Chinese Patients With Heart Valve Replacement Do Not Benefit From Warfarin Pharmacogenetic Testing on Anticoagulation Outcomes.

BACKGROUND: Genotype-guided warfarin dosing has been shown in some randomized trials to improve anticoagulation outcomes in individuals of European ancestry; yet, its utility in Chinese patients with heart valve replacement remains unresolved. METHODS: A total of 2264 patients who underwent heart valve replacement at Wuhan Asia Heart Hospital were enrolled in this study. Patients were randomly divided into 2 groups, namely, a genotype-guided and a traditional clinically guided warfarin dosing group. In the genotype-guided group (n = 1134), genotyping for CYP2C9 and VKORC1 (-1639 G→A) was performed using TaqMan genotyping assay. Warfarin doses were predicted with the International Warfarin Pharmacogenetics Consortium algorithm. Patients in the control group (n = 1130) were clinically guided. The primary outcome was to compare the incidence of adverse events (major bleeding and thrombotic) during a 90-day follow-up period between 2 groups. Secondary objectives were to describe effects of the pharmacogenetic intervention on the first therapeutic-target-achieving time, the stable maintenance dose, and the hospitalization days. RESULTS: A total of 2245 patients were included in the analysis. Forty-nine events occurred during follow-up. Genotype-guided dosing strategy did not result in a reduction in major bleeding (0.26% versus 0.63%; hazard ratio, 0.44; 95% confidence interval, 0.13-1.53; P = 0.20) and thrombotic events (0.89% versus 1.61%; hazard ratio, 0.56; 95% confidence interval, 0.27-1.17; P = 0.12) compared with clinical dosing group. Compared with traditional dosing, patients in the genotype-guided group reached their therapeutic international normalized ratio in a shorter time (3.8 ± 2.0 versus 4.4 ± 2.0 days, P < 0.001). There was no difference in hospitalization days (P = 0.28). CONCLUSIONS: Warfarin pharmacogenetic testing according to the International Warfarin Pharmacogenetics Consortium algorithm cannot improve anticoagulation outcomes in Chinese patients with heart valve replacement.

Soluble ST2 for Prediction of Clinical Outcomes in Patients with ST-Segment Elevation Myocardial Infarction Receiving Primary PCI.

Soluble suppression of tumorigenicity 2 (sST2), a biomarker representing myocardial fibrosis and inflammation, has been applied in risk stratification of patients with myocardial infarction (MI). However, whether primary PCI (PPCI) will eliminate the predictive value of sST2 in STEMI patients has not been well studied. Here, we conducted a prospective clinical trial to evaluate the correlation between sST2 and prognosis in STEMI patients undergoing PPCI. sST2 levels were measured in 295 STEMI patients (60.2 ± 10.8 years) at admission using a high sensitivity assay. Baseline sST2 levels were significantly associated with heart function, biomarkers of inflammation, and myocardial injury. During a 12-month follow-up, 19 patients had major adverse cardiovascular events (MACEs). Greater sST2 was continuously associated with a higher risk of incident MACEs. Such association remained even after adjusting for other risk factors in a multivariate Cox analysis. A baseline sST2 level in the highest quartile (≥ 58.7 ng/mL) was independently associated with mortality (HR: 5.01, 95%CI: 1.02-16.30, P = 0.048). More incident heart failure was seen in the group with greater sST2, however, the association was not significant after adjustment. Therefore, baseline sST2 may be useful to predict MACEs, especially mortality, in STEMI patients receiving PPCI.

Plasma Resistin Levels in Patients with Acute Aortic Dissection: A Propensity Score-Matched Observational Case-Control Study.

