AC-ModNet: Molecular Reverse Design Network Based on Attribute Classification.

Deep generative models are becoming a tool of choice for exploring the molecular space. One important application area of deep generative models is the reverse design of drug compounds for given attributes (solubility, ease of synthesis, etc.). Although there are many generative models, these models cannot generate specific intervals of attributes. This paper proposes a AC-ModNet model that effectively combines VAE with AC-GAN to generate molecular structures in specific attribute intervals. The AC-ModNet is trained and evaluated using the open 250K ZINC dataset. In comparison with related models, our method performs best in the FCD and Frag model evaluation indicators. Moreover, we prove the AC-ModNet created molecules have potential application value in drug design by comparing and analyzing them with medical records in the PubChem database. The results of this paper will provide a new method for machine learning drug reverse design.

Serum prolactin and gonadal hormones in hemodialysis women: a meta-analysis.

BACKGROUND: A meta-analysis followed by PRISMA 2020 statement was performed aiming to present a whole prolactin and sex hormone profile in hemodialysis women. METHODS: Literatures were searched in PubMed, Cochrane library, Embase, and Web of science before March 11, 2023. Trial sequential analysis (TSA) was performed to test the conclusiveness of this meta-analysis. Egger's test and trim-and-fill analysis was used to test publication bias. We took standardized mean difference (SMD) as pool effect of hormones values including prolactin (PRL), follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2) and progesterone (P). This study was registered in PROSPERO and the number was CRD42023394503. RESULTS: Twenty-two articles from 13 countries were analyzed. Combining the results of TSA and meta-analysis, we found that compared with healthy control, hemodialysis women had higher PRL, follicular FSH and LH values and lower P levels (PRL: I2 = 87%, SMD 1.24, 95% CI: 0.79-1.69, p < 0.00001; FSH: I2 = 0%, SMD 0.34, 95% CI: 0.13-0.55, p = 0.002; LH: I2 = 39%, SMD 0.64, 95% CI: 0.34-0.93, p < 0.00001; P: I2 = 30%, SMD - 1.62, 95% CI: -2.04 to -1.20, p < 0.00001). What's more, compared with women after renal transplantation, hemodialysis women had higher PRL levels (I2 = 0%, SMD 0.51, 95% CI: 0.25-0.78, p = 0.0001). There was not enough evidence to draw a conclusion on the comparison of hormones between regular and irregular menses hemodialysis women. Egger's test and trim-and-fill analysis didn't show significant publication bias. CONCLUSIONS: Hemodialysis women had higher serum PRL, follicular phase FSH, LH and lower serum P values compared with healthy control. PRL values of hemodialysis women were also higher than that of women after renal transplantation.

Internal Grasper and Magnetic Anchoring Guidance System in Gynecologic Laparoendoscopic Single-site Surgery: A Case Series.

STUDY OBJECTIVE: To evaluate and report preliminary data after the use of an internal grasper and magnetic anchoring guidance system (MAGS) to allow free movement and optimal triangulation in the abdominal cavity during gynecologic laparoendoscopic single-site surgery (LESS). DESIGN: A prospective, single-center case series. SETTING: The First Affiliated Hospital of Xi'an Jiaotong University. PATIENTS: Eighteen female patients underwent MAGS-assisted LESS with an internal grasper. INTERVENTIONS: A single surgeon performed MAGS-assisted LESS on patients with benign gynecologic diseases while documenting operative time, device insertion time, surgeon assessment of technical adaptation, patient-evaluated pain and cosmetic outcomes, adverse events, and blood loss. MEASUREMENTS AND MAIN RESULTS: Eighteen patients underwent transumbilical MAGS-assisted LESS using an internal grasper from November 1, 2019, to December 31, 2019. The mean operative time and insertion time were 98.7 minutes and 1 minute, respectively. The use of MAGS was easily mastered by the surgeon and considered consistently useful in overcoming the limitations of LESS. The patients reported average pain scores of 4.8, 2.3, and 0.5 immediately, 24 hours, and 1 week after surgery, respectively. All patients expressed satisfaction with the postoperative cosmetic results. No serious complications were observed. The mean blood loss was 43.6 mL. CONCLUSION: MAGS-assisted LESS is easy to deploy and use for benign gynecologic disease and seems to result in positive outcomes. Larger randomized controlled trials are warranted.

