Perinatal outcomes of twin emergency cerclage: comparison with expectant treatment and singleton emergency cerclage.

The present study aimed to evaluate the perinatal outcomes and influencing factors in twin pregnancies undergoing emergency cervical cerclage. The present retrospective cohort study included clinical data that were recorded between January 2015 and December 2021 at The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University (China). The study included data from 103 pregnancies (26 twin and 77 singleton pregnancies) that underwent emergency cerclage and 17 twin pregnancies that underwent expectant treatment. The median gestational age of twin emergency cerclage was significantly lower than that of singleton emergency cerclage, but higher than that of expectant treatment (28.5, 34.0 and 24.0 weeks, respectively). The median interval to delivery of twin emergency cerclage was significantly lower than that of singleton emergency cerclage, but significantly higher than that of expectantly treated twin pregnancies (37.0, 78.0 and 7.0 days, respectively).IMPACT STATEMENTWhat is already known on this subject? An important cause of premature birth is cervical insufficiency. Cervical cerclage extends the gestational period of women with cervical insufficiency. According to 2019 SOGC's No. 373-Cervical Insufficiency and Cervical Cerclage, both twin and single pregnancies benefit from emergency cerclage. However, there is minimal information about the pregnancy outcomes of emergency cerclage in twin pregnancies.What the results of this study add? This study shows that the outcomes of pregnancy in twin pregnancies undergoing emergency cerclage were better than that of expectant treatment but worse than that in singleton pregnancies undergoing emergency cerclage.What the implications are of these findings for clinical practice and/or further research? In this study, pregnant women with cervical insufficiency in twin pregnancies can benefit from emergency cerclage, we should treat those pregnant women as early as possible.

The effects of intrauterine growth on physical and intellectual development of one-year-old infants: a study on monochorionic twins with selective intrauterine growth restriction.

This study aimed to evaluate physical and intellectual development of one-year-old infants of monochorionic twins with selective intrauterine growth restriction (sIUGR). A total of 31 pairs of sIUGR twins ageing 1 year old were included in the study. Each pair of sIUGR twins was divided into low birthweight-twin group (L-twin group) and high birthweight-twin group (H-twin group) according to twins' birthweight. The differences in height, weight, head circumstance and body mass index (BMI) in each stage were statistically significant for all measures from birth until 1 year old (p < .05), and there was a disappointed catch-up growth in lighter twins. Psychomotor development index (PDI) and mental development index (MDI) at 1 year old were significantly different between the two groups (p < .05). Stepwise regression analysis showed that the effects of weight on both PDI and MDI were statistically significant (p < .05). Intrauterine growth inconsistencies in monochorionic twins with sIUGR persist until the first year of life and affect low-birthweight infants' physical and intellectual development.Impact StatementWhat is already known on this subject? Selective intrauterine growth restriction in monochorionic twins increases the risks of intrauterine foetal demise, preterm birth, caesarean delivery and adverse neonatal outcomes, especially in the smaller foetus.What do the results of this study add? Previous studies have concentrated on the clinical management of sIUGR, while little attention has been paid to the growth and development of twins after birth. Given the adverse neurobiological effects of suboptimal nutrition on the brain development, it is important to determine whether IUGR causes long-term cognitive deficits and physical retardation. The current study has assessed the physical and intellectual development of one-year-old infants of monochorionic twins with sIUGR.What are the implications of these findings for clinical practice and/or further research? Intrauterine growth inconsistencies in monochorionic twins with sIUGR persist until the first year of life and affect low-birthweight infants' physical and intellectual development. Further research on the longer-term effects of sIUGR is needed.

Physical growth and intelligence development of discordant dizygotic twins from birth to preschool age: a prospective cohort study.