BACKGROUND The aim of this observational case-control study was to compare the levels of plasma resistin between patients with acute aortic dissection and matched controls, and to use propensity score matching (PSM) to reduce case selection bias and clinical confounders. MATERIAL AND METHODS With the use of PSM, this study included 43 pairs of patients with acute aortic dissection (type-A and type-B dissection) and matched controls. Plasma resistin levels and other laboratory parameters were compared between the two groups, including white blood cell (WBC) count, glucose, high sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and D-dimer. The correlations between resistin and other laboratory parameters were evaluated in patients with acute aortic dissection. RESULTS Following PSM adjustment for clinical variables, including age, sex, body mass index, smoking, alcohol drinking, hypertension, diabetes mellitus, coronary heart disease and stroke, plasma resistin levels were significantly increased in patients with acute aortic dissection when compared with controls (35.2±13.8 vs. 18.4±9.1 ng/ml) (p<0.001). WBC counts, and levels of glucose, hs-CRP, IL-6, TNF-α and D-dimer were also significantly increased in the patients with aortic dissection compared with the control group. After adjustment for these variables, the association between plasma resistin levels and acute aortic dissection remained significant (OR, 1.114; 95% CI, 1.036-1.224) (p<0.001). Plasma resistin levels was positively correlated with WBC count (r=0.368, p=0.015), hs-CRP (r=0.359, p=0.022), IL-6 (r=0.306, p=0.046) and TNF-α levels (r=0.315, p=0.040) in patients with acute aortic dissection. CONCLUSIONS Acute aortic dissection is associated with elevated levels of plasma resistin and other pro-inflammatory cytokines. Plasma resistin levels is positively associated with other pro-inflammatory cytokines in acute aortic dissection.

Application of ultrasound-guided percutaneous intrahepatic portal vein catheterization with antibiotic injection for treating unliquefied bacterial liver abscess.

AIM: To investigate whether ultrasound-guided percutaneous portal vein catheterization can be successfully carried out in the intrahepatic region of patients with unliquefied bacterial liver abscess (UBLA), who are subsequently treated with an injection of antibiotics. METHODS: Thirty-two UBLA patients were enrolled in this study. Among them, 13 patients were included in the experimental group; an ultrasound-guided percutaneous portal vein catheterization was undertaken in the intrahepatic region of these patients, and they also received an injection of antibiotics. The remaining 19 patients were retrospectively included in the control group; these patients only received systemic antibiotic therapy. The efficacy of intervention was compared with that of systemic treatment. RESULTS: The catheterization procedures were successful in all the patients of the experimental group. However, two cases (15.4%) developed complications postoperatively. Compared to the control group, the following parameters of the experimental group were significantly shorter/lower: (i) duration for regaining normal body temperature; (ii) time period for achieving normal white blood cell count; (iii) length of hospitalization; (iv) cases of liquefied liver abscess during follow-up; and (v) cost of hospitalization (P < 0.05). CONCLUSION: Ultrasound-guided percutaneous portal vein catheterization is a simple, minimally invasive, and effective treatment for UBLA. It must be carried out in the intrahepatic region and a subsequent injection of antibiotics must be given.

[p53 gene mutations of familial breast cancer and early-onset breast cancer in part population of southern China].

OBJECTIVE: To investigate the site and characteristic of p53 gene mutations in familial or early-onset breast cancer patients in part population of southern China.
 Methods: A total of 150 patients with familial and early-onset breast cancer in parts population of southern China were enrolled. Genomic DNA was isolated from each peripheral blood sample, and the entire coding sequence and exon and intron splicing region of p53 gene were amplificated by PCR in the 150 patients. The mutation analysis were detected by denaturing high performance liquid chromatography (DHPLC) and confirmed by DNA sequence analysis.
 Results: In the 150 patients with familial and early-onset breast cancer, 6 mutations including one novel pathogenic mutation 869_888 ins20 (insert mutation) and 5 previously reported pathogenic mutations (deletion mutation 643_660del18 and 4 missense mutation 91G>A, 215C>G, 537T>G, 743G>A) were identified in p53 gene encoding region in 9 patients of breast cancer. Moreover, one same sense mutation 141G>A in exon 4, one 16 bases deletion in intron 3, and 9 single nucleotide polymorphisms in p53 gene introns were also identified. The total mutation frequency of p53 gene in 150 patients with familial breast cancer and early-onset breast cancer from part population of southern China was 6.00%, and the mutation frequency of familial breast cancer and early-onset breast cancer was 6.81% and 6.25%, respectively.
 Conclusion: The total mutation frequency of p53 gene in 150 patients with familial breast cancer and early-onset breast cancer from partpopulation of southern China is higher than the frequency previously reported. The pathogenicity of the novel mutations (insert mutation) 869_888ins20 will be confirmed by function analysis in the future study. The deletion mutation 643_660del18 enriches the p53 gene mutation database among Chinese population, which is probably the specific mutation of breast cancer in Chinese population.

