Applications of Data Characteristic AI-Assisted Raman Spectroscopy in Pathological Classification.

Raman spectroscopy has been widely used for label-free biomolecular analysis of cells and tissues for pathological diagnosis in vitro and in vivo. AI technology facilitates disease diagnosis based on Raman spectroscopy, including machine learning (PCA and SVM), manifold learning (UMAP), and deep learning (ResNet and AlexNet). However, it is not clear how to optimize the appropriate AI classification model for different types of Raman spectral data. Here, we selected five representative Raman spectral data sets, including endometrial carcinoma, hepatoma extracellular vesicles, bacteria, melanoma cell, diabetic skin, with different characteristics regarding sample size, spectral data size, Raman shift range, tissue sites, Kullback-Leibler (KL) divergence, and significant Raman shifts (i.e., wavenumbers with significant differences between groups), to explore the performance of different AI models (e.g., PCA-SVM, SVM, UMAP-SVM, ResNet or AlexNet). For data set of large spectral data size, Resnet performed better than PCA-SVM and UMAP. By building data characteristic-assisted AI classification model, we optimized the network parameters (e.g., principal components, activation function, and loss function) of AI model based on data size and KL divergence etc. The accuracy improved from 85.1 to 94.6% for endometrial carcinoma grading, from 77.1 to 90.7% for hepatoma extracellular vesicles detection, from 89.3 to 99.7% for melanoma cell detection, from 88.1 to 97.9% for bacterial identification, from 53.7 to 85.5% for diabetic skin screening, and mean time expense of 5 s.

A negative feedback loop between KLF9 and the EMT program dictates metastasis of hepatocellular carcinoma.

Metastasis is the primary cause of death of hepatocellular carcinoma (HCC), while the mechanism underlying this severe disease remains largely unclear. The Kruppel-like factor (KLF) family is one of the largest transcription factor families that control multiple physiologic and pathologic processes by governing the cellular transcriptome. To identify metastatic regulators of HCC, we conducted gene expression profiling on the MHCC97 cell series, a set of subclones of the original MHCC97 that was established by in vivo metastasis selection therefore harbouring differential metastatic capacities. We found that the expression of KLF9, a member of the KLF family, was dramatically repressed in the metastatic progeny clone of the MHCC97 cells. Functional studies revealed overexpression of KLF9 suppressed HCC migration in vitro and metastasis in vivo, while knockdown of KLF9 was sufficient to promote cell migration and metastasis accordingly. Mechanistically, we found the expression of KLF9 can reverse the pro-metastatic epithelial-mesenchymal transition (EMT) program via direct binding to the promoter regions of essential mesenchymal genes, thus repressing their expression. Interestingly, we further revealed that KLF9 was, in turn, directly suppressed by a mesenchymal transcription factor Slug, suggesting an intriguing negative feedback loop between KLF9 and the EMT program. Using clinical samples, we found that KLF9 was not only downregulated in HCC tissue compared to its normal counterparts but also further reduced in the HCC samples of whom had developed metastatic lesions. Together, we established a critical transcription factor that represses HCC metastasis, which is clinically and mechanically significant in HCC therapies.

Identification of Anhydrodebromoaplysiatoxin as a Dichotomic Autophagy Inhibitor.

Dysfunctional autophagy is associated with various human diseases, e.g., cancer. The discovery of small molecules modulating autophagy with therapeutic potential could be significant. To this end, we screened the ability of a series of metabolites isolated from marine microorganisms to modulate autophagy. Anhydrodebromoaplysiatoxin (ADAT), a metabolite yielded by the marine red algae Gracilaria coronopifolia, inhibited autophagosome-lysosome fusion in mammalian cells, thereby inducing the accumulation of autophagosomes. Treatment of cells with ADAT alkalinized lysosomal pH. Interestingly, ADAT also activated the mTOR/p70S6K/FoxO3a signaling pathway, likely leading to the inhibition of autophagy induction. ADAT had little effect on apoptosis. Our results suggest that ADAT is a dichotomic autophagy inhibitor that inhibits both late-stage (autophagosome-lysosome fusion) and early-stage (autophagy induction) autophagy.

Relationship between Vitamin D Level and Subclinical Hypothyroidism in Patients with Gestational Diabetes Mellitus.

