Selective inhibition of c-Met signaling pathways with a bispecific DNA nanoconnector for the targeted therapy of cancer.

Hepatocyte growth factor receptor (c-Met) is a suitable molecular target for the targeted therapy of cancer. Novel c-Met-targeting drugs need to be developed because conventional small-molecule inhibitors and antibodies of c-Met have some limitations. To synthesize such drugs, we developed a bispecific DNA nanoconnector (STPA) to inhibit c-Met function. STPA was constructed by using DNA triangular prism as a scaffold and aptamers as binding molecules. After c-Met-specific SL1 and nucleolin-specific AS1411 aptamers were integrated with STPA, STPA could bind to c-Met and nucleolin on the cell membrane. This led to the formation of the c-Met/STPA/nucleolin complex, which in turn blocked c-Met activation. In vitro experiments showed that STPA could not only inhibit the c-Met signaling pathways but also facilitate c-Met degradation through lysosomes. STPA also inhibited c-Met-promoted cell migration, invasion, and proliferation. The results of in vivo experiments showed that STPA could specifically target to tumor site in xenograft mouse model, and inhibit tumor growth with low toxicity by downregulating c-Met pathways. This study provided a novel and simple strategy to develop c-Met-targeting drugs for the targeted therapy of cancer.

Cerebral venous congestion alters CNS homeostatic plasticity, evoking tinnitus-like behavior.

BACKGROUND: Brain function and neuronal activity depend on a constant supply of blood from the cerebral circulation. The cerebral venous system (CVS) contains approximately 70% of the total cerebral blood volume; similar to the cerebral arterial system, the CVS plays a prominent role in the maintenance of central nervous system (CNS) homeostasis. Impaired venous autoregulation, which can appear in forms such as cerebral venous congestion, may lead to metabolic abnormalities in the brain, causing severe cerebral functional defects and even chronic tinnitus. However, the role of cerebral venous congestion in the progression of tinnitus is underrecognized, and its pathophysiology is still incompletely understood. This study elucidated the specific pathogenetic role of cerebral venous congestion in the onset and persistence of tinnitus and the possible neurophysiological mechanisms. RESULTS: We found that a rat model of cerebral venous congestion exhibited tinnitus-like behavioral manifestations at 14 days postoperatively; from that point onward, they showed signs of persistent tinnitus without significant hearing impairment. Subsequent neuroimaging and neurochemical findings showed CNS homeostatic plasticity disturbance in rats with cerebral venous congestion, reflected in increased neural metabolic activity, ultrastructural synaptic changes, upregulated synaptic efficacy, reduced inhibitory synaptic transmission (due to GABA deficiency), and elevated expression of neuroplasticity-related proteins in central auditory and extra-auditory pathways. CONCLUSION: Collectively, our data suggest that alternations in CNS homeostatic plasticity may play a vital role in tinnitus pathology caused by cerebral venous congestion. These findings provide a new perspective on tinnitus related to cerebral venous congestion and may facilitate the development of precise interventions to interrupt its pathogenesis.

Cell Membrane-Anchored DNA Nanoinhibitor for Inhibition of Receptor Tyrosine Kinase Signaling Pathways via Steric Hindrance and Lysosome-Induced Protein Degradation.

Receptor tyrosine kinase (RTK) plays a crucial role in cancer progression, and it has been identified as a key drug target for cancer targeted therapy. Although traditional RTK-targeting drugs are effective, there are some limitations that potentially hinder the further development of RTK-targeting drugs. Therefore, it is urgently needed to develop novel, simple, and general RTK-targeting inhibitors with a new mechanism of action for cancer targeted therapy. Here, a cell membrane-anchored RTK-targeting DNA nanoinhibitor is developed to inhibit RTK function. By using a DNA tetrahedron as a framework, RTK-specific aptamers as the recognition elements, and cholesterol as anchoring molecules, this DNA nanoinhibitor could rapidly anchor on the cell membrane and specifically bind to RTK. Compared with traditional RTK-targeting inhibitors, this DNA nanoinhibitor does not need to bind at a limited domain on RTK, which increases the possibilities of developing RTK inhibitors. With the cellular-mesenchymal to epithelial transition factor (c-Met) as a target RTK, the DNA nanoinhibitor can not only induce steric hindrance effects to inhibit c-Met activation but also reduce the c-Met level via lysosome-mediated protein degradation and thus inhibition of c-Met signaling pathways and related cell behaviors. Moreover, the DNA nanoinhibitor is feasible for other RTKs by just replacing aptamers. This work may provide a novel, simple, and general RTK-targeting nanoinhibitor and possess great value in RTK-targeted cancer therapy.