[PTEN and NBS1 gene mutations in familial breast cancer and early-onset breast cancer from Hunan Province in China].

OBJECTIVE: To investigate the profile and potential significance of PTEN and NBS1 mutations among patients with familial or at early onset breast cancer in Hunan province.
 METHODS: A total of 131 breast cancer patients with familial history or suffered from breast cancer at the age of less than 35 years old were included in this study. A comprehensive phosphatase and tensin homolog (PTEN) and nibrin (NBS1) mutation analysis was performed through denaturing high performance liquid chromatography (DHPLC) and subsequent DNA direct sequencing.
 RESULTS: Among 131 patients, a reported mutation IVS4+109insTCTTA in PTEN gene were identified in two patients. The mutation frequency of IVS4+109insTCTTA was 1.15%. Two mutations in PTEN gene, 225 A>C (Thr 160 Pro) and IVS5+13T>C, was firstly discovered. Another reported missense mutation was rs121909229 G>A (Arg 130 Gln). Three mutations were detected in NBS1 gene, of which IVS6+43A>G and IVS6+127A>G were firstly discovered and another reported synonymous mutations was rs1805794 G>C (Glu 185 Gln).
 CONCLUSION: The novel mutations in PTEN and NBS1 might be specific to the familial and early-onset breast cancer of Chinese Hunan population.

Attenuation of cardiac dysfunction and remodeling of myocardial infarction by microRNA-130a are mediated by suppression of PTEN and activation of PI3K dependent signaling.

OBJECTIVE: Activation of PI3K/Akt signaling protects the myocardium from ischemia/reperfusion injury. MicroRNAs have been demonstrated to play an important role in the regulation of gene expression at the post-transcriptional level. In this study, we examined whether miR-130a will attenuate cardiac dysfunction and remodeling after myocardial infarction (MI) via PI3K/Akt dependent mechanism. APPROACHES AND RESULTS: To determine the role of miR-130a in the proliferation and migration of endothelial cells, HUVECs were transfected with miR-130a mimics before the cells were subjected to scratch-induced wound injury. Transfection of miR-130a mimics stimulated the migration of endothelial cells into the wound area and increased phospho-Akt levels. To examine the effect of miR-130a on cardiac dysfunction and remodeling after MI, Lentivirus expressing miR-130a (LmiR-130a) was delivered into mouse hearts seven days before the mice were subjected to MI. Cardiac function was assessed by echocardiography before and for up to 21 days after MI. Ejection fraction (EF%) and fractional shortening (FS%) in the LmiR-130a transfected MI hearts were significantly greater than in LmiR-control and untransfected control MI groups. LmiR-130a transfection increased capillary number and VEGF expression, and decreased collagen deposition in the infarcted myocardium. Importantly, LmiR-130a transfection significantly suppressed PTEN expression and increased the levels of phosphorylated Akt in the myocardium. However, treatment of LmiR-130a-transfected mice with LY294002, a PI3K inhibitor, completely abolished miR-130a-induced attenuation of cardiac dysfunction after MI. CONCLUSIONS: miR-130a plays a critical role in attenuation of cardiac dysfunction and remodeling after MI. The mechanisms involve activation of PI3K/Akt signaling via suppression of PTEN expression.

Knockdown of ANLN by lentivirus inhibits cell growth and migration in human breast cancer.

