Incidence and outcome of brain and/or leptomeningeal metastases in HER2-low metastatic breast cancer in the French ESME cohort.

BACKGROUND: Breast cancer (BC) is the second most common cancer that metastasizes to the brain. Particularly up to half of patients with human epidermal growth factor receptor 2 (HER2)-positive (HER2+) metastatic breast cancer (mBC) may develop brain metastases over the course of the disease. Nevertheless, little is known about the prevalence and the outcome of brain and leptomeningeal metastases (BLMM) in HER2-low BC. We compared the cumulative incidence of BLMM and associated outcomes among patients with HER2-low, HER2-negative (HER2-) and HER2+ mBC. PATIENTS AND METHODS: This cohort study was conducted from the Epidemiological Strategy and Medical Economics (ESME) mBC database and included patients treated for mBC between 2012 and 2020 across 18 French comprehensive cancer centers and with known HER2 and hormone receptor (HR) status. The cumulative incidence of BLMM after metastatic diagnosis was estimated using a competing risk methodology with death defined as a competing event. RESULTS: 19 585 patients were included with 6118 (31.2%), 9943 (50.8%) and 3524 (18.0%) being HER2-low, HER2- and HER2+ mBC, respectively. After a median follow-up of 48.6 months [95% confidence interval (CI) 47.7-49.3 months], BLMM were reported in 4727 patients: 1192 (25.2%) were diagnosed with BLMM at first metastatic diagnosis and 3535 (74.8%) after metastatic diagnosis. Multivariable analysis adjusted for age, histological grade, metastases-free interval and HR status showed that the risk of BLMM at metastatic diagnosis was similar in patients with HER2- compared to HER2-low mBC [odds ratio (OR) (95% CI) 1.00 (0.86-1.17)] and higher in those with HER2+ compared to HER2-low [OR (95% CI) 2.23 (1.87-2.66)]. Similar results were found after metastatic diagnosis; the risk of BLMM was similar in HER2- compared to HER2-low [subdistribution hazard ratio (sHR) (95% CI) 1.07 (0.98-1.16)] and higher in the HER2+ group [sHR (95% CI) 1.56 (1.41-1.73)]. CONCLUSIONS: The prevalence and evolution of BLMM in HER2-low mBC are similar to those in patients with HER2- tumors. In contrast to patients with HER2+ mBC, the prognosis of BLMM remains dismal in this population.

Safety and efficacy of the anti-PD1 immunotherapy with nivolumab in trichoblastic carcinomas.

Trichoblastic carcinoma is a rare malignant cutaneous adnexal tumor with a risk of local invasion and distant metastasis. As of today, there is no consensus for the treatment of locally advanced or metastatic trichoblastic carcinoma. "AcSé Nivolumab" is a multi-center Phase II basket clinical trial (NCT03012581) evaluating the safety and efficacy of nivolumab in several cohorts of rare, advanced cancers. Here we report the results of nivolumab in patients with trichoblastic carcinoma. Of the eleven patients enrolled in the study, five patients had been previously treated by sonic hedgehog inhibitors. The primary endpoint 12-week objective response rate was 9.1% (N = 1/11) with 1 partial response. Six patients who progressed under previous lines of treatment showed stable disease at 12 weeks, reflecting a good control of the disease with nivolumab. Furthermore, 54.5% of the patients (N = 6/11) had their disease under control at 6 months. The 1-year overall survival was 80%, and the median progression-free survival was 8.4 months (95%CI, 5.7 to NA). With 2 responders (2 complete responses), the best response rate to nivolumab at any time was 18.2% (95%CI, 2.3-51.8%). No new safety signals were identified, and adverse events observed herein were previously described and well known with nivolumab monotherapy. These results are promising, suggesting that nivolumab might be an option for patients with advanced trichoblastic carcinomas. Further studies on larger cohorts are necessary to confirm these results and define the role of nivolumab in the treatment of trichoblastic carcinomas.

