Search

Abstract Background Programmed cell death protein 1 (PD-1) blockade is essential in treating progressive colorectal cancer (CRC). However, some patients with CRC do not respond well to immunotherapy, possibly due to the exhaustion of CD8+ T cells in the tumor microenvironment. N-Acetylcysteine (NAC) can reduce CD8+ T cell exhaustion in vitro and induce their differentiation into long-lasting phenotypes, thus enhancing the anti-tumor effect of adoptive T cell transfer. However, whether NAC can be combined with PD-1 blockade in CRC treatment and how NAC regulates CD8+ T cell differentiation remain unclear. Hence, in this study, we aimed to investigate whether NAC has a synergistic effect with PD-1 blockers against CRC progression. Methods We constructed a mouse CRC model to study the effect of NAC on tumors. The effect of NAC on CD8 + T cell differentiation and its potential mechanism were explored using cell flow assay and other studies in vitro and ex vivo. Results We demonstrated that NAC synergized PD-1 antibodies to inhibit CRC progression in a mouse CRC model mediated by CD8+ T cells. We further found that NAC can induce TCF1+PD1+CD8+ T cell differentiation and reduce the formation of exhausted T cells in vitro and in vivo. Moreover, NAC enhanced the expression of Glut4 in CD8+ T cells, promoting the differentiation of TCF1+PD1+CD8+ T cells. Conclusions Our study provides a novel idea for immunotherapy for clinically progressive CRC and suggests that Glut4 may be a new immunometabolic molecular target for regulating CD8+ T cell differentiation. Graphical Abstract

Objective: The recombinant adenovirus Ad-apoptin-hTERTp-E1a (Ad-VT) to have a bi-specific oncolytic character in many tumor cells, but its action pathway in killing tumor cells has not been accurately elucidated. Here, we studied the mechanism of apoptosis and autophagy induced by Ad-VT and the interaction between autophagy and apoptosis. Methods: Crystal Violet staining and CCK-8 assays were used to detect the inhibitory effect of Ad-VT on ovarian cancer cells. The antitumor effect of Ad-VT in vivo was analyzed by tumor bearing nude mouse model. Subsequently, flow cytometry and fluorescence staining were used to analyze the main types of apoptosis and autophagy induced by Ad-VT. Results: In this study, through the in vitro cell inhibition assays, we found that Ad-VT has a significant inhibitory effect on ovarian cancer A2780 cells, but no significant inhibitory effect on normal ovarian epithelial cells. Then in vivo experiments showed that Ad-VT significantly inhibited tumor growth and extended the survival time of mice. Subsequent detection of the level of apoptosis found that Ad-VT can cause a strong apoptotic response and kill cells mainly through the endogenous apoptotic pathway. Through the staining analysis of LC3 and the analysis of autophagy-related proteins, it was found that Ad-VT could significantly increase the level of autophagy in A2780 cells, and this was a protective mechanism. Conclusions: Ad-VT, which replicates under the control of the hTERT promoter and expresses apoptin protein, have significant inhibitory effect on ovarian cancer A2780 cells and promote their apoptosis and autophagy.

"Firstly, Eucommia ulmoides gum (EUG) was epoxidized to obtain epoxidized EUG (EEUG). Then, EEUG grafted silicon dioxide (SiO2) composite (EEUG-g-SiO2) was prepared by wet graf-ting SiO2 onto EEUG. The structure and properties of EEUG-g-SiO2 composite were studied. The results showed that compared with EUG/SiO2 and EEUG/SiO2 mechanical blends, the dispersion of nano SiO2 in EEUG-g-SiO2 vulcanizate was significantly improved and the mechanical properties were greatly improved. Compared with EUG/SiO2 vulcanizates, the tear strength of EEUG-g-SiO2 vulcanizate increased by 30.9%, fatigue resistance increased by 575%, and abrasion decreased by 94%. Compared with EEUG/SiO2 vulcanizate, the tear strength of EEUG-g-SiO2 vulcanizate increased by 10.5%, fatigue resistance increased by 68.6%, abrasion decreased by 72%, and the compression heat build-up decreased significantly."

Abstract Background Neutrophil extracellular traps (NETs) promote neuroinflammation and, thus, central nervous system (CNS) disease progression. However, it remains unclear whether CNS-associated NETs affect pain outcomes. A fasting-mimicking diet (FMD) alleviates neurological disorders by attenuating neuroinflammation and promoting nerve regeneration. Hence, in this study, we explore the role of NETs in the CNS during acute pain and investigate the role of FMD in inhibiting NETs and relieving pain. Methods The inflammatory pain model was established by injecting complete Freund’s adjuvant (CFA) into the hind paw of mice. The FMD diet regimen was performed during the perioperative period. PAD4 siRNA or CI-amidine (PAD4 inhibitor) was used to inhibit the formation of NETs. Monoamine oxidase-B (MAO-B) knockdown occurred by AAV-GFAP-shRNA or AAV-hSyn-shRNA or was inhibited by selegiline (an MAO-B inhibitor). The changes in NETs, neuroinflammation, and related signaling pathways were examined by western blot, immunofluorescence, ELISA, and flow cytometry. Results In the acute phase of inflammatory pain, NETs accumulate in the spinal cords of mice. This is associated with exacerbated neuroinflammation. Meanwhile, inhibition of NETs formation alleviates allodynia and neuroinflammation in CFA mice. FMD inhibits NETs production and alleviates inflammatory pain, which is enhanced by treatment with the NETs inhibitor CI-amidine, and reversed by treatment with the NETs inducer phorbol 12-myristate 13-acetate (PMA). Mechanistically, the neutrophil-recruiting pathway MAO-B/5-hydroxyindoleacetic acid (5-HIAA) / G-protein-coupled receptor 35 (GPR35) and NETs-inducing pathway MAO-B/ Reactive oxygen species (ROS) are significantly upregulated during the development of inflammatory pain. MAO-B is largely expressed in astrocytes and neurons in the spinal cords of CFA mice. However, knockdown or inhibition of MAO-B effectively attenuates CFA-induced inflammatory pain, NETs formation, and neuroinflammation in the spinal cord. Moreover, within rescue experiments, MAO-B inhibitors synergistically enhance FMD-induced pain relief, NETs inhibition, and neuroinflammation attenuation, whereas supplementation with MAO-B downstream molecules (i.e., 5-HIAA and PMA) abolished this effect. Conclusions Neutrophil-released NETs in the spinal cord contribute to pain development. FMD inhibits NETs formation and NETs-induced neuroinflammation by inhibiting the MAO-B/5-HIAA/GPR35 and MAO-B/ROS pathways in astrocytes and neurons, thereby relieving pain progression. Video Abstract

