Nanoengineered Gallium Ion Incorporated Formulation for Safe and Efficient Reversal of PARP Inhibition and Platinum Resistance in Ovarian Cancer.

Platinum-based chemotherapy remains the main systemic treatment of ovarian cancer (OC). However, the inevitable development of platinum and poly (adenosine diphosphate-ribose) polymerase inhibitor (PARPi) resistance is associated with poor outcomes, which becomes a major obstacle in the management of this disease. The present study developed "all-in-one" nanoparticles that contained the PARPi olaparib and gallium (Ga) (III) (olaparib-Ga) to effectively reverse PARPi resistance in platinum-resistant A2780-cis and SKOV3-cis OC cells and in SKOV3-cis tumor models. Notably, the olaparib-Ga suppressed SKOV3-cis tumor growth with negligible toxicity. Moreover, the suppression effect was more evident when combining olaparib-Ga with cisplatin or carboplatin, as evaluated in A2780-cis and SKOV3-cis cells. Mechanistically, the combined treatment induced DNA damage, which elicited the activation of ataxia telangiectasia mutated (ATM)/AMT- and Rad3-related (ATR) checkpoint kinase 1 (Chk1)/Chk2 signal transduction pathways. This led to the arrest of cell cycle progression at S and G2/M phases, which eventually resulted in apoptosis and cell death due to unrepairable DNA damage. In addition, effective therapeutic responses to olaparib-Ga and cisplatin combination or olaparib-Ga and carboplatin combination were observed in SKOV3-cis tumor-bearing animal models. Altogether, the present findings demonstrate that olaparib-Ga has therapeutic implications in platinum-resistant OC cells, and the combination of olaparib-Ga with cisplatin or carboplatin may be promising for treating patients with OC who exhibit resistance to both PARPi and platinum.

Clinicopathologic Features and Frozen Diagnostic Pitfalls of Bronchiolar Adenoma/Ciliated Muconodular Papillary Tumors (BA/CMPTs).

To describe the histologic features of bronchiolar adenoma/ciliated muconodular papillary tumors (BA/CMPTs) and analyze the pitfalls in diagnosis from frozen sections. A total of 208 frozen and permanent sections of BA/CMPTs from Shanghai Chest Hospital from July 2018 to July 2021 were retrospectively analyzed. The median age of BA/CMPT patients was 65 years (15 to 79 y), and women accounted for 61.62% (122/198). The median size of BA/CMPTs was 0.6 cm (range 0.2 to 2 cm), of which 88.94% were small (≤1 cm, 185/208). In terms of location, the right lower lobe accounted for 44.23% (92/208), and the left lower lobe accounted for 33.65% (70/208). In 10 patients with 2 independent BA/CMPTs, 5 lesions were located in the left lower lobe and 4 in the right lower lobe. A total of 86.06% of the CT images of BA/CMPT showed solid/subsolid nodules (179/208). Among 208 tumors, 68.75% were distal type (143/208), and 31.25% were proximal type (65/208). The qualitative error rate of frozen sections was 21.33% (32/150), of which the distal type accounted for 75% (24/32); most of them were misdiagnosed as invasive adenocarcinoma during frozen diagnosis. The frozen diagnosis of BA/CMPTs might result in misdiagnosis as invasive adenocarcinoma. A careful search for characteristics of BA/CMPT, such as bilayer epithelial cells with basal cells and a lack of cellular atypia and invasive growth patterns, may be helpful for frozen diagnosis.

Predicting Physical Activity in Chinese Pregnant Women Using Multi-Theory Model: A Cross-Sectional Study.

