A rapid, high-volume cervical screening project using self-sampling and isothermal PCR HPV testing.

OBJECTIVE: Rapid, high-volume screening programs are needed as part of cervical cancer prevention in China. METHODS: In a 5-day screening project in Inner Mongolia, 3345 women volunteered following a community awareness campaign, and self-swabbed to permit rapid HPV testing. Two AmpFire™ HPV detection systems (Atila Biosystems) were sufficient to provide pooled 15-HPV type data within an hour. HPV+ patients had same-day digital colposcopy (DC) performed by 1 of 6 physicians, using the EVA™ system (MobileODT). Digital images were obtained and, after biopsy of suspected lesions for later confirmatory diagnosis, women were treated immediately based on colposcopic impression. Suspected low- grade lesions were offered treatment with thermal ablation (Wisap), and suspected high-grade lesions were treated with LLETZ. RESULTS: Of 3345 women screened, 624 (18.7%) were HPV+. Of these, 88.5% HPV+ women underwent same-day colposcopy and 78 were treated. Later consensus histology results obtained on 197 women indicated 20 CIN2+, of whom 15 were detected and treated/referred at screening (10 by thermal ablation, 4 by LLETZ, 1 by referral). CONCLUSIONS: Global control of cervical cancer will require both vaccination and screening of a huge number of women. This study illustrates a cervical screening strategy that can be used to screen-and-treat large numbers of women. HPV self-sampling facilitates high-volume screening. Specimens can be tested rapidly, promoting minimal loss-to-follow-up. Specifically, the AmpFire™ system used in this study is highly portable, simple, rapid (92 specimens per 65 min per unit), and economical. Visual triage can be performed on HPV+ women with a portable digital colposcope that provides magnification, lighting, and a recorded image. Diagnosis and appropriate treatment remain the most subjective elements. The digital image is under study for deep-learning based automated evaluation that could assist the management decision, either by itself or combined with HPV typing.

ACOX1 destabilizes p73 to suppress intrinsic apoptosis pathway and regulates sensitivity to doxorubicin in lymphoma cells.

Lymphoma is one of the most curable types of cancer. However, drug resistance is the main challenge faced in lymphoma treatment. Peroxisomal acyl-CoA oxidase 1 (ACOX1) is the rate-limiting enzyme in fatty acid ß-oxidation. Deregulation of ACOX1 has been linked to peroxisomal disorders and carcinogenesis in the liver. Currently, there is no information about the function of ACOX1 in lymphoma. In this study, we found that upregulation of ACOX1 promoted proliferation in lymphoma cells, while downregulation of ACOX1 inhibited proliferation and induced apoptosis. Additionally, overexpression of ACOX1 increased resistance to doxorubicin, while suppression of ACOX1 expression markedly potentiated doxorubicin-induced apoptosis. Interestingly, downregulation of ACOX1 promoted mitochondrial location of Bad, reduced mitochondrial membrane potential and provoked apoptosis by activating caspase-9 and caspase-3 related apoptotic pathway. Overexpression of ACOX1 alleviated doxorubicin-induced activation of caspase-9 and caspase-3 and decrease of mitochondrial membrane potential. Importantly, downregulation of ACOX1 increased p73, but not p53, expression. p73 expression was critical for apoptosis induction induced by ACOX1 downregulation. Also, overexpression of ACOX1 significantly reduced stability of p73 protein thereby reducing p73 expression. Thus, our study indicated that suppression of ACOX1 could be a novel and effective approach for treatment of lymphoma. [BMB Reports 2019; 52(9): 566-571].

[Human umbilical cord mesenchymal stem cells co-cultured with dental pulp cells in vitro and its effect on cell biological behaviors].

PURPOSE: To investigated the effect of human umbilical cord mesenchymal stem cells (hUCMSCs) and human dental pulp cells (hDPCs) on cell biological behaviors by co-culture system in vitro. METHODS: hUCMSCs and hDPCs were obtained by primary culture. A culture system of hUCMSCs and hDPCs induced by BMP2 was established in vitro. hUCMSCs and hDPCs were co-cultured at the ratio of 1:1, 1:5 and 5:1. The optimum ratio of each group was selected to further experiment. The formation of calcium nodule was stained by alizarin red staining at 21 day. The expression of DSPP，ALP，DMP1，OCN，VEGF，HGF and Nanog gene was detected by real-time quantitative PCR at 7 day and 14 day. 1:1 group and hUCMSCs, hDPCs group were selected for alizarin red staining at 21 day according to PCR results. Statistical analysis was performed using SPSS 21.0 software package. RESULTS: Calcified nodules formation in 1:1 group was significantly higher than in hUCMSCs group (P<0.05), close to that in hDPCs. qPCR showed that the mRNA expression of DSPP, ALP, DMP1, OCN, VEGF and HGF in 1:1 group was significantly higher than that in hUCMSCs (P<0.05); mRNA expression of Nanog in 1:1 group was significantly lower than in hUCMSCs group (P<0.05). The results of alizarin red staining showed that the OD value of 1:1 group was significantly higher than that of hUCMSCs group (P<0.05). CONCLUSIONS: The cells can be induced to differentiate into odontoblastoid-like cells and the mRNA expression of angiogenic factors was stimulated by hUCMSCs co-culure wih hDPCs.