Abstract Background Whether material deprivation-related childhood socio-economic disadvantages (CSD) and care-related adverse childhood experiences (ACE) have different impacts on depressive symptoms in middle-aged and older people is unclear. Methods In the Guangzhou Biobank Cohort Study, CSD and ACE were assessed by 7 and 5 culturally sensitive questions, respectively, on 8,716 participants aged 50+. Depressive symptoms were measured by 15-item Geriatric Depression Scale (GDS). Multivariable linear regression, stratification analyses, and mediation analyses were done. Results Higher CSD and ACE scores were associated with higher GDS score in dose-response manner (P for trend

Objectives: To study the characteristics of intestinal microbiota at different stages of Mycobacterium tuberculosis infection. Methods: Fecal samples of 19 active tuberculosis (ATB) patients, 21 latent tuberculosis infection (LTBI) individuals, and 20 healthy controls (HC) were collected. Gut microbiota of all the participants were analyzed by 16S rDNA sequencing. Clinical information of ATB patients was also collected and analyzed. Results: Both ATB and LTBI groups showed significant decreases in microbial diversity and decline of Clostridia. For ATB patients, bacteria within phylum Proteobacteria increased. While for LTBI individuals, genera Prevotella and Rosburia enriched. The abundance of Faecalibacterium, Clostridia and Gammaproteobacteria has the potential to diagnose ATB, with the area under the curve (AUC) of 0.808, 0.784 and 0.717. And Prevotella and Rosburia has the potential to diagnose LTBI, with the AUC of 0.689 and 0.689. Notably, in ATB patients, the relative abundance of Blautia was negatively correlated with the proportions of peripheral T cells and CD8+T cells. And serum direct bilirubin was positively correlated with Bacteroidales, while negatively correlated with Clostridiales in ATB patients. Conclusions: The specifically changed bacteria are promising markers for ATB and LTBI diagnosis. Some gut bacteria contribute to anti-MTB immunity through interactions with T cells and bilirubin.

Powerful chemotherapeutics have been used to combat tumor cells, but serious adverse effects and poor therapeutic efficiency restrict their clinical performance. Herein, we developed reduction-responsive supramolecular hybridized paclitaxel nanoparticles (PTX@HOMNs) for improved tumor treatment. The nanocarrier is composed of F127 and strengthened by a disulfide bond linked organosilica network, which ensures the desirable stability during blood circulation and controlled drug release at tumor sites. The as-prepared PTX@HOMNs could effectively accumulate at tumor regions. After entering tumor cells, PTX@HOMNs can respond to intracellular glutathione, and trigger active drug release for chemotherapy. As a result, PTX@HOMNs exhibited potent antitumor activity against ovarian tumors in vitro and in vivo. Our work provides a deep insight into constructing simple and controlled drug delivery nanoplatforms for improved tumor treatment.

Abstract Objectives Currently, endometrial adenocarcinoma lacks an effective prognostic indicator. This study was to develop and validate a gene biomarker and a nomogram to predict the survival of endometrial adenocarcinoma, explore potential mechanisms and select sensitive drugs. Methods 425 endometrial adenocarcinoma cases with RNA sequencing data from TCGA were used to identify the most immune-related module by WGCNA. As an external test set, 103 cases from GSE17025 were used. Immune-related genes were downloaded from Innate DB. The three sets of data were used to identify the prognostic genes. Based on 397 cases with complete clinical data from TCGA, randomly divided into the training set (n = 199) and test set (n = 198), we identified CXCR3 as the prognostic gene biomarker. Age, grade, FIGO stage, and risk were used to develop and validate a predictive nomogram. AUC, C-index, calibration curve and K–M estimate evaluated the model's predictive performance. KEGG enrichment analysis, immune functions, TMB, the effectiveness of immunotherapy, and drug sensitivity between the high-risk and low-risk groups. Results CXCR3 was identified as a prognostic biomarker. We calculated the risk score and divided the cases into the high-risk and low-risk groups by the median value of the risk score. The OS of the high-risk group was better than the low-risk group. The risk was the prognostic indicator independent of age, grade, and FIGO stage. We constructed the nomogram including age, grade, FIGO stage, and risk to predict the prognosis of endometrial adenocarcinoma. The top five KEGG pathways enriched by the DEGs between the high- and low-risk groups were viral protein interaction with cytokine and cytokine receptors, cytokine-cytokine receptor interaction, chemokine signaling pathway, natural killer cell-mediated cytotoxicity, and cell adhesion molecules. We analyzed the difference in immune cells and found that CD8+ T cells, activated CD4+ T cells, T helper cells, monocytes, and M1 macrophages were infiltrated more in the low-risk group. However, M0 macrophages and activated dendritic cells were more in the high-risk group. The immune function including APC coinhibition, APC costimulation, CCR, checkpoint, cytolytic activity, HLA, inflammation-promoting, MHC-I, parainflammation, T cell coinhibition, T cell costimulation, type I-IFN-response, and type II-IFN-response were better in the low-risk group. TMB and TIDE scores were both better in the low-risk group. By ‘the pRRophetic’ package, we found 56 sensitive drugs for different risk groups. Conclusion We identified CXCR3 as the prognostic biomarker. We also developed and validated a predictive nomogram model combining CXCR3, age, histological grade, and FIGO stage for endometrial adenocarcinoma, which could help explore the precise treatment.

Flagship species’ conservation strategies hold significant prominence in biodiversity preservation. The giant panda, a globally recognized species, has drawn attention to its benefits and constraints as a flagship species. This study aimed to assess the potential benefits of a dual flagship strategy using both the giant panda and snow leopard, compared to an approach solely using the giant panda. We identified the number of potential beneficiary species based on their habitat overlap with the giant panda and snow leopard in Sichuan and Gansu, China. Subsequently, we examined public preferences for these two flagships and their influencing factors through questionnaire surveys within and outside China. The dual flagship strategy covered the habitats of more species and amplified existing protection for those species already benefiting from giant panda conservation efforts. The giant panda was commonly perceived as “Adorable”, “Innocent”, and “Rare”, while perceptions of the snow leopard leaned towards “Mighty”, “Mysterious”, and “Rare”. Though the giant panda is widely favored, the survey indicates a notable preference for snow leopards among a proportion of respondents. The dual flagship strategy offers expanded wildlife habitat coverage and benefits a broader range of species. Moreover, the combined appeal of the snow leopard and giant panda, each possessing unique charm and symbolism, holds the potential to garner broader societal interest and support. This study may serve as a reference for policy decisions in the Giant Panda National Park and other similar protected areas, optimizing conservation management and outreach initiatives for flagship species strategies. It may also benefit conservation strategies centered on other flagship species.