BACKGROUND: The aim was to investigate the relationship between the vitamin D (VitD) level and the incidence rate of subclinical hypothyroidism in patients with gestational diabetes mellitus (GDM) in early pregnancy. METHODS: Ninety eligible patients who underwent physical examination from March 2015 to September 2017 were selected. The levels of serum 25-hydroxyvitamin D (25-OH-VD), free thyroxine (FT4), free triiodothyronine (FT3), thyroid stimulating hormone (TSH), and thyroid peroxidase antibody (TPOAb) were measured. The correlations of VitD level with those of thyroid function-related indices were analyzed. RESULTS: The serum 25-OH-VD level was (17.82 ± 3.45) ng/mL in the 90 GDM patients in early pregnancy, including 64.44% patients in VitD deficiency group, 22.22% patients in VitD insufficiency group, and 13.33% in VitD sufficiency group. No significant differences in the levels of serum FT4, FT3, and TSH were found among different VitD groups (p > 0.05), but the level of TPOAb gradually decreased (p < 0.05). There was no significant difference in the incidence rate of subclinical hypothyroidism among different VitD groups (p > 0.05). VitD level was not correlated with those of FT4, FT3, and TSH (p > 0.05), but negatively correlated with that of TPOAb (p < 0.05). An increase of TPOAb level raised the risk of VitD deficiency in pregnant women (p < 0.05). Patients suffered from significant 25-OH-VD deficiency in spring and winter (p < 0.05). CONCLUSIONS: GDM patients in early pregnancy display VitD deficiency, and their serum 25-OH-VD level is affected by seasons and not significantly related to subclinical hypothyroidism. However, the increased level of TPOAb may raise the risk of VitD deficiency in pregnant women.

LncRNA FGD5-AS1 drives the malignant development of gastric cancer by negatively interacting with FZD3.

We aimed to detect the expression pattern of long non-coding RNA (lncRNA) FGD5-AS1 in gastric cancer (GC) samples and its impact on driving the development of GC. FGD5-AS1 levels in 66 cases of GC tissues and paracancerous ones were detected. Its influences on clinical features and prognosis in GC patients were analyzed. In AGS and SGC-7901 cells with FGD5-AS1 knockdown, phenotype changes were assessed through cell counting kit-8 (CCK-8), Transwell and wound healing assay. The downstream target of FGD5-AS1 was searched by a bioinformatics tool and confirmed by dual-luciferase reporter assay. Their interaction in regulating the malignant development of GC was finally explored. FGD5-AS1 was upregulated in GC tissues compared to paracancerous ones. GC patients expressing a high level of FGD5-AS1 had higher risk of lymphatic metastasis or distant metastasis and worse prognosis than those with a low level. Knockdown of FGD5-AS1 weakened proliferative and metastatic abilities in AGS and SGC-7901 cells. FZD3 was the downstream target of FGD5-AS1. Protein levels of FZD3 and FZD5 were upregulated, while b-catenin, TGF-b and MMP9 were downregulated in GC cells with FGD5-AS1 knockdown. Knockdown of FZD3 abolished the regulatory effects of FGD5-AS1 on malignant phenotypes of GC cells. FGD5-AS1 is upregulated in GC samples, which is linked to metastasis and prognosis in GC. It drives proliferative and metastatic abilities in GC cells via negatively interacting with FZD3.

Application of hysteroscopy in female fertility preservation. / å®«è ”é•œåœ¨å¥³æ€§ç”Ÿè‚²åŠ›ä¿æŠ¤ä¸­çš„åº”ç”¨.

Under the background of the trend in late marriage and the relaxation of family planning policy, the reproductive behavior of women has changed and the proportion of elderly pregnant women has increased progressively year by year. Thus the female fertility preservation is particularly important. As the cradle of life, uterine malformation and uterine cavity diseases may have adverse effects on embryo implantation and development. Several common intrauterine diseases, such as uterine submucosal fibroids, endometrial polyps, intrauterine adhesions, uterine malformation, cesarean scar diverticulum, and embryo residues, may affect female fertility. Hysteroscopy is the gold standard for the diagnosis and treatment for intrauterine diseases. With the progress in science and technology, the refinement of hysteroscopy instruments and the promotion of transvaginal endoscopic technology, hysteroscopy will yield brilliant results in female fertility preservation. The knowledge and training related to hysteroscopy should be continuously promoted and popularized, so that it can be mastered by more clinicians and applied in clinical practice to benefit more female patients.