New doctor-patient communication learning software to help interns succeed in communication skills.

BACKGROUND: Nowadays, the research of doctor-patient communication is becoming increasingly important not only in China but also around the world. METHODS: The study designs a type of learning software to train the interns to advance their communication skills, and whose validity for improving doctor-patient communication in self-controlled trials is evaluated. With the aid of the new learning software, the self-controlled tests were carried out among 183 interns to assess the quality of their communication skill acquisition. The learning effectiveness of the preparation stage, information collection, information given, patient understanding, and inquisition ending was evaluated with the Set Elicit Give Understand End (SEGUE) framework after 3 months of training. RESULTS: More interns (37.16% vs. 10.98%, P < 0.001) could accurately identify the psychosocial or emotional factors contributing to the diseases. An increased number of interns (42.62% vs. 10.40%, P < 0.001) were able to openly discuss lifestyle issues and prevention strategies with patients. The study also revealed that interns who had completed training tended to allow patients more time to describe their feelings and concerns about their illnesses. In addition, more of the trained interns roved capable of being caring and respectful to patients and showing empathetic communication behavior (53.01% vs. 26.59%, P < 0.001). CONCLUSIONS: The doctor-patient communication software may help the interns known more about communication skills.

High-expressed ACAT2 predicted the poor prognosis of platinum-resistant epithelial ovarian cancer.

BACKGROUND: Acetyl-CoA acetyltransferase 2 (ACAT2) is a lipid metabolism enzyme and rarely was researched in epithelial ovarian cancer (EOC). METHODS: ACAT2 expressions were confirmed in two pairs of cell lines (A2780 and A2780/DDP, OVCAR8 and OVCAR8/DDP) from Gene Expression Omnibus database by bioinformatics analysis, and in A2780 and A2780/DDP cell lines by quantitative real-time polymerase chain reaction and western blotting. Tissue samples were stained by immunohistochemistry and scored for ACAT2 expression. The relationships between ACAT2 expression and clinicopathological characteristics were analyzed by χ2 test. The prognosis of ACAT2 was analyzed by the log-rank tests and Cox regression models. RESULTS: ACAT2 was remarkably upregulated in the above drug-resistant cell lines by mRNA (all P < 0.05) and protein expression (P = 0.026) than those in sensitive ones. Patients were classified as ACAT2-high (n = 51) and ACAT2-low (n = 26) according to immunohistochemical score. ACAT2 expression had a significantly inverse correlation with FIGO stage (P = 0.030) and chemo-response (P = 0.041). A marginal statistical significance existed in ACAT2 expression and ascites volume (P = 0.092). Univariate analysis suggested that high-expressed ACAT2 was associated with decreased platinum-free interval (PFI) (8.57 vs. 14.13 months, P = 0.044), progression-free survival (PFS) (14.12 vs. 19.79 months, P = 0.039) and overall survival (OS) (36.89 vs. 52.40 months, P = 0.044). Multivariate analysis demonstrated that ACAT2 expression (hazard ratio = 2.18, 95% confidence interval: 1.15-4.11, P = 0.017) affected OS independently, rather than PFI and PFS. CONCLUSION: The expression of ACAT2 in A2780/DDP and OVCAR8/DDP was higher than the corresponding A2780 and OVCAR8. High-expressed ACAT2 was associated with advanced FIGO stage, chemo-resistance, and decreased PFI, PFS and OS. It was an independent prognostic factor of OS in EOC.