BACKGROUND: The majority of studies are limited to adverse perinatal outcomes and poor cognitive abilities in the short term in discordant monochorionic twins. METHODS: To determine whether small and large discordant dizygotic twins differ in physical growth and intelligence development and weight and height from birth up to 6 years of age were measured in 34 dizygotic twin pairs with ≥ 20% birth weight discordance. Mental developmental index (MDI) and psychomotor developmental index (PDI) were calculated at 1 year, while the Wechsler Intelligence Scale for Children-IV (WISC-IV) full-scale intelligence quotient (IQ) was assessed at the age of 6. RESULTS: The difference in height and weight in each stage differed significantly from birth to 72-months-old (P < 0.05), although there was disappointing catch-up growth in smaller twins. PDI but not MDI at 1 year of age was significantly different between the two groups (P < 0.05), and smaller twins experienced higher psychomotor retardation rates (P < 0.05). Also, the influence of height and weight on PDI was statistically significant (P < 0.05). No significant difference was detected in the WISC-IV full-scale IQ at the age of 6; however, the full-scale IQ may be affected by the history of suffocation and the S/D value (P = 0.011, P = 0.022). CONCLUSIONS: Intrauterine fetal growth and development lead to birth weight differences in twins and sustain an impact on the children's physical growth in height and weight from birth to preschool age, causing psychomotor developmental differences at 1 year of age. However, the differences in psychomotor development decrease gradually by the age of 6.

Pulmonary Nodule Clinical Trial Data Collection and Intelligent Differential Diagnosis for Medical Internet of Things.

In this paper, the medical Internet of things (IoT) is used to pool data from clinical trials of pulmonary nodules, and on this basis, intelligent differential diagnosis techniques are investigated. A filtered orthogonal frequency division multiplexing model based on polarisation coding is proposed, where the input data are fed to a modulator after polarisation cascade coding, and the system performance is analysed under a medical Internet of things modulated additive Gaussian white noise channel. The above polarisation-coded filtered orthogonal frequency division multiplexing system components are applied to electroencephalogram (EEG) signal transmission, to which a threshold compression module and a vector reconstruction module are added to address the system power burden associated with the acquisition and transmission of large amounts of real-time EEG data in the medical IoT. In the threshold compression module, the inherent characteristics of EEG signals are analysed, and the generated EEG data are decomposed into multiple symbolic streams and compressed by applying different thresholds to improve the compression ratio while ensuring the quality of service of the application. A deep neural network-based approach is proposed for the detection and diagnosis of lung nodules. Automatic identification and measurement of simulated lung nodules and the corresponding volumes of nodules in images under different conditions are applied. The sensitivity of each AIADS in identifying lung nodules under different convolution kernel conditions, false positives (FP), false negatives (FN), relative volume errors (RVE), the miss detection rate (MDR) for different types of lung nodules, and the performance of each system in predicting the four types of nodules are calculated. In this paper, an interpretable multibranch feature convolutional neural network model is proposed for the diagnosis of benign and malignant lung nodules. It is demonstrated that the proposed model not only yields interpretable lung nodule classification results but also achieves better lung nodule classification performance with an accuracy rate of 97.8%.

miR-498/DNMT3b Axis Mediates Resistance to Radiotherapy in Esophageal Cancer Cells.

Objective: To explore the role of miR-498 in the radiotherapy resistance of esophageal cancer (EC) and its underlying mechanism. Methods: In vivo models of EC tissues with radioresistance or radiosensitivity were isolated from 72 EC patients who received radiotherapy. In vitro models were established after irradiation of KYSE30 cells. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot were employed to measure the expression levels of miR-498 and DNMT3b in EC cells sensitive or resistant to irradiation. Then, protein expression of DNMT3b was verified by immunohistochemistry. The cell viability, colony formation rate, and cell apoptotic rate of EC were correspondingly assessed by CCK-8, colony formation assay, and Annexin V/PI (propidium iodide) double staining. Western blot was utilized to perform the expression levels of PI3K, p-PI3K, AKT, and p-AKT in EC cell lines after irradiation. Results: Highly expressed DNMT3b and lowly expressed miR-498 were found in EC tissues. EC tissues with radiosensitivity had higher miR-498 level and lower DNMT3b expression than EC tissues with radioresistance. Overexpression of miR-498 or knockdown of DNMT3b enhanced the radiosensitivity of EC cells. DNMT3b was a target gene of miR-498. DNMT3b diminished the radiosensitization of miR-498 in EC cells. Conclusions: MiR-498 enhances the sensitivity of EC cells to radiation by DNMT3b inhibition, and exerts biological functions by inactivating the PI3K/AKT signaling pathway.

Subclinical Hypothyroidism with Negative for Thyroid Peroxidase Antibodies in Pregnancy: Intellectual Development of Offspring.

