Fibrinogen as a potential diagnostic marker for prediction and evaluation of postpartum hemorrhage: a retrospective study.

OBJECTIVE: To investigate whether prenatal fibrinogen (FIB) or other related factors could be utilized to evaluate the risk of postpartum hemorrhage (PPH). METHODS: A retrospective study was conducted in a database from January 2015 to December 2019. A total of 128 patients were enrolled and evaluated with FIB, in which 55 patients were assigned to low FIB and 73 in normal FIB. RESULTS: According to the volume of blood loss, the mean of the low FIB group (<4 g/L) was markedly higher than that of the normal FIB group (≥4 g/L). Prenatal FIB was negatively correlated with PPH volume. The receiver operating characteristic (ROC) curve results indicated that the value of prenatal FIB was 0.701 to predict refractory PPH. CONCLUSIONS: Prenatal FIB was significantly related to thrombin time (TT), which may be an independent factor to predict the coagulation state of prenatal pregnancy.

Circ_0001589/miR-1248/HMGB1 axis enhances EMT-mediated metastasis and cisplatin resistance in cervical cancer.

Cervical cancer is the fourth most common malignant tumors in female worldwide. Cirular RNAs (circRNA) represent a new class of regulatory RNA and play a pivotal role in the carcinogenesis and development of tumors. However, their functions have not been fully elucidated in cervical cancer. In this study, we identified an upregulated circRNA, circ_0001589, both in fresh clinical samples and tissue microarray of cervical cancer. Transwell assay and cell apoptosis assay by flow cytometry demonstrated circ_0001589 promotes epithelial-mesenchymal transition (EMT)-mediated cell migration and invasion, and enhanced cisplatin resistance in vitro. In addition, in nude mice model, circ_0001589 increased the number of lung metastases and recovered xenograft growth from cisplatin treatment in vivo. Mechanistically, RNA pull-down assay, RNA immunoprecipitation, and dual-luciferase reporter assay disclosed that circ_0001589 function as an competing endogenous RNA to sponge miR-1248, which directly target the 3' untranslated region of high mobility group box-B1 (HMGB1). Thereby, circ_0001589 upregulated HMGB1 protein expression and accelerate cervical cancer progression. The rescue experiments also revealed that miR-1248 overexpression or HMGB1 knockdown partially reversed the regulatory functions of circ_0001589 on cell migration, invasion, and cisplatin resistance. In summary, our findings suggest the upregulation of circ_0001589 promoted EMT-mediated cell migration and invasion, and enhanced cisplatin resistance via regulating miR-1248/HMGB1 axis in cervical cancer. These results provided new evidence for understanding the carcinogenesis mechanism and finding new therapeutic target for cervical cancer.

Atomic Cu-N-P-C Active Complex with Integrated Oxidation and Chlorination for Improved Ethylene Oxychlorination.

Fine constructing the chemical environment of the central metal is vital in developing efficient single-atom catalysts (SACs). Herein, the atomically dispersed Cu on the N-doped carbon is modulated by introducing CuP moiety to CuNC SAC. Through fine-tuning with another heteroatom P, the Cu SAC shows the superior performance of ethylene oxychlorination. The Cu site activity of Cu-NPC is four times higher than the P-free Cu-NC catalyst and 25 times higher than the Ce-promoted CuCl2 /Al2 O3 catalyst in the long-term test (>200 h). The selectivity of ethylene dichloride can be splendidly kept at ≈99%. Combined experimental and simulation studies provide a theoretical framework for the coordination of Cu, N, and P in the complex active center and its role in effectively catalyzing ethylene oxychlorination. It integrates the oxidation and chlorination reactions with superior catalytic performance and unrivaled ability of corrosive-HCl resistance. The concept of fine constructing with another heteroatom is anticipated to provide with inspiration for rational catalyst design and expand the applications of carbon-based SACs in heterogeneous catalysis.

Evaluation of the presence of SARS-CoV-2 in vaginal and anal swabs of women with omicron variants of SARS-CoV-2 infection.