Intelligent classification of cardiotocography based on a support vector machine and convolutional neural network: Multiscene research.

OBJECTIVE: To propose a computerized system utilizing multiscene analysis based on a support vector machine (SVM) and convolutional neural network (CNN) to assess cardiotocography (CTG) intelligently. METHODS: We retrospectively collected 2542 CTG records of singleton pregnancies delivered at the maternity ward of the First Affiliated Hospital of Xi'an Jiaotong University from October 10, 2020, to August 7, 2021. CTG records were divided into five categories (baseline, variability, acceleration, deceleration, and normality). Apart from the category of normality, the other four different categories of abnormal data correspond to four scenes. Each scene was divided into training and testing sets at 9:1 or 7:3. We used three computer algorithms (dynamic threshold, SVM, and CNN) to learn and optimize the system. Accuracy, sensitivity, and specificity were performed to evaluate performance. RESULTS: The global accuracy, sensitivity, and specificity of the system were 93.88%, 93.06%, and 94.33%, respectively. In acceleration and deceleration scenes, when the convolution kernel was 3, the test data set reached the highest performance. CONCLUSION: The multiscene research model using SVM and CNN is a potential effective tool to assist obstetricians in classifying CTG intelligently.

Positive Rate of Malignant Cells in Endometrial Cytology Samples of Ovarian Cancer, Fallopian Tube Cancer, and Primary Peritoneal Cancer Patients: A Systematic Review and Meta-Analysis.

To estimate the feasibility of diagnosing ovarian cancer, fallopian tube cancer, and primary peritoneal cancer through endometrial cytology, we performed a systematic review and meta-analysis to calculate the pooled positive rate of malignant cells in endometrial cytology samples. We queried PubMed, EMBASE, Medline, and Cochrane Central Register of Controlled Trails from inception to November 12, 2020 for studies estimating positive rates of malignant cells in endometrial cytology samples from patients with ovarian cancer, fallopian tube cancer, and primary peritoneal cancer. The positive rates of the included studies were calculated as pooled positive rate through meta-analyses of proportion. Subgroup analysis based on different sampling methods was conducted. Seven retrospective studies involving 975 patients were included. Pooled positive rate of malignant cells in endometrial cytology specimens of ovarian cancer, fallopian tube cancer, and primary peritoneal cancer patients was 23% (95% CI: 16% - 34%). Statistical heterogeneity between the included studies was considerable (I2 = 89%, P < 0.01). The pooled positive rates of the group of brushes and the group of aspiration smears were 13% (95% CI: 10% - 17%, I2 = 0, P = 0.45) and 33% (95% CI: 25% - 42%, I2 = 80%, P < 0.01), respectively. Although endometrial cytology is not an ideal diagnostic tool for ovarian cancer, fallopian tube cancer, and primary peritoneal cancer, it is a convenient, painless, and easy-to-implement adjunct to other tools. Sampling method is one of the factors that affect the detection rate.

Micro-histology combined with cytology improves the diagnostic accuracy of endometrial lesions.

BACKGROUND: In the study, we aimed to evaluate the ability of micro-histology combined with cytology to improve the quality of slides and diagnose endometrial lesions. METHODS: Endometrial specimens were collected from Li Brushes. Every specimen was prepared for micro-histological and cytological slides, using cell block (CB) and liquid-based cytology (LBC) technologies. Semi-quantitative scoring system was used to evaluate the qualities of slides. CB slides were assessed by 5-category scoring system. Diagnostic accuracy was calculated in LBC, CB, and LBC + CB groups based on the histological gold standard. Endometrial atypical hyperplasia, and endometrial cancer were considered positive, whereas others were considered negative. RESULTS: A total of 167 patients were enrolled. CB slides were inferior to LBC slides only in cellularity (p < 0.001), but superior in the other six parameters (all p < 0.001). The satisfaction rate of micro-histology accounted for 92.3%. The accuracy index in the CB group was higher than in the LBC group in terms of sensitivity (85.5% vs. 82.7%) and specificity (98.9% vs. 95.7%). The sensitivity and specificity in the LBC + CB group were increased to 94.2% and 99.0%, respectively. CONCLUSIONS: The quality of micro-histological slides was higher than that of cytological slides. By combining micro-histology with cytology, higher accuracy was achieved for endometrial lesions diagnosis.

