Lipid metabolites abnormally expressed in pelvic fluid as potential biomarkers for ovarian cancer: A case-control study.

BACKGROUND: Ovarian cancer is insidious and usually detected in advanced stages of the disease. As the ovaries are pelvic organs, changes in their pelvic fluid metabolites may be associated with ovarian cancer. METHODS: Metabolomic changes in the pelvic fluid were detected using liquid chromatography-tandem mass spectrometry (LC-MS/MS) in patients with ovarian cancer, ovarian cysts and uterine fibroids. Area under the curve (AUC) analysis was used to assess the diagnostic performance of lipid metabolites and blood tumor indices. The Pearson correlation algorithm was used to analyze the correlation between clinical characteristics and lipid metabolites in ovarian cancer patients. RESULTS: There were 24 lipid metabolites significantly changed in the pelvic fluid of ovarian cancer patients (p < 0.05). Palmitoylcarnitine, lipoamide, lipid metabolites, and blood tumor indices (CA15-3 and CA125) showed AUC > 0.8, with palmitoylcarnitine reaching a high of 0.942. In addition, we found that some lipid metabolites were significantly associated with the clinical stage, abdominal water volume, lymphatic metastasis, and recurrence (p < 0.05, r > 0.5). CONCLUSION: Levels of specific lipid metabolites are potential biomarkers of ovarian cancer and may play a key role in the early diagnosis and prognostic assessment of ovarian cancer. SIGNIFICANCE: Our results showed that pelvic metabolites, especially some lipid metabolites, play an important role in the diagnosis of ovarian cancer. Meanwhile, partial lipid metabolites were closely associated with the clinical presentation and prognosis of patients with ovarian cancer. We believe that our study makes a significant contribution to the literature because it provides a potential approach that is more effective for ovarian cancer detection.

Preoperative supine time for adrenal venous sampling: a prospective randomized controlled trial.

BACKGROUND: Primary aldosteronism (P.A.) is the most common form of secondary hypertension, accounting for 5% of hypertensive patients and 17-23% of patients with resistant hypertension. Compared to primary hypertension, P.A. is more prone to cause severe organ damage and even early death. Adrenal venous sampling (AVS) is a practical confirmatory test for subtyping aldosterone-producing adenoma and bilateral adrenal hyperplasia, helping physicians to make an accurate decision between surgery or medication. According to guidelines, supine in bed before AVS is recommended for a desirable result of AVS. However, investigations about the most optimal preoperative supine time before AVS are lacking. METHODS/DESIGN: This is a multi-center prospective randomized controlled study. One hundred twenty patients diagnosed as P.A. and willing for AVS examination will be included. Participants will be randomly allocated to a 15-min supine time group or 2-h supine time group. The primary outcome is the degree of biochemical remission (serum potassium and orthostatic ARR). The secondary outcomes are degrees of clinical remission (blood pressure, type and dose of antihypertensive drugs), the technical success rate, and the adverse event of AVS (selective index ≥ 2 is considered successful surgery without corticotropin stimulation). DISCUSSION: P.A. is an intractable public health problem, and many techniques including AVS have been developed to identify this disease correctly. This study will help to understand whether the length of preoperative supine time would affect the diagnostic efficacy of AVS and thus help to formulate a more reasonable AVS procedure. TRIAL REGISTRATION: ClinicalTrials.gov NCT05658705. Registered on 10 September 2022.

Prior water availability modifies the effect of heavy rainfall on dengue transmission: a time series analysis of passive surveillance data from southern China.