Abstract Aurora A kinase is a cell cycle regulator that is dysregulated in several different malignancies. Nevertheless, its regulatory mechanisms are still not fully understood. Here, we report that ubiquitin specific peptidase 3 (USP3) promotes proliferation and metastasis of esophageal squamous cell carcinoma (ESCC) cells by mediating deubiquitination of Aurora A. Analysis of human clinical samples indicated that USP3 and Aurora A are highly expressed in ESCC. Cellular experiments confirmed that high expression of USP3 and Aurora A in ESCC cells promoted malignant cell proliferation and invasion. In this mechanism, USP3 leads to suppression of Aurora A ubiquitination, resulting less proteasome degradation. We constructed the deubiquitinated mimetic K143R of Aurora A and found that K143R significantly promoted the proliferation and invasion of ESCC cells and was not regulated by the deubiquitination of USP3. Moreover, Aurora A K143R potentiated the kinase activity of Aurora A in ESCC cells. Thus, our findings demonstrate that the tumorigenic feature of ESCC is in part mediated by USP3-facilitated deubiquitination of Aurora A.

AimTo establish prediction models for 2-year overall survival of ovarian cancer patients with metastasis.MethodsIn total, 4,929 participants from Surveillance, Epidemiology, and End Results (SEER) database were randomly divided into the training set (n = 3,451) and the testing set (n = 1,478). Univariate and multivariable regression were conducted in the training set to identify predictors for 2-year overall survival of metastatic ovarian cancer patients. The C-index was calculated for assessing the performance of the models. The nomogram for the model was plotted. The prediction value of the model was validated in the testing set. Subgroup analysis were performed concerning surgery and chemotherapy status of patients and the metastatic site of ovarian cancer in the testing set. The calibration curves were plotted and the decision curve analysis (DCA) were conducted.ResultsAt the end of follow-up, 2,587 patients were survived and 2,342 patients were dead within 2 years. The 2-year survival rate was 52.5%. The prediction models were constructed based on predictors including age, radiation, surgery and chemotherapy, CA125, and bone, liver, and lung metastasis. The prediction model for 2-year overall survival of ovarian cancer patients with metastasis showed good predictive ability with the C-index of the model of 0.719 (95% CI: 0.706–0.731) in the training set and 0.718 (95% CI: 0.698–0.737) in the testing set. In terms of patients with bone metastasis, the C-index was 0.740 (95% CI: 0.652–0.828) for predicting the 2-year overall survival of ovarian cancer patients. The C-index was 0.836 (95% CI: 0.694–0.979) in patients with brain metastasis, 0.755 (95% CI: 0.721–0.788) in patients with liver metastasis and 0.725 (95% CI: 0.686–0.764) in those with lung metastasis for predicting the 2-year overall survival of ovarian cancer patients.ConclusionThe models showed good predictive performance for 2-year overall survival of metastatic ovarian cancer patients.

Abstract Background Hepatocyte growth factor (HGF) binds to the c-mesenchymal-epithelial transition (C-MET) receptor and activates downstream signaling pathways, playing an essential role in the development of various cancers. Given the role of this signaling pathway, the primary therapeutic direction focuses on identifying and designing HGF inhibitors, antagonists and other molecules to block the binding of HGF to C-MET, thereby limiting the abnormal state of other downstream genes. Methods This study focuses on the analysis of immune-related genes and corresponding immune functions that are significantly associated with the HGF/c-MET pathway using transcriptome data from 11 solid tumors. Results We systematically analyzed 11 different cancers, including expression correlation, immune infiltration, tumor diagnosis and survival prognosis from HGF/c-MET pathway and immune regulation, two biological mechanisms having received extensive attention in cancer analysis. Conclusion We found that the HGF/c-MET pathway affected the tumor microenvironment mainly by interfering with expression levels of other genes. Immune infiltration is another critical factor involved in changes to the tumor microenvironment. The downstream immune-related genes activated by the HGF/c-MET pathway regulate immune-related pathways, which in turn affect the degree of infiltration of immune cells. Immune infiltration is significantly associated with cancer development and prognosis.

Colorectal cancer (CRC) is one of the most fatal cancers of the digestive system. Although cancer stem cells and metabolic reprogramming have an important effect on tumor progression and drug resistance, their combined effect on CRC prognosis remains unclear. Therefore, we generated a 21-gene mRNA stemness index-related metabolic risk score model, which was examined in The Cancer Genome Atlas and Gene Expression Omnibus databases (1323 patients) and validated using the Zhongshan Hospital cohort (200 patients). The high-risk group showed more immune infiltrations; higher levels of immunosuppressive checkpoints, such as CD274, tumor mutation burden, and resistance to chemotherapeutics; potentially better response to immune therapy; worse prognosis; and advanced stage of tumor node metastasis than the low-risk group. The combination of risk score and clinical characteristics was effective in predicting overall survival. Zhongshan cohort validated that high-risk score group correlated with malignant progression, worse prognosis, inferior adjuvant chemotherapy responsiveness of CRC, and shaped an immunoevasive contexture. This tool may provide a more accurate risk stratification in CRC and screening of patients with CRC responsive to immunotherapy.