Influence of HER2 expression on prognosis in metastatic triple-negative breast cancer-results from an international, multicenter analysis coordinated by the AGMT Study Group.

BACKGROUND: Triple-negative breast cancer (TNBC) is associated with poor prognosis, and new treatment options are urgently needed. About 34%-39% of primary TNBCs show a low expression of human epidermal growth factor receptor 2 (HER2-low), which is a target for new anti-HER2 drugs. However, little is known about the frequency and the prognostic value of HER2-low in metastatic TNBC. PATIENTS AND METHODS: We retrospectively included patients with TNBC from five European countries for this international, multicenter analysis. Triple-negativity had to be shown in a metastatic site or in the primary breast tumor diagnosed simultaneously or within 3 years before metastatic disease. HER2-low was defined as immunohistochemically (IHC) 1+ or 2+ without ERBB2 gene amplification. Survival probabilities were calculated by the Kaplan-Meier method, and multivariable hazard ratios (HRs) were estimated by Cox regression models. RESULTS: In total, 691 patients, diagnosed between January 2006 and February 2021, were assessable. The incidence of HER2-low was 32.0% [95% confidence interval (CI) 28.5% to 35.5%], with similar proportions in metastases (n = 265; 29.8%) and primary tumors (n = 425; 33.4%; P = 0.324). The median overall survival (OS) in HER2-low and HER2-0 TNBC was 18.6 and 16.1 months, respectively (HR 1.00; 95% CI 0.83-1.19; P = 0.969). Similarly, in multivariable analysis, HER2-low had no significant impact on OS (HR 0.95; 95% CI 0.79-1.13; P = 0.545). No difference in prognosis was observed between HER2 IHC 0/1+ and IHC 2+ tumors (HR 0.89; 95% CI 0.69-1.17; P = 0.414). CONCLUSIONS: In this large international dataset of metastatic TNBC, the frequency of HER2-low was 32.0%. Neither in univariable nor in multivariable analysis HER2-low showed any influence on OS.

Adenosine diphosphate-ribosylation factor-like 15 can regulate glycolysis and lipogenesis related genes in colon cancer.

This study was designed to investigate the potential key genes of ADP-ribosylation factor-like 15 (ARL15) regulating glycolysis and lipogenesis in colon cancer. Hematoxylin-eosin (HE) staining and immunohistochemistry were used to observe the expression of ARL15 in 10 normal colon tissues and 10 colon cancer tissues. Immunofluorescence staining was used to observe the expression position of ARL15 in normal human colorectal mucosa cells (FHC) and colon cancer cells (HCT116 and SW620) with a confocal microscope. The ARL15 plasmid and small interfering RNA (siRNA) were constructed. After transfection, the expression levels of glycolysis and lipogenesis regulatory enzymes and messenger RNA (mRNA) transcription of ARL15 in over-expressed and silenced colon cancer cells were detected by Western blotting and real-time quantitative PCR (qRT-PCR). High expression of ARL15 in colon cancer tissue and low expression in normal colon tissue, and all expression are in the cytosol. The expression position of ARL15 in the FHC, HCT116, and SW620 cells was consistent and mainly distributed in the cytosol. After the pCMV-3Tag-2-ARL15 plasmid was transfected in HCT116, the protein expressions of FASN, AKT, P-AKT, P-GSK, SREBP-1 (p125) (p<0.01), and AMPK (p<0.001) were higher than those in the control group. The mRNA transcription level of FASN, GSK, AMPKa1, and SREBP-1 gene was higher than control group after the over-expression of ARL15. After the ARL15-siRNA was transfected in HCT116, the protein expression levels of PKM2, PFK, FASN, AKT, P-AKT, P-GSK, and AMPK decreased compared with the control group, (p<0.05). The mRNA transcription level of FASN, GSK, AMPKα1 gene was lower than control group after the low-expression of ARL15 (p<0.05). After adding 2 µM JIB-04, ARL15 in HCT116 showed statistical differences compared with the control group at 12 h, 24 h and 36 h (p<0.05). After adding 2 µM JIB-04, the protein expression levels of AKT, p-GSK, FASN, AMPK and SREBP-1 in HCT116 cells decreased significantly after 24 h. It was also found that the expression levels of AKT, P-GSK, FASN, AMPK and SREBP-1 genes in the dose-adding group were significantly lower than those in the control group. In summary, ARL15 may promote the occurrence of colon cancer by increasing the expression of protein kinase B/AMP-activated protein kinase (AKT/AMPK) downstream regulatory enzymes for glycogenesis and lipogenesis. JIB-04 can target ARL15 and affect its expression as well as the expressions of glucose and lipid metabolity-related proteins in AKT and AMPK signaling pathways.