Introduction: Given the rapid geographic spread of dengue and the growing frequency and intensity of heavy rainfall events, it is imperative to understand the relationship between these phenomena in order to propose effective interventions. However, studies exploring the association between heavy rainfall and dengue infection risk have reached conflicting conclusions, potentially due to the neglect of prior water availability in mosquito breeding sites as an effect modifier. Methods: In this study, we addressed this research gap by considering the impact of prior water availability for the first time. We measured prior water availability as the cumulative precipitation over the preceding 8 weeks and utilized a distributed lag non-linear model stratified by the level of prior water availability to examine the association between dengue infection risk and heavy rainfall in Guangzhou, a dengue transmission hotspot in southern China. Results: Our findings suggest that the effects of heavy rainfall are likely to be modified by prior water availability. A 24-55 day lagged impact of heavy rainfall was associated with an increase in dengue risk when prior water availability was low, with the greatest incidence rate ratio (IRR) of 1.37 [95% credible interval (CI): 1.02-1.83] occurring at a lag of 27 days. In contrast, a heavy rainfall lag of 7-121 days decreased dengue risk when prior water availability was high, with the lowest IRR of 0.59 (95% CI: 0.43-0.79), occurring at a lag of 45 days. Discussion: These findings may help to reconcile the inconsistent conclusions reached by previous studies and improve our understanding of the complex relationship between heavy rainfall and dengue infection risk.

Prior water availability modifies the effect of heavy rainfall on dengue transmission: a time series analysis of passive surveillance data from southern China.

Background: Given the rapid geographic spread of dengue and the growing frequency and intensity of heavy rainfall events, it is imperative to understand the relationship between these phenomena in order to propose effective interventions. However, studies exploring the association between heavy rainfall and dengue infection risk have reached conflicting conclusions. Methods: In this study, we use a distributed lag non-linear model to examine the association between dengue infection risk and heavy rainfall in Guangzhou, a dengue transmission hotspot in southern China, stratified by prior water availability. Results: Our findings suggest that the effects of heavy rainfall are likely to be modified by prior water availability. A 24-55 day lagged impact of heavy rainfall was associated with an increase in dengue risk when prior water availability was low, with the greatest incidence rate ratio (IRR) of 1.37 (95% credible interval (CI): 1.02-1.83) occurring at a lag of 27 days. In contrast, a heavy rainfall lag of 7-121 days decreased dengue risk when prior water availability was high, with the lowest IRR of 0.59 (95% CI: 0.43-0.79), occurring at a lag of 45 days. Conclusions: These findings may help to reconcile the inconsistent conclusions reached by previous studies and improve our understanding of the complex relationship between heavy rainfall and dengue infection risk.

A Water-Soluble Hydrogen Sulfide Donor Suppresses the Growth of Hepatocellular Carcinoma via Inhibiting the AKT/GSK-3ß/ß-Catenin and TGF-ß/Smad2/3 Signaling Pathways.

Hepatocellular carcinoma (HCC) is a disease with high morbidity, high mortality, and low cure rate. Hyaluronic acid (HA) is widely adopted in tissue engineering and drug delivery. 5-(4-Hydroxyphenyl)-3H-1, 2-dithiol-3-thione (ADT-OH) is one of commonly used H2S donors. In our previous study, HA-ADT was designed and synthesized via coupling of HA and ADT-OH. In this study, compared with sodium hydrosulfide (NaHS, a fast H2S-releasing donor) and morpholin-4-ium (4-methoxyphenyl)-morpholin-4-ylsulfanylidenesulfido-λ5-phosphane (GYY4137, a slow H2S-releasing donor), HA-ADT showed stronger inhibitory effect on the proliferation, migration, invasion, and cell cycle of human HCC cells. HA-ADT promoted apoptosis by suppressing the expressions of phospho (p)-protein kinase B (PKB/AKT), p-glycogen synthase kinase-3ß (GSK-3ß), p-ß-catenin, and also inhibited autophagy via the downregulation of the protein levels of p-Smad2, p-Smad3, and transforming growth factor-ß (TGF-ß) in human HCC cells. Moreover, HA-ADT inhibited HCC xenograft tumor growth more effectively than both NaHS and GYY4137. Therefore, HA-ADT can suppress the growth of HCC cells by blocking the AKT/GSK-3ß/ß-catenin and TGF-ß/Smad2/3 signaling pathways. HA-ADT and its derivatives may be developed as promising antitumor drugs.