A ten-genes-based diagnostic signature for atherosclerosis.

BACKGROUND: Atherosclerosis is the leading cause of cardiovascular disease with a high mortality worldwide. Understanding the atherosclerosis pathogenesis and identification of efficient diagnostic signatures remain major problems of modern medicine. This study aims to screen the potential diagnostic genes for atherosclerosis. METHODS: We downloaded the gene chip data of 135 peripheral blood samples, including 57 samples with atherosclerosis and 78 healthy subjects from GEO database (Accession Number: GSE20129). The weighted gene co-expression network analysis was applied to identify atherosclerosis-related genes. Functional enrichment analysis was conducted by using the clusterProfiler R package. The interaction pairs of proteins encoded by atherosclerosis-related genes were screened using STRING database, and the interaction network was further optimized with the cytoHubba plug-in of Cytoscape software. RESULTS: The logistic regression diagnostic model was constructed to predict normal and atherosclerosis samples. A gene module which included 532 genes related to the occurrence of atherosclerosis were screened. Functional enrichment analysis basing on the 532 genes identified 235 significantly enriched GO terms and 44 significantly enriched KEGG pathways. The top 50 hub genes of the protein-protein interaction network were identified. The final logistic regression diagnostic model was established by the optimal 10 key genes, which could distinguish atherosclerosis samples from normal samples. CONCLUSIONS: A predictive model based on 10 potential atherosclerosis-related genes was obtained, which should shed light on the diagnostic research of atherosclerosis.

Clinical characteristics and outcomes in pregnant women with epilepsy.

BACKGROUND: Epilepsy in pregnancy can lead to substantial maternal and neonatal morbidity and mortality. Early intervention in pregnant women with epilepsy (WWE), accurate assessment of the severity of their condition, and effective treatment are required to improve maternal and neonatal prognosis. Many obstetricians lack experience in monitoring and treating pregnant WWE. AIMS: The aim of this study was to describe the demographic and clinical characteristics of pregnant WWE and examine maternal and neonatal outcomes. METHODS: Medical records of 75 pregnant women with a history of epilepsy who delivered at Beijing Tiantan Hospital, China between January 2006 and December 2019 were retrospectively reviewed. Pregnant women with a history of epilepsy were matched 1:2 with a control group of 150 pregnant women without epilepsy who delivered at Beijing Tiantan Hospital during the same time period. Information including type and frequency of epilepsy and seizures, maternal complications, medication, delivery mode, newborn weight, and newborn Apgar score were recorded. In subgroup analyses, pregnant WWE were stratified according to presence or absence of seizures during pregnancy and generalized seizure vs. nongeneralized seizure. RESULTS: The incidence of anemia, hypertensive disorder of pregnancy, premature rupture of membranes (PROM), cesarean section, and postpartum hemorrhage was significantly higher (p < 0.05), and mean newborn weight and newborn Apgar score were significantly lower (p < 0.05) in pregnant WWE compared with pregnant women without epilepsy. The incidence of premature delivery was significantly higher (p < 0.05), and mean newborn weight was significantly lower (p < 0.05) in pregnant WWE with seizures vs. without seizures. Mean newborn weight was significantly lower (p = 0.01) in pregnant WWE with nongeneralized seizures vs. generalized seizures. CONCLUSION: Pregnant WWE are at high risk of anemia, gestational hypertension, PROM, cesarean section, postpartum hemorrhage, and low newborn weight and Apgar score. Women with epilepsy who experience seizures during pregnancy are at high risk of preterm birth and having low birth weight infants. Pregnant WWE who experience nongeneralized seizures are at high risk of having low birth weight infants. These data emphasize the need to routinely monitor fetal weight on ultrasound and offer appropriate intervention. These findings highlight the need for healthcare providers to take a multidisciplinary approach to the management of pregnant WWE. SYNOPSIS: Pregnant WWE are at high risk of obstetric complications. Women with epilepsy who experience seizures during pregnancy are at high risk of preterm birth and having low birth weight infants. Pregnant WWE who experience nongeneralized seizures are at high risk of having low birth weight infants. These data highlight the need for healthcare providers to take a multidisciplinary approach to the management of pregnant WWE.

Comparison of Combined Bipolar Radiofrequency Impedance-Controlled Endometrial Ablation with Levonorgestrel Intrauterine System versus Bipolar Radiofrequency Endometrial Ablation Alone in Women with Abnormal Uterine Bleeding.

