[Relationship between amniotic fluid inflammatory factors and pregnancy outcomes after emergency cervical cerclage].

Objective: To explore the relationship between amniotic fluid and peripheral blood inflammatory factors and the pregnancy outcomes after emergency cervical cerclage, and to identify effective indicators for predicting adverse pregnancy outcomes after the procedure. Methods: A case-control study was conducted, including pregnant women who were hospitalized at Sun Yat-sen Memorial Hospital, from January 1, 2013, to July 31, 2019, and underwent emergency cervical cerclage due to cervical dilatation at gestational age between 16 and 28 weeks. A total of 85 pregnant women who underwent amniocentesis for the detection of amniotic fluid inflammatory factors during the perioperative period were included. Based on whether their baby was perinatal death, the participants were divided into the case group (28 cases with perinatal death) and the control group (57 cases with live births). Univariate logistic regression analysis was performed to identify risk factors associated with adverse pregnancy outcomes, followed by multivariate logistic regression analysis to establish a regression model and nomogram. Results: (1) The levels of tumor necrosis factor α (TNF-α), interleukin (IL)-1ß, IL-6, IL-8, IL-10 in the amniotic fluid during the perioperative period and postoperative serum C-reactive protein (CRP) were significantly higher in the case group compared to the control group (all P<0.05). The case group underwent emergency cervical cerclage at an earlier gestational age compared to the control group, and their cervical dilation was greater than that of the control group (all P<0.05). However, there were no significant differences in the white blood cell counts, neutrophil percentage, and the level of preoperative CRP in the peripheral blood of pregnant women during the perioperative period (all P>0.05). (2) Univariate logistic regression analysis showed that the levels of amniotic fluid WBC, TNF-α, IL-1ß, IL-2 receptor (IL-2R), IL-6, IL-8, IL-10, postoperative CRP in the peripheral blood, gestational age at cerclage and cervical dilation were associated with adverse pregnancy outcomes (all P<0.05). Multivariate regression analysis indicated that only the levels of amniotic fluid WBC and TNF-α were independent risk factors for perinatal death. (3) Based on clinical practice, a multivariate logistic regression model was constructed including the levels of amniotic fluid TNF-α, WBC, gestational age at cervical cerclage, and cervical dilation. A nomogram and calibration curve were plotted, which suggested its good predictive value for adverse pregnancy outcomes. Conclusions: During the perioperative period of emergency cervical cerclage, the levels of amniotic fluid WBC, TNF-α, IL-1ß, IL-2R, IL-6, IL-8, IL-10 are associated with adverse pregnancy outcomes, with amniotic fluid WBC and TNF-α showing the closest relationship. However, there is no significant correlation between maternal peripheral hemogram during the perioperative period and adverse pregnancy outcomes. A model constructed by amniotic fluid TNF-α, WBC, cervical cerclage gestational age, and cervical dilation has a good predictive effect on adverse pregnancy outcomes.

Retraction Note: Disruption of the Bcr-Abl/Hsp90 protein complex: a possible mechanism to inhibit Bcr-Abl-positive human leukemic blasts by novobiocin.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Bone marrow mesenchymal stem cells repair brachial plexus injury in rabbits through ERK pathway.

