The potential mechanism of Guizhi Fuling Wan effect in the treatment of cervical squamous cell carcinoma: A bioinformatics analysis investigation.

As a global malignancy with high mortality rate, targeted drug development for Uterine Cervical Neoplasms is an important direction. The traditional formula Guizhi Fuling Wan (GFW) is widely used in gynecological diseases. However, its potential mechanism of action remains to be discovered. We retrieved GFW and cervical squamous cell carcinoma (CSCC) targets from public databases. The protein-protein interaction network was obtained by string computational analysis and imported Cytoscape_v3.9.0 to obtain the core network and the top 10 Hub genes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes were used for enrichment analysis of the core network, and then molecular docking to verify whether the selected signaling pathway binds well to the core node. Finally, clinical prognostic analysis and expression differences of Hub genes were validated using the Cancer Genome Atlas database and R language. Our search yielded 152 common targets for GFW and CSCC. The interleukin-17 signaling pathway, tumor necrosis factor signaling pathway, and Toll-like signaling pathway were then selected for further molecular docking from the hub genes enrichment analysis results, which showed good binding. Among the Hub genes, JUN, VEGFA, IL1B, and EGF had a poor prognosis for CSCC. In conclusion, this study illustrates that GFW can have adjuvant therapeutic effects on CSCC through multiple targets and multiple pathways, providing a basis for further research.

Percutaneous intramyocardial septal radiofrequency ablation after 5-year follow-up.

OBJECTIVE: The objective is to evaluate the 5-year follow-up results of percutaneous intramyocardial septal radiofrequency ablation (PIMSRA) for hypertrophic obstructive cardiomyopathy (HOCM), including clinical status, electrocardiographic and echocardiographic characteristics. METHODS: 27 patients (age: 44.3±15.5 years; 67% men, 33% women) with severely symptomatic HOCM who underwent PIMSRA from October 2016 to September 2017 were included. Their clinical status, resting and exercise stress echocardiography, electrocardiography and cardiac MRI (CMRI) after long-term follow-up were assessed. RESULTS: One patient died of intracerebral haemorrhage 1 year post procedurally. The New York Heart Association class, Canadian Cardiovascular Society class and exercise-induced syncopal attacks improved significantly in 26 patients (all p<0.01). Left ventricular (LV) outflow tract gradients revealed sustained reduction (resting: from 95.0 to 9.0 mm Hg, p<0.001; post exercise: from 130.5 to 21.0 mm Hg, p<0.001). The echocardiographic evaluation revealed decreased septal thickness, LV posterior wall thickness and left atrial (LA) diameter (all p<0.001). CMRI data revealed decrease in LV mass index and LA volume index and increase in LV end-diastolic volume index and stroke volume index between baseline and long-term follow-up (all p<0.05). The global longitudinal strain of LV improved from (-11.9%±3.7%) before the procedure to (-13.1%±3.9%) at the last check (p<0.001). Malignant ventricular arrhythmia and heart failure events were not observed. CONCLUSIONS: PIMSRA can effectively alleviate symptoms in patients with HOCM and improve their hemodynamics in the long term. TRIAL REGISTRATION NUMBER: NCT02888132.

High Selectivity Cofactor NADH Regeneration Organic Iridium Complexes Used for High-Efficiency Chem-Enzyme Cascade Catalytic Hydrogen Transfer.

Our research demonstrated that novel pentamethylcyclopentadienyl (Cp*) iridium pyridine sulfonamide complex PySO2NPh-Ir (7) could highly specifically catalyze nicotinamide adenine dinucleotide (NAD+) into the corresponding reducing cofactor NADH in cell growth media containing various biomolecules. The structures and catalytic mechanism of 7 were studied by single-crystal X-ray, NMR, electrochemical, and kinetic methods, and the formation of iridium hydride species Ir-H was confirmed to be the plausible hydride-transfer intermediate of 7. Moreover, benefiting from its high hydrogen-transfer activity and selectivity for NADH regeneration, 7 was used as an optimal metal catalyst to establish a chem-enzyme cascade catalytic hydrogen-transfer system, which realized the high-efficiency preparation of l-glutamic acid by combining with l-glutamate dehydrogenase (GLDH).

Retrospective study to assess the effect of epidural analgesia on labor progress and women's pelvic floor muscle from the perspective of electromyography.