Construction and validation of prognostic prediction established on N6-methyladenosine related genes in cervical squamous cell carcinoma.

Background: Cervical cancer (CESC) is the second most common cancer death in middle-aged women. The N6-methyladenosine (m6A) plays an essential role in the epitranscriptomics of cancer and affects immune cell infiltration. Our study used The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) data to construct and validate prognostic prediction established on m6A-related genes in CESC. Methods: We gained gene expression and clinical characteristics from TCGA and GEO. After differentially expression analysis of the m6A-related genes, we identified eight genes of CESC development. Next, we executed consensus clustering to analyze CESC types established on the differential expression of the m6A-related genes and found different subtypes significantly correlate with survival prognosis, immune microenvironment, and PD-L1 expression. Then, based on Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression analysis, a five-gene (IGF2BP1, IGF2BP2, HNRNPA2B1, YTHDF1, RBM15) predictive model was built in the TCGA training cohort. Finally, we checked the predictive model with survival analysis and receiver operating characteristic (ROC) curve both in the training cohort (TCGA) and in the validation cohort (GSE44001). We found the expression and variation of the five genes significantly correlate with immune cell infiltration. Results: The CESC could be divided into subtypes according to eight expression m6A-related genes. Different subtypes are related to various immune cells, immune scores, and the expression of the PD-L1. We develop a risk prediction model: risk score = (0.023558929) * Exp IGF2BP1 + (0.021148829) * Exp IGF2BP2 + (0.045035491) * Exp HNRNPA2B1 + (-0.106566550) * Exp YTHDF1 + (-0.001037932) * Exp RBM15. Moreover, different m6A-related genes significantly correlated with immune cells. Conclusions: The m6A-related genes risk prediction model plays an essential role in predicting CESC patients. The m6A-related genes affected the immune cell infiltration in CESC. These results suggest that the expression of m6A-related genes may influence the immune therapy of CESC and be the potential therapeutic target.

HA-ADT suppresses esophageal squamous cell carcinoma progression via apoptosis promotion and autophagy inhibition.

Esophageal squamous cell carcinoma (ESCC) is a major cause of cancer-related deaths. We have previously connected a non-sulfated glycosaminoglycan, hyaluronic acid (HA), with a common hydrogen sulfide (H2S) donor, 5-(4-hydroxyphenyl)-3H-1,2-dithiol-3-thione (ADT-OH), to reconstruct a novel conjugate, HA-ADT. In this study, we determined the effect of HA-ADT on the growth of ESCC. Our data suggested that HA-ADT exerted more potent effects than sodium hydrosulfide (NaHS, a fast H2S-releasing donor) and morpholin-4-ium (4-methoxyphenyl)-morpholin-4-ylsulfanylidenesulfido-λ5-phosphane (GYY4137, a slow H2S-releasing donor) on inhibiting the viability, proliferation, migration, and invasion of human ESCC cells. HA-ADT increased apoptosis by suppressing the protein expressions of phospho (p)-Ser473-protein kinase B (PKB/AKT), p-Tyr199/Tyr458-phosphatidylinositol 3-kinase (PI3K), and p-Ser2448-mammalian target of rapamycin (mTOR), but suppressed autophagy through the inhibition of the protein levels of p-Ser552-ß-catenin, p-Ser9-glycogen synthase kinase-3ß (GSK-3ß), and Wnt3a in human ESCC cells. In addition, HA-ADT was more effective in terms of the growth inhibition of human ESCC xenograft tumor than NaHS and GYY4137. In conclusion, HA-ADT can suppress ESCC progression via apoptosis promotion and autophagy inhibition. HA-ADT might be efficacious for the treatment of cancer.

Polyethyleneimine incorporated chitosan/α-MnO2 nanorod honeycomb-like composite foams with remarkable elasticity and ultralight property for the effective removal of U(VI) from aqueous solution.