High-flow nasal cannula therapy for pediatric obstructive sleep apnea: a systematic review and meta-analysis.

OBJECTIVE: Heated and humidified high-flow nasal cannula (HFNC) therapy has been used to manage different respiratory conditions in pediatric patients. However, no review has summarized its efficacy for the management of pediatric obstructive sleep apnea (OSA). MATERIALS AND METHODS: PubMed, Embase, CENTRAL, and Google Scholar were searched for all types of studies assessing the efficacy of HFNC for pediatric OSA. We compared pre-treatment and post-treatment obstructive apnea-hypopnea index (OAHI), obstructive hypopnea index (OHI), obstructive apnea index (OAI), SPO2 nadir and SPO2 mean values in a random-effect meta-analysis model. RESULTS: Six studies reporting data of 67 pediatric patients treated with HFNC were included. Most of the data were from one-time titration. Meta-analysis revealed a statistically significant reduction in OAHI with HFNC therapy (MD: 15.58 95% CI: 8.30, 22.86 I2=77% p=0.001). Similarly, pooled analysis revealed that both OHI (MD: 12.35 95% CI: 0.78, 23.92 I2=98% p=0.04) and OAI (MD: 7.54 95% CI: 2.10, 12.98 I2=79% p=0.007) were significantly reduced with HFNC treatment. Also, HFNC led to statistically significant improvement in SPO2 nadir values (MD: -8.17 95% CI: -10.40, -5.94 I2=21% p<0.00001) but it did not change the mean SPO2 values before and after treatment (MD: -0.85 95% CI: -1.94, 0.25 I2=52% p=0.13). CONCLUSIONS: Evidence from a limited number of heterogeneous and uncontrolled titration studies indicates that HFNC improves OAHI and minimum oxygen saturation in pediatric patients with OSA. However, further research is required on the long-term efficacy and compliance of HFNC therapy with a focus on different pediatric age groups.

Transcatheter aortic valve replacement in atypical valve anatomy using the Lotus valve : A Chinese single-center experience.

BACKGROUND: In the West, the safety and efficacy of the Lotus valve have been demonstrated; however, data in the Chinese population are still lacking. Few studies have compared the clinical outcomes of transcatheter aortic valve replacement (TAVR) with the Lotus valve in patients with bicuspid or tricuspid aortic valve stenosis. Our aim was to assess TAVR outcomes with the Lotus aortic valve in a Chinese patient cohort. METHODS: In total, 23 symptomatic, high-surgical risk patients with severe aortic valve stenosis were enrolled. Among them, nine patients (39%) had bicuspid aortic valves, and three patients had a large annulus dimension. The Lotus valve was successfully implanted in all patients. To facilitate accurate positioning, partial re-sheathing was attempted in ten patients (43.5%), while one patient had a full retrieval. One-year clinical follow-up was completed in all patients. RESULTS: There were no deaths, strokes, or major adverse cardiac and cerebrovascular events in 22 of the 23 patients at 30 days; the all-cause mortality rate at 1 year was 4.4% (1 of 23 patients). The mean aortic valve gradient decreased from 51.5 ± 8.8 mm Hg at baseline to 13.4 ± 4.9 mm Hg (p < 0.001) and the valve area increased from 0.6 ± 0.2 cm2 to 1.5 ± 0.4 cm2 (p < 0.001) at 30 days. Paravalvular leakage was absent or mild (22%), and no patient had severe paravalvular leakage. Six patients (26.1%) required a postprocedural pacemaker. There was no difference regarding the procedural and the 1­year outcomes between patients with bicuspid and tricuspid aortic valve stenosis. CONCLUSION: Our single-center experience demonstrated that the Lotus valve is feasible and effective for Chinese patients with aortic valve stenosis, including atypical cases with bicuspid aortic valves or large aortic annulus size.