The feasibility of laparoscopically assisted, hysteroscopic removal of interstitial pregnancies: A case series.

OBJECTIVE: The study objective was to assess the feasibility of the management of interstitial pregnancy by laparoscopically assisted hysteroscopic removal. METHODS: This retrospective study included a case series of 17 patients who were diagnosed interstitial pregnancy with dilated proximal tubal ostium by transvaginal ultrasonography at the Women's hospital, School of Medicine, Zhejiang University between August 2017 and October 2020. Laparoscopically assisted hysteroscopic removals of the products of conception were performed. Various data were collected including age, surgical and obstetric history, gestational age, preoperative symptoms, human chorionic gonadotropin level and ultrasonography results. The outcomes measured were intraoperative bleeding, pathologic findings, conversions. RESULTS: Eleven cases were successfully resected the interstitial gestational products with laparoscopically assisted hysteroscopy. There were four cases failed of hysteroscopic removal, for the proximal tubal ostia were too small for the surgical instruments to enter. Then cornual wedge resections were performed. Two cases were identified as intramural pregnancy by hysteroscopic and laparoscopic view. Most of the intramural pregnancy tissue of one patient was removed by hysteroscopy. The other one converted to laparoscopy. CONCLUSION: Laparoscopically assisted hysteroscopic management could be a feasible surgical option to interstitial pregnancies. Further clinical studies are needed to establish detailed criteria to select the appropriate cases for hysteroscopic management.

The comparison of placental abruption coupled with and without preeclampsia and/or intrauterine growth restriction in singleton pregnancies.

BACKGROUND: To compare the clinical features of placental abruption coupled with and without preeclampsia and/or intrauterine growth restriction in singleton pregnancies. METHODS: A retrospective study of 229 cases of placental abruption was performed and the subjects were collected from Tianjin Central Hospital of Gynecology and Obstetrics between January 2016 and December 2017. The abruption cases were divided into two groups: the abruption with other conditions of ischemic placental disease (IPD group) and the abruption without them (non-IPD group). The clinical features, such as maternal age, gravidity, parity, gestational age at delivery, maternal complications, bleeding volume, fetal gender, sensitivity of ultrasonography, primary symptoms, onset-to-delivery time, mode of delivery, birth weight, and Apgar score at 1 min, were compared between two groups. RESULTS: The primary symptoms in the top three were the central nervous system symptoms involving headache, dizziness or blurred vision (55.0%), decreased fetal movements (13.75%), and abdominal pain (10.0%) in IPD group, while in non-IPD group the top three were vaginal bleeding combined with abdominal pain (31.54%), abdominal pain (22.82%), and vaginal bleeding (16.11%). Compared with non-IPD group, the neonatal outcomes including birth weight, Apgar score at 1 min, and gestation age at delivery were significantly poorer in the IPD group (p < .000, p = .044, and p = .001, respectively). And the sensitivity of ultrasonography was significantly higher in non-IPD group (p = .002). In both preterm and term abruption in IPD group, compared with non-IPD group, it was significantly different in terms of gestation age at delivery, onset-to-delivery time, and birth weight (p < .05). In preterm abruption, IPD group had a significantly higher cesarean section rate than non-IPD group (p = .019). It seemed patients in IPD group had a higher incidence of uterine apoplexy and disseminated intravascular coagulation (DIC), but there was no statistical difference between the two groups in maternal complications including uterine apoplexy, blood transfusion, and DIC (p = .310, p = .585, and p = .121, respectively). It seemed preterm abruption had a poorer maternal prognosis than term abruption in IPD and non-IPD group, but the result had no significant difference (p > .05). CONCLUSIONS: Placental abruption complicated with preeclampsia and/or intrauterine growth restriction had a poorer prognosis of newborns, while there was no significant difference in maternal prognosis. And patients with preeclampsia and/or intrauterine growth restriction deserved careful observation during pregnancy, especially when they had central nervous system symptoms of headache, visual changes, or dizziness.

