recruited. All participants underwent structural MRI scans with a 3.0 T MR system. FreeSurfer, an automated cortical surface reconstruction toolbox, was applied to compare the cortical morphology between patients and controls. The brain regions with significant group differences after multiple comparison correction were extracted in common space for each patient, and then correlated with their clinical characteristics (including onset age, duration of epilepsy, and mini-mental state examination (MMSE)) using partial correlation analysis with age, sex and intracranial volume as covariates. RESULTS: Compared with controls, IGE patients showed decreased cortical thickness in the left rostral middle frontal gyrus, decreased cortical volume in the right cuneus and left superior frontal gyrus that extended to the precentral gyrus, and decreased surface area in the right cuneus and right inferior parietal gyrus. None of these regions showed significant relationships with clinical measurements in the patient group. CONCLUSION: Our findings suggest that cortical thickness, cortical volume, and surface area changes occurred in the early stage of IGE. These findings provide structural neuroimaging evidence underlying the pathology of IGE.

Fn14 overcomes cisplatin resistance of high-grade serous ovarian cancer by promoting Mdm2-mediated p53-R248Q ubiquitination and degradation.

BACKGROUND: High-grade serous ovarian cancer (HGSOC) is the most lethal of all gynecological malignancies. Patients often suffer from chemoresistance. Several studies have reported that Fn14 could regulate migration, invasion, and angiogenesis in cancer cells. However, its functional role in chemoresistance of HGSOC is still unknown. METHODS: The expression of Fn14 in tissue specimens was detected by IHC. CCK-8 assay was performed to determine changes in cell viability. Apoptosis was measured by flow cytometry. The potential molecular mechanism of Fn14-regulated cisplatin resistance in HGSOC was investigated using qRT-PCR, western blotting, and Co-IP assays. The role of Fn14 in HGSOC was also investigated in a xenograft mouse model. RESULTS: In this study, we found that Fn14 was significantly downregulated in patients with cisplatin resistance. Patients with low Fn14 expression were associated with shorter progression-free survival and overall survival. Overexpression of Fn14 suppressed cisplatin resistance in OVCAR-3 cells, whereas knockdown of Fn14 did not affect cisplatin resistance in SKOV-3 cells. Interestingly, Fn14 could exert anti-chemoresistance effect only in OVCAR-3 cells harboring a p53-R248Q mutation, but not in SKOV-3 cells with a p53-null mutation. We isolated and identified primary cells from two patients with the p53-R248Q mutation from HGSOC patients and the anti-chemoresistance effect of Fn14 was observed in both primary cells. Mechanistic studies demonstrated that overexpression of Fn14 could reduce the formation of a Mdm2-p53-R248Q-Hsp90 complex by downregulating Hsp90 expression, indicating that degradation of p53-R248Q was accelerated via Mdm2-mediated ubiquitin-proteasomal pathway. CONCLUSION: Our findings demonstrate for the first time that Fn14 overcomes cisplatin resistance through modulation of the degradation of p53-R248Q and restoration of Fn14 expression might be a novel strategy for the treatment of HGSOC.

MicroRNA-449a Inhibits Tumor Metastasis through AKT/ERK1/2 Inactivation by Targeting Steroid Receptor Coactivator (SRC) in Endometrial Cancer.

Endometrial cancer represents the leading frequency in gynecological malignancy in developed countries. Even with early detection, metastasis and recurrence remain the main reasons for a high death rate. MicroRNA-449a (miR-449a) has been reported to function as a tumor suppressor, yet the role of miR-449a in endometrial cancer metastasis has not been investigated. The present study identified that miR-449a was downregulated in advanced endometrial cancer. Overexpression of miR-449a decreased the migration and invasion of KLE and AN3CA endometrial cancer cells. Using luciferase reporter assays, we identified that miR-449a directly targeted the steroid receptor coactivator (SRC) by binding to sites in the 3' untranslated regions. Elevated expressions of SRC have been witnessed in advanced endometrial cancer tissues and have promoted tumor metastasis. We also identified that the suppressive effect of miR-449a on metastasis could be mediated by downregulating SRC and that miR-449a could suppress AKT and ERK1/2 pathway activation in endometrial cancer cells. These findings contribute to the current understanding of the function of miR-449a in endometrial cancer.