The sealing effect of magnetic-sealing uterine manipulator in isolated uterus from patients with early-stage cervical cancer: a pre-clinical study.

OBJECTIVE: Traditional uterine manipulator is considered as the main reason for short survival of patients with early-stage cervical cancer during minimally invasive surgery. This study aims to assess the sealing effect of magnetic-sealing uterine manipulators (MUMs) in isolated uteruses. METHODS: The study was performed on isolated uterus from patients with early-stage cervical cancer who underwent open abdominal radical hysterectomy between November 2019 to April 2021. Right-angle forceps closure tests (groups 1 and 3) were defined as control tests. One experimental MUM closure test (group 2) and 2 control tests were respectively carried out in each of the isolated uterus. DNA ploidy analysis system was used to observe exfoliated cells. Statistical analysis was performed using Wilcoxon signed-rank test to assess the sealing effect of MUM. RESULTS: We identified 36 patients. No regional node metastasis was discovered and only one tumor was larger than 4.0 cm in diameter. The mean of exfoliated tumor cells in groups 1, 2, and 3 were 1, 1, and 2, respectively. There was no significant difference in the quantity of exfoliated cells between groups 1 and 3 (p=0.476), so the results of the 2 groups were merged. Subsequently, a significant difference was observed between combined right-angle forceps closure tests and MUM closure tests (p=0.022). CONCLUSION: The sealing effect of MUM was better than that of right-angle forceps. MUM can effectively seal cervical cancer cells in the cup cover, avoiding the dissemination of tumor cells. TRIAL REGISTRATION: Chinese Clinical Trial Register Identifier: ChiCTR1900026012.

Prevalence and Distribution of Osteopenia in Chinese Population: A System Review and Meta-Analysis.

Background: The number of patients with osteoporosis ranks first in the world in China and as a precursor state of osteoporosis, the number and incidence of osteopenia are much higher than that of osteoporosis. This meta-analysis was conducted to evaluate the incidence and distribution of osteopenia in adults in mainland of China over 10 years to provides reference for the early prevention of osteoporosis and policymaking. Methods: Relevant data were extracted from the databases including CNKI, Wanfang, VIP, Web of Science, PubMed, EMBASE, and Medline about the surveys on osteoporosis and bone loss from 2010 to 2021 by searching. The random effects model was adopted for Meta-analysis, and the funnel plot was used to test publication bias. Results: Forty-seven literatures were included in this study, covering 27 provinces and 38 regions in the mainland of China, with the study of 135,688 cases, showing that the prevalence of osteopenia in adults in the past decade was 28.3%(95% CI 24-33%), aged 40∼60 yr old, reaching the highest level. The incidence of osteopenia in males was higher than that in females (P<0.05), without significant difference in south and north China. Conclusion: There is a large population with osteopenia in China, especially middle-aged population, both men and women should pay attention to osteopenia to delay its further progression.

Blood Bacterial 16S rRNA Gene Alterations in Women With Polycystic Ovary Syndrome.