STUDY OBJECTIVE: This study aims to evaluate the efficacy of the combination of bipolar radiofrequency impedance-controlled endometrial ablation (NovaSure; Hologic Inc., Bedford, MA) and levonorgestrel intrauterine system (LNG-IUS; Mirena; Schering AG, Berlin, Germany) placement in comparison with NovaSure endometrial ablation alone in patients with abnormal uterine bleeding (AUB). DESIGN: A propensity score matching study. SETTING: Beijing Tiantan Hospital, Capital Medical University, Beijing, China. PATIENTS: A retrospective study was conducted on 246 patients with AUB who underwent NovaSure endometrial ablation with (NovaSure+LNG-IUS group) or without (NovaSure group) LNG-IUS between January 2013 and August 2016. To overcome selection bias, propensity score matching was used to establish a 1:1 match between these 2 groups. Accordingly, 41 patients were included in each group. INTERVENTION: NovaSure endometrial ablation, immediately followed by LNG-IUS insertion in the NovaSure+LNG-IUS group, and NovaSure endometrial ablation alone in the control group. MEASUREMENTS AND MAIN RESULTS: Follow-up assessments performed at postablation months 6, 12, and 24 revealed the following: The rate of amenorrhea (78.05% vs 46.34%, 85.37% vs 53.65%, and 87.80% vs 58.54%, respectively; p <.005) and the rate of dysmenorrhea remission (100% vs 70.59%, 100% vs 64.70%, and 100% vs 64.70% [p <.05, p <.01, and p <.01], respectively) were significantly higher in the NovaSure+LNG-IUS group than in the NovaSure group. The rate of reinterventions was similar for both groups at postablation month 6. However, at postablation months 12 and 24, these rates were significantly lower in the NovaSure+LNG-IUS group than in the NovaSure group (0 vs 14.63% and 2.44% vs 21.95% [p <.05 and p <.01], respectively). CONCLUSION: For women with AUB, the combination of NovaSure endometrial ablation and LNG-IUS is more effective than NovaSure alone in achieving amenorrhea, alleviating dysmenorrhea and reducing reinterventions.

Voltammetric determination of ofloxacin by using a laser-modified carbon glassy electrode.

A novel electrochemical sensor is described for the determination of ofloxacin (OFL) in environmental water samples. A laser-modified glassy carbon electrode (LGCE) was structured and characterized by scanning electron microscopy, atomic force microscopy, X-ray diffraction, X-ray photoelectron spectroscopy, and electrochemical impedance spectroscopy. The increase in electrochemical activity is due to a moderate increase in the surface roughness and to the presence of functional groups on the LGCE. Under optimal conditions (viz. a pH value of 5.5, a laser power of 1.8 W and an action time of 40 s), the sensor is capable of detecting OFL by differential pulse voltammetry at a working potential of +0.91 V (versus Ag/AgCl). Response is linear from 0.25 to 200 µM for OFL concentration range, and the detection limit is 75 nM (at S/N = 3). Removal of oxygen from samples is not required. The sensor was successfully applied to the determination of OFL in spiked groundwater, tap water and wastewater samples, with apparent recoveries from 94.0 to 108.0% and a relative standard deviation of less than 4.8%." Graphical abstractSchematic representation of a method for determination of ofloxacin (OFL) by differential pulse voltammetry. It is making use of a laser modified glassy carbon electrode (LGCE), which increases the number of active functional groups and the surface area compared to a conventional GCE.

Reference Intervals of Apolipoprotein E in Healthy Chinese Han Adults.

BACKGROUND: Reference intervals (RIs) of Apo E levels are an important parameter for the clinical evaluation of patient health, and the RIs of serum Apo E could be variable in different population. We plan to establish RIs of apolipoprotein E (Apo E) according to the CLSI EP28-A3 guideline in healthy Chinese Han adults. METHODS: Serum Apo E values of 1,206 healthy adults (from 19 to 87 years old) were measured by immunoturbidimetry. The relationship between Apo E and age was analyzed by using Spearman's correlation. The differences between the gender and age groups were compared using Mann-Whitney U test/Kruskal-Wallis H test. We calculated recommended nonparametric Q2.5 and Q97.5 percentile intervals and the 90% confidence intervals (CI) of lower and upper limits to define the age- and gender- related RIs. RESULTS: The level of Apo E was higher in females than males. Apo E was significantly associated with aging in adult females (r = 0.108, p < 0.05), but not in males (p = 0.518). The RIs of Apo E for females were 0.0268 - 0.0619, 0.0247 - 0.0603, and 0.0269 - 0.0658 g/L for 18 - 29, 30 - 59, and ≥ 60 years old, respectively, that for males was 0.0242 - 0.0579 g/L. CONCLUSIONS: Our results established the age- and gender-specific RIs of serum Apo E in healthy Chinese Han adults in our laboratory.