The development of new adsorbents is needed to address the environmental challenges of radioactive wastewater treatment. Herein we reported a novel polyethyleneimine incorporated chitosan/α-MnO2 nanorod honeycomb-like composite (PCM) foam with remarkable elasticity and ultralight property for U(VI) removal. Among different PCM sorbents, PCM-40 possessed the highest sorption capacity for U(VI) due to its highly developed macroporous structure and high content of amine/imine groups. The kinetics were well-simulated by the pseudo-second-order model, indicating chemisorption as the rate-controlling step. The isotherms could be described by the Langmuir model, suggesting mono-layer homogeneous sorption of U(VI). The maximum sorption U(VI) capacity for PCM-40 reaches up to 301.9 mg/g at pH 4.5 and 298 K. The thermodynamic parameters revealed the spontaneous and endothermic nature of the adsorption process. The main sorption mechanism is related to the complexation of uranyl ions with the amine/imine and hydroxyl groups. The high sorption capacity, fast kinetic rate and relatively good selectivity of PCM-40 highlights its promising application in radioactive pollution cleanup.

Selective biosorption of U(VI) from aqueous solution by ion-imprinted honeycomb-like chitosan/kaolin clay composite foams.

The radioactive pollution caused by the discharge of radioactive wastewater poses a serious threat to public health and ecosystem stability owing to its long-term detriments. Herein, the ion-imprinted honeycomb-like chitosan/kaolin clay (ICK) composite foams were successfully fabricated and applied to the selective biosorption of U(VI) from aqueous solution. It was found that the ICK-2 was the best among various ICK foams owing to its well-developed honeycomb-like structure and the presence of abundant functional groups. As compared to the non-imprinted sorbent (NICK-2), the ion-imprinted sorbent (ICK-2) presents higher sorption and better selectivity since it can smartly recognize the target ions. The sorption isotherms was well-fitted with Langmuir model, and the maximum sorption capacity of ICK-2 was evaluated as 286.85 mg/g for U(VI) at 298 K and pH 5.0. The kinetic data could be described by pseudo-second order model. The FTIR and XPS results suggest that both amine and hydroxyl groups are responsible for U(VI) coordination. The ICK-2 presents high sorption capacity, good selectivity and fast kinetic rate, and thus it has potential application for U(VI) separation from radioactive wastewater.

Metabolically healthy obesity increases the prevalence of stroke in adults aged 40 years or older: Result from the China National Stroke Screening survey.

Debate over the cardio-cerebrovascular risk associated with metabolically healthy obesity (MHO) continues. In this study we investigated the association of MHO with the risk of stroke among 221,114 individuals aged 40 years or older based on data from the China National Stroke Screening and Prevention Project (CNSSPP), a nationally representative cross-sectional study, during 2014 to 2015. Different metabolic health and obesity phenotypes were defined according to the Adult Treatment Panel III (ATP III) criteria, where obesity was defined as a body mass index (BMI) ≥28 kg/m2. Logistic regression models were used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for stroke risk associated with different metabolically healthy phenotypes. BMI was used to estimate the mediation effect for metabolic abnormalities to stroke. Compared with the metabolically healthy non-obesity (MHNO) group, individuals with MHO (adjusted OR: 1.21, 95% CI: 1.10,1.33), metabolically unhealthy non-obesity (MUNO) (adjusted OR:1.41, 95% CI: 1.36,1.46), or metabolically unhealthy obesity (MUO) (adjusted OR: 1.70, 95% CI: 1.61,1.80) were found to have an increased risk of stroke. The findings were confirmed robustly by various sensitivity analyses and subgroup analyses. Furthermore, obesity and metabolic abnormalities had an additive interaction for stroke risk with an attributable proportion (AP) of 14.0% in females. BMI played a partial mediating role with the proportion of the effect (PE) at 11.1% in the relationship between metabolic abnormalities and stroke. This study strengthens the evidence that management and interventions in the MHO population may contribute to the primary prevention of stroke.