BackgroundPerioperative anemia and transfusion are intertwined with each other, and both have adverse impacts on the survival of colorectal cancer (CRC) patients. But the treatment of anemia still relies on transfusion in several countries, which leads us to question the effects of anemia tolerance and transfusion on the long-term outcomes of CRC patients. We investigated the combined effect of preoperative anemia and postoperative anemia and of preoperative anemia and blood transfusion, which imposes a greater risk to survival, to compare the effects of anemia tolerance and transfusion on overall survival (OS) and disease-free survival (DFS) in patients undergoing CRC surgery.MethodsA retrospective propensity-score-matched analysis included patients with CRC undergoing elective surgery between January 1, 2008, and December 31, 2014. After propensity-score matching, Kaplan–Meier survival analysis and univariable and multivariable Cox proportional hazards models were used to study the prognostic factors for survivals. In univariate and multivariate Cox regression analysis, two novel models were built.ResultsOf the 8,121 patients with CRC, 1,975 (24.3%) and 6,146 (75.7%) patients presented with and without preoperative anemia, respectively. After matching, 1,690 patients remained in each group. In the preoperative anemia and postoperative anemia model, preoperative anemia and postoperative anemia was independent risk factor for OS (HR, 1.202; 95% CI, 1.043–1.385; P=0.011) and DFS (HR, 1.210; 95% CI, 1.050–1.395; P=0.008). In the preoperative anemia and transfusion model, preoperative anemia and transfused was the most dangerous independent prognostic factor for OS (HR, 1.791; 95% CI, 1.339–2.397; P

BackgroundThe correlation between high white blood cell (WBC) count and poor prognosis has been identified in various types of cancer; however, the clinical significance and immune context of WBC count in colorectal cancer remains unclear.MethodsBetween February 2009 and November 2014, 7,433 patients at the Shanghai Cancer Center who had undergone elective surgery for colorectal cancer were enrolled in this retrospective cohort study. Patients were divided into two groups: low and high preoperative WBC groups. Propensity score matching was used to address the differences in baseline characteristics. The Kaplan–Meier method and Cox regression analysis were used to identify independent prognostic factors in colorectal cancer patients. Tumor-infiltrating immune cells in the high and low preoperative WBC groups were compared using immunohistochemical staining.ResultsOf the 7,433 patients who underwent colorectal cancer surgery and were available for analysis, 5,750 were included in the low preoperative WBC group, and 1,683 were included in the high preoperative WBC group. After propensity score matching, 1,553 patients were included in each group. Kaplan–Meier survival curves showed that a high preoperative WBC count was associated with a decreased overall survival (P = 0.002) and disease-free survival (P = 0.003), and that preoperative WBC count was an independent risk factor for overall survival (hazard ratio, 1.234; 95% confidence interval, 1.068–1.426; P = 0.004) and disease-free survival (hazard ratio, 1.210; 95% confidence interval, 1.047–1.397, P = 0.01). Compared to the low preoperative WBC group, the high preoperative WBC group exhibited higher expression of regulatory T cells (P = 0.0034), CD68+ macrophages (P = 0.0071), and CD66b+ neutrophils (P = 0.0041); increased expression of programmed cell death protein 1 (P = 0.005) and programmed cell death ligand 1 (P = 0.0019); and lower expression of CD8+ T cells (P = 0.0057) in colorectal cancer patients.ConclusionsOur research indicates that a high preoperative WBC count is a prognostic indicator in colorectal cancer patients and is associated with an immunosuppressive tumor microenvironment, which could aid in future risk stratification.

BackgroundMyeloperoxidase (MPO) has been demonstrated to be a local mediator of inflammation in tissue damage in various inflammatory diseases. Given its controversial effect on colorectal cancer (CRC), there has been growing interest in investigating the role of this enzyme in CRC. The mechanism underlying MPO activity and CRC progression requires further clarification.MethodsThe expression and function of MPO in CRC were evaluated using TCGA analysis. TCGA, TIMER, and Human Cell Landscape analyses were used to analyze the correlation between MPO expression and neutrophil infiltration in CRC. Spearman’s bivariate correlation analysis was used to verify the correlation between MPO levels in CRC and the peripheral neutrophil count. In the clinical analysis, 8,121 patients who underwent elective surgery for CRC were enrolled in this retrospective cohort study from January 2008 to December 2014. Propensity score matching was used to address the differences in baseline characteristics. The Kaplan–Meier method and Cox regression analysis were used to identify independent prognostic factors in patients with CRC.ResultsMPO was upregulated in CRC tissues, which is related to malignant progression and worse survival in CRC patients from TCGA analysis. MPO was significantly correlated with the infiltration level of neutrophils in CRC in TCGA, TIMER, and Human Cell Landscape analyses. MPO was positively correlated with the peripheral neutrophil count. Data of the 8,121 patients who underwent CRC surgery were available for analysis. After propensity score matching, 3,358 patients were included in each group. Kaplan–Meier survival curves showed that high preoperative neutrophil levels were associated with decreased overall survival (OS; P < 0.001) and disease-free survival (DFS; P = 0.015). The preoperative neutrophil count was an independent risk factor for OS (hazard ratio [HR], 1.157; 95% confidence interval [CI], 1.055–1.268; P = 0.002) and DFS (HR, 1.118; 95% CI, 1.009–1.238; P = 0.033).ConclusionsOur research indicates that increased MPO levels in CRC are significantly correlated with high preoperative neutrophil counts, and both serve as prognostic indicators for worse survival in CRC patients. Our study suggests that neutrophils may be key players in the mechanism linking MPO levels with poor CRC outcomes.

Roads, acting as barriers, hamper wildlife movements and disrupt habitat connectivity. Bridges and culverts are common structures on roads, and some of them can function to allow wildlife passage. This study investigated the effects of traffic, the surrounding landscape, human disturbance, and bridge and culvert structures on the utilization of bridges and culverts as dedicated passages by wildlife, using motion-activated infrared camera traps along a 64 km road in Giant Panda National Park, Sichuan, China. The results show that both species richness and counts of wildlife recorded at the bridge and culvert were significantly lower than those observed at sites distant from roads. No large-sized wildlife was recorded at the bridges and culverts. Human activities and traffic volume significantly and negatively affect medium-sized wildlife utilization of bridges and culverts. We conclude that bridges and culverts serve as wildlife crossings, but their efficacy is weak. This emphasizes the necessity of retrofitting bridges and culverts via mitigation facilities such as noise and light barriers, and vegetation restoration on both sides of the roads in Giant Panda National Park.

Background: To report a rare case of retiform hemangioendothelioma (RH) originated from the vulva and review the relative references. Case: A 38-year-old woman was admitted to our hospital with a vulvar subcutaneous nodule (diameter about 2 cm) for 2 years. The clinical examination findings, laboratory test results, including complete blood count and liver function test results were normal. The B mode ultrasound revealed that a hypoechoic nodule with a clear boundary was observed on the right side of the vulva. The size was measured to be 23 mm × 8 mm. An expanded resection with the excision range extending 1 cm and the depth reaching the fascia was performed. The histologic examination revealed that the elongated, arborizing, thin-walled vessels were abundant on the tumor, the inner wall of the vessels was arranged with monolayer cells with uniform morphology. Local infiltration of lymphocyte has been found around the vessels. Immunohistochemical examinations showed that the endothelial cells were CD31, CD34 and friend leukemia virus integration 1 (Fli-1) positive, the smooth muscle actin (SMA) was scattered positive, further confirming the diagnosis of RH. The patient was followed up for 15 months, no local recurrence was found. Conclusions: Vulvar region is the rare affected region of RH, which is lack of characteristic findings in clinical examinations and laboratory tests. The pathology and immunohistochemistry are necessary for the diagnosis of vulvar RH. Local expanded resection of tumor may be an effective method for the treatment of early-stage RH to reduce the risk of local recurrence.