Successful Pregnancies in Women with Diffuse Uterine Leiomyomatosis after Hysteroscopic Management Using the Hysteroscopy Endo Operative System.

STUDY OBJECTIVE: To evaluate the feasibility, effectiveness, and reproductive outcome of hysteroscopic management using the Hysteroscopy Endo Operative system (HEOS) in patients with diffuse uterine leiomyomatosis (DUL). DESIGN: Retrospective study (Canadian Task Force classification III). SETTING: Beijing Tiantan Hospital, Capital Medical University, Beijing, China. PATIENTS: Eight women of reproductive age suffering from menorrhagia and anemia or infertility diagnosed with DUL by ultrasonography and hysteroscopy. INTERVENTIONS: Hysteroscopic surgery using cold graspers combined with electric loop by the HEOS was performed to excise submucous myomas (including types 0, I, and II), leaving other intramural myomas in place. The fenestration method is used in electrical hysteroscopic myomectomy. Postoperative endometrial repair and synechiae, menstrual improvement, conception, and pregnancy were recorded. MEASUREMENTS AND MAIN RESULTS: Two patients underwent a single hysteroscopic myomectomy, whereas 6 patients underwent 2 to 3 myomectomies. No complications were observed. The mean follow-up period was 39.13 ± 17.01 months (range, 21-67). The endometrium recovered 2 to 3 months after the initial surgery, and 100% improvement in menstruation was observed. Two patients had mild synechia after the first hysteroscopic surgery. Seven patients conceived spontaneously (postoperative pregnancy rate, 87.5%), 6 of whom had a full-term pregnancy. One patient suffered a miscarriage in the second trimester (live birth rate, 75%). CONCLUSION: Hysteroscopic surgery using cold graspers combined with electric loop by the HEOS is a feasible and effective for treatment of DUL because it preserves the uterus and yields favorable reproductive outcomes. The cold surgery and fenestration method minimizes electrical and thermal damage to the endometrium surrounding the myoma, consequently reducing surgical risks.

Estrogen therapy before hysteroscopic adhesiolysis improves the fertility outcome in patients with intrauterine adhesions.

PURPOSES: To describe the fertility outcomes after hysteroscopic adhesiolysis combined with preoperative hormone treatment in women with intrauterine adhesion (IUA). METHODS: This study is a retrospective cohort study. A total of 230 patients with IUA underwent hysteroscopic adhesiolysis combined with hormone treatment from Jan 2012 to Jun 2018. 148 patients who received preoperative estrogen treatment were enrolled into group A and 82 patients without preoperative estrogen treatment were enrolled into group B. All the patients underwent hysteroscopic adhesiolysis and received postoperative estrogen therapy, intrauterine indwelling device. Second or third look was performed after 2-3 months. RESULTS: 90.87% (209/230) patients complete the study. The AFS scores at baseline were higher in the group A than group B. After the preoperative E2 treatment, group A achieved the comparable AFS score to group B before the surgery. The cumulative fertility rate in group A was comparable in group B, both in the ITT analysis (49.32% vs. 52.44%, p = 0.651) and the PP analysis (54.07% vs.58.10%, p = 0.575).The mean conception time was also similar in group A and group B (8.30 ± 6.47 vs. 8.54 ± 5.68 months, p = 0.837). Besides, the surgery times in group A were less than group B. There was no difference in the rate of adverse events between two groups. CONCLUSIONS: Hysteroscopic adhesiolysis combined with preoperative oestrogen could reduce the preoperative AFS scores and the times of surgery which yield a similar conception rate in women with less severe intrauterine adhesions.

Evaluation of Folate Receptor-Mediated Cervical Dyeing as a Method for Detection of Cervical Lesions.