Pain is a common problem in patients with ILD.

BACKGROUND: As it is less known about the prevalence and characteristics of pain in the patients with interstitial lung disease (ILD), this paper aims at determining the characteristics of the pain in the patients with ILD. METHODS: Subjects with ILD and health controls with the matched ages and genders completed Short Form McGill Pain Questionnaire (SF-MPQ) and part of the Brief Pain Inventory (BPI) Short Form to elicit the characteristics of the pain. The patients with ILD were also assessed through Pulmonary Function Test, Six Minutes Walking Test (6MWT), modified Medical Research Council Dyspnea Scale (mMRC) for state of the illness and measured health-related quality of life (HRQoL) by Short Form-36 (SF-36) and psychological associations by Hospital Anxiety and Depression Scale (HADS). RESULTS: A total of 63 subjects with ILD and 63 healthy controls (HC) were recruited in our study. The prevalence of the pain was 61.9% in ILD versus 25.3% in HC (P = 0.005) and the median score of the pain rank index (PRI) in ILD was higher than that in HC (P = 0.014). Chest (46.1%) accounted for the highest of overall pain locations in subjects with ILD. Associated clinical factors for pain intensity in the patients with ILD included exposure history of risk factors of ILD, with a longer distance of 6MWD (≥ 250 m), and a higher mMRC score (2-4). The patients with ILD and pain are more likely to suffer impaired HRQoL (P = 0.0014) and psychological problems (P = 0.0017, P = 0.044). CONCLUSION: The pain is common in those with ILD and the pain intensity is associated with exposure history, 6MWD, and mMRC score. The patients with ILD and pain were possibly to suffer depression, anxiety, and impaired HRQoL.

Novel coronavirus infection in children outside of Wuhan, China.

BACKGROUND: Since December 8, 2019, an epidemic of coronavirus disease 2019 (COVID-19) has spread rapidly, but information about children with COVID-19 is limited. METHODS: This retrospective and the single-center study were done at the Public Health Clinic Center of Changsha, Hunan, China. We identified all hospitalized children diagnosed with COVID-19 between January 8, 2019 and February 19, 2020, in Changsha. Epidemiological and clinical data of these children were collected and analyzed. Outcomes were followed until February 26th, 2020. RESULTS: By February 19, 2020, nine pediatric patients were identified as having 2019-nCoV infection in Changsha. Six children had a family exposure and could provide the exact dates of close contact with someone who was confirmed to have 2019-nCoV infection, among whom the median incubation period was 7.5 days. The initial symptoms of the nine children were mild, including fever (3/9), diarrhea (2/9), cough (1/9), and sore throat (1/9), two had no symptoms. Two of the enrolled patients showed small ground-glass opacity of chest computed tomography scan. As of February 26, six patients had a negative RT-PCR for 2019-nCoV and were discharged. The median time from exposure to a negative RT-PCR was 14 days. CONCLUSIONS: The clinical symptoms of the new coronavirus infection in children were not typical and showed a less aggressive clinical course than teenage and adult patients. Children who have a familial clustering or have a family member with a definite diagnosis should be reported to ensure a timely diagnosis.

Biomarkers and their potential functions in idiopathic pulmonary fibrosis.

Introduction: Idiopathic pulmonary fibrosis (IPF) is a chronic, devastating, and progressive lung disease that is characterized by fibrosis and respiratory failure. IPF holds high morbidity and poor prognosis and still faces considerable problems of reliable diagnosis and valid prognosis. A growing body of literature have reported changes in the level of various biomarkers in IPF patients, which means that they are expected to become a new tool for the clinical practice of IPF.Areas covered: We reviewed the recent literature about biomarkers and focus on the role they play in IPF. We systematically searched Medline/PubMed through February 2020. Many works of literature have shown that a variety of biomolecules and genomics played multiple roles in the diagnosis or differential diagnosis, prognosis, and indication of acute deterioration of IPF and so on.Expert opinion: Significant advances have been made in the role of biomarkers for IPF these years; however, current data indicate that a single biomarker is unlikely to have a transformative effect on clinical practice; therefore, the combined effect of various biomarkers can be considered to improve the accuracy of diagnosis and prognosis. Further research of biomarkers may provide new insights for the diagnosis, prognosis, and even therapy of IPF.