Background: The adverse impact of maternal negative TPOAb of gestational subclinical hypothyroidism (SCH-TPOAb-) on the development of the offspring has not yet been clearly identified. A lingering controversy exists over the treatment of SCH-TPOAb- diagnosed during pregnancy. Therefore, this study was designed to evaluate the intellectual development of children of mothers who had SCH-TPOAb-. Methods: A number of 139 children were recruited; 112 children were born to SCH TPOAb- and 27 children were born to euthyroid TPOAb- mothers. Based on the mothers' thyrotropin (TSH) levels during pregnancy and whether or not they received levothyroxine (LT4) treatment, the children were assigned to four groups: Group A (2.5 mIU/L < TSH ≤4.0 mIU/L, n = 31) and Group B (4.0 mIU/L < TSH ≤10.0 mIU/L, n = 26), whose mothers were treated with LT4 before eight gestational weeks, and Group C (2.5 mIU/L < TSH ≤4.0 mIU/L, n = 27) and Group D (4.0 mIU/L < TSH ≤10.0 mIU/L, n = 28), whose mothers received no treatment. A total number of 27 children whose mother's serum TSH was <2.5 mIU/L and were TPOAb- during their pregnancy served as the control group (Group E). The intellectual development of two-year-old children was assessed and compared using the Gesell Development Diagnosis Scale. Results: The developmental quotient (DQ) in Group D was 8.67 lower than this in Group E (p < 0.001). More specifically, gross motor quotient, fine motor quotient, adaptability quotient (ABQ), language quotient (LQ), and individual social behavior quotient (ISBQ) of DQ in Group D were significantly lower than those in Group E. No significant differences were observed in DQ among Group A, Group B, Group C, and Group E (p > 0.05). Spearman's rank correlation analysis showed that DQ, FMQ, ABQ, LQ, and ISBQ were significantly negatively correlated with the TSH level (r = -0.417, -0.253, -0.273, -0.436, and -0.272; p < 0.05). In addition, multivariate logistic regression analysis revealed that mothers' education (short education), mothers' education (medium education), and TSH level (4.0 mIU/L < TSH ≤10.0 mIU/L) were both risk factors affecting the intellectual development of the offspring (p < 0.05). Conclusion: The effects of the intellectual development of the offspring with SCH-TPOAb- are related to the level of TSH. Standardized treatment for SCH-TPOAb- pregnant women before eight gestational weeks, whose TSH level was from 4.0 to 10.0 mIU/L, may significantly improve the intellectual development levels of the approximately two-year-old offspring. Although our study was a historical cohort study, the data analyzed provide the foundation for further investigation. Further prospective intervention trials with large numbers of participants are needed to confirm our conclusions. The Clinical Trial Registration number is 2021-K-84-02.

Prognostic and Therapeutic Significance of Circulating Tumor Cell Phenotype Detection Based on Epithelial-Mesenchymal Transition Markers in Early and Midstage Colorectal Cancer First-Line Chemotherapy.

PURPOSE: Epithelial-mesenchymal transition (EMT) is related to the process of metastasis and challenges the detection of circulating tumor cells (CTCs) based on epithelial cell adhesion molecules. Circulating tumor cells (CTCs) have been proven to be a prognostic indicator of colorectal cancer (CRC). Although there is evidence that CTC heterogeneity based on EMT markers is associated with disease progression, no standard recommendations have been established for clinical practice. This study is aimed at evaluating the prognostic significance of dynamic CTC detection based on EMT for early and midstage colorectal cancer patients. METHODS: 101 patients with early to midterm CRC were admitted from January 2016 to September 2018. All patients underwent CRC radical surgery and standard chemotherapy. Patients in the postchemotherapy were able to epithelial mesenchymal transformed (EMT) CTC testing in peripheral blood using the CanPatrol™ system. Multiple CTC tests were performed according to patient's own condition and different follow-up time points. Based on patient's basic information and follow-up data, the Kaplan-Meier method was utilized to establish the progression-free survival model, and the log-rank test was utilized to compare the survival rates between the two groups. RESULT: Total CTC change of the patient is the best method to predict whether progression-free survival progresses in tumor patients (Area = 0.857). The second detection of total number of CTCs (P < 0.01) detected after chemotherapy, epithelial CTCs (P = 0.032), the increased total number of CTCs (P < 0.01), and the increased number of mesenchymal CTCs (P = 0.015) are significantly related with patient's poor progression-free survival. CONCLUSION: Analysis of the second CTC count and classification after follow-up are more related to the survival prognosis of the tumor. The joint analysis of CTC dynamic monitoring data is a good tool to judge patient's survival prognosis.