BACKGROUND: Physical activity (PA) brings many benefits to pregnant women and fetuses; however, the majority of pregnant women do not participate actively in PA during pregnancy. OBJECTIVES: This study aimed to: (1) assess the utility of Multi-Theory Model (MTM) to explain the intentions of PA behavior in Chinese pregnant women; (2) analyze the predictors in initiating and maintaining PA behavior based on MTM. METHODS: A cross-sectional study including pregnant women was conducted from March to June 2022 at a university hospital in Hangzhou, Zhejiang Province, China. Participants completed measures that included a self-developed demographic questionnaire and a 29-item MTM questionnaire. Descriptive statistics and stepwise multiple regression were used to analyze the data. The reliability was assessed by Cronbach's alpha and test-retest stability. The construct validity was evaluated by using exploratory factor (EFA) analysis and confirmatory factor analysis (CFA). RESULTS: A total of 450 pregnant women participated in this study. The score of the magnitude of intention to initiate and maintain PA behavior during pregnancy was 2.30 (1.08) and 2.24 (1.09). The overall Cronbach's alpha value was 0.857. A four-factor structure for initiation model and a three-factor structure for maintenance model were determined. Results of the CFA confirmed construct validity of subscales (initiation model: χ2 = 206.123, df = 140, p < 0.001, χ2/df = 1.472, RMSEA = 0.046, SRMR = 0.0432, GFI = 0.913, CFI = 0.982; maintenance model: χ2 = 49.742, df = 29, p < 0.001, χ2/df = 1.715, RMSEA = 0.057, SRMR = 0.0432, GFI = 0.958, CFI 0.985). The result of regression indicated that participatory dialogue (ß = 0.030; p = 0.002), behavioral confidence (ß = 0.128; p < 0.001), changes in physical environment (ß = 0.041; p = 0.005), trimester (ß = -0.192; p = 0.001), and Gestational Diabetes Mellitus (GDM) (ß = 0.408; p < 0.001) explained 52.1% variance in initiating PA behavior. Emotional transformation (ß = 0.197; p < 0.001), practice for change (ß = 0.083; p = 0.001), changes in social environment (ß = 0.063; p < 0.001), pre-pregnancy exercise habit (ß = -0.251; p = 0.001), and GDM (ß = 0.298; p = 0.003) were significantly associated with pregnant women's intentions to maintain PA behavior and explained 49.1% variance. CONCLUSIONS: The constructs of MTM were effective in explaining the intention to initiate and maintain PA behavior among Chinese pregnant women.

Cross-cultural adaptation and psychometric properties of the Chinese version of the postpartum depression literacy scale.

Background and aim: The postpartum depression literacy (PoDLi) of perinatal women is closely related to the occurrence, recognition, and treatment of postpartum depression, therefore valid instruments for evaluating the level of PoDLi are of great significance for both research and clinical practice. This study aimed to cross-culturally adapt the postpartum depression literacy scale (PoDLiS) into Chinese and to test its psychometric properties among Chinese perinatal women. Materials and methods: A cross-sectional study was conducted from April to May 2022 in a tertiary hospital in Hangzhou, Zhejiang Province, China. 619 out of the 650 perinatal women that were approached via a convenience sampling method completed the Chinese version of the PoDLiS (C-PoDLiS). Content validity [the content validity index of items (I-CVI) and scale-level content validity index (S-CVI)] was evaluated by an expert panel. Psychometric properties, including item analysis, structure validity (exploratory factor analysis, confirmatory factor analysis), convergent and discriminant validity, reliability (internal consistency, test-retest reliability), criterion validity (concurrent validity, predictive validity), and floor/ceiling effect were examined. Results: The final version of C-PoDLiS is a six-factor structure consisting of 27 items, which explained 61.00% of the total variance. Adequate content validity (I-CVI = 0.833-1.00, S-CVI = 0.920) was ensured by the expert panel. The modified confirmatory factor analysis model revealed that the 6-factor model fitted the data well (χ2/df = 1.532, root mean square error of approximation = 0.042, goodness of fit = 0.900, incremental fit index = 0.949, comparative fit index = 0.948, Tucker-Lewis index = 0.940). The total Cronbach's α was 0.862, the total McDonald's ω was 0.869, and the test-retest reliability coefficient was 0.856. Results of convergent validity (average variance extracted = 0.486-0.722) and discriminant validity provided good or acceptable psychometric support. Significant correlations between scores of the C-PoDLiS and Mental health literacy scale (r = 0.155-0.581, p < 0.01) and Attitudes toward seeking professional psychological help short form scale (r = 0.361-0.432, p < 0.01) supported good concurrent and predictive validity, respectively. No floor/ceiling effect was found. Conclusion: The C-PoDLiS was demonstrated to be a sound instrument with good reliability and validity for evaluating Chinese perinatal women's PoDLi levels. Its use in the future can facilitate data aggregation and outcome comparisons across different studies on this topic.

Web-based interventions for pregnant women with gestational diabetes mellitus: a systematic review and meta-analysis protocol.