Objectives: The study aimed to determine whether SARS-CoV-2 Omicron variant could be detected in the vaginal fluid and anal swabs of reproductive-aged and postmenopausal women infected with SARS-CoV-2 Omicron variant. Methods: Included in this study were 63 women who were laboratory confirmed as having SARS-CoV-2 Omicron variant infection and admitted to the responsible ward of Daping Hospital of at the National Exhibition and Convention Center(Shanghai) Makeshift Hospital from May 1-24, 2022.From them, vaginal and anal swabs were obtained with informed consent. The demographic and baseline clinical characteristics and the swab test results were analyzed. Results: The 63 included patients ranged in age from 18 to 72 years with a median of 47.71 ± 15.21 years. Of them, 38 women (60.3%) were in their reproductive years. Most of the participants (77.8%) were healthy without significant underlying diseases. Fourteen patients (22.2%) had asymptomatic infection and the remaining 49 (77.8%) had mild infection. The upper respiratory tract symptoms including cough (40/63.5%) and sore throat (18/28.6%)were the most common clinical manifestations of these mildly infected patients. Only 5 patients (7.8%) had gastrointestinal (GI) symptoms, including simple diarrhea in 4 patients, and diarrhea with vomiting in one patient. Pharyngeal,vaginal and anal swabs were collected simultaneously from all 63 patients 8-16 (mean 11.25 ± 2.23) days after SARS-Cov-2 Omicron variant infection. The vaginal swabs were negative for SARS-CoV-2 in all 63 patients, and the anal swabs were positive in 4 patients (6.5%). The overall median hospitalization duration was 16.73 ± 3.16 days. Conclusion: The results of the present study suggest that there is a low possibility of SARS-Cov-2 Omicron variant transmission via the digestive tract and vaginal fluid. The correlation between the GI symptoms and the presence of viral RNA in anal swabs is uncertain.

[Clinical characteristics in patients with persistent positive pharyngeal swab of omicron variant and analysis on nucleic acid testing of anal swabs].

OBJECTIVE: To analyze the clinical characteristics in patients with persistent positive pharyngeal swab of 2019 novel coronavirus Omicron variant and results of nucleic acid testing of anal swabs to provide basis for prevention and control measures. METHODS: This study included 93 patients whose pharyngeal swab nucleic acid test were persistent positive and admitted to the ward of Daping Hospital in the National Exhibition and Convention Center (Shanghai) Makeshift Hospital from May 1 to May 24, 2022. The gender, age, underlying diseases, vaccination status, clinical symptoms, interval between infection onset and anal sampling, length of hospital stay, the nucleic acid test result of pharyngeal swabs and anal swabs and the time turning negative were collected and analyzed. RESULTS: The age of 93 patients ranged from 8 to 72 years old with a median of (46.0±16.0) years old. Among them, 30 cases (32.3%) were male and 63 cases (67.7%) were female. Sixty-five patients (69.9%) received 2-3 shots of vaccine, 2 patients (2.1%) received 1 shot, and 26 patients (28.0%) did not receive any vaccination. Twenty patients (21.5%) had underlying diseases, of which hypertension (13 cases, 14.0%) and type 2 diabetes mellitus (6 cases, 6.5%) were the most common. Twenty-four patients (25.8%) had asymptomatic infection and the rest (69 cases, 74.2%) had mild symptoms. Cough (50 cases, 53.8%) and sore throat (28 cases, 30.1%) were the most common clinical manifestations of the upper respiratory tract in these patients. Only 6 patients (6.5%) had gastrointestinal symptoms (including diarrhea in 5 patients and diarrhea with vomiting in 1 patient). Pharyngeal and anal swabs were collected simultaneously from all 93 patients at 8-16th days [(11.55±2.27) days] after 2019 novel coronavirus Omicron variant infection. The pharyngeal swabs were positive in 79 patients (85.0%) and the anal swabs were positive in 5 patients (5.4%). The time of pharyngeal swabs turning negative was (14.7±2.9) days, and that of anal swab turning positive was (14.2±1.9) days. The median length of hospital stay was (16.7±2.9) days. CONCLUSIONS: In patients with persistent positive nucleic acid of the 2019 novel coronavirus Omicron variant, there were more mild infection than asymptomatic. The upper respiratory tract symptoms such as cough and sore throat were the most. The likelihood of transmission of 2019 novel coronavirus Omicron variant through the digestive tract may be low. The correlation between gastrointestinal symptoms and 2019 novel coronavirus Omicron variant RNA in the digestive tract is uncertain.

Atomically Dispersed CoN3 C1 -TeN1 C3 Diatomic Sites Anchored in N-Doped Carbon as Efficient Bifunctional Catalyst for Synergistic Electrocatalytic Hydrogen Evolution and Oxygen Reduction.