Diagnostic value of pulse oximetry combined with cardiac auscultation in screening congenital heart disease in neonates.

OBJECTIVE: This study aimed to investigate the feasibility and reliability of pulse oximetry combined with cardiac auscultation in screening neonatal congenital heart disease (CHD). METHODS: This was a retrospective, observational, screening study. All newborns included in the study were at the Second Affiliated Hospital of Wenzhou Medical University from July 2019 to January 2020. Primary screening of CHD was conducted by pulse oximetry combined with cardiac auscultation assays. Indices, including sensitivity, specificity, the positive/negative predictive value, the positive/negative likelihood ratio, and the diagnostic odds ratio, were calculated. The area under the relative operating characteristic curve of the subjects was measured. RESULTS: A total of 3327 neonates were enrolled, among whom 139 were diagnosed with CHD and the incidence of CHD was 4.2%. The sensitivity, specificity, diagnostic odds ratio, and area under the relative operating characteristic curve of pulse oximetry combined with cardiac auscultation were 89.9%, 94.7%, 169.0, and 0.923, respectively. CONCLUSIONS: Pulse oximetry combined with cardiac auscultation is a novel screening method with acceptable accuracy and feasibility for neonatal CHD. This combination method is worth promoting widely.

Short-term effects of delivery methods on postpartum pelvic floor function in primiparas: a retrospective study.

BACKGROUND: The present study sought to investigate the short-term effects of different delivery methods on postpartum pelvic floor function in Chinese primiparas. METHODS: Primiparous women who delivered a full-term, cephalic, singleton infant at our hospital between January 1, 2018 and August 15, 2019 were recruited into this study. All women underwent pelvic floor function screening at 6-8 weeks postpartum. Tests included postpartum Pelvic Organ Prolapse Quantification (POP-Q) score, incidence of urinary incontinence, pelvic floor muscle (PFM) strength, and Pelvic Floor Distress Inventory Questionnaire-Short Form 20 (PFDI-20) score. RESULTS: A total of 284 postpartum women were recruited into the study. Of the participants, 147 had undergone vaginal delivery, 37 had undergone intrapartum cesarean delivery (ICD), and 100 had undergone elective cesarean delivery (ECD). Points Aa, Ba, Ap, and Bp showed a greater degree of prolapse in the vaginal delivery group than in the ECD group (P≤0.05). UI was less prevalent in ECD group relative to the vaginal delivery group (P≤0.05). Tonic PFM contraction was weaker in the vaginal delivery group than in the ECD and ICD groups (P≤0.05). Significant differences were also observed between the vaginal delivery group and the ECD group with respect to PFDI-20 scores (P≤0.05). CONCLUSIONS: Compared with vaginal delivery, ECD was strongly linked to a lower risk of pelvic organ prolapse (POP) and UI, stronger tonic PFM strength, and lower PFDI-20 scores. ECD confers relatively better protection against pelvic floor dysfunction (PFD) than does ICD.

Kiwi Root Extract Inhibits the Development of Endometriosis in Mice by Downregulating Inflammatory Factors.

PURPOSE: To determine whether the kiwi root extract inhibits the development of endometriosis in mice by suppressing inflammatory factors. MATERIALS AND METHODS: The mouse model of endometriosis was induced by surgery after which the mice were continuously injected with the drug for 14 days. On the 14th day, the mice were sacrificed, and the peritoneal fluid was obtained for enzyme-linked immunosorbent assay. Endometrial ectopic tissue was weighed and analyzed by tissue immunochemistry, RT-PCR, western blotting, and gelatin zymography experiment. RESULTS: Kiwi root extract significantly reduced endometriotic lesion volume and downregulated the proinflammatory cytokines IL-6, IL-8, IL-1ß, and TNF-α, as well as the angiogenic factor VEGF-A. It also inhibited the mRNA and protein expression of COX-1 and COX-2, IL-6, TGF-ß1, EP2 receptor, and ER-ß in endometriotic lesions but did not affect the expression of MMP-9 and MMP-2. CONCLUSIONS: Kiwi root extract could significantly inhibit the growth of surgery-induced endometriosis in mice. Our results suggest that the kiwi root extract may inhibit the development and progression of ectopic endometrium through disruption of neovascularization and reducing inflammation, which may be beneficial in treating this common gynecological disease.