Abstract Objective To evaluate the efficacy and safety of PLD in treating of in patients who experience epithelial ovarian, fallopian tubal, and peritoneal cancer progression within 12 months after the first-line platinum-based therapy. Methods This was an open-label, single-arm and multicenter clinical trial. The ORR was the interim primary objective, and the DCR, AEs and QOL were the secondary objectives. The impact of factors on efficacy outcomes, the change trend of CA125 and the artificial platinum-free interval were exploratory endpoints. Results Totally, 115 patients were enrolled in this study and included in the ITT population. Moreover, 101 patients were included in the safety population. The median follow-up time was 4 months (IQR 2–6). In the ITT population, the confirmed ORR was 37.4% (95% CI, 28.4–46.4%), and the DCR was 65.2% (95% CI, 56.4–74.1%). The previous response status to platinum-based chemotherapy and baseline CA125 levels were significantly correlated with the ORR. The ORR was significantly higher in patients with a CA125 decrease after the first cycle than in the patients with a CA125 increase. The most common grade 3 or higher AE was hand-foot syndrome (3 [3.0%] of 101 patients). No statistically significant differences existed between the baseline and the postbaseline questionnaires. Conclusions For patients who experience platinum-resistant and platinum-refractory relapse, the use of PLD may be acceptable because of the associated satisfactory efficacy, low frequency of AEs and high patient QOL. Moreover, a low CA125 level at baseline and a reduction in CA125 after the first cycle are predictive factors for satisfactory efficacy.

Background: Selenium binding protein 1 (SELENBP1) is frequently downregulated in malignancies such as colorectal cancer (CRC), however, whether it is involved in tumor angiogenesis is still unknown. Methods: We analyzed the expression and localization of SELENBP1 in vessels from CRC and neighboring tissues. We investigated the in vitro and in vivo activity of SELENBP1 in angiogenesis and explored the underlying mechanism. Results: SELENBP1 was localized to endothelial cells in addition to glandular cells, while its vascular expression was decreased in tumor vessels compared to that in vessels from neighboring non-tumor tissues. Gain-of-function and loss-of-function experiments demonstrated that SELENBP1 inhibited angiogenesis in vitro, and blocked communications between HUVECs and CRC cells. Overexpression of SELENBP1 in CRC cells inhibited tumor growth and angiogenesis, and enhanced bevacizumab-sensitivity in a mouse subcutaneous xenograft model. Mechanic analyses revealed that SELENBP1 may suppress tumor angiogenesis by binding with Delta-like ligand 4 (DLL4) and antagonizing the DLL4/Notch1 signaling pathway. The inhibitory effects of SELENBP1 on in vitro angiogenesis could largely be rescued by DLL4. Conclusion: These results revealed a novel role of SELENBP1 as a potential tumor suppressor that antagonizes tumor angiogenesis in CRC by intervening the DLL4/Notch1 signaling pathway.

Cervical adenocarcinoma can present as a solid, mixed solid, cystic, or multiple cystic cervical mass in the endocervical canal. In this report, we present an extremely rare case of cervical adenocarcinoma with giant cystic lesions. A 37-year-old Chinese woman with a regular menstrual cycle presented to her local doctor complaining of mild abdominal distension. Abdominal ultrasonography suggested an ovarian cyst, whose mean diameter increased from 3 to 8 cm in 3 months. Thereafter, she was referred to our hospital. She had no abnormal vaginal bleeding or discharge. Transvaginal ultrasonography revealed a 95 × 80 mm cyst below the back of the uterus. Computed tomography revealed a 9.8 × 8.5 cm multilocular cyst between the cervix and right ovary. Human papillomavirus (HPV)-E6 and -E7 mRNA tests revealed HPV-16 positivity. The thin-layer, liquid-based cytological test of the cervix showed negative results. No tumor lesions were observed on the cervical biopsy histopathology. The lesion was misdiagnosed as an ovarian cyst prior to the surgery. Intraoperatively, a cyst of the size of a child's head was observed extending from the low posterior wall of the uterus to the posterior lip of the cervix, and the cervical cysts were resected. Histological examination revealed cervical adenocarcinoma. Subsequently, she underwent extensive hysterectomy, bilateral salpingectomy, and pelvic lymphadenectomy. The final diagnosis was stage IB3 cervical adenocarcinoma. After 21 months of follow-up, no clinical or radiological evidence of recurrence has been found.

Abstract Immunosenescence is a process of immune dysfunction that occurs with age and includes remodeling of lymphoid organs, leading to changes in the immune function of the elderly, which is closely related to the development of infections, autoimmune diseases, and malignant tumors. T cell–output decline is an important feature of immunosenescence as well as the production of senescence-associated secretory phenotype, increased glycolysis, and reactive oxygen species. Senescent T cells exhibit abnormal phenotypes, including downregulation of CD27, CD28, and upregulation of CD57, killer cell lectin-like receptor subfamily G, Tim-3, Tight, and cytotoxic T-lymphocyte-associated protein 4, which are tightly related to malignant tumors. The role of immunosenescence in tumors is sophisticated: the many factors involved include cAMP, glucose competition, and oncogenic stress in the tumor microenvironment, which can induce the senescence of T cells, macrophages, natural killer cells, and dendritic cells. Accordingly, these senescent immune cells could also affect tumor progression. In addition, the effect of immunosenescence on the response to immune checkpoint blocking antibody therapy so far is ambiguous due to the low participation of elderly cancer patients in clinical trials. Furthermore, many other senescence-related interventions could be possible with genetic and pharmacological methods, including mTOR inhibition, interleukin-7 recombination, and NAD+ activation. Overall, this review aims to highlight the characteristics of immunosenescence and its impact on malignant tumors and immunotherapy, especially the future directions of tumor treatment through senescence-focused strategies.