OBJECTIVES: The aim of the study was to evaluate the performance of a folate receptor-mediated tumor detection (FRD) assay for detection of cervical high-grade lesions. MATERIALS AND METHOD: A total of 1504 patients with abnormal cytology and/or positive human papillomavirus (HPV) testing during primary screening from November 2014 to August 2015 were enrolled. The patients were recruited from the Peking University People's Hospital and 12 other hospitals. Folate receptor-mediated tumor detection was applied in all the patients before colposcopy to compare the detection rate, sensitivity, specificity, positive predictive value, negative predictive value, and coincidence rate with HPV and cytology tests according to the pathologic diagnosis. RESULTS: In the total of 1504 patients, 503 patients were negative for intraepithelial lesion or malignancy, 440 patients were cervical intraepithelial neoplasia (CIN) 1, 254 patients were CIN 2, 257 patients were CIN 3, 46 patients were squamous cell carcinoma, and 4 patients were adenocarcinoma in situ. The sensitivity of FRD was 77.72%, which was less than cytology (80.39%) and HPV testing (95.54%). The specificity of FRD was 60.02%, which was greater than cytology (30.12%) and HPV testing (14.95%). The coincidence rate of FRD to the pathologic diagnosis (66.62%) was also significantly greater than atypical squamous cells of undetermined significance cytology and above (48.87%) and HPV testing (45.01%, p < .0001). The detection rate of FRD for all grades of lesions increased with the severity of lesions. CONCLUSIONS: Folate receptor-mediated tumor detection has a slightly lower sensitivity and a higher specificity than cytology and HPV testing for detection of CIN 2+. Simplicity of FRD requires less professional skill. Folate receptor-mediated tumor detection could be a candidate test for cervical cancer screening especially in low- and middle-income countries. However, FRD still needs more clinical trial data to demonstrate its ability in general screening population.

Effects of Freeze-Thaw Times on Screening Coagulation Tests and Factors VIII and IX Activities in Citrate-Anticoagulated Plasma at -20°C and -80°C.

BACKGROUND: Accurate determination of screening coagulation tests and factors VIII and IX activities (FVIII:C and FIX:C) in fresh plasma is very important for diagnosing abnormalities in the intrinsic or extrinsic coagulation pathways and factor deficiencies. If thawed samples cannot be detected for all required items at the same time, or need to be re-tested or re-stored, the thawed samples need to be re-frozen. We planned to perform in-house validation studies on freeze-thawed samples for screening coagulation tests, FVIII:C and FIX:C. METHODS: Mean percent changes, numbers of samples with > 10% changes, and difference plots were evaluated to determine clinically relevant differences between results for fresh and freeze-thawed samples. The statistical significance of differences between repeated-measure multiple groups and baseline values were evaluated by repeated-measures analysis of variance. RESULTS: The acceptable freeze-thaw cycles for activated partial thromboplastin time, fibrinogen, prothrombin time/international normalized ratio, thrombin time, and FIX:C were three times at -20°C/-80°C, while the acceptable freeze-thaw cycles for FVIII:C were three times at -80°C and once at -20°C. CONCLUSIONS: The freeze-thaw results on stabilities were affected by time and temperature, with lower temperature and fewer times associated with more stable activity.

Effect of Hexadecyl Azelaoyl Phosphatidylcholine on Cardiomyocyte Apoptosis in Myocardial Ischemia-Reperfusion Injury: A Hypothesis.

Reperfusion after myocardial ischemia can induce cardiomyocyte death, known as myocardial reperfusion injury. The pathophysiology of the process of reperfusion suggests the confluence multiple pathways. Recent studies have focused on the inflammatory response, which is considered to be the main mechanism during the process of myocardial ischemia-reperfusion injury and can cause cardiomyocyte apoptosis. Peroxisome proliferator-activated receptors gamma activated by endogenous ligands and exogenous ligand can decrease the inflammatory response in cardiomyocytes. Thiazolidinediones are synthetic, high-affinity, selective ligands for peroxisome proliferator-activated receptors gamma, and can inhibit the inflammatory response, decrease myocardial infarct size, and protect cardiac function. However, thiazolidinediones, including rosiglitazone and pioglitazone, can also contribute to adverse cardiovascular events such as congestive heart failure. Therefore, there are some limitations to the use of thiazolidinediones. Most endogenous ligands were of low affinity until hexadecyl azelaoyl phosphatidylcholine was identified as a high-affinity ligand and agonist for peroxisome proliferator-activated receptors gamma. Hexadecyl azelaoyl phosphatidylcholine binds recombinant peroxisome proliferator-activated receptors with an affinity (Kd(app) ≈40 nM) which is equivalent to rosiglitazone. Therefore, hexadecyl azelaoyl phosphatidylcholine is a specific peroxisome proliferator-activated receptors gamma agonist. Given these findings, we hypothesized that the use of hexadecyl azelaoyl phosphatidylcholine can activate the peroxisome proliferator-activated receptors gamma signal pathways and prevent the inflammatory response process of myocardial ischemia-reperfusion injury, with reduced cardiomyocyte apoptosis and death.