Hormone Replacement Therapy Reverses Gut Microbiome and Serum Metabolome Alterations in Premature Ovarian Insufficiency.

Objective: We explored the gut microbiome and serum metabolome alterations in patients with premature ovarian insufficiency (POI) and the effects of hormone replacement therapy (HRT) with the aim to unravel the pathological mechanism underlying POI. Methods: Fecal and serum samples obtained from healthy females (HC, n = 10) and patients with POI treated with (n = 10) or without (n = 10) HRT were analyzed using 16S rRNA gene sequencing and untargeted metabolomics analysis, respectively. Peripheral blood samples were collected to detect serum hormone and cytokine levels. Spearman's rank correlation was used to evaluate correlations between sex hormones and cytokines and between the gut microbiota and serum metabolites. To further confirm the correlation between Eggerthella and ovarian fibrosis, the mice were inoculated with Eggerthella lenta (E. lenta) through oral gavage. Results: The abundance of genus Eggerthella significantly increased in the fecal samples of patients with POI compared to that observed in the samples of HCs. This increase was reversed in patients with POI treated with HRT. Patients with POI showed significantly altered serum metabolic signatures and increased serum TGF-ß1 levels; this increase was reversed by HRT. The abundance of Eggerthella was positively correlated with altered metabolic signatures, which were, in turn, positively correlated with serum TGF-ß1 levels in all subjects. Estrogen ameliorated ovarian fibrosis induced by E. lenta in mice. Conclusions: The interactions between the gut microbiota, serum metabolites, and serum TGF-ß1 in patients with POI may play a critical role in the development of POI. HRT not only closely mimicked normal ovarian hormone production in patients with POI but also attenuated gut microbiota dysbiosis and imbalance in the levels of serum metabolites and TGF-ß1, which are reportedly associated with fibrosis. The findings of this study may pave the way for the development of preventive and curative therapies for patients with POI.

Evaluation of cervical length and optimal timing for pregnancy after cervical conization in patients with cervical intraepithelial neoplasia: A retrospective study.

To evaluate the change of cervical length and the best timing for pregnancy after cervical conization in patients with cervical intraepithelial neoplasia (CIN).This was a retrospective study including patients under 40 years with fertility desire treated by cervical conization for CIN. To assess the cervical length, the patients were divided into 2 groups according to different surgery procedure: loop electrosurgical excision procedure (LEEP) and cold knife conisation (CKC). Patients with cervical length < 2.5 cm in CKC group were divided into 2 groups according to whether receiving cervical cerclage. Trans-vaginal ultrasound examination was used to measure cervical length by fixed professional sonographers.In LEEP group, the cervical length preoperative was significantly longer than 3 months postoperatively (3.03 ±â€Š0.45 cm vs 2.84 ±â€Š0.44 cm, P = .000). In CKC group, the cervical length preoperative was significantly longer than 3 and 6 months postoperatively (2.90 ±â€Š0.41 cm vs 2.43 ±â€Š0.43 cm and 2.68 ±â€Š0.41 cm, respectively, P = .000). Cervical length was significantly longer at 12 and 9 months after cerclage compared to that without cerclage. Eighteen patients got pregnant in LEEP group, among which one was pregnant at 5 months postoperatively and had premature delivery. There was 1 inevitable abortion and 1 preterm birth among 39 pregnant patients from CKC group.Patients who have fertility desire with CIN were recommended for pregnancy at 6 and 9 months after LEEP and CKC, respectively. Cerclage effectively prolonged cervical length in patents with that less than 2.5 cm to prevent cervical incompetence.

Changes of Intestinal Microbiota in Ovarian Cancer Patients Treated with Surgery and Chemotherapy.