OBJECTIVE: To investigate the effect of bone marrow mesenchymal stem cells (BMSCs) on repairing brachial plexus injury in rabbits and their influence on expression of the extracellular signal-regulated kinase (ERK) pathway. MATERIALS AND METHODS: With big-ear rabbits as the objects, the BMSCs were first isolated, and the cluster of differentiation (CD)45- and CD90+ BMSCs were sorted out via flow cytometry. BMSCs were transfected with red fluorescent protein (RFP), and the transfection effect was detected. Then, the big-ear rabbits were subjected to brachial plexus root avulsion injury (BPAI) to establish injury Model group and sham-operation group (Sham group). Later, the BMSCs were transfected with RFP to construct RFP-BMSCs. The RFP-BMSCs (5×106, Treat group) and normal saline (Model group) were intraperitoneally injected, and the recovery rate of wet weight of the upper limb muscle was measured by weighing. The injured nerve tissues were embedded for hematoxylin and eosin (HE) staining and observation of pathological changes. The electrophysiological measurement of the compound muscle action potential (CMAP) on the injured side was conducted for the rabbits to be sacrificed immediately using an electromyogram instrument, and the CMAP amplitude and latency were applied to evaluate the recovery of upper limb muscle. Finally, the location of RFP-BMSCs in the nerve tissues was traced by a fluorescence microscope, and the protein expression levels of phosphorylated ERK (p-ERK) and phosphorylated mitogen-activated protein kinase (p-MAPK) in the injured nerve tissues were determined by means of Western blotting. RESULTS: Persistently expressed red fluorescence was observed in CD45- and CD90+ BMSCs sorted via flow cytometry under the fluorescence microscope, indicating that the RFP-BMSCs were constructed successfully. Compared with Sham group, Model group had a remarkably decreased recovery rate of wet muscle weight (p<0.05), while Treat group exhibited a notably increased recovery rate of wet muscle weight in comparison with Model group. The CMAP amplitude was reduced markedly (p<0.05), while the CMAP latency was prolonged significantly (p<0.05) in Model group compared with those in Sham group. Moreover, Treat group had distinctly higher CMAP amplitude and evidently shorter CMAP latency than Model group (p<0.05). It was discovered under the fluorescence microscope that RFP-BMSCs were visibly arranged on both sides of nerve fibers in Treat group. The expressions of p-MAPK and p-ERK were raised prominently in Model group in comparison with those in Sham group (p<0.05), and they were lowered apparently in Treat group compared with those in Model group (p<0.05). CONCLUSIONS: BMSCs can repair the impaired brachial plexus neurons and restore their physiological functions, and the protective effect of the BMSCs on the neurons is associated with the mediated MAPK/ERK pathway.

[Analysis of the factors affecting the efficacy of (131)I remnant ablation in patients after thyroidectomy for papillary thyroid microcarcinoma].

Objective: To investigate the influential factors of efficacy of the first (131)I ablation therapy for thyroid remnant in papillary thyroid microcarcinoma (PTMC) patients after thyroidectomy. Methods: Eighty-nine PTMC patients who underwent twice (131)I ablation therapy and (131)I whole body follow-up scan ((131)I-WBS) within 5 to 8 months in our department from September 2007 to October 2016 were identified and enrolled in present study. Patients were divided into complete-ablation group and uncomplete-ablation group according to whether or not radioactivity was detected at the thyroid bed in (131)I-WBS. The χ(2) test and multi-variance Binary logistic regression were performed for the factors which might affect the therapeutic efficacy. Results: The first (131)I ablation therapy was successful in 41 of 89 patients (46.07%). Residual thyroid weight was found to be associated with therapeutic efficacy (P<0.05), while gender, age, surgical method, lesions'maximum diameter, with or without LN metastasis, with or without distant metastasis, time of operation from first (131)I treatment, lesions'number, thyroid stimulating hormone (TSH), thyroglobulin (Tg), the consistency of (131)I-WBS and (99)Tc(m)-pertechnatate, TNM stage, ATA risk, Tg/TSH ratio were not significant associated with therapeutic efficacy. Binary logistic regression analysis was performed in these respects and it indicated that residual thyroid weight and ATA risk were not statistically significant independent variable (P>0.05). Conclusions: Residual thyroid weight might affect efficacy of the first (131)I ablation therapy on thyroid remnant in PTMC patients after thyroidectomy, but it is not an independent factor. Multiple interrelated factors should be considered when predicting the efficacy of the first (131)I ablation therapy.

Association between Ca/Mg/P status and suppurative tonsillitis in children.

Suppurative tonsillitis (ST) is a common respiratory disease in children. This study aims to investigate the association between calcium (Ca)/magnesium (Mg)/phosphorus (P) and the risk of onset of suppuration in tonsillitis in children. Seventy children with ST and 61 age- and sex-matched children with non-ST were enrolled in this study. The association between Ca/Mg/P and suppuration risk in tonsillitis was investigated. The relationship between Ca/Mg/P and the potential risk factors for ST were also studied. White blood cell (WBC), platelet (PLT), c-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) levels were significantly higher in the ST group than those in the non-ST group (p less than 0.05). Mg and P levels were significantly lower in the ST group than those in the non-ST group (p less than 0.05). There was no obvious difference in Ca level between the ST group and the non-ST group (p=0.762). A significantly negative association between P and PCT was noted (r=-0.236, p=0.035). The results indicated that Mg/P disorder may be associated with the susceptibility to suppuration in children with tonsillitis, inflammatory indexes may reflect this risk.

Extensible chip of optofluidic variable optical attenuator.