Anillin (ANLN), an actin-binding protein, is required for cytokinesis. Recently, ANLN has been identified as a biomarker in diverse human cancers; however, the precise role of ANLN in breast cancer remains unclear. In this study, we firstly detected the expression of ANLN in 71 patients with breast cancer by immunohistochemistry, and found ANLN was highly expressed in breast cancer tissues. To evaluate the function of ANLN in breast cancer cells, we employed lentivirus-mediated RNA interference to knock down ANLN expression in two human breast cancer cell lines, MDA-MB-231, and ZR-75-30. Knockdown of ANLN remarkably inhibited the proliferation rate and colony formation ability of both breast cancer cell lines. Moreover, flow cytometry analysis showed that depletion of ANLN in MDA-MB-231 cells blocked the cell cycle progression, with more cells delayed at G2/M phase, due to phosphorylation of Cdc2 and suppression of Cyclin D1. Furthermore, knockdown of ANLN strongly suppressed the migration of breast cancer cells, strengthening the evidence that ANLN could be involved in breast cancer progression. Our results may suggest ANLN as a potential target candidate in breast cancer.

Long noncoding RNA PCA3 gene promoter region is related to the risk of prostate cancer on Chinese males.

INTRODUCTION: Long noncoding RNA prostate cancer gene antigen 3 (PCA3) is one of the most prostate cancer-specific genes at present. Consequently, the prostate-specific expression and the sharp up-regulation of PCA3 RNA in prostate cancer suggest a unique transcriptional regulation, which possibly can be attributed to promoter polymorphism. In this study, we investigated a short tandem repeat (STR) polymorphism of TAAA in the promoter region of PCA3 gene found in our previous study in prostate cancer (PCa) patients and benign prostatic hypertrophy (BPH) patients, aiming to evaluate the association between the STR and increased risk for PCa. MATERIAL AND METHODS: 120 PCa cases and 120 benign prostatic hypertrophy (BPH) cases were identified among participants. The region encompassing the TAAA repeat was amplified with a specific primer set we designed and screened by PCR-based cloning and sequencing in paired peripheral blood leukocytes and prostate tissues. Genotype-specific risks were estimated as odds ratios (ORs) associated with 95% confidence intervals (CIs) and adjusted for age by means of unconditional logistic regression. RESULTS: 5 PCA3 TAAA STR polymorphisms and 8 genotypes were found in both peripheral blood leukocytes and prostate tissues, the carriers with more TAAA repeats were associated with increased risk for PCa than individuals having less TAAA repeats. Interestingly, 18 (15.0%) of 120 PCa patients had more (TAAA)n repeats in prostate tissues than that in peripheral blood leukocytes, and 3 (2.5%) of 120 had less (TAAA)n repeats in prostate tissues. CONCLUSIONS: The results of this study suggest that short tandem repeat polymorphism of TAAA in the promoter region of PCA3 gene is a risk-increasing factor for prostate cancer in the Chinese population. In addition to the hereditary factor, the insertion mutation of (TAAA)n in a local tissue maybe another mechanism of the onset of PCa.

[Effect of standardized PICC training and management on the clinical effect and complication of catheterization].

OBJECTIVE: To determine the clinical effect of standardized training and management of peripherally inserted central catheter (PICC) and catheter-related complications. METHODS: A total of 610 patients were divided into a control group and an observation group, the control group (n=300) were catheterized by trainees who received "short-term intensive training", the observation group (n=310) by "system standardized training and management". The clinical efficacy of catheterization and the rate of catheter-related complications were compared. RESULTS: There was significant difference in the one-time puncture success rate, one-time cannulation success rate, the time for operation and the pain score between the 2 groups (all P<0.01), and there was also significant difference in the occurrence of catheter extrusion, plug, arrhythmia, catheter-related thrombosis, phlebitis, puncture point effusion and catheter-related infection between the 2 groups (all P<0.05). CONCLUSION: Standardized PICC training and management can improve the effect of catheterization and reduce the incidence of PICC-related complication.

Experimental Study on the Mechanism and Law of Low-Salinity Water Flooding for Enhanced Oil Recovery in Tight Sandstone Reservoirs.