OBJECTIVE: Epidural analgesia has been widely used as a form of pain relief during labor and its safety has been gradually recognized. However, few studies of the effect of epidural analgesia on the pelvic floor are known. Thus, we aim to analyze the effect of epidural analgesia on labor progress and women's pelvic floor muscle from the perspective of electromyography systematically. In addition, obstetric risk factors for dysfunction of pelvic floor muscle after vaginal delivery were also evaluated. METHODS: Childbirth data of 124 primiparas who gave first birth vaginally in our hospital and their pelvic floor function assessment results at postpartum 7 weeks were retrospectively collected. Pelvic floor muscle electromyogram screenings were performed by a biofeedback electro-stimulant therapy instrument. RESULTS: There was no significant difference in the percentage of episiotomy, forceps, artificial rupturing membrane, and the application of oxytocin, except perineal laceration. Woman who implemented epidural analgesia experienced a longer stage of labor. Statistically, there was no significant difference in the total score and pelvic floor muscle strength. The risk factors for the value of the pre-rest phase include the age of pregnant women, the fetal weight, and the length of the second stage while the value of the post-rest phase was only associated with the fetal weight and the length of the second stage. In addition, the value of type I muscles was associated with the gravida and fetal weight while the value of type II muscles was only associated with forceps. The sustained contraction was correlated with the gravida and the total scores had a significant correlation with forceps. CONCLUSION: Epidural analgesia during labor is approved to be a safe and effective procedure to relieve pain with very low side effects on the mode of labor and pelvic floor muscle. The assessment of pelvic floor muscle before pregnancy is beneficial in guiding the better protection of pelvic floor muscle function. According to the evaluation results, the doctors can control the associated risk factors as much as possible to reduce the injury of pregnancy and parturition to the pelvic floor.

Rolipram suppresses migration and invasion of human choriocarcinoma cells by inhibiting phosphodiesterase 4-mediated epithelial-mesenchymal transition.

Rolipram is a selective phosphodiesterase-4 (PDE4) inhibitor. The effect of rolipram on the metastasis of choriocarcinoma is barely known. Here, we evaluated the role of rolipram in the migration and invasion of human choriocarcinoma cells in vitro. Human choriocarcinoma cells lines JEG3 and JAR were used in this study. The expression profile of PDE4 subfamily members in choriocarcinoma cells was evaluated using real-time PCR. The migration and invasion properties of choriocarcinoma cells before and after inhibition of PDE4 by rolipram or RNAi-directed knockdown were evaluated in vitro. Expression levels of MMP9, TIMP1, E-cadherin, vimentin, TGFß1, SMAD1, and SMAD4 of choriocarcinoma cells were compared before and after rolipram treatment, RNAi-directed knockdown of PDE4D, and overexpression of PDE4D. We found PDE4D was the most commonly expressed isoform of PDE4 both in JEG3 and JAR cells. Rolipram and knockdown of PDE4D were efficient to inhibit the migration and invasion of choriocarcinoma cells in vitro, accompanied by decreased expression of MMP9 and TIMP1. Furthermore, rolipram and knockdown of PDE4D promoted the expression of E-cadherin but reduced the expression of vimentin in choriocarcinoma cells, and overexpression of PDE4D decreased the expression of E-cadherin but promoted the expression of vimentin. Rolipram suppressed migration and invasion of human choriocarcinoma cells in vitro, possibly by inhibiting epithelial-mesenchymal transition through PDE4 inhibition.

New-onset Systemic Lupus Erythematosus in a Woman with Previous Lymphoma during Late Pregnancy: a case report and literature review.

BACKGROUND: Systemic lupus erythematosus (SLE) is most likely to occur during the first and second trimesters of pregnancy. There were few studies focused on the new-onset SLE during the late pregnancy or puerperium. SLE has been considered an important cause of thrombocytopenia. However, lymphoma may also be a cause of thrombocytopenia. Here, we reported a challenging case of new-onset SLE occurred at the gestational age of 33 weeks, and the pregnant woman suffered lymphoma before. CASE PRESENTATION: A 25-year-old primigravid Chinese woman with a medical history of non-Hodgkin lymphoma (NHL) suffered thrombocytopenia at 30+5 weeks of gestation. Her skin rashes occurred one week later. Her platelet count was decreased progressively. She had been misdiagnosed with the recrudescence of NHL. The final diagnosis of new-onset SLE was confirmed and a cesarean section was performed at the 34th week of pregnancy. Both the pregnant woman and the newborn were cured with good prognosis. CONCLUSION: SLE should be considered in a pregnant woman with a medical history of malignancy to rule out other diseases, especially the rheumatic immune diseases.

Praseodymia-titania mixed oxide supported gold as efficient water gas shift catalyst: modulated by the mixing ratio of oxides.