PURPOSE: Ovarian cancer is the leading cause of death in gynecologic malignancies. Growing evidences demonstrate that a complicated relationship exists between the gut microbiota and cancer treatment. However, there are few studies explored the alterations of gut microbiota in ovarian cancer patients following anti-cancer treatments. Therefore, we aim to analyze the changes of the gut microbiota in ovarian cancer patients treated with radical surgery and chemotherapy. PATIENTS AND METHODS: The microbial genes were examined from a total of 75 fecal samples from 18 ovarian cancer patients, including 10 preoperative fecal samples (Group B), 4 postoperative fecal samples (Group M0), as well as 61 fecal samples after first to fifth cycles of chemotherapy, using 16S rRNA sequencing. RESULTS: Our results showed that fecal samples collected in postoperative (Group M0) exhibited significant decreases in abundance of Bacteroidetes and Firmicutes, while a significant increase in abundance of Proteobacteria compared with preoperative (Group B) fecal samples. LEfSe analysis identified that Bilophila and Faecalibacterium are the key genera in Group B, while Klebsiella and Enterococcus are the key genus in Group M0. Compared with before chemotherapy, the abundance of Bacteroidetes and Firmicutes increased, and the abundance of Proteobacteria decreased after chemotherapy. In addition, anaerobic bacteria, such as Bacteroides, Collinsella and Blautia, exhibited significant increases after chemotherapy. Moreover, we observed that certain bacterial genera were significantly correlated with clinicopathological characteristics of ovarian cancer patients. CONCLUSION: Our study suggested that radical surgery and chemotherapy altered the composition of gut microbiota in ovarian cancer patients. Therapeutic strategies targeting the gut microbiota may be beneficial for the clinical treatment of ovarian cancer.

WTAP is a prognostic marker of high-grade serous ovarian cancer and regulates the progression of ovarian cancer cells.

BACKGROUND: The Wilms' tumor suppressor WT1 is reported to work in a range of physiological processes at both transcriptional and posttranscriptional level. WT1-associating protein (WTAP), a nuclear protein co-localized with splicing factors, also plays a vital role in cellular function and cancer progression. However, little is known about the role of WTAP in ovarian cancer and the underlying mechanism. MATERIALS AND METHODS: To evaluate the expression of WTAP, multiple means were applied in clinical tissues, including immunohistochemistry, quantitative reverse transcriptase PCR (qRT-PCR), and Western blot. Two representative ovarian cancer cell lines (3AO and SKOV3) were used to assess the malignant influence of WTAP on proliferation, apoptosis, and migration. To explore its function, WTAP was additionally down-regulated by lentivirus. RESULTS: High expression of WTAP in high-grade serous ovarian carcinoma (HGSOC) predicted a shorter overall survival (P<0.01). Furthermore, WTAP expression was higher in HGSOC, compared with that in normal ovary group (P<0.01), benign ovarian tumor group (P<0.01), and non-HGSOC group (P<0.05). In HGSOC, high expression of WTAP was significantly related with the lymph node metastasis (P<0.05). In ovarian cancer cell lines, cell proliferation and migration were considerably reduced after WTAP was down-regulated, while apoptotic rate was increased. Moreover, the effect of WTAP in 3AO and SKOV3 might be relevant with MAPK and AKT signaling pathways. CONCLUSION: WTAP is highly expressed in HGSOC, and indicates a worse survival outcome. Therefore, it is highly possible that WTAP has a prognostic implication in the patients of HGSOC. In addition, WTAP down-regulation also plays a tumor suppressor role in 3AO and SKOV3 cell lines.

SNHG15: a promising cancer-related long noncoding RNA.