Currently, research surrounding low-salinity water flooding predominantly focuses on medium- to high-permeability sandstone reservoirs. Nevertheless, further investigation is necessary to implement this technique with regard to tight sandstone reservoirs. The present study comprises a series of experiments conducted on the crude oil and core of the Ordos Chang 6 reservoir to investigate the influence of ionic composition on low-salinity water flooding in tight oil reservoirs. The change in wettability on the rock surface was analyzed by using the contact angle experiment. The change in recovery rate was analyzed using a core displacement experiment. The reaction between rock fluids was analyzed using an ion chromatography experiment. Additionally, a nuclear magnetic resonance (NMR) experiment was used to analyze the mobilization law of crude oil and the change in wettability on the scale of the rock core. This led to a comprehensive discussion of the law and mechanism of enhancing the recovery rate via low-salinity water flooding from various perspectives. Experiments show that low-salinity water flooding is an effective technique for enhancing recovery in tight sandstone reservoirs. Altering the ionic composition of injected water can improve the water wettability of the rock surface and enhance recovery. Decreasing the mass concentration of Ca2+ or increasing the mass concentration of SO42- can prompt the ion-exchange reaction on the rock surface and detachment of polar components from the surface. Consequently, the wettability of the rock surface strengthens, augmenting the recovery process. Nuclear magnetic resonance experiments evidence that low-salinity water injection, with ion adjustment, significantly alters the interactions between the rock and fluid in tight sandstone reservoirs. As a result, the T2 signal amplitude decreases significantly, residual oil saturation reduces considerably, and the hydrophilic nature of the rock surface increases.

Clinical utility of endoscopic ultrasound elastography for identification of malignant pancreatic masses: a meta-analysis.

BACKGROUND AND AIM: Endoscopic ultrasound (EUS) elastography is not used for detection but rather for characterization of solid pancreatic masses. A meta-analysis was used to assess the accuracy of EUS elastography for identification of malignant pancreatic masses. METHODS: PubMed, the Cochrane Library, and the ISI Web of Knowledge were searched. The studies relating to evaluation accuracy of qualitative or quantitative EUS elastography for identification of malignant pancreatic masses were collected. Language was limited to English. The sensitivity and specificity were used to examine the accuracy. Clinical utility was evaluated by likelihood ratio scattergram. RESULTS: A total of 10 studies including 893 pancreatic masses (646 malignant, 72.3%) were analyzed. The summary sensitivity and specificity for the diagnosis of malignant pancreatic masses were 0.98 (95% confidence interval [CI] 0.93-1.00) and 0.69 (95% CI 0.52-0.82) for qualitative EUS elastography, and 0.96 (95% CI 0.86-0.99) and 0.76 (95% CI 0.58-0.87) for quantitative EUS elastography, respectively. The hierarchical summary receiver operating characteristic curves were 0.94 and 0.93 for qualitative and quantitative EUS elastography. The accuracy of quantitative methods was similar to qualitative methods. The positive and negative likelihood ratios were 3.15 and 0.03 for qualitative EUS elastography, and 3.94 and 0.05 for quantitative EUS elastography, respectively. Both qualitative and quantitative methods were useful for exclusion of presence of malignant pancreatic masses and not for its confirmation. CONCLUSIONS: EUS elastography could be used as a good identification tool for benign and malignant pancreatic masses, with its good performance for exclusion of presence of malignant pancreatic masses.

Bidirectional flow in the vertebral artery is not always indicative of the subclavian steal phenomenon.

OBJECTIVE: To evaluate the causes of bidirectional flow in the vertebral artery detected by Doppler sonography and its differential diagnosis. METHODS: Twenty-nine patients with bidirectional flow in the vertebral artery were retrospectively studied. The vertebral artery parameters, including peak antegrade velocity (PAV), peak reversed velocity (PRV), maximum peak velocity (MPV), peak systolic velocity, resistive index (RI), and diameter, were measured. The MPV was defined as the MPV of bidirectional flow regardless of the velocity of antegrade or retrograde flow. To better predict the cause of bidirectional flow, receiver operating characteristic curves were constructed for these parameters, and the best cutoff values were obtained. The cause of bidirectional flow was determined by angiography. RESULTS: The causes of bidirectional flow were classified as the subclavian steal phenomenon (n = 21) and factors unrelated to the steal phenomenon (n = 8, including a hypoplastic vertebral artery [n = 4] and proximal vertebral artery stenosis and occlusion [n = 4]). Significant differences were observed between the steal phenomenon and non-steal phenomenon groups (P< .05) for MPV, PRV, PAV, target vertebral artery diameter, and contralateral RI. To determine the cause of bidirectional flow, areas under the receiver operating characteristic curves for the different parameters were obtained: 0.929 for MPV, 0.881 for PRV, 0.824 for PAV, 0.753 for target vertebral artery diameter, and 0.845 for contralateral RI. The cutoff value for MPV was 26.1 cm/s, and the accuracy was 93% (27 of 29). CONCLUSIONS: Bidirectional flow in the vertebral artery is not always indicative of the subclavian steal phenomenon. Measurement of hemodynamic parameters in the vertebral artery, such as MPV, can facilitate determination of the cause of bidirectional flow.