A encapsulation-adsorption-pyrolysis strategy for the construction of atomically dispersed Co-Te diatomic sites (DASs) that are anchored in N-doped carbon is reported as an efficient bifunctional catalyst for electrocatalytic hydrogen evolution reaction (HER) and oxygen reduction reaction (ORR). The as-constructed catalyst shows the stable CoN3 C1 -TeN1 C3 coordination structure before and after HER and ORR. The *OOH/*H intermediate species are captured by in situ Raman and in situ attenuated total reflectance-surface enhanced infrared absorption spectroscopy, indicating that the reactant O2 /H2 O molecule has a strong interaction with the Co site, revealing that Coδ+ is an effective active site. Theoretical calculations show that the Coδ+ has adsorption-activation function and the neighboring Teδ+ acts as an electron donor adjusting the electronic structure of Coδ+ , promoting the dissociation of H2 O molecules and the adsorption of H and oxygen-containing intermediates in HER and ORR. In the meanwhile, the nearest C atom around Co also profoundly affects the adsorption of H atoms. This results in the weakening of the OH adsorption and enhancement of H adsorption, as well as the more stable water molecule dissociation transition state, thus significantly boosting ORR and HER performance.

Prostaglandin E2 serves a dual role in regulating the migration of dendritic cells.

Dendritic cells (DCs) are the most potent antigen­presenting cells, and are indispensable in the immune system. Prostaglandin E2 (PGE2) has been demonstrated to modulate the migration of DCs, but with inconsistent results. The present study, based on our previous research, used murine bone marrow­derived DCs to elucidate the potential regulatory mechanism of PGE2 on the migration of DCs. The results indicated that PGE2 served a dual role in regulating the migration of DCs in a dose­dependent manner. High concentrations of PGE2 inhibited cell migration, whereas low concentrations exhibited the opposite effect. Flow cytometry revealed that the expression of CC chemokine receptor type 7 on the DC surface was increased following treatment with low concentrations of PGE2 and slightly decreased by high concentrations of PGE2. The effect of PGE2 was indicated to be exerted via reorganizing the F­actin cytoskeleton using confocal microscopy. Moreover, the regulatory effect of PGE2 on the migration of DCs was validated in vivo. Subsequent gene expression profile analyses using RNA­sequencing technology indicated that PGE2 induced alterations in the expression of multiple downstream genes and signaling pathway molecules associated with cell migration and the cytoskeleton. These findings may provide an improved understanding on the mechanism of DC migration under both pathological and physiological conditions. Moreover, the biological implications of these findings may provide a novel perspective of the immunological surveillance in the progression of different types of diseases.

RhoB/ROCK mediates oxygen-glucose deprivation-stimulated syncytiotrophoblast microparticle shedding in preeclampsia.

Increased circulating syncytiotrophoblast microparticles (STBMs) are often associated with preeclampsia (PE) but the molecular mechanisms regulating STBM shedding remain elusive. Experimental evidence has shown that actin plays a key role in STBM shedding and that Rho/ROCK is important in regulating actin rearrangement. To investigate the role of RhoB/ROCK-regulated actin arrangement in STBM shedding in PE, chorionic villous explants were prepared from placenta of patients with normotensive or PE pregnancies and BeWo cells were fused to imitate syncytiotrophoblasts. The oxygen-glucose deprivation (OGD) conditions were applied to imitate the pathophysiology of PE in vitro. The results showed that RhoB and ROCK were activated in the preeclamptic placenta, accompanied by increased actin polymerization and decreased outgrowing microvilli. In villous tissue cultures or BeWo cells, OGD activated RhoB, ROCK1 and ROCK2 and promoted STBM shedding and actin stress fibers formation. In BeWo cells, RhoB overexpression activated ROCK1 and ROCK2, leading to F-actin redistribution and STBM shedding and the OGD-induced actin polymerization and STBM shedding could be reversed by RhoB or ROCK knockdown. These results reveal that RhoB and ROCK play a key role in PE by targeting STBM shedding through actin rearrangement and that RhoB/ROCK intervention may be a potential therapeutic strategy for PE.

[Relationship between the level of waist circumference and the impaired fasting glucose of pre-diabetes].