Third-line treatment for metastatic colorectal cancer: anlotinib is superior to chemotherapy and similar to fruquintinib or regorafenib.

The clinical efficiency and adverse reactions of anlotinib in metastatic colorectal cancer (mCRC) as a third-line treatment compared with chemotherapy and regorafenib or fruquintinib was explored in this study. Clinical data from 105 mCRC patients who failed at least two lines of chemotherapy were collected. The patients were divided into three groups based on their third-line therapeutic regimen: third-line chemotherapy only (group A); anlotinib (group B); and fruquintinib or regorafenib (group C). The result showed that the ORR and DCR of group B (14.29%, 85.71%) were higher than those of group A (0%, 40.00%). The ORRs of group B and group C were 14.29% and 20.00%, respectively. Group B and group C had the same DCR, 85.71%. The mean PFS values of group B (3.46 months) and group C (3.33 months) were longer than that of group A (2.25 months) (χ2=84.255, p<0.001) and the mean PFS values of group B and group C were similar (χ2=0.884, p=0.347). The mean OS of group B was 9.22 months, which was longer than that of group A (6.95 months) (χ2=38.837, p<0.001). The mean OS values of group B (9.22 months) and group C (9.38 months) were not significantly different (χ2=0.456, p=0.499). The incidences of proteinuria, hand-foot skin reaction, myelosuppression, and gastrointestinal reaction were similar between group B and group C (p=0.173, 0.188, 1.00, 0.154, respectively). Myelosuppression and gastrointestinal reaction were more common in group A than in group B and group C (p<0.001). For mCRC, anlotinib as a third-line treatment is better than chemotherapy and similar to regorafenib or fruquintinib. The associated adverse reactions are tolerable.

[FibroTouch diagnostic efficiency and influencing factors for liver fibrosis in autoimmune liver diseases].

FibroTouch (FT) has been used widely in clinic. Studies of the FT diagnostic efficiency and influencing factors of liver stiffness measurement (LSM) of liver fibrosis in autoimmune liver diseases (AILD) have shown that FT has a good diagnostic efficiency and accuracy, especially in AIH. However, for patients with primary biliary cholangitis and overlap syndrome of autoimmune hepatitis, FT results should be vigilant. In addition, the diagnostic efficiency of FT. Notably, when using FT to diagnose AILD, the value of elastic stiffness depends on five influencing factors, such as, age, total bile acid, international standardized ratio, FIB-4 index, and prothrombin time.

Sex-specific aortic root anatomy in patients with bicuspid aortic valve undergoing TAVR in a Chinese cohort.