Clinical utility of acoustic radiation force impulse imaging for identification of malignant liver lesions: a meta-analysis.

OBJECTIVES: To assess the performance of acoustic radiation force impulse (ARFI) imaging for identification of malignant liver lesions using meta-analysis. METHODS: PubMed, the Cochrane Library, the ISI Web of Knowledge and the China National Knowledge Infrastructure were searched. The studies published in English or Chinese relating to evaluation accuracy of ARFI imaging for identification of malignant liver lesions were collected. A hierarchical summary receiver operating characteristic (HSROC) curve was used to examine the ARFI imaging accuracy. Clinical utility of ARFI imaging for identification of malignant liver lesions was evaluated by Fagan plot analysis. RESULTS: A total of eight studies which included 590 liver lesions were analysed. The summary sensitivity and specificity for identification of malignant liver lesions were 0.86 (95 % confidence interval (CI) 0.74-0.93) and 0.89 (95 % CI 0.81-0.94), respectively. The HSROC was 0.94 (95 % CI 0.91-0.96). After ARFI imaging results over the cut-off value for malignant liver lesions ("positive" result), the corresponding post-test probability for the presence (if pre-test probability was 50 %) was 89 %; in "negative" measurement, the post-test probability was 13 %. CONCLUSIONS: ARFI imaging has a high accuracy in the classification of liver lesions. KEY POINTS: Acoustic radiation force impulse (ARFI) imaging is a novel ultrasound-based elastography method. This study comprehensively assessed the published performance of ARFI for liver lesions. ARFI imaging appears to have high sensitivity and specificity for liver lesions. ARFI can help differentiate liver lesions and may prevent unnecessary biopsies.

Performance of platelet count/spleen diameter ratio for diagnosis of esophageal varices in cirrhosis: a meta-analysis.

BACKGROUND: Platelet count/spleen diameter ratio (PSR) is a non-invasive method for the assessment of esophageal varices (EV), developed as an alternative to endoscopy. AIM: To assess the performance of PSR for diagnosis of EV using meta-analysis. METHODS: PubMed, EMBASE, the Cochrane Library, ISI web of Knowledge, China National Knowledge Infrastructure, and article references were searched. We included studies using endoscopy as a reference standard, with the data necessary to calculate the true and false positive, true and false negative diagnostic results of PSR for EV. The quality of the studies was rated with the QUADAS tool. The hierarchical summary receiver operating characteristic (HSROC) was used to examine the PSR accuracy for the diagnosis of EV. Heterogeneity was explored using meta-regression. Clinical utility of PSR for EV was evaluated by a Fagan plot. RESULTS: In 20 studies (n = 3,063), the HSROC of the PSR for EV was 0.95 at various thresholds. At the threshold of 909, the summary sensitivities and specificities were 0.92 (95% CI, 0.79-0.97) and 0.87 (95% CI, 0.76-0.93), respectively. The HSROC was also 0.95 at the threshold of 909. If PSR was below 909 for EV ("positive" result), the post-test probability (if pre-test probability was 50%) was 87%, while if PSR was at or over 909 ("negative" result), the post-test probability was only 9%. PSR also had a high accuracy in diagnosis of EV in patients with compensated cirrhosis. CONCLUSIONS: PSR can identify EV in cirrhosis with a high accuracy. Application of this index may decrease the need for endoscopy among cirrhotic patients.

[The influence of different preparation methods on interappointment emergency and filling effect of root canal therapy].