[miRNA profile of the human dental pulp cells during odontoblast differentiation induced by BMP-2].

PURPOSE: To screen and verify the differentially expressed microRNAs (miRNAs) during the differentiation of human dental pulp cells (hDPCs) to odontoblasts induced by BMP-2. METHODS: The isolated hDPCs were cultured in vitro and induced by BMP-2. The levels of ALP, DMP-1 and DSPP were quantified by quantitative real-time polymerase chain reaction (qRT-PCR). The potential characteristics of hDPCs were investigated by miRNA microarray and highly expressed miRNAs were selected with bio-information software for predicting target genes and their biological functions. Then the results were validated using qRT-PCR analysis for the selected miRNAs. Statistical analysis was performed using SPSS 18.0 software package. RESULTS: The expression of ALP, DSPP, and DMP-1 showed significantly higher levels in BMP-2 induced groups compared to the control group(P<0.05). A total of 36 miRNAs were changed (i.e. 20 miRNAs were up-regulated and 16 were down-regulated). The results of qRT-PCR were consistent with the microarray results. GO categories revealed that they were mainly associated with biological process(37.8%), cellular component (29%), molecular function(33%), while the function of other 0.2% genes remained unknown. CONCLUSIONS: This study identified differential expression of miRNAs in BMP-2-induced odontoblastic differentiation of hDPCs, thus contributing to further investigations of regulatory mechanisms and biological effect of target genes in BMP-2-induced odontoblastic differentiation of hDPCs.

MicroRNA-144 mediates metabolic shift in ovarian cancer cells by directly targeting Glut1.

Warburg effect is characterized by an increased utilization of glucose via glycolysis in cancer cells, even when enough oxygen is present to properly respire. Recent studies demonstrate that deregulation of microRNAs contributes to the Warburg effect. In the present study, we show that miR-144 is downregulated while glucose transporter 1 (Glut1) is upregulated in ovarian cancers. In vitro studies further showed that miR-144 inhibits Glut1 expression through targeting its 3'-untranslated region. As a result, cells overexpressing miR-144 exhibited a metabolic shift, including enhanced glucose uptake and lactate production. The altered glucose metabolism induced by miR-144 also leads to a rapid growth of ovarian cancer cells. Taken together, our results indicate that miR-144 may serve as a molecular switch to regulate glycolysis in ovarian cancer by targeting the expression of Glut1.

Successful Laparoscopic Management of Type I Cesarean Scar Pregnancy A Case Series.

OBJECTIVE: To explore the efficacy of laparoscopic surgery without auxiliary treatment for type II cesarean scar pregnancy (CSP-II). STUDY DESIGN: This was a case series of 7 patients with CSP-II who underwent laparoscopic surgery without auxiliary treatment between April 2014 and April 2015. All cases were diagnosed by ultrasound, confirmed by laparoscopy, and managed by laparoscopic resection of scar and gestational tissue and wound repair. RESULTS: All 7 patients had successful surgeries without complication. Uterine scar and gestational tissues were resected, while also preserving the uterus. The operation time was 70.1 ± 16.3 min and blood loss was 65.7 ± 32.1 mL. Serum ß-hCG levels 24 hours after surgery declined by 84.8 ± 9.4%. Serum ß-hCG levels went back to <5 IU/L in all 7 patients by 14.4 ± 4.3 days after surgery. The time interval between surgery and first menstruation was 35.3 ± 4.5 days. CONCLUSION: These results suggest the possibility that skilled surgeons could use laparoscopy without auxiliary pretreatment to remove gestational tissues and uterine scar defect and to repair the wound in patients with CSP-II.

Single-agent maintenance therapy in non-small cell lung cancer: a systematic review and meta-analysis.