Transcription factor YY1 enhances the stemness of lung cancer cells by stabilizing hypoxia factor HIF-1α under a hypoxic microenvironment.

The hypoxic microenvironment can facilitate the tumor progression, and transcription factor YY1 holds promoting effects in various tumors. This work aims to investigate whether YY1 is involved in hypoxia-induced stemness of lung cancer cells. We showed that hypoxic microenvironment induced the expression of HIF-1α and YY1, and the stemness of lung cancer cells, which was attenuated by YY1 knockdown. Additionally, we found that YY1 regulates the hypoxia-induced stemness in a HIF-1α-dependent manner, but independent on p53 expression. Further analysis revealed that YY1 physically interacted with HIF-1α protein and stabilized HIF-1α protein. Our work indicates a novel YY1/HIF-1α axis regulating the stemness of lung cancer cells.

Meta-analysis of the genetic association between maternal GNB3 C825T polymorphism and risk of pre-eclampsia.

BACKGROUND: The relationship between the C825T polymorphism of GNB3 (encoding G-protein ß3 subunit) and pre-eclampsia risk is unclear. OBJECTIVE: To systematically explore the association between GNB3 C825T and pre-eclampsia. SEARCH STRATEGY: PubMed, EMBASE, Google Scholar, and Chinese National Knowledge Infrastructure (CNKI) databases were searched to September 1, 2020, using keywords including "GNB3 C825T" and "pre-eclampsia". SELECTION CRITERIA: Case-control and cohort studies investigating the relationship between GNB3 C825T polymorphism and pre-eclampsia were included. DATA COLLECTION AND ANALYSIS: Two reviewers collected the data independently and calculate odds ratios (ORs) with 95% confidence intervals (CIs). MAIN RESULTS: The meta-analysis involved eight studies from seven publications, including 2071 cases and 3419 controls. Overall analysis showed that GNB3 C825T was associated with increased pre-eclampsia risk in the recessive model (OR, 1.21; 95% CI, 1.01-1.44; P = 0.04). Subgroup analysis stratified by Hardy-Weinberg equilibrium revealed a relationship between GNB3 C825T and increased risk of pre-eclampsia in the allelic (OR, 1.66; 95% CI, 1.34-2.05; P < 0.001), homozygous (OR, 2.12, 95% CI, 1.04-4.32; P  = 0.04), dominant (OR, 1.91; 95% CI, 1.18-3.11; P = 0.009), and recessive (OR, 1.70; 95% CI, 1.03-2.81; P = 0.04) models. CONCLUSIONS: Maternal GNB3 C825T polymorphism seems to be a risk factor for pre-eclampsia.

Serum miR-195-5p is upregulated in gestational diabetes mellitus.

BACKGROUND: Gestational diabetes mellitus (GDM) is defined as varying degrees of glucose intolerance with an onset or first recognition during pregnancy in women without previously diagnosed diabetes. Accumulating evidence indicates that miRNAs exert crucial roles in the pathogenesis and development of diabetes, including GDM. In the present study, we aimed to determine the clinical performance of miR-195-5p in GDM. METHODS: First, the miR-195-5p expressions in serum samples from healthy pregnant women and women with GDM at 25 weeks pregnancy were detected using real-time polymerase chain reaction (RT-qPCR). Then, receive characteristic (ROC) curve was used to determine the diagnostic value of miR-195-5p in GDM. Finally, the correlation analysis of miR-195-5p expression with related clinicopathological factors was carried out to determine the clinical value of miR-195-5p in GDM. RESULTS: In this study, we found that miR-195-5p expression was significantly increased in serum samples from GDM patients as compared with that in healthy pregnancies. Furthermore, miR-195-5p might be a putative biomarker for GDM diagnosis with an area under the curve (AUC) of 0.8451; the cutoff value was 1.598, sensitivity was 73.69%, specificity was 96.85%, accuracy was 81.26%, and Youden index was 70.54%. Expression of miR-195-5p was positively associated with fasting plasma glucose, one-hour plasma glucose, and two-hour plasma glucose. CONCLUSION: miR-195-5p might function as a putative diagnostic biomarker for GDM and contribute to identifying at-risk mothers in pregnancy.