PURPOSE: To compare the effect of different root canal preparation methods on the incidence of interappointment emergencies (IAE) and root canal filling. METHODS: A total of 96 teeth requiring root canal therapy due to pulpitis or periapical periodontitis from August 2018 to August 2021 were selected. They were randomly divided into 2 groups: MT group was treated with Mtwo root canal preparation method modified by Mtwo machine nickel-titanium file, while synchronous group was treated with modified Mtwo preparation method and synchronous root canal length measurement. After root canal preparation, the trial point film was taken, calcium hydroxide was used to seal the root canal, and routine thermoplasticizied gutta-percha root canal filling was performed during the follow-up visit. SPSS 22.0 software package was used to analyze the incidence of IAE and filling effect after root canal therapy. RESULTS: There was no significant difference in the incidence of IAE between the two groups immediately after operation, three days and 1 week after operation(P＞0.05); the incidence of IAE in synchronous group was significantly lower than that in MT group at 1 and 2 days after operation(P＜0.05). The qualified rate of root canal filling in synchronous group was significantly higher than that in MT group (P＜0.05). CONCLUSIONS: Synchronous method can reduce mechanical stimulation of apical area during root canal preparation, strictly control the working length of root canal and maintain apical barrier, thus reducing the incidence of IAE and effectively improving the qualification rate of root canal filling.

ECSIT inhibits cell death to increase tumor progression and metastasis via p53 in human breast cancer.

Background: Currently, breast cancer has surpassed lung cancer as the most common cancer and the molecular mechanism involved in tumor initiation and metastasis was unclear. Therefore, it is necessary to advance our understanding of tumor progression and metastasis and find out new targets. An evolutionarily conserved signaling intermediate in Toll pathways (ECSIT) is involved in the innate immune response and has been shown as tumor suppressors by downregulating nuclear factor-kappa B (NF-κB) pathway. However, the role of ECSIT in the progression and metastasis of human breast cancer remains unknown. Methods: We overexpressed ECSIT by transfection of a eukaryotic expression plasmid and constructed a breast cancer cell line with stable knockdown of ECSIT by short hairpin RNA. And we silenced p53 through small interfering RNA. In vivo, we replicated a xenograft mouse model in nude mice. The effects on the proliferation, viability, migration and invasion were studied by 5-ethynyl-2-deoxyuridine, cell counting Kit-8, wound healing and invasion assays. Propidium iodide/Hoechst 33342 staining and cleaved-caspase-3 staining were used to verify cell death. Western blot, immunohistochemistry (IHC) and histological analyses were used to explore the regulatory mechanism of tumor changes. Results: We reported the association of ECSIT with human breast cancer. In vitro assays demonstrated that ECSIT promoted MDA-MB-231 cell proliferation (by 66.15%), migration and invasion (by 58.29%). Knockdown of ECSIT significantly decreased cell proliferation (by 38.33%), viability, migration and invasion (by 62.37%), and increased cell death (by 41.1%). The in vivo results further confirmed that knockdown of ECSIT depressed tumorigenicity (by 29.46%) and metastasis (by 76.19%). Mechanistic investigations indicated that silencing of ECSIT could decrease the expression of p65 (by 46.05%), a subunit of NF-κB, and increase p53 protein expression in nuclei (by 89.53%). Moreover, we demonstrated that knockdown of p53 abolished the protection against cell death, which indicated that ECSIT might be involved in breast cancer progression through a p53-dependent pathway. Conclusions: Our studies provide new insight into the mechanisms underlying the role of ECSIT as well as a novel target for human breast cancer, and the development of novel ECSIT inhibitors is important for the management of TNBC.

LncRNA KCNQ1OT1 enhances the radioresistance of lung squamous cell carcinoma by targeting the miR-491-5p/TPX2-RNF2 axis.