A core chip of optofluidic variable optical attenuator (VOA) is reported. The chip, with a simple structure, utilizes microfluid and compressed air to regulate the optical attenuation, and it can be expanded to form a number of VOAs by using different microfluidic driving technologies. Three VOAs based on this chip and different driving technologies are introduced. The theoretical and experimental results show that the proposed chip possesses the advantages of large optical attenuation range (> 50dB) and low insertion loss (0.55 dB). Moreover it is a broadband optical device which can be operated in visible and near infrared wavelengths. The proposed chip provides a new method for seeking miniaturized VOAs with good performances, and it is promising to develop a number of different VOAs.

Significant association between the MTHFR A1298C polymorphism and hepatocellular carcinoma risk: a meta-analysis.

The A1298C polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene has been reported to be associated with hepatocellular carcinoma (HCC), but there are conflicting results from previous studies. The present study aimed to investigate the association between this polymorphism and the risk of HCC using a meta-analysis of the published studies. Published literature from PubMed and Embase databases was systematically searched to identify relevant studies before October 2014. The Begg test was used to measure publication bias. Sensitivity analyses were performed to ensure the authenticity of the outcome. The meta-analysis results showed significant association between the MTHFR A1298C polymorphism and HCC risk (CC vs AA: OR = 0.52, 95%CI = 0.33-0.81; CC vs AC: OR = 0.50, 95%CI = 0.32-0.79; dominant model: OR = 1.94, 95%CI = 1.24-3.02; recessive model: OR = 1.00, 95%CI = 0.84-1.18). In the subgroup analysis, significant associations between the MTHFR A1298C polymorphism and HCC risk were found in Asians (CC vs AA: OR = 0.46, 95%CI = 0.27-0.78; CC vs AC: OR = 0.41, 95%CI = 0.24-0.71; dominant model: OR = 2.27, 95%CI = 1.33-3.86; recessive model: OR = 1.03, 95%CI = 0.86-1.24). Our results suggest that the MTHFR A1298C polymorphism might be related to increased risk of HCC in Asians. Further large and well-designed studies are needed to confirm these conclusions.

Effect of HIF-1a/VEGF signaling pathway on plasma progesterone and ovarian prostaglandin F2a secretion during luteal development of pseudopregnant rats.

The corpus luteum is a temporary endocrine structure in mammals that plays an important role in the female reproductive cycle and is formed from a ruptured and ovulated follicle with rapid angiogenesis. Vascular endothelial growth factor (VEGF) is thought to be vital in normal and abnormal angiogenesis in the ovary, but the molecular regulation of luteal VEGF expression during corpus luteum development in vivo is still poorly understood at present. Therefore, we examined whether hypoxia-inducible factor-1a (HIF-1a) is induced and regulates VEGF expression and luteal function in vivo using a pseudopregnant rat model treated with a small-molecule inhibitor of HIF-1a, echinomycin. Corpus luteum development in the pseudopregnant rat ovary was determined after measuring plasma progesterone concentration and ovarian prostaglandin F2a content to reflect changes in HIF-1a and VEGF on different days of this developmental process. At day 7, the corpus luteum was formed and the expression of HIF- 1a/VEGF reached a maximum, while a significant decrease in HIF-1a/ VEGF expression was observed when luteolysis occurred at day 13. Additionally, echinomycin blocked luteal development by inhibiting VEGF expression mediated by HIF-1a and following luteal function by detecting the progesterone changes at day 7. These results demonstrated that HIF-1a-mediated VEGF expression might be an important mechanism regulating ovarian luteal development in mammals in vivo, which may provide new strategies for fertility control and for treating some types of ovarian dysfunction, such as polycystic ovarian syndrome, ovarian hyperstimulation syndrome, and ovarian neoplasia.

Retrospective epidemiological analysis of sparganosis in mainland China from 1959 to 2012.

In this study, epidemiological factors of sparganosis cases reported in mainland China from 1959 to December 2012 were analysed. A total of 1061 valid cases were distributed throughout most of the provinces of mainland China, with most cases occurring in Southern and Eastern China. The average age of patients was 29 years (range 0-80 years). Modes of transmission to humans were via contact (54·6%), mainly by application of frog meat as a poultice, foodborne (33·8%), mainly through ingesting frogs or snakes, and waterborne (11·5%) through drinking raw water. The tissue/organs involved were subcutaneous/muscle (43·1%), eyes (31·0%), central nervous system (CNS) (17·9%), urogenital system (3·9%) and visceral organs (3·2%). Obvious differences existed in main risk factors for different areas. Close correlation was found between tissue/organs and risk factors. Main modes of transmission changed during the past decades, from contact (83·8% pre-1979) to foodborne (63·9% post-2000). The tissue/organs involved also changed at the same time. Cases involving eyes fell from 50·0% pre-1979 to 8·3% post-2000, and cases involving CNS increased from 0% pre-1979 to 47·8% post-2000. These results illustrate that China is one of the main epidemic countries of sparganosis in the world. Consumption of frog/snake meat was the main risk factor, although application of frog flesh as a poultice was the main risk factor before 2000. Sparganosis has become one of the neglected but important foodborne/waterborne parasitic diseases in mainland China.