[Preparation of multifunctional nanoparticles targeting tongue cancer and in vitro study].

OBJECTIVE: This study aims to prepare docetaxel (DOC)-loaded multifunctional nanoparticles containing indocyanine green (ICG) and perfluorohexane (PFH) as targeted drug delivery system, which is supplemented with stromal cellderived factor-1 (SDF-1), and characterize their properties. METHODS: Multifunctional nanoparticles were prepared by using the double emulsion method. SDF-1 was covalently conjugated to the surface of the nanoparticles through thioether bonding. Their particle size, distribution, and surface potential were determined with the Malvern measuring instrument. The conjugation of SDF-1 was evaluated by confocal laser scanning microscope. Encapsulation efficiency (ELC), drug loading capacity (DLC), and release regularity of the nanoparticles were determined by high-performance liquid chromatography (HPLC). In vitro photothermal property was recorded by a thermal imager. The in vitro imaging capacity was observed by a photoacoustic instrument and an ultrasonic diagnostic apparatus. Targeting capability was assessed by flow cytometry. The cell activity on SCC-15 cells was checked by CCK-8 method. RESULTS: The targeted multifunctional nanoparticles showed regularly sphericity. The diameter was (502.88±17.92) nm. The zeta potential was (-11.5±3.15) mV. ELC was 54.12%±1.74%. DLC was 1.08 mg·mL-1. In vitro drug release was initially fast and subsequently slow. The photothermal characteristics were related to the concentration; the higher the concentration, the higher the temperature. Nanoparticles could detect significant photoacoustic and ultrasound signals. The in vitro targeting rate was 89.99%. No significant differences of cell viability in the SINPs groups were observed at each concentration (P>0.05). The inhibition effect of DOC-SINPs was stronger than that of SINPs whether or not in the presence of laser irradiation among the groups of 150 and 200 µg·mL-1 (P<
0.05). CONCLUSIONS: Multifunctional nanoparticles for diagnosis and treatment were successfully prepared and displayed dualmode ultrasound/photoacoustic imaging and antitumor effects of chemotherapy and photothermal therapy.

Structural Changes Induced by Acupuncture in the Recovering Brain after Ischemic Stroke.

The aim of this study was to observe the grey matter (GM) tissue changes of ischemic stroke patients, to explore the therapy responses and possible mechanism of acupuncture. 21 stroke patients were randomly assigned to receive either acupuncture plus conventional (Group A) or only conventional (Group B) treatments for 4 weeks. All patients in both groups accepted resting-state functional magnetic resonance (fMRI) scan before and after treatment, and the voxel-based morphometry (VBM) analysis was performed to detect the cerebral grey structure changes. The modified Barthel index (MBI) was used to evaluate the therapeutic effect. Compared with the patients in Group B, the patients in Group A exhibited a more significant enhancement of the changes degree of MBI from pre- to post-treatment intervention. VBM analyses found that after treatment the patients in Group A showed extensive changes in GMV. In Group A, the left frontal lobe, precentral gyrus, superior parietal gyrus, anterior cingulate cortex, and middle temporal gyrus significantly increased, and the right frontal gyrus, inferior parietal gyrus, and middle cingulate cortex decreased (P < 0.05, corrected). In addition, left anterior cingulate cortex and left middle temporal gyrus are positively related to the increase in MBI score (P < 0.05, corrected). In Group B, right precentral gyrus and right inferior frontal gyrus increased (P < 0.05, corrected). In conclusion, acupuncture can evoke pronounced structural reorganization in the frontal areas and the network of DMN areas, which may be the potential therapy target and the potential mechanism where acupuncture improved the motor and cognition recovery.

Necroptosis as a potential therapeutic target in multiple organ dysfunction syndrome.