Cancer is expected to rank as the leading cause of death worldwide due to increasing morbidity and mortality. Long noncoding RNAs (lncRNAs) have been found to play pivotal roles in multiple biological processes, such as transcriptional interference, posttranscriptional regulation and epigenetic modification. Small nucleolar RNA host gene 15 (SNHG15), a snoRNA host gene which produces a short half-lived lncRNA, was reported to be upregulated in tumor cells and participate in the occurrence and development of multiple cancers. And more than half of the SNHG15 research in cancers has been published within the last 2 years. In this review, we summarized the current evidence concerning the biological functions and molecular mechanisms of SNHG15 in various cancers, including gastric, hepatocellular, pancreatic, colorectal, breast, and thyroid cancer, osteosarcoma, glioma, lung cancer, renal cell carcinoma, and epithelial ovarian cancer. SNHG15 plays critical roles in regulation of cell proliferation, migration and invasion of tumors via different potential mechanisms. Moreover, the abnormal expression of SNHG15 was associated with clinical features of patients with cancers. Consequently, SNHG15 could be considered as a promising biomarker for cancer diagnosis, prognosis or treatment.

Hierarchically Nanostructured Fe3O4/C Composite as a Promising Magnetic Targeted Drug Nanocarrier.

Nanostructured Fe3O4/C composites are very attractive for high-performance magnetic targeted drug carriers. Herein, Fe3O4/C composite nanospheres with good dispersity are prepared by a simple one-step hydrothermal synthesis and subsequent heat treatment in Ar. The composite nanospheres consist of clustered primary nanoparticles, and exhibit a hierarchical architecture with a high specific surface area of 119.3 m² g-1. The Fe3O4/C composite nanospheres show a high saturation magnetization value of 101 emu g-1 and good biocompatibility. In particular, the composite nanospheres deliver a large loading content (85.8%) of epirubicin hydrochloride (EPI), resulting from their unique composition and microstructure. More importantly, the release of EPI from the EPI-loaded magnetic carrier (Fe3O4/C-EPI) may be enhanced by both a slightly acidic environment and a rotating magnetic field induced by a simple motor-driven magnet system. The above favorable properties make the hierarchical Fe3O4/C composite sample a promising candidate for magnetic targeting nanocarriers of EPI.

A novel hydrogen sulfide-releasing donor, HA-ADT, suppresses the growth of human breast cancer cells through inhibiting the PI3K/AKT/mTOR and Ras/Raf/MEK/ERK signaling pathways.

Breast cancer is one of the most frequent cancers among women worldwide. Hyaluronic acid (HA) is one of the best biopolymers in terms of safety issues and has been widely used in drug delivery and tissue engineering. 5-(4-hydroxyphenyl)-3H-1,2-dithiol-3-thione (ADT-OH) is a commonly used H2S donor. In this study, we designed and synthesized a conjugate, HA-ADT, by connecting HA with ADT-OH through chemical reactions. Our results indicated that HA-ADT could produce more H2S than NaHS and GYY4137. HA-ADT exerted more potent inhibitory effects than NaHS and GYY4137 in the proliferation, viability, migration, and invasion of human breast cancer cells. Similar trends were observed in the apoptosis and the protein levels of phospho (p)-PI3K, p-AKT, p-mTOR, H-RAS, p-RAF, p-MEK, and p-ERK in human breast cancer cells. Furthermore, HA-ADT exhibited more powerful inhibitory effects on the growth of human breast cancer xenograft tumors in nude mice. In conclusion, HA-ADT could suppress the growth of human breast cancer cells through the inhibition of the PI3K/AKT/mTOR and RAS/RAF/MEK/ERK signaling pathways. HA-ADT and its derivatives might be of great potential in the treatment of different types of cancer.

Short-term recurrence and distant metastasis following robotic-assisted radical hysterectomy with pelvic lymphadenectomy and chemoradiotherapy for a stage IB1 cervical adenocarcinoma: A case report and literature review.