OBJECTIVES: The aim of this study is to investigate the sex-specific aortic root anatomy in patients with bicuspid aortic valve (BAV). PATIENTS AND METHODS: This retrospective study includes 73 consecutive patients with BAV who underwent CT evaluation before transcatheter aortic valve replacement (TAVR) between July 2013 and April 2017 in the Second Affiliated Hospital of Zhejiang University. RESULT: The size of the annulus, diameter and height of the sinotubular junction (STJ), height of the coronary artery ostia, and dimension of the aorta were measured. Women had significantly smaller annulus parameters (mean diameter: 23.4 ± 1.8 vs. 26.1 ± 2.1 mm; area: 425.3 ± 59.4 vs. 527.4 ± 84.6 mm2; perimeter: 74.3 ± 5.2 vs. 83.2 ± 6.4 mm), and STJ diameter (29.7 ± 3.1 vs. 32.6 ± 4.5 mm) than men (p < 0.01 for all), even after adjustment for their smaller body surface area (BSA). Dimension of aorta and height of right coronary artery were also significantly smaller in women, although not when indexing for the BSA. The left ventricular ejection fraction of women is significantly higher than that of men before discharge (60.2 ± 9.7% vs. 53.7 ± 13.6%, p = 0.01). There were no differences between women and men in the all-cause 30-day and 1­year mortality. CONCLUSION: Women with BAV had smaller annulus and STJ diameter after indexing for BSA, reflecting a sex-specific difference. There were no differences in 30-day and 1­year mortality between the two groups.

Budesonide and Poractant Alfa prevent bronchopulmonary dysplasia via triggering SIRT1 signaling pathway.

OBJECTIVE: This study aimed to evaluate effect of budesonide combining Poractant Alfa on preventing bronchopulmonary dysplasia (BPD). PATIENTS AND METHODS: A total of 120 preterm infants were involved. pH value, partial pressure of oxygen (PO2), and blood gas analysis were evaluated. Peripheral blood was collected and mononuclear cells were isolated. Reactive oxygen species (ROS) in peripheral blood mononuclear cells (PBMCs) were detected with laser confocal. Sirtuin 1 (SIRT1) in PBMCs was detected using immunofluorescence. SIRT1 and small ubiquitin-like modifier (SUMO)-specific protease 1 (SENP1) were detected with Western blot. RESULTS: Compared with group B, pH value and PO2 were improved significantly in group C and D (p<0.01). Compared with group B, oxygen inhalation duration, rate of having a respirator assisted ventilation, and using pulmonary surfactant (PS) again, and BPD incidence were significantly decreased in other groups (p<0.05). BPD incidence in group D was less than group C (χ2=4.00, p<0.05). Compared with control group, ROS level of neonatal respiratory distress syndrome (NRDS) group was significantly increased, SENP1 was increased, and SIRT1 was decreased in SIRT1 group. Compared with NRDS, when budesonide combined with Poractant Alfa, ROS decreased, SENP1 decreased, SIRT1 nuclear pulp shuttling rate reduced, nuclear SIRT1 increased (p<0.01). Compared with control, ROS level of NRDS group was significantly increased, SENP1 increased, and SIRT1 in nucleus decreased (p<0.05). Compared with NRDS group, when treated with budesonide and Poractant Alfa, ROS levels decreased, SENP1 decreased, nuclear SIRT1 increased (p<0.01). CONCLUSIONS: Budesonide combining Poractant Alfa can prevent BPD in preterm infants by activating the SIRT1 signaling pathway.

[Application and evaluation of urine measurement at different times methods for estimating salt intake].

Salt reduction is the most cost-effective population strategy to prevent and control hypertension and cardiovascular disease. Accurate measurement of salt intake is an important basis for implementing salt reduction interventions, while the urine sodium measurement is the most objective method to evaluate salt intake. According to different time spans, it is mainly divided into 24-h urine, overnight urine and spot urine collection methods. This article reviewed the application and evaluation of these three urine measurement methods, and compared their advantages and disadvantages. According to the accuracy and feasibility of different urine measurement methods, it is suggested that the 24-h urine collection method can be applied to the correlation study with small sample size, and the overnight urine method and the spot urine method can be applied to the daily population salt reduction interventions and monitoring activities.

[Protective effect of carbon monoxide releasing molecules 2 on post-resuscitation myocardial dysfunction in rats].