INTRODUCTION: Gestational diabetes mellitus (GDM) is one of the most prevalent diseases during pregnancy, which is closely associated with many short-term and long-term maternal and neonatal complications and can incur heavy financial burden on both families and society. Web-based interventions have been used to manage GDM because of the advantages of high accessibility and flexibility, but their effectiveness has remained inconclusive. This systematic review and meta-analysis aims to comprehensively investigate the multidimensional effectiveness of web-based interventions for pregnant women with GDM, thereby aiding implementation decisions in clinical settings. METHODS AND ANALYSIS: This systematic review protocol strictly adheres to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines. Six electronic databases (PubMed, Web of Science, Cochrane Central Register of Controlled Trials, Embase, CINAHL and PsycINFO) will be comprehensively searched from their inception to 26 January 2022 to identify randomised controlled trials and controlled clinical trials regarding the efficacy of web-based interventions for pregnant women with GDM on glycaemic control, behavioural outcomes, cognitive and attitudinal outcomes, mental health, maternal and neonatal clinical outcomes, and medical service utilisation and costs. Two reviewers will independently conduct the study selection, data extraction and quality assessment. The methodological quality of included studies will be assessed using the Effective Public Health Practice Project assessment tool. The overall meta-analyses for each of the interested outcomes will be performed if the outcome data are sufficient and provides similar effect measures, as well as subgroup analyses for glycaemic control indicators based on the different types of intervention format, interactivity and technology. We will conduct a qualitative synthesis for studies that cannot be quantitatively synthesised. ETHICS AND DISSEMINATION: Ethics approval is not required for this review as no human participants will be involved. The results will be disseminated via a peer-reviewed journal or an academic conference. PROSPERO REGISTRATION NUMBER: CRD42022296625.

Decreased green autofluorescence of lung parenchyma is a biomarker for lung cancer tissues.

It is highly valuable to discover novel biomarkers for differentiating noninvasively the cancerous tissues from the nonneoplastic tissues of lung cancer. In current study, we determined the green autofluorescence (AF) of the pulmonary parenchyma of lung cancer patients, indicating that decreased green AF of pulmonary parenchyma may be the biomarker of this type: First, the green AF intensity of the cancerous tissues was significantly lower than that of the nonneoplastic tissues of the lung cancer patients; second, the green AF intensity of the nonneoplastic tissues of the lung squamous cell carcinoma was significantly lower than that of the lung adenocarcinoma; and third, "decreased green AF intensity" could be used for differentiating the nonneoplastic tissues and the cancerous tissues. Collectively, our study has suggested that decreased green AF of lung parenchyma is a biomarker for differentiating the cancerous tissues from the nonneoplastic tissues of lung cancer.

Safety and feasibility of oral carbohydrate consumption before cesarean delivery on patients with gestational diabetes mellitus: A parallel, randomized controlled trial.

AIM: To investigate the safety and feasibility of taking low-concentration carbohydrate solution at 2 h before induction of anesthesia for gestational diabetes mellitus (GDM) patients. METHODS: GDM patients undergoing cesarean section were randomly assigned to experimental group (n = 43) and control group (n = 42). Two hours before induction of anesthesia, participants in experimental group orally received 300 mL low-concentration carbohydrate solution, while those in control group received equivalent warm water. Blood glucose and serum insulin were measured at 2 h before induction of anesthesia, right before induction of anesthesia, and the morning of postoperative day 1. Neonatal blood glucose level was monitored at birth. Maternal gastrointestinal function and well-being were assessed perioperatively. RESULTS: The levels of blood glucose and serum insulin right before induction of anesthesia in the experimental group were significantly higher than those in the control group. There were four cases with hypoglycemia in the experimental group and 19 cases in the control group right before induction of anesthesia (9.3% vs 45.2%, p < 0.001). The incidence of neonatal hypoglycemia was 2.3% in the experimental group and 7.1% in the control group with no significance. Hunger score of the participants between the two groups right before induction of anesthesia was significantly different. No aspiration, nausea, and vomiting occurred in both groups before, during, and after surgery. No significant difference was found in the time to the first flatus and abdominal distension between the two groups. CONCLUSION: Taking low-concentration carbohydrate solution is safe and feasible for patients with GDM undergoing elective cesarean section.

circEYA1 Functions as a Sponge of miR-582-3p to Suppress Cervical Adenocarcinoma Tumorigenesis via Upregulating CXCL14.

Circular RNAs (circRNAs) function as efficient microRNA (miRNA) sponges that regulate gene expression in the pathogenesis of many human malignancies. However, their roles in cervical adenocarcinoma remain largely unknown. In this study, we aimed to seek novel circRNAs that regulate cervical adenocarcinoma carcinogenesis and to explore their regulatory mechanisms as well as clinical significance. We identified that 24 circRNAs were differentially expressed in cervical adenocarcinoma tissues by RNA sequencing. Among them, circEYA1 was the most significantly downregulated circRNA in cervical adenocarcinoma. In cervical adenocarcinoma cells, circEYA1 overexpression led to suppression of cell viability and colony formation, promotion of apoptosis, and a decrease of the xenograft tumor growth. The mechanism underlying these observations is that circEYA1 functioned as a sponge of miR-582-3p and abrogated its suppression of CXCL14 expression. Consistently, miR-582-3p inhibition phenocopied the biological effects of circEYA1 overexpression in cervical adenocarcinoma cells. Moreover, miR-582-3p overexpression reversed the suppressive behaviors of circEYA1 in vitro and in vivo. In addition, the expression, correlation, and clinical diagnostic value of circEYA1/miR-582-3p/CXCL14 were confirmed in 198 clinical cervical tissue samples. In summary, our findings highlight a novel tumor suppressive role of circEYA1 in cervical adenocarcinoma tumorigenesis and may provide a potential diagnostic marker and therapeutic target for patients with cervical adenocarcinoma.