Modulating the active sites for controllable tuning of the catalytic activity has been the goal of much research, however, this remains challenging. The O vacancy is well known as an active site in reducible oxides. To modify the activity of O vacancies in praseodymia, we synthesized a series of praseodymia-titania mixed oxides. Varying the Pr : Ti mole ratio (2 : 1, 1 : 2, 1 : 1, 1 : 4) allows us to control the electronic interactions between Au, Pr and Ti cations and the local chemical environment of the O vacancies. These effects have been studied study by X-ray photoelectron spectroscopy (XPS), CO diffuse reflectance Fourier transform infrared spectroscopy (CO-DRIFTS) and temperature-programmed reduction (CO-TPR, H2-TPR). The water gas shift reaction (WGSR) was used as a benchmark reaction to test the catalytic performance of different praseodymia-titania supported Au. Among them, Au/Pr1Ti2O x was identified to exhibit the highest activity, with a CO conversion of 75% at 300 °C, which is about 3.7 times that of Au/TiO2 and Au/PrO x . The Au/Pr1Ti2O x also exhibited excellent stability, with the conversion after 40 h time-on-stream at 300 °C still being 67%. An optimal ratio of Pr content (Pr : Ti 1 : 2) is necessary for improving the surface oxygen mobility and oxygen exchange capability, a higher Pr content leads to more O vacancies, however with lower activity. This study presents a new route for modulating the active defect sites in mixed oxides which could also be extended to other heterogeneous catalysis systems.

Synthesis of stable and highly efficient Au@ZIF-8 for selective hydrogenation of nitrophenol.

A series of nanoparticles (NPs) with different Au content was successfully encapsulated into metal organic framework ZIF-8 with highly porous structure through room-temperature crystallization. X-ray diffraction, Fourier transform infrared spectroscopy, N2 adsorption and transmission electron microscopy were carried out to characterize the obtained Au@ZIF-8 heterogeneous catalytic material comprehensively. Au NPs were dispersed uniformly in the ZIF-8 and the Au NP diameter was 5-6 nm. The crystal structure of ZIF-8 was unchanged when compared with that before Au loading. It was found that the Au content plays an important role in the hydrogenation reaction. The obtained Au@ZIF-8 exhibited high hydrogenation activity to nitrophenol and excellent selectivity to aminophenol. The recyclability of the Au@ZIF-8 catalysts showed excellent catalytic performance and great stability in the recycling reaction.

Double triggers, nasal induction of a Parkinson's disease mouse model.

Animal models of Parkinson's disease (PD), a chronic and progressive neurodegenerative disease of the central nervous system (CNS), play a key role in investigating the pathogenesis and developing new therapeutic strategies of PD. However, this goal has been limited by certain weaknesses in the available animal models of PD, e.g., induction by either pro-inflammatory or neurotoxic reagents, or they are too time-/effort-consuming. Here, we report a double triggers, nasal induction of a PD mouse model that mimics the clinical, pathological features and pathogenesis of PD by intranasal (i.n.) administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) combined with lipopolysaccharide (LPS). After administration once every three days for 7 consecutive weeks, these mice displayed enhanced motor dysfunction, loss of dopaminergic neurons, α-synuclein accumulation, as well as activation of microglia and astrocytes in the substantia nigra pars compacta compared with mice that were administered MPTP or LPS alone. This study provides a novel and basic research tool for investigating the pathogenesis and therapeutic intervention of PD.

Reference-free determination of tissue absorption coefficient by modulation transfer function characterization in spatial frequency domain.

BACKGROUND: Spatial frequency domain (SFD) measurement allows rapid and non-contact wide-field imaging of the tissue optical properties, thus has become a potential tool for assessing physiological parameters and therapeutic responses during photodynamic therapy of skin diseases. The conventional SFD measurement requires a reference measurement within the same experimental scenario as that for a test one to calibrate mismatch between the real measurements and the model predictions. Due to the individual physical and geometrical differences among different tissues, organs and patients, an ideal reference measurement might be unavailable in clinical trials. To address this problem, we present a reference-free SFD determination of absorption coefficient that is based on the modulation transfer function (MTF) characterization. METHODS: Instead of the absolute amplitude that is used in the conventional SFD approaches, we herein employ the MTF to characterize the propagation of the modulated lights in tissues. With such a dimensionless relative quantity, the measurements can be naturally corresponded to the model predictions without calibrating the illumination intensity. By constructing a three-dimensional database that portrays the MTF as a function of the optical properties (both the absorption coefficient µ a and the reduced scattering coefficient [Formula: see text]) and the spatial frequency, a look-up table approach or a least-square curve-fitting method is readily applied to recover the absorption coefficient from a single frequency or multiple frequencies, respectively. RESULTS: Simulation studies have verified the feasibility of the proposed reference-free method and evaluated its accuracy in the absorption recovery. Experimental validations have been performed on homogeneous tissue-mimicking phantoms with µ a ranging from 0.01 to 0.07 mm-1 and [Formula: see text] = 1.0 or 2.0 mm-1. The results have shown maximum errors of 4.86 and 7% for [Formula: see text] = 1.0 mm-1 and [Formula: see text] = 2.0 mm-1, respectively. We have also presented quantitative ex vivo imaging of human lung cancer in a subcutaneous xenograft mouse model for further validation, and observed high absorption contrast in the tumor region. CONCLUSIONS: The proposed method can be applied to the rapid and accurate determination of the absorption coefficient, and better yet, in a reference-free way. We believe this reference-free strategy will facilitate the clinical translation of the SFD measurement to achieve enhanced intraoperative hemodynamic monitoring and personalized treatment planning in photodynamic therapy.