PURPOSE: To investigate how necroptosisis, i.e. programmed necrosis, is involved in MODS, and to examine whether Nec-1, a specific necroptosis inhibitor, ameliorates multiorgan injury in MODS. EXPERIMENTAL DESIGN: A model of MODS was established in six-week old SD rats using fracture trauma followed by hemorrhage. Control animals received sham surgery. Cell death form and necrosome formation were measured by fluorescence-activated cell sorting and western blotting. MODS rats were randomly assigned to receive Nec-1 or saline with pretreatment and once daily. The first end-point was 72 hours survival. Organ injury and dysfunction, inflammatory cytokine levels, and necroptotic execution protein expression were also recorded. RESULTS: Organ injury and dysfunction were significantly more severe in the MODS group than the sham group (all p<0.01). Furthermore, MODS-induced liver, lung and kidney tissue injury was characterized by necroptosis rather than apoptosis, and accompanied by necrosome formation. Compared to MODS group, Nec-1 administration significantly improved 72 hours survival (p<0.01). Nec-1 administration significantly reduced necroptosis-induced liver, lung and kidney injury and dysfunction, inhibited inflammatory cytokines production, inhibited release of necroptotic execution proteins such as high-mobility group box 1 and mixed-lineage kinase domain-like protein pseudokinase in MODS rats (all p<0.01). CONCLUSIONS: These results suggest that necroptosis is involved the pathology of MODS. Further, a necroptotic inhibitor Nec-1 may be considered as an adjunct treatment for MODS.

Regional brain structural abnormality in ischemic stroke patients: a voxel-based morphometry study.

Our previous study used regional homogeneity analysis and found that activity in some brain areas of patients with ischemic stroke changed significantly. In the current study, we examined structural changes in these brain regions by taking structural magnetic resonance imaging scans of 11 ischemic stroke patients and 15 healthy participants, and analyzing the data using voxel-based morphometry. Compared with healthy participants, patients exhibited higher gray matter density in the left inferior occipital gyrus and right anterior white matter tract. In contrast, gray matter density in the right cerebellum, left precentral gyrus, right middle frontal gyrus, and left middle temporal gyrus was less in ischemic stroke patients. The changes of gray matter density in the middle frontal gyrus were negatively associated with the clinical rating scales of the Fugl-Meyer Motor Assessment (r = -0.609, P = 0.047) and the left middle temporal gyrus was negatively correlated with the clinical rating scales of the nervous functional deficiency scale (r = -0.737, P = 0.010). Our findings can objectively identify the functional abnormality in some brain regions of ischemic stroke patients.

Postoperative hormone replacement therapy for epithelial ovarian cancer patients: a systematic review and meta-analysis.

BACKGROUND: Hormone replacement therapy (HRT) has been proven highly effective for menopausal symptoms caused by radical surgery. However, the impact of postoperative HRT on the clinical outcomes of patients previously treated for epithelial ovarian cancer (EOC) remains unclear. OBJECTIVE: To determine whether postoperative HRT use has any positive or negative impacts on prognosis and recurrence among EOC survivors. METHODS: Studies that provided an assessment of postoperative HRT use and prognosis or recurrence in EOC patients were included for analysis. Two reviewers independently evaluated the eligibility of identified studies and abstracted the data. A fixed effects model was used to pool study-specific estimates of hazard ratios (HRs) or relative risks (RRs) with 95% confidence intervals (CIs). RESULTS: Two randomized controlled trials (RCTs) and four cohort studies included 419 EOC survivors who used HRT and 1029 non-users. The aggregated HR of overall survival (OS) suggested that HRT use after surgery for EOC had a favorable impact on OS (HR=0.69, 95% CI: 0.61-0.79), but when these studies were categorized into cohort study and RCT subgroups, not all of them demonstrated positive results (HR=0.63, 95% CI: 0.49-0.81 and HR=1.03, 95% CI: 0.58-1.83, respectively). The meta-analysis of EOC recurrence of three available studies demonstrated that postoperative HRT use was not associated with an increased risk of recurrence in EOC survivors (RR=0.83, 95% CI: 0.64-1.07). This pattern also emerged in the subgroup analysis for the stage and type of HRT. CONCLUSIONS: In EOC patients, postoperative HRT does not have a negative effect on overall survival and tumor recurrence. However, well-designed and large-scale RCTs are needed to verify this relationship in the future.