Objective: To investigate the protective effect of carbon monoxide releasing molecule 2 (CORM-2) on post-resuscitation myocardial dysfunction in rats. Methods: Forty male SD rats which were healthy were randomly divided into 5 groups: sham operated group(sham group), cardiopulmonary resuscitation(PCR) group, DMSO group, inactivated CORM-2(iCORM-2) group and CORM-2 group (n=8 each). Established the model of post-cardiac arrest myocardial dysfunction by intravenous potassium chloride (4 ℃) injection combined with asphyxiation for 4 minutes and then followed by artificial chest compression for 3 minutes. Sham group: rats were instrumented with catheter without inducing cardiac arrest and resuscitation, and intraperitoneal injection of 0.9% normal saline (4 ml/kg) was performed 12 hours before catheterization. CPR group: rats were instrumented with catheters and underwent CPR, and intraperitoneal injection of 0.9% normal saline (4 ml/kg) was performed 12 hours before surgery.CORM-2 group: rats were instrumented with catheters and underwent CPR, intraperitoneally injected the prepared CORM-2 solution (4 mg/kg) at 12 hours before surgery. DMSO group: rats were instrumented with catheters and underwent CPR, intraperitoneally injected the prepared DMSO solution (4 ml/kg) at 12 hours before surgery. iCORM-2 group: rats were instrumented with catheters and underwent CPR, iCORM-2 solution (4 mg/kg) was intraperitoneally injected at 12 hours before surgery. Hemodynamic data (MAP, +dp/dtmax, -dp/dt) were continuously monitored and recorded for 4 hours after resuscitation (or catheterization) in each group. Myocardial tissue specimen and blood samples were taken after resuscitation (or catheterization). The myocardial ultrastructure was observed by transmission electron microscope. Lactate dehydrogenase (LDH) activity was measured by lactate-pyruvate method. Serum creatine kinase isoenzyme (CK-MB) concentration was measured by ELISA. Western blot was used to detect the levels of Caspase-3, Caspase-9 and Cyt-C protein in myocardial tissue. Results: MAP, +dp/dtmax and -dp/dt at 0.5, 1, 2, 3 and 4 hours post resuscitation were significantly lower than those immediately after catheterization in CRP, DMSO, iCORM-2 groups (all P<0.05). MAP at 0.5, 1, 2, 3, and 4 hours post resuscitation were significantly lower in CRP, DMSO and iCORM-2 groups than those at respective time points in sham group (all P<0.05), while MAP was similar between CORM-2 group and Sham group at these time points (all P>0.05). +dp/dtmax and -dp/dt values at 0.5, 1, 2, 3, and 4 hours post resuscitation were lower than those at respective time points in sham group and significance was found at 0.5, 1 and 2 hours post resuscitation (both P<0.05), while +dp/dtmax and -dp/dt values were similar between CORM-2 group and sham group at various time points (all P>0.05). Myocardial ultrastructure, especially mitochondrial structural integrity was better preserved in the CORM-2 group than those in the other resuscitation groups at 4 hours after resuscitation. Serum LDH activity and CK-MB concentration were significantly elevated at 4 hours after resuscitation in the CPR group, DMSO group and iCORM-2 group than those in sham group (all P<0.01); CK-MB concentration was also higher in CORM-2 group than that in sham group,and LDH level was similar between CORM-2 group and sham group (P>0.05). Serum LDH activity and CK-MB concentrations were significantly lower in the CORM-2 group than those in the other resuscitation groups (all P<0.01). The myocardial expressions of Caspase-3, Caspase-9 and Cyt-C at 4 hours after resuscitation were significantly higher in the CPR group, DMSO group and iCORM-2 group than those in sham group; the myocardial expressions of Caspase-3 and Caspase-9 were significantly higher in CORM-2 group than those in sham group (both P<0.05), while Cyt-C expression was similar between CORM-2 group and sham group. The expressions of the above 3 proteins were significantly lower in the CORM-2 group than those in the other resuscitation groups (all P<0.05). Conclusions: CORM-2 can effectively alleviate post-resuscitation myocardial injury in rats with cardiopulmonary resuscitation and improve cardiac function. Protecting myocardial mitochondria and inhibiting mitochondrial apoptosis pathway may serve as the protective mechanisms in this model.