OBJECTIVE: To explore the relationship between the level of waist circumference (WC) and the impaired fasting glucose (IFG) in people working for the Kailuan Enterprise. METHODS: A total of 101 510 subjects from the employees of Kailuan Group who took part in the health examination between 2006 to 2007, with fasting plasma glucose (FPG) < 6.1 mmol/L, no history of diabetes, completed data on FPG and WC examination and without using hypoglycemic agents, were selected as the observation cohort. Subjects who did not participate in the health examination from 2010 to 2011 and had incomplete data were finally excluded, ended up with 52 099 subjects available for final analysis. According to the baseline WC measurements and its quartile in the health examinations during 2006 to 2007, people under observation were divided into four groups (first, second, third and the forth quartile groups). Multiple logistic regression analysis was used to test the relation between the increasing of WC and IFG. RESULTS: (1) The incidence rate of IFG in the obese group was higher than that in non-obese group (10.5% vs. 6.8% , P < 0.01), along with an increasing WC noticed in the 4 quartile groups and the incidence rates of IFG were progressively increased, being 6.0%, 7.1%, 8.6% and 11.0% respectively in the total population(7.0%, 7.9%, 9.1% and 11.4% in males, 2.5%, 4.6%, 6.8% and 9.8% in females). (2)Results from the multiple logistic regression analysis showed that, when compared with the first quartile group, the second, third and fourth quartile groups had increased risks of IFG after adjustment on age, gender and other risk factors in the total population, with the OR values being 1.03, 1.15 and 1.30 respectively. After adjusting the above factors in genders, we also noticed the increased risks of IFG, with the OR value being 1.45, 1.66 and 2.08 in males, while 1.00, 1.09 and 1.23 in females, respectively. The influence of the second and third quartile groups on IFG was not significant in females, however. CONCLUSION: The incidence of IFG showed an increasing trend with the increase of WC.

Clinical significance of hTERC gene detection in exfoliated cervical epithelial cells for cervical lesions.

OBJECTIVE: To investigate the clinical significance of abnormal human telomerase RNA gene component (hTERC) gene amplification tested by fluorescence in situ hybridization in cervical lesions. METHODS: In 373 patients with cytologic abnormalities, high-risk human papilomavirus (HR-HPV) was detected by the hybrid capture II method, and abnormal amplification of the hTERC gene in exfoliated cells was detected by fluorescence in situ hybridization. RESULTS: Cell smear findings suggested atypical squamous cells in 148 patients, low-grade squamous intraepithelial lesion in 62 patients, and high-grade squamous intraepithelial lesion in 107 patients, squamous cell carcinoma in 56 patients, and cervical biopsy-revealed inflammation in 89 patients, cervical intraepithelial neoplasia (CIN) I in 36 patients, CIN II in 43 patients, CIN III in 129 patients, and infiltrating carcinoma in 76 patients. In the inflammation, CIN I, CIN II, CIN III, and infiltrating carcinoma groups, the infection rates of HR-HPV were 29.21%, 52.78%, 74.42%, 92.25%, and 93.42% (P < 0.01), respectively; the positive rates of hTERC gene amplification were 0.00%, 13.89%, 41.86%, 78.29%, and 89.47% (P < 0.01), respectively. With respect to advanced cervical lesions (≥CIN II), cytology (≥ low-grade squamous intraepithelial lesion), HR-HPV testing, and hTERC testing differed insignificantly in the negative predictive value (P > 0.05), but they differed significantly in the sensitivity, specificity, and positive predictive value (P < 0.01). Among the 3 methods, hTERC testing showed the highest specificity and positive predictive value, and HR-HPV testing showed the highest sensitivity. In 41 patients with untreated CIN I and CIN II, the sensitivity of detection of hTERC gene amplification to predict lesion progression was 88.89%, and the specificity was 93.75%. CONCLUSION: Detection of abnormal amplification of the hTERC gene can assist in screening cervical lesions and identifying CIN I/II patients with a high progression risk.

Development of a PCR/LDR/capillary electrophoresis assay with potential for the detection of a beta-thalassemia fetal mutation in maternal plasma.

OBJECTIVE: Analysis of fetal DNA in maternal plasma has recently been introduced for non-invasive prenatal diagnosis. We have now investigated the feasibility of polymerase chain reaction (PCR)/ligase detection reaction (LDR)/capillary electrophoresis for the detection of fetal point mutations, such as the beta-thalassemia mutation, IVS2 654(C --> T), in maternal plasma DNA. METHODS: The sensitivity of LDR/capillary electrophoresis was examined by quantifying the mutant PCR products in the presence of a vast excess of non-mutant competitor template, a situation that mimics the detection of rare fetal mutations in the presence of excess maternal DNA. PCR/LDR/capillary electrophoresis was applied to detect the mutation, IVS2 654(C --> T), in an experimental model at different sensitivity levels and from 10 maternal plasma samples. RESULTS: Our results demonstrated that this approach to detect a low abundance IVS2 654(C --> T) mutation achieved a sensitivity of approximately 1:10,000. The approach was applied to maternal plasma DNA to detect the paternally inherited fetal IVS2 654(C --> T) mutation, and the results were equivalent to those obtained by PCR/reverse dot blot of amniotic fluid cell DNA. CONCLUSIONS: PCR/LDR/capillary electrophoresis has a very high sensitivity that can distinguish low abundance single nucleotide differences and can detect paternally inherited fetal point mutations in maternal plasma.