A Functional Polymorphism in the Promoter of miR-17-92 is Associated with a Reduced Risk of Cervical Squamous Cell Carcinoma.

miR-17-92 cluster was differentially expressed in cervical cancer, playing an important role in regulating cell proliferation, apoptosis, migration, and invasion. The purpose of this study was to investigate the association between polymorphisms (i.e., rs9588884, rs982873, and rs1813389) in the promoter of miR-17-92 and the risk of cervical squamous cell carcinoma (CSCC). The rs9588884 polymorphism was genotyped using a Taqman assay and the rs982873 and rs1813389 polymorphisms were genotyped using a polymerase chain reaction-restriction fragment length polymorphism method. The expression levels of miR-17-92 were determined using a quantitative PCR analysis. The rs9588884 GG genotype was associated with a reduced risk of CSCC in homozygote comparison (adjusted OR = 0.47, 95% CI, 0.30-0.75, P = 0.001), dominant model (adjusted OR = 0.67, 95% CI, 0.50-0.91, P = 0.01), and recessive model (adjusted OR = 0.57, 95% CI, 0.38-0.85, P = 0.01). The rs9588884 G allele was also associated with a reduced risk of CSCC in allele comparison (adjusted OR = 0.71, 95% CI, 0.58-0.88, P = 0.002). Moreover, patients with the rs9588884 GG genotype had lower levels of miR-20a compared with the rs9588884 CC genotype (P = 0.03). These findings indicate that the rs9588884 GG genotype was associated with lower levels of miR-20a and eventually related to the risk of CSCC in Chinese women.

Diversity in Genotype Distribution of Mycoplasma pneumoniae Obtained from Children and Adults.

The aim of this study was to explore whether there was any specific genotype responsible for the high prevalence of Mycoplasma pneumoniae infection in children. A total of 247 M. pneumoniae-DNA positive clinical specimens including 200 from children and 47 from adults, collected in Beijing, China, during the same period, were analyzed. We performed P1-restriction fragment length polymorphism analysis (RFLP), multi-locus variable number tandem repeat analysis (MLVA) and detected the macrolide resistance-associated mutations in 23S rRNA of the clinical specimens. In the present study, we observed P1 genotype 1 and MLVA type M4-5-7-2 accounted for the majority of the cases across all ages in Beijing. Macrolide resistance-associated mutants of M. pneumoniae were also at a high level with 90.5% (181/200) in children and 76.6% (36/47) in adults. However, more diverse genotypes and a higher prevalence of macrolide resistance-associated mutations were found in the pediatric specimens. Further investigations are warranted to help to explain the difference of morbidity and molecular characteristics across the demographic spectrum.

Tetrathienylethene-based Positional Isomers with Aggregation-induced Emission Enabling Super Red-shifted Reversible Mechanochromism and Naked-eye Sensing of Hydrazine Vapor.

AIE-active positional isomers, TTE-o-PhCHO, TTE-m-PhCHO and TTE-p-PhCHO, tetrathienylethene (TTE) derivates with peripherally attached ortho-/meta-/para-formyl phenyl groups, were designed and synthesized. The formyl substitution position can effectively modulate their photophysical properties, mechanochromism and fluorescent response to hydrazine. TTE-o-PhCHO and TTE-m-PhCHO exhibit remarkable AIE characteristics, and TTE-p-PhCHO possesses aggregation-induced emission enhancement performance. They all exhibit high contrast mechanochromism, and TTE-m-PhCHO shows larger red-shift (164 nm) than TTE-o-PhCHO (104 nm) and TTE-p-PhCHO (125 nm) due to the more twisted molecular conformation and much looser molecular packing. Moreover, TTE-o-PhCHO with a higher contrast color change can be used as ink-free rewritable paper. In addition, TTE-p-PhCHO, as a turn-on fluorescent probe, can selectively detect hydrazine with significant color changes that are visible by the naked eye . Therefore, the position dependence of groups would be an effective method to modulate the molecular arrangement, as well as develop AIE compounds for mechano-stimuli responsive materials, ink-free rewritable papers and chemosensors.

Molecular and clinical characteristics of severe Mycoplasma pneumoniae pneumonia in children.