Black TiO2 with abundant oxygen vacancies (OVs)/B-doped graphitic carbon nitride (g-C3N4) Z-scheme heterojunction nanocomposites are successfully prepared by the one-pot strategy. The OVs can improve not only photogenerated carrier separation, but also the sorption and activation of antibiotic compounds (tetracycline hydrochloride, TC). The prepared heterojunction photocatalysts with a narrow bandgap of ∼2.13 eV exhibit excellent photocatalytic activity for the degradation of tetracycline hydrochloride (65%) under visible light irradiation within 30 min, which is several times higher than that of the pristine one. The outstanding photocatalytic property can be ascribed to abundant OVs and B element-dope reducing the bandgap and extending the photo-response to the visible light region, the Z-scheme formation of heterojunctions preventing the recombination of photogenerated electrons and holes, and promoting their effective separation.

B cells are well known as key mediators of humoral immune responses via the production of antibodies. Immunoglobulin A (IgA) is the most abundantly produced antibody isotype and provides the first line of immune protection at mucosal surfaces. However, IgA has long been a divisive molecule with respect to tumor progression. IgA exerts anti- or pro-tumor effect in different tumor types. In this review, we summarize emerging evidence regarding the production and effects of IgA and IgA+ cells in the tumor microenvironment (TME). Moreover, we discuss that the TME cytokines, host diet, microbiome, and metabolites play a pivotal role in controlling the class-switch recombination (CSR) of IgA. The analysis of intratumoral Ig repertoires and determination of metabolites that influence CSR may help establish novel therapeutic targets for the treatment of cancers.

Retiform hemangioendothelioma (RH) is a rare borderline-malignant vascular tumor with specific histological characteristics, usually occurring in the limbs and trunk. We report the case of a 63-year-old woman who presented with a painless, oval nodule that had been growing slowly on her left vulva for 3 years. Magnetic resonance imaging of the pelvic cavity revealed a 4.4- × 2.7- × 1.8-cm cystic lesion in the subcutaneous fat of the left vulva. Resection beyond the macroscopic border was performed. Pathology revealed vascular structures with elongated and narrow arborizing vascular channels that were arranged in a retiform pattern resembling rete testis tissue. Immunohistochemical endothelial staining was positive for CD31, CD34, and Friend leukemia integration-1 (FLI-1). The above features confirmed a diagnosis of RH. There was no local recurrence or metastasis during the 26-month follow-up. RH of the vulva is rare, and its diagnosis is supported by specific histological characteristics and immunohistochemical staining for CD31, CD34, and FLI-1. Wide surgical resection with tumor-free margins is important for a favorable prognosis.

ObjectiveThis study assessed the predictive value of preoperative computed tomography (CT) scans and clinical factors for optimal debulking surgery (ODS) in patients with advanced ovarian cancer (AOC).MethodsPatients with AOC in International Federation of Gynecology and Obstetrics (FIGO) stage III-IV who underwent primary debulking surgery (PDS) between 2016 and 2019 from nine tertiary Chinese hospitals were included. Large-volume ascites, diffuse peritoneal thickening, omental cake, retroperitoneal lymph node enlargement (RLNE) below and above the inferior mesenteric artery (IMA), and suspected pelvic bowel, abdominal bowel, liver surface, liver parenchyma and portal, spleen, diaphragm and pleural lesions were evaluated on CT. Preoperative factors included age, platelet count, and albumin and CA125 levels.ResultsOverall, 296 patients were included, and 250 (84.5%) underwent ODS. The prediction model included age >60 years (P=0.016; prediction index value, PIV=1), a CA125 level >800 U/ml (P=0.033, PIV=1), abdominal bowel metastasis (P=0.034, PIV=1), spleen metastasis (P0.750), and the Hosmer-Lemeshow test indicated its stable calibration (P=0.600>0.050). With the aim of maximizing the accuracy of prediction and minimizing the rate of inappropriate explorations, a total PIV ≥5 achieved the highest accuracy of 85.47% and identified patients who underwent suboptimal PDS with a specificity of 100%.ConclusionsWe developed a prediction model based on two preoperative clinical factors and four radiological criteria to predict unsatisfactory debulking surgery in patients with AOC. The accuracy of this prediction model needs to be validated and adjusted in further multicenter prospective studies.

Estimating net primary productivity (NPP) is significant in global climate change research and carbon cycle. However, there are many uncertainties in different NPP modeling results and the process of NPP is challenging to model on the absence of data. In this study, we used meteorological data as input to simulate vegetation NPP through climate-based model, synthetic model and CASA model. Then, the results from three models were compared with MODIS NPP and observed data over China from 2000 to 2015. The statistics evaluation metrics (Relative Bias (RB), Pearson linear Correlation Coefficient (CC), Root Mean Square Error (RMSE), and Nash-Sutcliffe efficiency coefficient (NSE)) between simulated NPP and MODIS NPP were calculated. The results implied that the CASA-model performed better than the other two models in terms of RB, RMSE, NSE and CC whether on the national or the regional scale. It has a higher CC with 0.51 and a smaller RMSE with 111.96 g C·m-2·yr-1 in the whole country. The synthetic model and CASA-model has the same advantages at some regions, and there are lower RMSE in Southern China (86.35 g C·m-2·yr-1), Xinjiang (85.53 g C·m-2·yr-1) and Qinghai-Tibet Plateau (93.22 g C·m-2·yr-1). The climate-based model has widespread overestimation and large systematic errors, along with worse performances (NSEmax = 0.45) and other metric indexes unsatisfactory, especially Qinghai-Tibet Plateau with relatively lower accuracy because of the unavailable observation data. Overall, the CASA-model is much more ideal for estimating NPP all over China in the absence of data. This study provides a comprehensive intercomparison of different NPP-simulated models and can provide powerful help for researchers to select the appropriate NPP evaluation model.

The high moisture content of lignite restricts its extensive and efficient use. Furthermore, the reabsorption of lignite is also a factor that affects lignite spontaneous combustion. Therefore, it is of great importance to study the process and mechanism of water molecule desorption and adsorption on lignite and coke (25–950°C) to achieve the clean and efficient utilization of lignite and environmental protection. Proton nuclear magnetic resonance (1H-NMR), thermogravimetric analysis, and other techniques were used in this study to explore the water molecule absorption and desorption processes of lignite pyrolysis at different temperatures (25–950°C) and the special contributions of ether bonds to water molecule adsorption. A mechanism of lignite water molecule adsorption was proposed. The results showed that ether bonds played a special role in the water molecule adsorption by pyrolyzed lignite. The ether bond content was greater in the coal samples at 300 and 950°C, which changed the trend of lignite water molecule absorption and the distribution of water (T2) detected in the 1H-NMR experiments and delayed the escape of water molecules during moisture desorption. The total amount of adsorbed water decreased first and then increased in the coal samples as the pyrolysis temperature increased. However, the maximum adsorption interactions of each coal sample increased first and then decreased. This was the result of the interactions between the pores and the oxygen-containing functional groups. Based on the above analysis, water molecule adsorption mechanism models of lignite and coke were constructed. This study offers a new approach for investigating the water molecule adsorption and adsorption mechanisms of lignite and coke.