Background: Lung cancer, especially lung squamous cell carcinoma (LUSC), is one of the most common malignant tumors worldwide. Currently, radiosensitization research is a vital direction for the improvement of LUSC therapy. Long non-coding RNAs (lncRNAs) can be novel biomarkers due to their multiple functions in cancers. However, the function and mechanism of lncRNA KCNQ1OT1 in the radioresistance of LUSC remain to be elucidated. Methods: The clonogenic assay was employed to determine the radioresistance of SK-MES-1R and NCI-H226R cells. Real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot were conducted for the detection of gene expression. Cell proliferation was determined by the methyl thiazolyl tetrazolium (MTT) assay, colony formation assay, and 5-ethynyl-2'-deoxyuridine (EdU) staining, and cell apoptosis was assessed by flow cytometry. The relationships between genes were also evaluated by applying the luciferase reporter and radioimmunoprecipitation (RIP) assays. Results: Radioresistant LUSC cells (SK-MES-1R and NCI-H226R) had strong resistance to X-ray irradiation, and lncRNA KCNQ1OT1 was highly expressed in SK-MES-1R and NCI-H226R cells. Moreover, knockdown of lncRNA KCNQ1OT1 prominently suppressed proliferation, attenuated radioresistance, and accelerated the apoptosis of SK-MES-1R and NCI-H226R cells. More importantly, we verified that miR-491-5p was a regulatory target of lncRNA KCNQ1OT1, and Xenopus kinesin-like protein 2 (TPX2) and RING finger protein 2 (RNF2) were the target genes of miR-491-5p. The rescue experiment results also demonstrated that miR-491-5p was involved in the inhibition of cell proliferation and the downregulation of TPX2 and RNF2 expression mediated by lncRNA KCNQ1OT1 knockdown in SK-MES-1R and NCI-H226R cells. Conclusions: LncRNA KCNQ1OT1 was associated with the radioresistance of radioresistant LUSC cells, and the lncRNA KCNQ1OT1/miR-491-5p/TPX2-RNF2 axis might be used as a therapeutic target to enhance the radiosensitivity of radioresistant LUSC cells.

A web-based survey of SARS-CoV-2 vaccination and its adverse effects in Chinese postoperative patients with breast cancer: a cross-sectional study.

Background: Vaccination against SARS-CoV-2 has been the most important strategy for preventing infection and controlling pandemics of coronavirus disease 2019 (COVID-19). Cancer patients have a significantly higher risk of infection with COVID-19 because of their impaired immunity. Breast cancer is the most common female malignant tumor in the world. However, studies on COVID-19 vaccination in breast cancer patients are scarce, so that more information is needed to guide vaccination in these. Methods: We conducted a web-based questionnaire survey on SARS-CoV-2 vaccination in breast cancer patient. Questionnaires completed by non-postoperative patients will be considered invalid. The main variables in the questionnaire including vaccination status, willingness to get the vaccines, candidate factors, and measures of adverse events in vaccinated individuals were used for analysis. Univariate and multivariate logistic regression was used to estimate the associations. Results: Among 947 valid online questionnaires, 341 (36.0%) accepted SARS-CoV-2 vaccination, while 606 (64.0%) did not. There were significant differences in age, current treatment, time since surgery, and symptoms of anxiety and depression between the two groups. Compared to vaccinated patients, we identified current treatment [odds ratio (OR) =0.51 for endocrine therapy; 95% confidence interval (CI): 0.29-0.89], time since surgery (OR =22.49 for 1-2 years; 95% CI: 12.31-41.10; OR =8.49 for 2-5 years; 95% CI: 4.98-14.46; OR =1.79 for >5 years; 95% CI: 1.11-2.89), and symptoms of depression (OR =2.48; 95% CI: 1.19-5.15) as significant factors for being unvaccinated. The overall incidence of adverse reactions was 43.1%, and the most common local and systemic adverse reactions were pain (28.4%) and fatigue (8.8%). However, about 76.6% of the unvaccinated participants were willing to be vaccinated. Conclusions: Compared to the general population, postoperative patients with breast cancer had a lower rate of vaccination for SARS-CoV-2. Receiving treatment, a shorter time since surgery, and symptoms of depression were associated with being unvaccinated. However, about 76.6% of the unvaccinated participants were willing to be vaccinated. Although our study showed that there were adverse effects of SARS-CoV-2 vaccines, such as pain, fatigue, they are common adverse effects of routine vaccination. We believe that vaccination against COVID-19 is safe in postoperative patients with breast cancer.