Background: Evidence proved the association between gut microbiome dysbiosis and polycystic ovary syndrome (PCOS) in metabolic disorder, decreased fertility, and hyperandrogenism. However, alterations in blood microbiome of PCOS remained unknown. Objective: This study aims to measure the blood microbiome profile of PCOS patients compared with healthy controls by 16S rRNA sequencing and to investigate its association with PCOS. Methods: In this case-control study, bacterial DNA in blood of 24 PCOS patients and 24 healthy controls was investigated by 16S rRNA gene sequencing using the MiSeq technology. Alpha and beta diversity were used to analyze within-sample biodiversity and similarity of one group to another, respectively. Linear discriminant analysis effect size (LEfSe) was calculated to determine biomarkers between groups. Kyoto Encyclopedia of Genes and Genomes (KEGG) functional prediction was performed at genera level. Result: Alpha diversity of blood microbiome decreased significantly in women with PCOS, and beta diversity analysis demonstrated a major separation between the two groups. In the PCOS group, the relative abundance of Proteobacteria, Firmicutes, and Bacteroidetes decreased significantly, while Actinobacteria increased significantly. Cladogram demonstrated the microbiome differences between the two groups at various phylogenic levels. Meanwhile, linear discriminant analysis (LDA) presented significant decreases in Burkholderiaceae, Lachnospiraceae, Bacteroidaceae, Ruminococcaceae, and S24-7 and significant increases in Nocardioidaceae and Oxalobacteraceae of the PCOS group. KEGG pathway analysis at genera level suggested that 14 pathways had significant differences between the two groups. Conclusion: Our findings demonstrated that blood microbiome had a significantly lower alpha diversity, different beta diversity, and significant taxonomic variations in PCOS patients compared with healthy controls.

Relapsed and refractory yolk sac tumor of the peritoneum (mesentery): A case report and literature review.

Background: Extragonadal yolk sac tumor (YST) of peritoneum is a rare malignancy. Case Description: A 37-year-old Chinese woman was admitted to hospital with a 3-month abdominal pain 4 years ago. Alpha-fetoprotein was 228,499.0 ng/mL. Computed tomography scan revealed a massive mass in the left lower abdomen. Exploratory laparotomy exposed a huge mesenteric mass. Then, mesenteric tumor resection, partial sigmoidectomy, and single-lumen fistula of sigmoid colon were performed. Postoperative pathologic diagnosis reported a stage IV mesenteric YST. After surgery, the patient received 6 courses of BEP (bleomycin, etoposide, and cisplatin) chemotherapy. Seven months later, the patient underwent stoma reversion of sigmoid colon and received another 2 courses of BEP chemotherapy. Three months after the last chemotherapy, liver metastases were diagnosed. She subsequently underwent 3 surgeries, radiotherapy for liver metastases, and multiple tiers of palliative chemotherapies, including TP (docetaxel and carboplatin), VIP (ifosfamide, cisplatin, and etoposide), TIP (paclitaxel, ifosfamide, and cisplatin), and so on. After the third surgery (left hepatic lesion resection and right iliac lymph node resection), she received 4 cyclic chemotherapies of BEP´ (boanmycin, etoposide, and cisplatin) without pulmonary toxic side effects. Conclusion: Postoperative histopathology and immunohistochemistry are gold standards for the diagnosis of peritoneal YST. The standard first-line treatment is surgery plus BEP chemotherapy. Second-line therapy regimens and above, including VIP and TIP, improve the prognosis of recurrent germ cell tumors. This relapsed and refractory patient with peritoneal YST benefits from the secondary BEP´ chemotherapy.

Extremely high serum CA19-9 level along with elevated D-dimer in assisting detection of ruptured ovarian endometriosis.