Effect of diclofenac on the pharmacokinetics of moxifloxacin in rats.

A sensitive and specific method was developed and validated for the determination of moxifloxacin in plasma using HPLC. The effect of diclofenac (12.5, 25, 50 mg/kg) on the pharmacokinetics of orally administered moxifloxacin (40 mg/kg) in rats was investigated. Pharmacokinetic parameters of moxifloxacin were determined in rats following oral administration to rats in the presence and absence of diclofenac. The coadministration of the 2 drugs resulted in 10~29.5% decrease of the AUC and a 24.7~34% decrease of t1/2 for moxifloxacin; Tmax for moxifloxacin was 1.41~1.9-fold higher than that after the administration of moxifloxacin alone; Cmax for moxifloxacin decreased by 20.5~49%, as compared to that after the administration of moxifloxacin alone. Consequently, moxifloxacin and diclofenac should be monitored closely for potential drug interactions.

A simply HPLC method for determination of cefpodoxime in Chinese volunteer and pharmacokinetic study.

A sensitive HPLC method was developed for the determination of cefpodoxime in human plasma. After protein precipitation with acetonitrile, sample was injected into the HPLC system for analysis. The chromatographic separation was carried out on a Diamonsil C18 column with a mobile phase consisting of acetonitrile-water. The mobile phase composed of water (containing 20 mmol/L monoammonium phosphate) and acetonitrile (90: 10, v/v). The detection wavelength was set at 254 nm. The standard curve for cefpodoxime was linear over the concentration range of 0.05-8 µg/mL with a lower limit of quantification of 0.05 µg/mL. The intra- and inter-day RSD values were lower than 10%, and the RE values were within±5%. For the pharmacokinetic analysis of plasma, the mean (SD) values obtained for the formulation were: Cmax, 4.21 (0.62) µg/mL; Tmax, 2.47 (0.61) h; t1/2, 2.38 (0.46) h; AUC0-24 h, 21.13 (3.39) µg/mL/h; and AUC0-∞, 23.34 (3.87) µg/mL/h; MRT, 2.21 (0.41) h, respectively.

Disruption of the Bcr-Abl/Hsp90 protein complex: a possible mechanism to inhibit Bcr-Abl-positive human leukemic blasts by novobiocin.

The Bcr-Abl fusion gene encodes for the p210(Bcr-Abl) or p185(Bcr-Abl) tyrosine kinase (TK) implicated in the pathogenesis of chronic myelogenous leukemia (CML) or acute lymphoblastic leukemia, respectively. Because Bcr-Abl TK is chaperoned by Hsp90 (90 kDa heat-shock protein), we investigated the effects of novobiocin (NB), an Hsp90 C-terminal inhibitor, on the viability of the Bcr-Abl-positive human leukemia cells HL-60/Bcr-Abl and K562, the expression of Bcr-Abl protein and the interaction between Hsp90 and Bcr-Abl TK. Present studies demonstrate that NB is a potent inhibitor of the growth of Bcr-Abl-positive human leukemia cells. NB induces cytosolic accumulation of cytochrome c and activation of caspase-9 and caspase-3, triggering apoptosis of HL-60/Bcr-Abl and K562 cells. Treatment of cell lines with NB disrupts Bcr-Abl /Hsp90 and Bcr-Abl /Hsp70 interactions, resulting in a decreased amount of intracellular Bcr-Abl protein levels. Co-treatment with the proteasome inhibitor N-acetyl leucyl-leucyl norlucinal increases NB-mediated accumulation of Bcr-Abl in the detergent-insoluble cellular fraction, which demonstrates that NB promotes proteasomal degradation of Bcr-Abl. Moreover, both imatinib-resistant K562/G01 and primary CML CD34(+) cells are sensitive to NB.