An effective inflation treatment for frozen section diagnosis of small-sized lesions of the lung.

BACKGROUND: The accuracy of intraoperative pathological diagnosis of small-sized pulmonary nodules including ground-glass opacity (GGO) is important for the surgeon to choose a suitable surgical procedure. Diagnosis of the small-sized lesions of the lung by frozen section (FS) is very difficult for the pathologist because of limited FS technology. Here we tested an effective inflation treatment for FS to improve the diagnostic accuracy of small-sized lung lesions. METHODS: The lung specimens were derived from 113 patients who underwent the surgery at Shanghai Chest Hospital in 2018-2019. The specimens were randomly divided into two groups-uninflated or inflated with diluted embedding medium (Tissue-Tek OCT; Sakura Finetek-USA, CA). The qualities of the FSs were compared with that of corresponding permanent paraffin sections. The FS diagnoses were compared with the final pathologic diagnoses of corresponding permanent sections. RESULTS: Our results showed that the quality of FS of lung tissue was excellent after inflation with diluted embedding medium (1:1). The total consistency between diagnosis of inflated FS and final pathological diagnosis was 85.7%. In control group, however, the consistency was only 70.2%. When the lesions were less than 1cm, the consistency between diagnosis of inflated FS and final pathological diagnosis was 90.3%, compared to 64.9% consistency in uninflated group (P=0.014, <0.05). When the lesions' computed tomography (CT) measurement threshold ≤-350 HU, the consistency between diagnosis of inflated FS and final pathological diagnosis was 88% compared to 73.2% consistency in uninflated group (P=0.071, >0.05). Accuracy, sensitivity and specificity were observed about 90% for adenocarcinoma in situ (AIS), whereas it is drop to more than 80% for minimally invasive adenocarcinoma (MIA) in inflated FS. CONCLUSIONS: Inflation with diluted embedding medium (1:1) could make lung tissue expand well during FS. By using this method, small-sized lesions (especially less than 1 cm) could be correctly diagnosed to enable adequate surgical procedure, and evaluation of which can be easily based on the intraoperative pathological diagnosis. The small lesions especially AIS could be readily identified on FS. Therefore, this method improves the diagnostic accuracy of FSs for small-sized lung lesions, and has important practical consequences for further therapy.

Ex-vivo imaging and plaque type classification of intracranial atherosclerotic plaque using high resolution MRI.

BACKGROUND AND AIMS: Recent development of high resolution MRI techniques have enabled imaging of intracranial atherosclerotic plaque in vivo. However, identifying plaque composition remains challenging given the small size and the lack of histological validation. This study aims to quantify the relaxation times of intracranial plaque components ex vivo at 3 T and to determine whether multi-contrast MRI could classify intracranial plaque according to the American Heart Association classification with histological validation. METHODS: A total of 53 intracranial arteries with atherosclerotic plaques from 20 cadavers (11 male, age 73.8 ± 10.9) were excised. Quantitative T1/T2/T2* mapping sequences and multi-contrast fast-spin echo sequences (T1, T2, proton-density weighted and short time inversion recovery) were acquired. Plaque components including: fibrous cap, lipid core, fibrous tissue, calcification, and healthy wall were segmented on histology, and their relaxation times were derived from quantitative images. Two radiologists independently classified plaque type blinded to the histology results. RESULTS: Relaxation times of plaque components are distinct and different. T2 and T2* values of lipid core are lower than fibrous cap (p = 0.026 & p < 0.0001), but are comparable with fibrous tissue and healthy wall (p = 0.76 & p = 0.42). MRI reliably classified plaque type compared with histology (κ = 0.69) with an overall accuracy of 80.7%. The sensitivity and specificity using MRI to identify fibro-lipid atheroma (type IV-V) was 94.8% and 77.1%, respectively. Inter-observer agreement was excellent (κ = 0.77). CONCLUSION: Intracranial plaque components have distinct and different relaxation times at 3 T. High-resolution MRI is able to characterize intracranial plaque composition and classify plaque types ex vivo at 3 T.