BACKGROUND: To clarify clinical importance of serum CA19-9, CA-125, and plasma D-dimer (D-D) levels in detecting spontaneously ruptured ovarian endometriosis (OE). MATERIALS AND METHODS: We retrospectively examined 173 patients with endometriosis out of 735 cases of OE between 2013 and 2019. Among these, 21 cases were diagnosed as "spontaneously ruptured" after surgery, while the remaining cases were unruptured. Venous blood was collected pre-operatively to detect CA19-9, CA-125, and D-D levels. A receiver operating characteristic curve analysis was applied to test clinical value of each marker. RESULTS: Among the 21 patients with ruptured OE, 16 had a history of pelvic cysts, 19 claimed sudden onsets of lower abdominal pain, and fluid accumulation were detected in cul-de-sac in only six participants by ultrasound. For serological investigation, both CA19-9 and D-D were significantly elevated in the ruptured OE group (343.09 ± 367.67 U/ml vs. 36.84 ± 40.01 U/ml, 3.39 ± 4.90 mg/L vs. 0.43 ± 0.29 mg/L, both p < .0001). The area under curve (AUC) value for the combination of CA19-9 and D-D was 0.975 (95% CI, 0.939 - 0.993), with specificity of 96.69%, and sensitivity of 85.71%. The combination of CA-125, CA19-9 and D-D showed the highest AUC value that up to 0.976 (95% CI, 0.940-0.993), with sensitivity of 95.24%, and specificity of 87.50%. CONCLUSION: The combination of CA19-9 and D-D can be chosen as an effective and economical indicators to identify patients with spontaneously ruptured OE in pre-operation assessment. However, from the perspective of differential diagnosis, the combination of CA-125, CA19-9 and D-D is the best choice. Key messagesTaking into account the economic effect, the combination of CA19-9 and D-D can be chosen as an effective indicators to identify patients with spontaneously ruptured OE in pre-operation assessment.From the perspective of differential diagnosis, the combination of CA-125, CA19-9 and D-D is the best choice to identify patients with spontaneously ruptured OE.

A Computer-Aided Diagnosis System of Fetal Nucleated Red Blood Cells With Convolutional Neural Network.

CONTEXT.­: The rapid recognition of fetal nucleated red blood cells (fNRBCs) presents considerable challenges. OBJECTIVE.­: To establish a computer-aided diagnosis system for rapid recognition of fNRBCs by convolutional neural network. DESIGN.­: We adopted density gradient centrifugation and magnetic-activated cell sorting to extract fNRBCs from umbilical cord blood samples. The cell-block method was used to embed fNRBCs for routine formalin-fixed paraffin sectioning and hematoxylin-eosin staining. Then, we proposed a convolutional neural network-based, computer-aided diagnosis system to automatically discriminate features and recognize fNRBCs. Extracting methods of interested region were used to automatically segment individual cells in cell slices. The discriminant information from cellular-level regions of interest was encoded into a feature vector. Pathologic diagnoses were also provided by the network. RESULTS.­: In total, 4760 pictures of fNRBCs from 260 cell-slides of 4 umbilical cord blood samples were collected. On the premise of 100% accuracy in the training set (3720 pictures), the sensitivity, specificity, and accuracy of cellular intelligent recognition were 96.5%, 100%, and 98.5%, respectively, in the test set (1040 pictures). CONCLUSIONS.­: We established a computer-aided diagnosis system for effective and accurate fNRBC recognition based on a convolutional neural network.

Clinically Applicable Pathological Diagnosis System for Cell Clumps in Endometrial Cancer Screening via Deep Convolutional Neural Networks.

OBJECTIVES: The soaring demand for endometrial cancer screening has exposed a huge shortage of cytopathologists worldwide. To address this problem, our study set out to establish an artificial intelligence system that automatically recognizes and diagnoses pathological images of endometrial cell clumps (ECCs). METHODS: We used Li Brush to acquire endometrial cells from patients. Liquid-based cytology technology was used to provide slides. The slides were scanned and divided into malignant and benign groups. We proposed two (a U-net segmentation and a DenseNet classification) networks to identify images. Another four classification networks were used for comparison tests. RESULTS: A total of 113 (42 malignant and 71 benign) endometrial samples were collected, and a dataset containing 15,913 images was constructed. A total of 39,000 ECCs patches were obtained by the segmentation network. Then, 26,880 and 11,520 patches were used for training and testing, respectively. On the premise that the training set reached 100%, the testing set gained 93.5% accuracy, 92.2% specificity, and 92.0% sensitivity. The remaining 600 malignant patches were used for verification. CONCLUSIONS: An artificial intelligence system was successfully built to classify malignant and benign ECCs.