[Heat shock response induces resistance to hydrogen peroxide and increases synthesis of interleukin-6 in rat astrocyte in vitro].

Cell viability and cell membrane disruption of rat astrocyte after heat shock response (HSR) were assessed by the analysis of MTT reduction and lactate dehydrogenase (LDH) release. We studied whether HSR would modulate the susceptibility of astrocyte to H2O2-induced oxidative stress. Cell viability was assessed by reduction of MTT. HSR in 43 degrees C water bath for 30 min decreased H2O2 toxicity (P < 0.01) to astrocyte. HSR induced decrease in H2O2 (50 mumol/L) toxicity was also shown by the reduction in the release of LDH, which was a marker of cell membrane disruption. The result also showed that prior to the incubation in 43 degrees C water bath for 30 min strongly increased IL-6 release 6 h (P < 0.05) after HSR. The above data suggest that the enhanced release of IL-6 from astrocyte may be one of the mechanisms underlying the cell protective effect induced by HSR.

Transient expression of virus-specific promoters in murine resident peritoneal macrophages.

Monocyte-macrophages (MO), being non-permissive for most viruses, play an important role in resistance to virus infection. In order to establish the mechanism of abortive infection of murine resident peritoneal MO (ResPMO) by herpes simplex virus type 1 (HSV-1), it is desirable to transfect these cells with viral promoters linked to an assayable gene, for example, the bacterial chloramphenicol acetyl transferase (CAT) gene. This will facilitate studies designed to measure levels of promoter activation or repression in these specialized cells. Transient expression of CAT in ResPMO was achieved with DEAE-dextran, but not using either calcium phosphate precipitate or lipofectin. CAT expression driven by various virus-specific promoters was less efficient in ResPMO compared with Vero cells and approximately 50% of input plasmid DNA remained in Vero cells at 48 h post transfection, but only 9% was detectable in ResPMO. However, approximately 6% of ResPMO and 9% of Vero cells contained CAT-specific DNA at 24 h post transfection. In addition, 2% of cells of either cell type contained CAT-specific polypeptide at 48 h. This is therefore the first report that the non-replicating murine ResPMO can be transfected in vitro and more importantly, that these cells express the transfected gene products.

Impaired interleukin 1 and interleukin 2 production following in vitro abortive infection of murine spleen mononuclear cells by Semliki Forest virus.

The effect of Semliki Forest virus (SFV) infection of murine spleen mononuclear cells was investigated in vitro. A small percentage of spleen macrophages expressed viral antigens, but no infectious virus particles were released, indicating an abortive-type infection. Wild-type SFV infected a higher percentage of macrophages than the attenuated, demyelinating mutant A7. The proliferation of spleen mononuclear cells under Con A stimulation was inhibited by the viral infection. The supernatant (SN) harvested from infected and Con A-stimulated spleen adherent cells could not stimulate thymocytes in an interleukin 1 (IL-1) assay and indomethacin treatment of infected cultures had no effect. The stimulatory effect of SN from noninfected cultures in the IL-1 assay was reduced when SN from infected cultures was added, suggesting the presence of an IL-1 inhibitor. Interleukin 2 (IL-2) production by splenocytes also decreased after viral infection, but exogenous IL-2 restored the response to Con A stimulation of infected spleen cells. This study demonstrates that abortive SFV infection of spleen macrophages has an immunosuppressive effect which may lead to an aberrant immune regulation.

Effect of viral infection on experimental allergic encephalomyelitis in mice.

BALB/c mice were irradiated with 350 R and injected with mouse spinal cord homogenate (MSCH) in complete Freund's adjuvant. Only 15-30% of these animals developed signs of experimental allergic encephalomyelitis (EAE) at 21-28 days after inoculation. Intraperitoneal infection with the non-lethal A7 strain of Semliki forest virus (SFV) 7 days after sensitization reduced the mean appearance time of the EAE symptoms to 14 days and the number of animals with clinical EAE increased up to 70%. In contrast, virus inoculation 10 days before induction of EAE decreased significantly the incidence of clinical EAE in both BALB/c and SJL mice. Demyelination with increased cellularity, presence of macrophages, stripping of myelin from the axons and sparing of oligodendrocytes was observed in spinal cords of animals at days 13-16 after induction of EAE and subsequent virus infection. No demyelination was seen in specimens taken at the same time from mice inoculated with MSCH or SFV alone. Combined MSCH and virus inoculations induced changes in the general immune response which may be one of the major reasons for the increase or decrease in demyelination in this model.