OBJECTIVES: To analyze the molecular and the clinical characteristics of Mycoplasma pneumoniae (Mp) pneumonia (MPP) and to explore the related factors predicting severe MPP (SMPP). METHODS: A total of 423 pediatric cases of MPP were retrospectively analyzed, in 2013-2017, in Beijing, China. Clinical information was collected from the medical records. Mp-positive specimens were characterized using P1 typing and multiple locus variable-number tandem repeat analysis (MLVA). The macrolide resistance-associated mutations were also detected. RESULTS: The predominant genotype was P1-1 (88.2%) and M4-5-7-2 (87.5%), whereas percentages of type P1-2 and M3-5-6-2 increased across the 5-year period. The mutation rate of genotype M4-5-7-2 (365/370, 98.6%) was significantly higher than that of the genotype M3-5-6-2 (15/48, 32.25%; P = 0.000). Overall, 180 (42.6%) of the 423 Mp-positive patients were coinfected with other pathogens. Respiratory syncytial virus coinfection (24/180, 13.3%) was more common in cases typed M3-5-6-2 (4/23, 17.4%) than that of M4-5-7-2 (20/155, 12.9%; P = 0.038). Pleural effusion accounted for 52.6% (169/321) of the observed complications. In the mono-infection cases, cases typed M3-5-6-2 (56%, 14/25) were significantly (P = 0.020) associated with pleural effusion compared with those typed M4-5-7-2 (32.6%, 70/215); 84% (21/25) of specimens typed M3-5-6-2 were diagnosed as SMPP, whereas 63.7% (137/215) of specimens typed M4-5-7-2 were diagnosed as SMPP (P = 0.043). CONCLUSIONS: In our study, we proposed for the first time that the mono-infection patients with Mp typed M3-5-6-2 appear to have a higher risk for progressing to SMPP. MLVA typing can provide hints on the clinical characteristics of Mpp.

Exploration of the Effect of Blue Light on Functional Metabolite Accumulation in Longan Embryonic Calli via RNA Sequencing.

Light is an important factor that affects the synthesis of functional metabolites in longan embryogenic calli (ECs). However, analysis of the effect of light on functional metabolites in longan ECs via RNA sequencing has rarely been reported and their light regulation network is unclear. The contents of various functional metabolites as well as the enzymatic activities of superoxide dismutase and peroxidase and the level of H2O2 in longan ECs were significantly higher under blue light treatment than under the other treatments (dark, white). In this study, we sequenced three mRNA libraries constructed from longan ECs subjected to different treatments. A total of 4463, 1639 and 1806 genes were differentially expressed in the dark versus blue (DB), dark versus white (DW) and white versus blue (WB) combinations, respectively. According to GO and KEGG analyses, most of the differentially expressed genes (DEGs) identified were involved in transmembrane transport, taurine and hypotaurine metabolism, calcium transport and so forth. Mapman analysis revealed that more DEGs were identified in each DB combination pathway than in DW combination pathways, indicating that blue light exerts a significantly stronger regulatory effect on longan EC metabolism than the other treatments. Based on previous research and transcriptome data mining, a blue light signaling network of genes that affect longan functional metabolites was constructed and HY5, PIF4 and MYC2 were shown to be the key regulatory genes in the network. The results of this study demonstrate that the expression levels of phase-specific genes vary with changes in longan EC functional metabolites.

Paradoxical Reaction In The Form Of New Pulmonary Mass During Anti-Tuberculosis Treatment: A Case Series And Literature Review.

INTRODUCTION: Paradoxical reaction refers to deterioration of the original tuberculosis lesions or emergence of new infiltrative lesions during anti-tuberculosis treatment. The common manifestations of paradoxical reaction include new pleural effusion, cerebral tuberculosis and lymphadenitis. Paradoxical reaction manifested by new pulmonary mass is rare. PATIENTS AND METHODS: This article summarizes and analyzes the clinical manifestations, chest CT, laboratory findings, treatments, pathological biopsy results of five patients diagnosed as paradoxical reaction in the form of new pulmonary mass. A literature review related to paradoxical reaction was conducted. RESULTS: Five patients diagnosed as pulmonary tuberculosis or tuberculous pleuritis received systematic anti-tuberculosis treatmensssts. New pulmonary masses were found by CT scans during the follow-ups. The patients were negative for tumor markers, examination of rheumatoid connective tissue disease and G/GM test. The original anti-tuberculosis treatments were continued. All of the masses were diminished gradually. CONCLUSION: Paradoxical reaction needs to be taken into consideration when a new pulmonary mass occurs during anti-tuberculosis treatments. The diagnosis should be based on the patients' clinical manifestations, laboratory results, imaging examinsssations and lung biopsy examinations. The original anti-tuberculosis therapy can be continued in patients without severe clinical symptoms. A close follow-up is needed.