Objective To examine the associations of change in body mass index (BMI) and waist circumference (WC) over an average of 4 years with subsequent mortality risk in middle-aged to older Chinese.Design Prospective cohort study based on the Guangzhou Biobank Cohort Study.Setting Community-based sample.Participants 17 773 participants (12 956 women and 4817 men) aged 50+ years.Primary and secondary outcome measures Primary outcome measure was all-cause mortality. Secondary outcome measures were cardiovascular disease (CVD) and cancer mortality. Causes of death were obtained via record linkage, and coded according to the International Classification of Diseases (tenth revision).Results 1424 deaths (53.4% women) occurred in the 17 773 participants (mean age 61.2, SD 6.8 years) during an average follow-up of 7.8 (SD=1.5) years, and 97.7% of participants did not have an intention of weight loss . Compared with participants with stable BMI, participants with BMI loss (>5%), but not gain, had a higher risk of all-cause mortality (HR=1.49, 95% CI 1.31 to 1.71), which was greatest in those who were underweight (HR=2.45, 95% CI 1.31 to 4.59). Similar patterns were found for WC. In contrast, for participants with a BMI of ≥27.5 kg/m2, BMI gain, versus stable BMI, was associated with 89% higher risk of all-cause mortality (HR=1.89, 95% CI 1.25 to 2.88), 72% higher risk of CVD mortality (HR=1.72, 95% CI 0.80 to 3.72) and 2.27-fold risk of cancer mortality (HR=2.27, 95% CI 1.26 to 4.10).Conclusion In older people, unintentional BMI/WC loss, especially in those who were underweight was associated with higher mortality risk. However, BMI gain in those with obesity showed excess risks of all-cause and cancer mortality, but not CVD mortality. Frequent monitoring of changes in body size can be used as an early warning for timely clinical investigations and interventions and is important to inform appropriate health management in older Chinese.

The fungal strain BS5 was isolated from a soil sample collected in the Tibetan Plateau, which displayed good insecticidal activity and was identified as Talaromyces purpureogenus based on morphological and molecular analysis. This study aimed to evaluate the insecticidal activity and identify the active compound of the strain BS5 against the locust Locusta migratoria manilensis. The insecticidal activity of the fermented broth of BS5 was at 100% after 7 days against locusts. We extracted the fermented broth of BS5 and then evaluated the insecticidal activity of the extracts against locusts. The ethyl acetate extract exhibited promising activity levels with an LC50 value of 1077.94 μg/mL and was separated through silica gel column chromatography. The UPLC-Q-Exactive Orbitrap/MS system was employed to analyze the active fraction Fr2.2.2 (with an LC50 value of 674.87 μg/mL), and two compounds were identified: phellamurin and rubratoxin B.

Pea protein isolate (PPI), as an emerging plant protein, has gradually aroused the attention of the public, but the PPI, especially high-concentration PPI’s low stability in the acidic aqueous system, was still a problem that limited its application. In this research, we investigated the interactions between relatively high concentrations of PPI (3.0%) and carboxymethylcellulose (CMC, 0–0.5%) in neutral and acid aqueous systems to explore the change of the phase behavior and stability of PPI as affected by CMC. It showed that the stability of PPI in the aqueous systems strongly depended on the CMC concentration, especially at the acidic aqueous systems. At neutral aqueous system, a certain amount addition of CMC into the PPI caused serious phase separation. While stable PPI solutions can be obtained at a narrow region around pH 4.5 to 5.5 by adding different amounts of CMC. The enhancement in the electrostatic repulsion and steric hindrance between the newly formed PPI-CMC biopolymers, as well as the increase in bulk viscosity with the adding of CMC at pH 4.5, contributed to the higher stability of PPI in acidic aqueous systems.

Currently, stem cells are reported to be involved in tumor formation, drug resistance and recurrence. Inhibiting the proliferation of tumor cells, promoting their senescence and apoptosis has been the most important anti-tumor therapy. Epigenetics is involved in the regulation of gene expression and is closely related to cancer and stem cells. It mainly includes DNA methylation, histone modification, and chromatin remodeling. Histone methylation and demethylation play an important role in histone modification. Histone 3 lysine 27 trimethylation (H3K27me3) induces transcriptional inhibition and plays an important role in gene expression. Jumonji domain-containing protein-3 (JMJD3), one of the demethyases of histone H3K27me3, has been reported to be associated with the prognosis of many cancers and stem cells differentiation. Inhibition of JMJD3 can reduce proliferation and promote apoptosis in tumor cells, as well as suppress differentiation in stem cells. GSK-J4 is an inhibitor of demethylase JMJD3 and UTX, which has been shown to possess anti-cancer and inhibition of embryonic stem cells differentiation effects. In this review, we examine how JMJD3 regulates cellular fates of stem cells and cancer cells and references were identified through searches of PubMed, Medline, Web of Science.

It is postulated that high-sensitivity C-reactive protein (hs-CRP) and tumor necrosis factor α (TNF-α) are diagnostic utilities for pleural effusion. This study was designed to explore the detection and significance of TNF-α and hs-CRP in the pleural effusion of patients with diabetes and pulmonary tuberculosis. A total of 60 patients with diabetes and pulmonary tuberculosis pleural effusion were selected as the study group, while 60 patients with pulmonary tuberculosis pleural effusion were considered as the control group. The expression of TNF-α and hs-CRP in the two groups was determined from pleural effusion by enzyme-linked immunosorbent assay (ELISA). The expression levels of TNF-α and hs-CRP in pleural effusion of the study group were significantly ( P

Chromosome instability (CIN) is deleterious to normal cells because of the burden of aneuploidy. However, most human solid tumors have an abnormal karyotype implying that gain and loss of chromosomes by cancer cells confers a selective advantage. CIN can be induced in the mouse by inactivating the spindle assembly checkpoint. This is lethal in the germline but we show here that adult T cells and hepatocytes can survive conditional inactivation of the Mad2l1 SAC gene and resulting CIN. This causes rapid onset of acute lymphoblastic leukemia (T-ALL) and progressive development of hepatocellular carcinoma (HCC), both lethal diseases. The resulting DNA copy number variation and patterns of chromosome loss and gain are tumor-type specific, suggesting differential selective pressures on the two tumor cell types.