Epidermal growth factor stimulates human trophoblast cell migration through Rho A and Rho C activation.

This study investigated the roles of Rho protein in epidermal growth factor (EGF)-induced trophoblast cell migration and its mechanism. Using choriocarcinoma cell lines JEG-3 and JAR and first-trimester human chorionic villus explant cultures on matrigel, we examined EGF-mediated stimulation of trophoblast migration. EGF is shown to have a dose-dependent effect on trophoblast migration. A low concentration of EGF (1 ng/ml) has a stimulatory effect on cell migration, whereas high concentrations of EGF (100 ng/ml) shows an inhibitory effect. EGF (1 ng/ml) activates RhoA and RhoC, but not RhoB, through elevated protein levels and activity. EGF-induced migration was shown to be inhibited by either cell-permeable C3 exoenzyme transferase or selective RhoA or RhoC small interfering RNAs. The inhibition was not mitigated by the addition of EGF, suggesting that RhoA and RhoC play an important role in trophoblast migration and are obligatory for EGF action. Treatment of JEG-3 and JAR cells with RhoA small interfering RNA induced F-actin cytoskeleton disruption and cell shrinkage, which is consistent with the effect of C3 exoenzyme transferase, and this action was not mitigated by EGF treatment. RhoC small interfering RNA had no apparent effect on the F-actin arrangement, suggesting that RhoA but not RhoC takes part in the EGF-induced migration through F-actin rearrangement. These results indicate that RhoA and RhoC play more important roles than RhoB in EGF-mediated migration of trophoblast cells, and RhoA but not RhoC regulates this migration through F-actin cytoskeleton reorganization.

Expression and clinical implications of homeobox gene Six1 in cervical cancer cell lines and cervical epithelial tissues.

INTRODUCTION: The homeobox gene Six1 is overexpressed in multiple human tumors, playing a role in promoting tumorigenesis and metastasis. The present study was aimed to investigate the clinical implications of Six1 expression in cervical cancer. METHODS: Six1 messenger RNA (mRNA) and protein expression was detected by reverse transcription (RT) polymerase chain reaction and Western blotting, respectively, in human cervical cancer cell lines CaSki, HeLa, C33A and 20 normal cervical specimens, 21 specimens of cervical intraepithelial neoplasias (CINs), and 54 specimens of cervical cancer tissue, and the clinical implications of Six1 gene expression was analyzed. RESULTS: There was Six1 mRNA and protein overexpression in cervical cancer cell lines CaSki, HeLa, and C33A. The Six1 expression level was higher in CaSki and HeLa cells than in C33A cells (P < 0.05). Six1 mRNA and protein expression increased from normal cervical epithelial tissues, to CINs, and then to cervical cancer tissue (normal cervical epithelial tissue vs CIN, P < 0.05; normal cervical epithelial tissue vs cervical cancer, and CIN vs cervical cancer, P < 0.01). The status of Six1 overexpression was correlated to clinical staging and lymph node metastasis of cervical cancer (P < 0.01) but not to pathological grading, tumor size, and age of the patient (P > 0.05). CONCLUSION: Six1 was overexpressed in cervical cancer cell lines and in cervical cancer tissues. Alteration of Six1 expression might contribute to the occurrence and development of cervical cancer.

Prenatal detection of beta-thalassemia CD17 (A-->T) mutation by polymerase chain reaction/ligase detection reaction/capillary electrophoresis for fetal DNA in maternal plasma--a case report.

OBJECTIVES: It was the aim of this study to investigate the feasibility of polymerase chain reaction (PCR)/ligase detection reaction (LDR)/capillary electrophoresis for the detection of paternally inherited fetal CD17 (A-->T) mutation of beta-thalassemia in maternal plasma. METHODS: The target DNA in maternal plasma was amplified by PCR and the mutant signal was detected by LDR. Unique LDR products were produced and separated by capillary electrophoresis. PCR/LDR/capillary electrophoresis was applied to detect CD17 (A-->T) mutation in an experimental model at different sensitivity levels and from 3 maternal plasma samples. RESULTS: The sensitivity of PCR/LDR/capillary electrophoresis for detecting low-abundance CD17 (A-->T) mutation was 1:5,000 at least. The technique was applied in maternal plasma DNA for detecting paternally inherited fetal CD17 (A-->T) mutation, and the results were concordant with that of PCR/reverse dot blot of amniotic fluid cell DNA. CONCLUSIONS: PCR/LDR/capillary electrophoresis has a very high sensitivity to distinguish low-abundance single nucleotide differences and probably detects paternally inherited fetal point mutations in maternal plasma.