High-throughput sequencing of small RNAs revealed the diversified cold-responsive pathways during cold stress in the wild banana (Musa itinerans).

BACKGROUND: Cold stress is one of the most severe abiotic stresses affecting the banana production. Although some miRNAs have been identified, little is known about the role of miRNAs in response to cold stress in banana, and up to date, there is no report about the role of miRNAs in the response to cold stress in the plants of the cultivated or wild bananas. RESULT: Here, a cold-resistant line wild banana (Musa itinerans) from China was used to profile the cold-responsive miRNAs by RNA-seq during cold stress. Totally, 265 known mature miRNAs and 41 novel miRNAs were obtained. Cluster analysis of differentially expressed (DE) miRNAs indicated that some miRNAs were specific for chilling or 0 °C treated responses, and most of them were reported to be cold-responsive; however, some were seldom reported to be cold-responsive in response to cold stress, e.g., miR395, miR408, miR172, suggesting that they maybe play key roles in response to cold stress. The GO and KEGG pathway enrichment analysis of DE miRNAs targets indicated that there existed diversified cold-responsive pathways, and miR172 was found likely to play a central coordinating role in response to cold stress, especially in the regulation of CK2 and the circadian rhythm. Finally, qPCR assays indicated the related targets were negatively regulated by the tested DE miRNAs during cold stress in the wild banana. CONCLUSIONS: In this study, the profiling of miRNAs by RNA-seq in response to cold stress in the plants of the wild banana (Musa itinerans) was reported for the first time. The results showed that there existed diversified cold-responsive pathways, which provided insight into the roles of miRNAs during cold stress, and would be helpful for alleviating cold stress and cold-resistant breeding in bananas.

Association between genetic polymorphisms in the promoters of let-7 and risk of cervical squamous cell carcinoma.

Numerous reports showed low levels of let-7 family in cervical cancer, acting as tumor suppressors by regulating multiple target genes. Genetic variants in the promoter of miRNA have been reported to influence individuals' susceptibility to human diseases. We aimed to investigate the association of rs10877887 and rs13293512 polymorphisms in the promoters of let-7 with risk of cervical squamous cell carcinoma (CSCC). A total of 331 patients with CSCC and 358 controls were included. Genotyping of rs10877887 was done using polymerase chain reaction-restriction fragment length polymorphism analysis. Genotyping of rs13293512 was performed using Taqman allelic discrimination. Relative expression of let-7 family was determined using quantitative real-time polymerase chain reaction. The rs10877887CC genotype was significantly associated with an increased risk of CSCC compared with the rs10877887TT (adjusted OR=2.11, 95% CI, 1.31-3.40, p-value=0.002) or rs10877887 TT/CT genotypes (adjusted OR=2.11, 95% CI, 1.34-3.31, p-value<0.001). Similarly increased risk of CSCC was observed when compared rs10877887T with rs10877887C allele (adjusted OR=1.35, 95% CI, 1.08-1.69, p-value=0.008). Combined analysis showed that individuals carrying the genotypes of rs10877887CC+rs13293512CC had a 4.78-fold higher risk to develop CSCC compared with those carrying the genotypes of rs10877887CT/TT+rs13293512CT/TT (OR=4.78, 95% CI, 1.78-12.84, p-value=0.001). Additionally, patients harboring rs10877887CC genotype had a lower level of let-7i in CSCC tissues (p-value=0.02). This observation indicates that rs10877887 may be a useful biomarker for the etiology of CSCC.