Formyl-peptide receptor 2 suppresses proliferation, migration and invasion in human extravillous trophoblastic cells.

Although FPR2 receptor is distributed in the endometrium and placenta, its function in human extravillous trophoblastic (TEV-1) cells still remains enigmatic. In this study, overexpression of FPR2 was performed in TEV-1 cells. Then, CCK8 transwell and wound healing assays were used to assess the cell proliferation, migration and invasion, respectively. The results showed that FPR2 overexpression significantly inhibited proliferation, invasion and migration in TEV-1 cells. In addition, FPR2 overexpression significantly decreased mRNA and protein levels of integrin-linked kinase (ILK), nuclear factor-kappa B (NF--κB), matrix metalloproteinase 9 (MMP9) and vascular endothelial growth factor (VEGF) in TEV-1 cells. These findings indicated that FPR2 overexpression alters proliferation, migration and invasion in human extravillous trophoblastic cellsthrough the ILK/NF-κB signaling pathway; ideal FPR2 levels are important for TEV-1 cells functions.

Lipoxin A4 interferes with embryo implantation via suppression of epithelial-mesenchymal transition.

PROBLEM: To test whether lipoxin A4 (LXA4) interferes with embryo implantation via suppression of epithelial-mesenchymal transition (EMT). METHOD OF STUDY: We developed a mouse model of LXA4 blocking embryo implantation and detected the indicators of EMT to confirm that LXA4 inhibits EMT might be a mechanism of interfering with the embryo implantation. We detected integrin-linked kinase (ILK), N-formylpeptide receptor 2 (FPR2), vascular endothelial growth factor, matrix metalloproteinases (MMPs), Akt, GSK3ß, NF-ĸB, twist, vimentin, fibronectin, and ß-catenin mRNA expression using reverse transcriptase-polymerase chain reaction (RT-PCR) and real-time RT-PCR; localized protein expression using immunohistochemistry and Western blotting assay; MMPs activity assay by gelatin zymography; and the status of implantation in pregnant animals assessed by pontamine blue reaction test. RESULTS: Preimplantation administration of LXA4 resulted in implantation failure. LXA4 has a time- and dose-dependent effect on embryo implantation. Day 0.5 after fertilization is the most effective time to use LXA4 to block embryo implantation. (a) LXA4 reduced endometrial stroma edema; (b) LXA4 inhibited the activity of MMP9 and significantly upregulated the expression of ß-catenin, and downregulated the expression of vimentin, fibronectin, twist, NF-κB, Akt, and Gsk-3ß in the endometrium and TEV-1 cells; (c) LXA4 upregulated the expression of FPR2, and downregulated the expression of ILK; FPR2-overexpressing had an inhibitory effect on ILK in TEV-1 cells. CONCLUSION: LXA4 inhibits EMT which attenuates ILK action by enhancing FPR2; therefore, this might be a mechanism of interfering with embryo implantation.

Formononetin may protect aged hearts from ischemia/reperfusion damage by enhancing autophagic degradation.

Myocardial infarction is a leading cause of mortality worldwide, and timely blood/oxygen reperfusion may substantially improve the outcome of infarction. However, ischemia/reperfusion (I/R) may cause severe side effects through excess reactive oxygen species generation. To develop novel methods to relieve I/R induced cell damage, the present study used a component of traditional Chinese medicine. In the present study, isolated heart tissue from aged mice and H9C2 cells with chemically­induced aging were used as experimental subjects, and it was demonstrated that formononetin was able to alleviate I/R­induced cell or tissue apoptosis. By applying formononetin to I/R­damaged tissue or cells, it was demonstrated that formononetin was able to enhance autophagy and thus alleviate I/R­induced cell damage. Furthermore, it was observed that I/R was able to inhibit lysosomal degradation processes in aged tissues or cells by impairing the lysosome acidification level, and formononetin was able to reverse this process via the re­acidification of lysosomes. In conclusion, the present study demonstrated that formononetin was able to alleviate I/R­induced cellular apoptosis in aged cells by facilitating autophagy.

Metformin partially reverses the carboplatin-resistance in NSCLC by inhibiting glucose metabolism.