Efficacy and Safety of Placebo During the Maintenance Therapy of Ovarian Cancer in Randomized Controlled Trials: A Systematic Review and Meta-analysis.

Introduction: This meta-analysis evaluated the efficacy and safety of placebo during the maintenance therapy of ovarian cancer (OC) patients in randomized controlled trials (RCTs). Methods: A comprehensive literature review was performed for RCTs published up to and including August 2020 from four electronic databases. We analyzed the efficacy and safety in the control arms of the maintenance therapy in advanced OC patients. Hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) of progression-free survival (PFS) and overall survival (OS) were estimated in the placebo arms and the observation arms, respectively, using the Frequency Framework method. We also calculated the incidences of common adverse effects (AEs) in the placebo arms. Results: In total, 41 articles with 20,099 (4,787 in the placebo arms, 3,420 in the observation arms, and 11,892 in the experiment arms) patients were included in this meta-analysis. Compared with observation, placebo did not improve or reduce PFS (HR, 1.02; 95% CI, 0.87-1.20; P = 0.81) and OS (HR, 1.02; 95% CI, 0.89-1.16; P = 0.76) of OC patients, while other treatments, except for radiotherapy, significantly improved PFS and OS (all P < 0.05). The incidences of AEs produced by placebo were 94.03% in all grades and 20.22% in grade ≥3. The incidences of AEs were 29.75% in fatigue, 26.38% in nausea, 24.34% in abdominal pain, 18.92% in constipation, 16.65% in diarrhea, 14.55% in vomiting, 13.89% in hypertension, and 13.14% in headache. Conclusions: Placebo did not improve or reduce the PFS and OS benefits of OC patients in RCTs but increased the incidences of AEs.

Hypermethylated CDO1 and ZNF454 in Cytological Specimens as Screening Biomarkers for Endometrial Cancer.

We aimed to estimate the diagnostic value of DNA methylation levels in cytological samples of endometrial cancer (EC) and atypical hyperplasia (AH). Two hypermethylated genes, namely, cysteine dioxygenase type 1 (CDO1) and zinc finger protein 454 (ZNF454), in patients with EC were identified from The Cancer Genome Atlas database. In 103 endometrial histological specimens (the training set), the methylation levels of candidate genes were verified by quantitative methylation-specific polymerase chain reaction (qMSP). The methylation levels of another 120 cytological specimens (the testing set) were evaluated. Sensitivity (Se), specificity (Sp), accuracy, and area under the curve (AUC) were determined, with diagnosis verified by histopathological results. CDO1 and ZNF454 verified hypermethylation in histological specimens of patients with EC and AH compared with those with benign and normal endometrium (P < 0.001). In cytological specimens, hypermethylated CDO1 showed 86.36% Se and 90.79% Sp with the cutoff value of 6.0 to distinguish between malignant and benign groups; ZNF454 showed 79.55% Se and 93.42% Sp with the cutoff value of 7.1. When the two genes were combined, Se increased to 90.91% and Sp was 86.84%. AUC reached 0.931 (95% CI: 0.885-0.976). The diagnostic accuracy with cytology had no significant difference with endometrial tissue (P = 0.847 for CDO1, P = 0.108 for ZNF454, and P = 0.665 for their combination). Hypermethylated CDO1 and ZNF454 in endometrial cytology showed high Se, Sp, and AUC to detect EC and AH. Methylation analysis of endometrial cytology is promising biomarker for the screening of EC and AH.

A Systematic Review and Meta-Analysis of the Prognostic Impact of Pretreatment Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Parameters in Patients with Locally Advanced Cervical Cancer Treated with Concomitant Chemoradiotherapy.