BACKGROUND: Can single-agent maintenance therapy be considered as an ideal strategy for non-small cell lung cancer (NSCLC) treatment to achieve prolonged survival and tolerated toxicity? A systematic review and meta-analysis was performed to elucidate this issue. METHODS: The electronic databases were searched for RCTs comparing single-agent maintenance therapy with placebo, best support care or observation. The required data for estimation of response, survival and toxicity were extracted from the publications and the combined data were calculated. RESULTS: Eleven RCTs involving 3686 patients were identified. We found a statistically significant higher probability of tumor response for patients with maintenance therapy versus control patients (OR: 2.80, 95%CI: 2.15 - 3.64). Patients receiving maintenance therapy had significantly longer progression-free survival (PFS) (HR: 0.67, 95%CI: 0.62 - 0.71) and overall survival (OS) (HR: 0.84, 95%CI: 0.78 - 0.90). However, maintenance therapy was associated with more severe toxicities (OR: 6.45, 95%CI: 4.61 - 9.01). CONCLUSION: In patients with advanced NSCLC, the use of single-agent maintenance therapy is associated with higher response rate and significantly prolongs PFS and OS despite of the risk of additional toxicity.

Diagnostic efficiency and complication rate of CT-guided lung biopsy: a single center experience of the procedures conducted over a 10-year period.

BACKGROUND: Computed tomography (CT)-guided transthoracic lung biopsy is a well-established technique for the diagnosis of pulmonary lesions. The objective of this study was to evaluate the diagnostic efficiency and complication rate of CT-guided lung biopsy in a Chinese population. METHODS: CT-guided cutting needle lung biopsies were performed in our institution on 1014 patients between January 2000 and October 2010. A chest radiograph was taken after the biopsy. Data about basic patient information, final diagnosis, and complications secondary to biopsy procedure (pneumothorax and bleeding) were extracted. RESULTS: The diagnostic efficiency of CT-guided lung biopsy was 94.8%; only 53 patients did not get a final diagnosis from lung biopsy. Final diagnoses found 639 malignant lesions (63.0%) and 322 benign lesions (31.8%). Pneumothorax occurred in 131 patients and 15 required insertion of an intercostal drain. Small hemoptysis occurred in 41 patients and mild parenchymal hemorrhage occurred in 16 patients. The overall complication rate was 18.5%. CONCLUSIONS: CT-guided cutting needle biopsy of pulmonary lesions is a relatively safe technique with a high diagnostic accuracy. It can be safely performed in clinical trials.

Synthesis and antitumor activity of novel podophyllotoxin derivatives against multidrug-resistant cancer cells.

Seven novel 4ß-N-substituted podophyllotoxin derivatives with indole rings were prepared and evaluated for cytotoxicity against human cancer cell lines HeLa, KB, KBV, K562, and K562/AO2. Most of them demonstrated improved antitumor activity and weak multidrug resistance compared to the drugs currently available.

2-(1-Ethyl-5-meth-oxy-1H-indol-3-yl)-N-(4-meth-oxy-phen-yl)-2-oxoacetamide.

The title compound, C(20)H(20)N(2)O(4), crystallizes with four independent mol-ecules in the asymmetric unit. In the mol-ecules, the dihedral angles between the benzene rings and indole mean planes are 24.5 (1), 22.5 (1), 8.8 (1) and 13.9 (1)°. In the crystal, inter-molecular N-H⋯O hydrogen bonds are present between the imino groups and the adjacent carbonyl groups. π-π stacking is also observed with a centroid-centroid distance between nearly parallel pyrrole rings of 3.745 (3) Å.

[Screening of early lung cancer with low-dose computed tomography in high-risk populations: a meta-analysis].

OBJECTIVE: To explore the values of low-dose computed tomography (LDCT) in the screening of high-risk populations for early lung cancer through a meta-analysis of the relevant literature. METHODS: PubMed, EBSCO, Cochrane and other databases were searched with key words. And the studies were selected by the inclusion and exclusion criteria. The baseline data were collected and analyzed by statistical software. RESULTS: Ten random controlled trials (RCTs) were selected. Compared to the chest X ray (CXR) screening and no screening controls, LDCT screening had an odds ratio (OR) of 3.705, 95%CI 3.527 - 3.891. And in the subgroup analysis, a higher number of stage I lung cancer was detected (OR 4.464, 95%CI 2.860 - 6.969) by LDCT. Moreover, LDCT screening showed an increased detection of adenocarcinoma in lung cancer (OR 4.652, 95%CI 2.877 - 7.522). CONCLUSION: LDCT is superior to CXR in the early detection of lung cancer, especially stage I and adenocarcinoma.

[An angiographic trial to evaluate the efficacy and safety of tenecteplase in Chinese patients with acute myocardial infarction].