Combined analysis of pri-miR-34b/c rs4938723 and TP53 Arg72Pro with cervical cancer risk.

miR-34 family members can form a p53-miR-34 positive feedback loop and induce apoptosis, DNA repair, angiogenesis, and cell cycle arrest. We conducted a case-control study to examine whether two polymorphisms (i.e., rs4938723 in the promoter of pri-miR-34b/c and TP53 Arg72Pro) were linked to the carcinogenesis of cervical cancer among Chinese Han women. Genotypes of the two polymorphisms in 328 cervical cancer patients and 568 control subjects were determined by using a polymerase chain reaction-restriction fragment length polymorphism assay. We found a significantly increased cervical cancer risk in the pri-miR-34b/c rs4938723 under dominant and overdominant model (CT/CC vs. TT: adjusted OR = 1.34, 95 % CI = 1.01-1.77; CT vs. TT/CC: adjusted OR = 1.37, 95 % CI = 1.05-1.80, respectively). Increased cervical cancer risks were also found in the TP53 Arg72Pro under a heterozygous comparison and overdominant model (CG vs. GG: adjusted OR = 1.44, 95 % CI = 1.06-1.95; CG vs. GG/CC: adjusted OR = 1.47, 95 % CI = 1.12-1.94, respectively). Stratification analysis showed that patients carrying the pri-miR-34b/c rs4938723 CT genotype had a significantly increased risk for developing poorly differential status and clinical stage I. Moreover, increased cancer risks were observed for the TP53 Arg72Pro polymorphism in patients with poorly differential status, clinical stage II, and without lymph node metastasis. Combined analysis revealed that the genotypes of rs4938723 CT/CC and TP53 Arg72Pro CG/CC had an increased cervical cancer risk (OR = 2.21, 95 % CI = 1.38-3.53). These findings suggest that the pri-miR-34b/c rs4938723 and TP53 Arg72Pro polymorphisms may contribute to the genesis of cervical cancer.

An insertion/deletion polymorphism at miRNA-122 binding site in the IL1A is associated with a reduced risk of cervical squamous cell carcinoma.

OBJECTIVE: Previous studies have shown that miRNA plays a key role in cervical carcinogenesis. Interleukin (IL)-1α can promote tumor growth, invasion, migration, and angiogenesis. An insertion/deletion polymorphism (rs3783553) in the IL1A 3' untranslated region may disrupt a binding site for miR-122 and miR-378 and thus change the transcription of IL-1α. The purpose of this study was to evaluate the association between the rs3783553 polymorphism and the risk of cervical squamous cell carcinoma (CSCC). METHODS: Polymerase chain reaction was used to genotype the IL1A rs3783553 polymorphism in 235 patients with CSCC and 326 controls. RESULTS: We found that the ins/ins genotype had a decreased risk to develop CSCC (odds ratio [OR]=0.48, 95% confidence interval [CI], 0.25-0.95). However, no significant association was observed between the IL1A rs3783553 genotype and clinical features. CONCLUSION: These findings indicate that the IL1A rs3783553 polymorphism may be associated with the etiology of CSCC.

Inconformity of CXCL3 plasma level and placenta expression in preeclampsia and its effect on trophoblast viability and invasion.

As a member of the chemokine family, CXCL3 was previously known to participate in many pathophysiological events. However, whether CXCL3 stimulates trophoblast invasion as a key process of preeclampsia pathogenesis remains largely unknown. Therefore, the aim of this study was to investigate this hypothesis and determine the effect of CXCL3 on the first trimester trophoblast. Seventy gravidas were included in this study. ELISA was used to detect CXCL3 plasma levels on preeclampsia and normal pregnant groups. CXCL3 protein and mRNA levels were detected via Western blot and real-time quantitative PCR analysis after immunolocalized in human placenta. Moreover, the CXCL3 function in HTR-8/Svneo was analyzed via WST-1 assay, flow cytometry and invasion test. The plasma CXCL3 level in preeclampsia was significantly higher than that in normal pregnancy. CXCL3 expression was observed in the cytoplasm of placental trophoblasts and vascular endothelium in all groups without significant difference between maternal and fetal sides. In addition, placenta CXCL3 expression in severe preeclampsia was significantly lower than those in normal and mild PE groups. Moreover, exogenous CXCL3 can promote the proliferation and invasion of HTR-8/Svneo; however, its effect on apoptosis remains unclear. In summary, a significant abnormality of plasma CXCL3 level and placental CXCL3 expression was discovered in severe preeclampsia; CXCL3 had a function in trophoblast invasion, which indicated its participation in shallow implantation. Therefore CXCL3 might be involved in severe preeclampsia pathogenesis.