BACKGROUNDS: The purpose of this paper is to investigate the prognostic value of fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) parameters in patients treated with concurrent chemoradiotherapy (CCRT) for locally advanced cervical cancer (LACC). METHODS: Studies that met the following criteria were retrieved from PubMed and Embase: patients treated with CCRT for LACC; FDG PET/CT scans performed before CCRT treatment; and a detected relationship between the parameters of FDG PET/CT and the prognosis of patients. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were used to estimate the overall survival (OS) or event-free survival (EFS). RESULTS: In total, 14 eligible studies with 1313 patients were included in this meta-analysis. Patients with a high maximum standardized uptake value (SUVmax) have a shorter OS than those with a low SUVmax (HR = 2.582, 95% = CI 1.936-3.443, p < 0.001). Primary tumor SUVmax values (HR = 1.938, 95% CI = 1.203-3.054, p = 0.004) were significantly correlated with EFS, with a relatively high heterogeneity (I2 = 84% and I2 = 69.4%, respectively). Based on the limited data, the combined HR for EFS with the highest primary tumor total lesion glycolysis (TLG) and metabolic tumor volume (MTV) was 1.843 (95% CI = 1.100-3.086, p = 0.02) and 2.06 (95% CI = 1.21-3.51, p = 0.007), respectively. Besides, the combined HR for OS with the highest nodal SUVmax was 2.095 (95% CI = 2.027-2.166, p < 0.001). CONCLUSION: A high primary SUVmax has a significant correlation with the OS and EFS of patients treated with CCRT for LACC and may therefore serve as a prognostic predictor. Due to the limited data, to explore the correlation between survival and TLG, MTV, and nodal SUVmax, further large-scale prospective studies are needed.

A polygenic methylation prediction model associated with response to chemotherapy in epithelial ovarian cancer.

To identify potential aberrantly differentially methylated genes (DMGs) correlated with chemotherapy response (CR) and establish a polygenic methylation prediction model of CR in epithelial ovarian cancer (EOC), we accessed 177 (47 chemo-sensitive and 130 chemo-resistant) samples corresponding to three DNA-methylation microarray datasets from the Gene Expression Omnibus and 306 (290 chemo-sensitive and 16 chemo-resistant) samples from The Cancer Genome Atlas (TCGA) database. DMGs associated with chemotherapy sensitivity and chemotherapy resistance were identified by several packages of R software. Pathway enrichment and protein-protein interaction (PPI) network analyses were constructed by Metascape software. The key genes containing mRNA expressions associated with methylation levels were validated from the expression dataset by the GEO2R platform. The determination of the prognostic significance of key genes was performed by the Kaplan-Meier plotter database. The key genes-based polygenic methylation prediction model was established by binary logistic regression. Among accessed 483 samples, 457 (182 hypermethylated and 275 hypomethylated) DMGs correlated with chemo resistance. Twenty-nine hub genes were identified and further validated. Three genes, anterior gradient 2 (AGR2), heat shock-related 70-kDa protein 2 (HSPA2), and acetyltransferase 2 (ACAT2), showed a significantly negative correlation between their methylation levels and mRNA expressions, which also corresponded to prognostic significance. A polygenic methylation prediction model (0.5253 cutoff value) was established and validated with 0.659 sensitivity and 0.911 specificity.

Detection of carcinoma in serous effusions: a review.

A malignant serous effusion is one of the most common complications of advanced tumors, indicating a poor prognosis and having a profound impact on diagnosis, treatment, and prognosis. It is of great significance to identify benign and malignant effusions quickly and accurately. Both cellular and non-cellular components in the effusion can be employed for detection, diagnostic methods are necessary to obtain a definite diagnosis and more relevant information such as tumor classification. In this review, we focus on the comparison of several widespread cytological preparation methods, enrichment technology of exfoliated cells, and present tests for serous effusions, mainly including routine and special stains, immunocytochemistry, electron microscopy, enzyme-linked immunosorbent assay, flow cytometry, and molecular analysis.