OBJECTIVE: In this randomized, open-label, multicenter, angiographic trial, we compared the efficacy and safety of tenecteplase (TNK-tPA) with alteplase (rt-PA) in Chinese patients with acute myocardial infarction. METHOD: Patients with acute ST-elevation myocardial infarction and pain to hospital time within 6 hours from October 2002, to March 2004 were randomly assigned a body weight-adjusted bolus of TNK-tPA (0.53 mg/kg over more than 10 s, n = 58) or front loaded rt-PA (< or = 100 mg, n = 52). Coronary angiography was performed at 90 min after initiating study drugs. All patients received aspirin and heparin (target activated partial thromboplastin time: 50-70 s). The primary end point of the trial was the rate of TIMI grade 3 flow at 90 minutes. Other end points included the rate of TIMI grade 2/3 flow at 90 minutes, all cause mortality at 30 days, the moderate/severe hemorrhage without intracranial hemorrhage (ICH) and ICH within 30 days. RESULTS: TIMI grade 3 flow at 90 minutes (68.4% vs. 66.7%, P = 1.00), TIMI grade 2 or 3 at 90 minutes (89.5% vs. 80.4%, P = 0.278), total mortality at 30 days (13.8% vs. 9.6%, P = 0.565), the rate of moderate/severe hemorrhage (8.6% vs. 5.8%, P = 0.72) and incidence of ICH (3.5% vs. 1.9%, P = 1.00) were all similar in TNK-tPA treated patients compared to rt-PA treated patients. CONCLUSION: The efficacy of single-bolus, weight-adjusted TNK-tPA fibrinolytic regimen is equivalent to front-loaded alteplase in terms of the rates of TIMI grade 3 flow, TIMI 2 or 3 flow. Incidences of moderate/severe hemorrhage, ICH and 30-days mortality were similar in TNK-tPA and rt-PA treated patients.

[Effects of intensive antiplatelet therapy in patients with high platelet aggregability after percutaneous coronary intervention].

OBJECTIVE: Post percutaneous coronary intervention (PCI) major cardiac event rate is high in patients with high platelet aggregability. We observed the effects of intensive antiplatelet therapy in these patients. METHODS: ADP-induced platelet inhibition rates were less than 30% after 24 h treatment with Clopidogrel (300 mg) in 402 patients out of 1556 patients who underwent PCI in our institute between January 2004 to June 2006. These patients were randomly divided into control group (Clopidogrel 75 mg/d and aspirin 100 mg/d, n = 201) or treatment group (Clopidogrel 75 mg/d and aspirin 100 mg/d plus cilostazol 200 mg/d, n = 201). Major adverse cardiac events were analyzed after 6 months treatments. RESULTS: Patients with ADP-induced platelet inhibition rates < 30% were significantly lower in treatment group compared to control group after 28 days treatments (9.4% vs. 89.6%, P < 0.05). Thrombosis complication (0.5% vs. 3.0%), death (0 vs. 1.0%), non-fatal myocardial infarction (0.5% vs. 1.5%), hemorrhagic (6% vs. 4%) rates were similar between treatment and control group while target vessel revascularization rate was significantly lower in treatment group compared to control group (6.5% vs. 15.9%, P < 0.05). Total MACE rate was therefore significantly lower in treatment group than that in control group (13.5% vs. 25.4%, P < 0.05). CONCLUSION: Intensive anti-platelet treatment could significantly reduce major cardiac event rates in patients with high platelet aggregability after percutaneous coronary intervention.

A prospective randomized antiplatelet trial of cilostazol versus clopidogrel in patients with bare metal stent.

BACKGROUND: Cilostazol is a newly developed antiplatelet drug that has been widely applied for clinical use. Its antiplatelet action appears to be mainly related to inhibition of intracellular phosphodiesterase activity. Recently, cilostazol has been used for antiplatelet therapy after coronary bare metal stent implantation for thrombosis and restenosis prevention. This prospective randomized and double blind trial was designed to investigate the safety and efficacy of cilostazol for the prevention of late restenosis and acute or subacute stent thrombosis. METHODS: One hundred and twenty patients who underwent elective stent were randomly assigned to treatment group with cilostazol 200 mg/d (n = 60), clopidogrel 75 mg/d and aspirin 100 mg/d or to control group with clopidogrel treatment 75 mg/d (n = 60) and aspirin 100 mg/d. Follow-up coronary angiography was performed 6 - 9 months later. RESULTS: Nine months major adverse cardio-cerebral event (MACCE) were lower in treatment groups (P < 0.05). The quantitative coronary angiography (QCA) at 6 months follow-up showed that minimum lumen diameter (MLD) was higher in treatment group than that of control group [(2.14 +/- 0.52) mm vs (1.82 +/- 0.36) mm, P < 0.05]. Late lumen loss (LL) [(0.82 +/- 0.42) mm vs (1.31 +/- 0.58) mm; P < 0.01], restenosis rate (RR) (14% vs 32%; P < 0.05) and target lesion revascularizaion (TLR) rate (5% vs 17%; P < 0.05) were lower in treatment group than in control group. CONCLUSION: Cilostazol therapy is an effective regimen for prevention not only stent thrombosis but also RR and TLR through reducing MLD without the risk of increasing bleeding.