RATIONALE: Postoperative concurrent chemoradiotherapy (CCRT) is considered the standard treatment for patients with early stage cervical cancer with positive pelvic nodes, yet many patients with high-risk factors treated with CCRT still suffered from distant metastasis. PATIENT CONCERNS: A 48-year-old woman presented with abnormal vaginal bleeding for 5 months. Thin prep liquid-based cytology test revealed low-grade squamous intraepithelial lesion and the human papillomavirus test (type 58) was positive. Magnetic resonance imaging showed a mass measuring 17 × 15 mm, located predominantly in the posterior lip of uterine cervix. Colposcopy biopsy reported adenocarcinoma of the cervix. DIAGNOSIS: Cervical adenocarcinoma stage IB1. INTERVENTIONS: A robotic-assisted radical hysterectomy with pelvic lymphadenectomy was performed followed by postoperative CCRT. OUTCOMES: Distant metastasis was occurred shortly after postoperative CCRT and the patient died 9 months from initial diagnosis. LESSONS: In cases of new nodule in bones, lower abdominal distension and bloating occurring shortly after CCRT in early stage cervical adenocarcinoma, clinicians should bear in mind that recurrence should be considered. Development of more effective treatment to improve the survival outcomes of patients with postoperative metastasis is needed.

Combined laparoscopic and hysteroscopic management of cesarean scar pregnancy with temporary occlusion of bilateral internal iliac arteries: A case report and literature review.

RATIONALE: Cesarean scar pregnancy is a rare event that carries a risk of heavy hemorrhage and emergency hysterectomy. Many treatment modalities have been reported, but with no consensus. Here we report a case of combined laparoscopic and hysteroscopic treatment with temporary occlusion of the bilateral internal iliac arteries. PATIENT CONCERNS: A 28-year-old woman presented with amenorrhea diagnosed as an 11-week cesarean scar pregnancy after an unsuccessful abortion. The patient's serum human chorionic gonadotropin level was 40,542 mIU/mL. Magnetic resonance imaging revealed a mass measuring 5 × 4.5 cm over the anterior uterine isthmus. DIAGNOSE: Type III cesarean pregnancy. INTERVENTIONS: Diagnostic and operative laparoscopy were performed to remove the pregnancy tissue and repair the scar dehiscence after temporary occlusion of the bilateral internal iliac arteries, followed by hysteroscopy to confirm no pregnancy remnants and to free intrauterine adhesions. OUTCOMES: Intraoperative and postoperative bleeding were minimal. The postoperative recovery was uneventful. Human chorionic gonadotropin normalized after 3 weeks. LESSONS: Temporary occlusion of the bilateral internal iliac arteries seems to be a good strategy to reduce hemorrhage in cesarean scar pregnancy. Hysteroscopy is necessary to deal with intrauterine lesions.

Interleukin enhancer binding factor 2 is a prognostic biomarker for breast cancer that also predicts neoadjuvant chemotherapy responses.

Interleukin enhancer binding factor 2 (ILF2) participates in several aspects of DNA and RNA metabolism and regulates gene expression at multiple levels; however, its role in breast cancer remains undefined. The variant statuses of ILF2 in human breast cancer were evaluated using the COSMIC database. Altered ILF2 expression in normal breast tissue relative to cancer tissue and in breast cancer patients with different clinicopathological characteristics, molecular subtypes, clinical outcomes and chemotherapy responses were examined using the Oncomine, GOBO, Kaplan-Meier plotter and GEO datasets. To explore possible biological networks connected to ILF2 in breast cancer, we performed ingenuity pathway analysis on ILF2-related differentially expressed genes. We found that many breast cancers had increased ILF2 copy number variations and increased ILF2 expression. We also observed that elevated ILF2 expression was correlated with aggressive features, such as high histological grade, BRCA1 mutations, and the triple-negative/basal-like subtype, which resulted in shorter survival in these cases. Moreover, ILF2 expression predicted responses to anthracycline/taxane-based treatment. Ingenuity pathway analysis revealed that ILF2-related biological functions included promoting cell survival, viability, and proliferation, as well as cell cycle progression and DNA repair. Certain well-known oncogenes (MYC and HGF), cytokines (CSF2, IFNG and IL5) and microRNAs (miR-21, miR-155-5p and let-7) may participate in the ILF2 expression network in breast cancer. In summary, ILF2 is involved in the development and progression of breast cancer and may be a predictive biomarker for better responses to anthracycline/taxane-based treatments.