Lipid Biomarkers in Acute Myocardial Infarction Before and After Percutaneous Coronary Intervention by Lipidomics Analysis.

BACKGROUND Reperfusion injury is one of the leading causes of myocardial cell death and heart failure. This study was performed to identify new candidate lipid biomarkers for the purpose of optimizing the diagnosis of myocardial ischemia reperfusion (I/R) injury, assessing the severity of myocardial I/R injury and trying to find the novel mechanism related to lipids. MATERIAL AND METHODS Forty patients who were diagnosed with ST-segment elevation myocardial infarction (STEMI) were randomly selected for this study. Serum samples from all the patients with STEMI were collected at 3 time periods: after STEMI diagnosis but prior to reperfusion (T0); and then at 2 hours (T2) and 24 hours (T24) after the end of the percutaneous coronary intervention procedure. Plasma lipidomics profiling analysis was performed to identify the lipid metabolic signatures of myocardial I/R injury using lipidomics. RESULTS Sixteen types of potential lipid biomarkers at different time periods (T0, T2, T24) were identified by using lipidomics technology. The T0 time periods exhibited 16 differentially metabolized lipid peaks in the patients after STEMI diagnosis but prior to reperfusion. With the increase of reperfusion times, the contents of these 16 lipid biomarkers decreased gradually, but there was a 1.5- to 2-fold increase of those 16 lipid biomarkers contents at T2 compared with T24. CONCLUSIONS Lipidomics analysis demonstrated differential change before and after reperfusion, suggesting a potential role of some of these lipids as biomarkers for optimizing the diagnosis of myocardial I/R, as well as for therapeutic targets against myocardial I/R injury.

MicroRNA Expression Profiling of Pancreatic Cancer Cell Line L3.6p1 Following B7-H4 Knockdown.

BACKGROUND/AIMS: Co-stimulating molecule B7-H4 regulates T cell-mediated immune responses, participates in tumor immune escape, and promotes the proliferation and metastasis of pancreatic cancer cells. However, the specific mechanisms are unclear. MicroRNAs (miRNAs) participated in the pathogenesis and progression of cancer. METHODS: In this study, a microarray technique was used to screen B7-H4-related differentially expressed miRNAs in a pancreatic cancer cell line find those associated with pancreatic cancer. Using a miRCURYTM LNA Array approach, we compared the miRNA expression profiles of L3.6p1 pancreatic cancer cells transfected with B7-H4 siRNA for 72 h with those transfected with non-target siRNAs. RESULTS: B7-H4 siRNA significantly up-regulated 57 miRNAs and down-regulated 14 miRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway analysis of predicted miRNA targets showed that these genes were mainly involved in protein binding, pathways in cancer, mitogen-activated protein kinase (MAPK) signaling pathway, and phosphatidylinositol 3-kinase-Akt (PI3K-Akt) signaling pathway. CONCLUSIONS: This is the first description of target genes of B7-H4, showing that miRNAs participate in the B7-H4 mediated regulation of oncogenicity and pathogenesis of pancreatic cancer. These results may help us better understand the role of B7-H4 in the progression of pancreatic cancer and its possible mechanisms. We also provide novel biomarkers for potential treatments of pancreatic cancer.

Hysteroscopic treatment of Robert's uterus with laparoscopy.

Herein is described the case of a 26-year-old woman whose Robert's uterus was treated with hysteroscopy and who then successfully became pregnant and gave birth. The uterus anomaly was diagnosed on combined hysteroscopy and ultrasonography, which showed an asymmetric septate uterus with one blind cavity, causing menstrual retention. The surgery was uncomplicated, with satisfactory results. The patient underwent successful cesarean section delivery of a baby boy weighing 3250 g on 24 March 2014.