CYP1B1 enhances the resistance of epithelial ovarian cancer cells to paclitaxel in vivo and in vitro.

Ovarian cancer (OC) is the most frequent cause of mortality among gynecological malignancies, with a 5-year survival rate of approximately 30%. The standard regimen for OC therapy includes a platinum agent combined with a taxane, to which the patients frequently acquire resistance. Resistance arises from the oxidation of anticancer drugs by CYP1B1, a cytochrome P450 enzyme overexpressed in malignant OC. The aim of the present study was to determine the role of CYP1B1 expression in the drug resistance of OC to the taxane, paclitaxel (PTX). Immunohistochemical staining was used to assess CYP1B1 expression in a panel of ovarian samples (53 primary cancer samples, 14 samples of metastastic cancer, 30 benign tumor samples and 19 normal tissue samples). Semi-quantitative RT-PCR was also performed to determine CYP1B1 expression in several OC cell lines. Finally, we used proliferation and toxicity assays, as well as a mouse xenograft model using nude mice to determine whether α-naphthoflavone (ANF), a CYP1B1 specific inhibitor, reduces resistance to PTX. CYP1B1 was overexpressed in the samples from primary and metastatic loci of epithelial ovarian cancers. In some cell lines, PTX induced CYP1B1 expression, which resulted in drug resistance. Exposure to ANF reduced drug resistance and enhanced the sensitivity of OC cells to PTX in vitro and in vivo. The expression profile of CYP1B1 suggests that it has the potential to be a useful diagnostic marker and prognostic factor for malignant OC. The inhibition of CYP1B1 expression by specific agents may provide a novel therapeutic strategy for the treatment of patients resistant to PTX and may improve the prognosis of these patients.

[Effect of ghrelin on duodenal migrating myoelectric complex in rats with chronic renal failure].

OBJECTIVE: To investigate the effect of ghrelin on duodenal migrating myoelectric complex (MMC) in rats with chronic renal failure (CRF). METHODS: Thirty healthy male SD rats were randomly assigned into sham-operated group (n=6) and CRF group (n=24), and the latter group was divided into 4 subgroups according to ghrelin doses administered with or without pretreatment with the receptor antagonist D-Lys(3)-GHRP-6. After a 18-h fasting, the rats with or without pretreatment with D-Lys(3)-GHRP-6 were given subcutaneous injections of ghrelin at different doses to observe the changes in duodenal MMC recorded using a multi lead physiological recording system. RESULTS: Ghrelin significantly increased the MMC cycle duration and dose-dependently enhanced the frequency, amplitude and percentage of phase III MMC cycle. This effect was inhibited by the pretreatment with ghrelin receptor antagonist D-Lys(3)-GHRP-6. CONCLUSION: Ghrelin can promote gastrointestinal motilities of rats with CRF, and the receptor of ghrelin can regulate the activity of MMC.

Enhanced expressions of matrix metalloproteinase (MMP)-2 and -9 and vascular endothelial growth factors (VEGF) and increased microvascular density in the endometrial hyperplasia of women with anovulatory dysfunctional uterine bleeding.

OBJECTIVE: To evaluate the roles of endometrial matrix metalloproteinase (MMP)-2 and -9, vascular endothelial growth factors (VEGF), and microvascular density (MVD) in the occurrence of anovulatory dysfunctional uterine bleeding (DUB). DESIGN: A prospective analytical design. SETTING: The obstetrics and gynecology department of an academic training hospital. PATIENT(S): Sixty women with anovulatory DUB and 20 control women. INTERVENTION(S): Endometrial biopsies were obtained for the assessment of immunohistochemical staining of MMP-2 and -9, VEGF, and endometrial MVD using an antibody to CD34. MAIN OUTCOME MEASURE(S): The results were determined through the expressions of MMP-2 and -9, VEGF, and CD34. RESULT(S): The frequencies of MMP-2 and -9 expression in endometrial stroma and of VEGF expression in endometrial glands were all significantly higher in the endometrial hyperplasia of women with anovulatory DUB than they were in the control group. Additionally, the mean score of endometrial MVD was significantly higher in the endometrial hyperplasia of women with anovulatory DUB than it was in the control group. In women with anovulatory DUB, VEGF expression in endometrial glands was statistically correlated with MMP-2 and -9 expressions in endometrial stroma and endometrial MVD. CONCLUSION(S): These results suggest that enhanced expressions of MMP-2 and -9, VEGF, and increased MVD in endometrial hyperplasia may play important roles in the pathogenesis of women with anovulatory DUB.