Platinum-based chemotherapeutic drugs are irreplaceable for the treatment of advanced non-small cell lung cancer (NSCLC). However, acquired drug resistance has become a major obstacle for the clinical application of chemotherapy on NSCLC. In the present study, we established carboplatin-resistant NSCLC models on A549 and PC9 cell lines, which were named A549/R and PC9/R. Besides the low sensitivity of A549/R and PC9/R to carboplatin treatment, they exhibited higher metabolism rate of glucose compared to their parental A549 and PC9 cells, respectively. Mechanically, we confirmed that overexpression of PKM2 in A549/R and PC9/R was responsible for the high glucose metabolism and carboplatin resistance. Metformin, an antidiabetic drug, was observed to increase the sensitivity of carboplatin-resistant NSCLC cells to carboplatin treatment in vitro and in vivo. Mechanically, metformin decreased expression of PKM2 and subsequently inhibited the glucose uptake, lactate generation and ATP production in A549/R and PC9/R. Therefore, metformin promoted carboplatin-induced apoptosis through the mitochondria pathway. In addition, we demonstrated that metformin treatment also impaired the cross-resistance of A549/R and PC9/R to cisplatin, etoposide and 5-fluorouracil.

High Expression of PTGR1 Promotes NSCLC Cell Growth via Positive Regulation of Cyclin-Dependent Protein Kinase Complex.

Lung cancer has been the most common cancer and the main cause of cancer-related deaths worldwide for several decades. PTGR1 (prostaglandin reductase 1), as a bifunctional enzyme, has been involved in the occurrence and progression of cancer. However, its impact on human lung cancer is rarely reported. In this study, we found that PTGR1 was overexpressed in lung cancer based on the analyses of Oncomine. Moreover, lentivirus-mediated shRNA knockdown of PTGR1 reduced cell viability in human lung carcinoma cells 95D and A549 by MTT and colony formation assay. PTGR1 depletion led to G2/M phase cell cycle arrest and increased the proportion of apoptotic cells in 95D cells by flow cytometry. Furthermore, silencing PTGR1 in 95D cells resulted in decreased levels of cyclin-dependent protein kinase complex (CDK1, CDK2, cyclin A2, and cyclin B1) by western blotting and then PTGR1 is positively correlated with cyclin-dependent protein by using the data mining of the Oncomine database. Therefore, our findings suggest that PTGR1 may play a role in lung carcinogenesis through regulating cell proliferation and is a potential new therapeutic strategy for lung cancer.

Features of fatigue in patients with early-stage non-small cell lung cancer.

BACKGROUND: The objective of this study was to investigate the fatigue status and related factors in patients with early-stage non-small cell lung cancer (NSCLC) 1-5 years after surgery. MATERIALS AND METHODS: This cross-sectional study included 254 patients with stage IA or IB NSCLC, who had undergone surgery. They completed several surveys, including the Brief Fatigue Inventory, Karnofsky Performance Scale, Physical Activity Questionnaire, Baseline Dyspnea Index, Hospital Anxiety and Depression Scale. The association between fatigue and functional status was assessed using Chi-square analysis. Spearman rank correlation and multivariate logistic regression analysis were used to assess the correlation between fatigue and various other factors. RESULTS: The overall incidence of postoperative fatigue was 59.8%. Among patients with moderate to severe fatigue, 21.1% had obvious dysfunction, whereas only 9.6% of patients with mild or no fatigue (χ(2) = 5.369; P = 0.02) showed obvious dysfunction. Multivariate logistic regression analysis showed that functional status (odds ratio [OR]: 3.57; 95% confidence interval [CI]: 1.17-6.19), concurrent lung disease (OR: 2.34; 95% CI: 1.08-4.99), depression (OR: 6.39; 95% CI: 2.42-17.35), and anxiety (OR: 2.45; 95% CI: 1.13-4.87) were independent risk factors for fatigue, whereas physical activity (OR: 0.27; 95% CI: 0.11-0.73) could prevent fatigue. CONCLUSION: More than half of the patients with early-stage NSCLC experienced fatigue 1-5 years after surgery, and moderate to severe fatigue was often associated with obvious dysfunction. The strong association of fatigue with anxiety, depression, and lung complications suggests that fatigue and other symptoms constitute a symptom cluster. Therefore, comprehensive treatment methods may achieve better therapeutic results.