Pyruvate dehydrogenase kinase 1 (PDK1) is overexpressed in ovarian cancer and thus is a promising anticancer therapeutic target. Our previous work suggests that coumarin compounds are potential inhibitors of PDKs. In this study, we used the ovarian cancer cell line SKOV3 as the model system and examined whether dicumarol (DIC), a coumarin compound, could inhibit ovarian cancer through targeting PDK1. We showed that DIC potently inhibited the kinase activity of PDK1, shifted the glucose metabolism from aerobic glycolysis to oxidative phosphorylation, generated a higher level of reactive oxygen species (ROS), attenuated the mitochondrial membrane potential (MMP), induced apoptosis, and reduced cell viability in vitro. The same phenotypes induced by DIC also were translated in vivo, leading to significant suppression of xenograft growth. This study not only identifies a novel inhibitor for PDK1, but it also reveals novel anticancer mechanisms of DIC and provides a promising anticancer therapy that targets the Warburg effect.

The macerals, including fusinitic coal containing 72.20% inertinite and xyloid coal containing 91.43% huminite, were separated from Shengli lignite using an optical microscope, and their combustion reactivity was examined by thermogravimetric analysis. Several combustion parameters, including ignition and burnout indices, were analyzed, and the combustion kinetics of the samples were calculated by regression. Fusinitic coal presented a porous structure, while xyloid coal presented a compact structure. The specific surface area of fusinitic coal was 2.5 times larger than that of xyloid coal, and the light-off temperature of the former was higher than that of the latter. However, the overall combustion reactivity of fusinitic coal was better than that of xyloid coal. The combustion processes of fusinitic and xyloid coals can be accurately described by both the homogeneous model and the shrinking core model. The features of xyloid coal agree with the shrinking core model when its conversion rate is 10%–90%. The activation energy of fusinitic coal during combustion can be divided into three phases, with the middle phase featuring the highest energy. The activation energy of xyloid coal is lower than that of fusinitic coal in the light-off phase, which may explain the low light-off temperature of this coal.

Both schizophrenia and antipsychotic treatment are known to modulate brain morphology. However, it is difficult to establish whether observed structural brain abnormalities are due to disease or the effects of treatment. The aim of this study was to investigate the effects of illness and antipsychotic treatment on brain structures in antipsychotic-naïve first-episode schizophrenia based on a longitudinal short-term design. Twenty antipsychotic-naïve subjects with first-episode schizophrenia and twenty-four age- and sex-matched healthy controls underwent 3T MRI scans. Voxel-based morphometry (VBM) was used to examine the brain structural abnormality in patients compared to healthy controls. Nine patients were included in the follow-up examination after 8 weeks of treatment. Tensor-based morphometry (TBM) was used to identify longitudinal brain structural changes. We observed significantly reduced grey matter volume in the right superior temporal gyrus in antipsychotic-naïve patients with schizophrenia compared with healthy controls. After 8 weeks of treatment, patients showed significantly increased grey matter volume primarily in the bilateral prefrontal cortex, insula, right thalamus, left superior occipital cortex and the bilateral cerebellum. In addition, a greater enlargement of the prefrontal cortex is associated with the improvement in negative symptoms, and a more enlarged thalamus is associated with greater improvement in positive symptoms. Our results suggest the following: (1) the abnormality in the right superior temporal gyrus is present in the early stages of schizophrenia, possibly representing the core region related to schizophrenia; and (2) atypical antipsychotics could modulate brain morphology involving the thalamus, cortical grey matter and cerebellum. In addition, examination of the prefrontal cortex and thalamus might facilitate an efficient response to atypical antipsychotics in terms of symptom improvement.

Identifying the metabolic differences in the livers of modern broilers and local chicken breeds is important for understanding their biological characteristics, and many proteomic changes in their livers are not well characterized. We therefore analyzed the hepatic protein profiles of a commercial breed, Arbor Acres (AA) broilers, and a local dual purpose breed, Big Bone chickens, using two-dimensional electrophoresis combined with liquid chromatography-chip/electrospray ionization-quadruple time-of-flight/mass spectrometry (LC-MS/MS). A total of 145 proteins were identified as having differential abundance in the two breeds at three growth stages. Among them, 49, 63 and 54 belonged to 2, 4, and 6 weeks of age, respectively. The higher abundance proteins in AA broilers were related to the energy production pathways suggesting enhanced energy metabolism and lipid biosynthesis. In contrast, the higher abundance proteins in Big Bone chickens showed enhanced lipid degradation, resulting in a reduction in the abdominal fat percentage. Along with the decrease in fat deposition, flavor substance synthesis in the meat of the Big Bone chickens may be improved by enhanced abundance of proteins involved in glycine metabolism. In addition, the identified proteins in nucleotide metabolism, antioxidants, cell structure, protein folding and transporters may be critically important for immune defense, gene transcription and other biological processes in the two breeds. These results indicate that selection pressure may have shaped the two lines differently resulting in different hepatic metabolic capacities and extensive metabolic differences in the liver. The results from this study may help provide the theoretical basis for chicken breeding.

BACKGROUND: Previous epidemiological studies have shown that fish consumption may modify the risk of ovarian cancer. However, these studies yielded controversial results. The present meta-analysis was undertaken to evaluate the relationship between fish intake and ovarian cancer risk. METHODS: A literature search was carried out using Pubmed, Embase, and Cochrane Library Central database for all relevant studies up to August 2013. We pooled the relative risks (RR) from individual studies using fixed-effect or random-effect model, and carried out heterogeneity and publication bias analyses. RESULTS: A total of 15 (ten case-control, and five cohort) studies were included in the present meta-analysis, representing data for 889,033 female subjects and 6,087 ovarian cancer cases. We found that total fish intake was not significantly associated with the risk of ovarian cancer among cohort studies (RR = 1.04 95% CI [0.89, 1.22]) as well as case-control studies (RR = 0.90, 95% CI [0.73,1.12]). There was no evidence of publication bias as suggested by Begg's test (P = 0.55) and Egger's test(P = 0.29). CONCLUSIONS: The present meta-analysis showed that total fish consumption was not significantly associated with the risk of ovarian cancer. Further analysis on different fish species and food preparation methods should be conducted in future studies.