A Review of Magnetic Particle Imaging and Perspectives on Neuroimaging.

Magnetic particle imaging is an emerging tomographic technique with the potential for simultaneous high-resolution, high-sensitivity, and real-time imaging. Magnetic particle imaging is based on the unique behavior of superparamagnetic iron oxide nanoparticles modeled by the Langevin theory, with the ability to track and quantify nanoparticle concentrations without tissue background noise. It is a promising new imaging technique for multiple applications, including vascular and perfusion imaging, oncology imaging, cell tracking, inflammation imaging, and trauma imaging. In particular, many neuroimaging applications may be enabled and enhanced with magnetic particle imaging. In this review, we will provide an overview of magnetic particle imaging principles and implementation, current applications, promising neuroimaging applications, and practical considerations.

[Observation on the distribution of nerve fibers and neural cells morphology in Aspidogaster conchiola].

OBJECTIVE: To understand the distribution of nerve fibers and the types of neural cells in Aspidogaster conchiola. METHODS: Whole worms were subjected to silver staining, histochemical staining and hematoxylin-eosin (HE) staining, and the nervous systems of the worms were observed. RESULTS: There were 3 types of neural cells in the worm head near the cerebral ganglion, including unipolar, bipolar and multipolar neurons, which were divided into 7 types according to the morphology. There was a nerve network on the surface of pharynx and intestinal tract, as well as the reproductive organ, including testis, ovary, lower uterus and penis sac. The nerve network was consisted of circular and longitudinal nerve fibers, and the structure of the nerve network around the mouth was similar to central nerve. CONCLUSIONS: The structure of the A. conchiola central nervous system is very complicated, and the neural networks may be associated with the physiologic activity of the worm. Different neural cells may have diverse functions.

[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.

Combined pathologic-genomic algorithm for early-stage breast cancer improves cost-effective use of the 21-gene recurrence score assay.

Background: The 21-gene recurrence score (RS) (Oncotype DX®; Genomic Health, Redwood City, CA) partitions hormone receptor positive, node negative breast cancers into three risk groups for recurrence. The Anne Arundel Medical Center (AAMC) model has previously been shown to accurately predict RS risk categories using standard pathology data. A pathologic-genomic (P-G) algorithm then is presented using the AAMC model and reserving the RS assay only for AAMC intermediate-risk patients. Patients and methods: A survival analysis was done using a prospectively collected institutional database of newly diagnosed invasive breast cancers that underwent RS assay testing from February 2005 to May 2015. Patients were assigned to risk categories based on the AAMC model. Using Kaplan-Meier methods, 5-year distant recurrence rates (DRR) were evaluated within each risk group and compared between AAMC and RS-defined risk groups. Five-year DRR were calculated for the P-G algorithm and compared with DRR for RS risk groups and the AAMC model's risk groups. Results: A total of 1268 cases were included. Five-year DRR were similar between the AAMC low-risk group (2.7%, n = 322) and the RS < 18 low-risk group (3.4%, n = 703), as well as between the AAMC high-risk group (22.8%, n = 230) and the RS > 30 high-risk group (23.0%, n = 141). Using the P-G algorithm, more patients were categorized as either low or high risk and the distant metastasis rate was 3.3% for the low-risk group (n = 739) and 24.2% for the high-risk group (n = 272). Using the P-G algorithm, 44% (552/1268) of patients would have avoided RS testing. Conclusions: AAMC model is capable of predicting 5-year recurrences in high- and low-risk groups similar to RS. Further, using the P-G algorithm, reserving RS for AAMC intermediate cases, results in larger low- and high-risk groups with similar prognostic accuracy. Thus, the P-G algorithm reliably identifies a significant portion of patients unlikely to benefit from RS assay and with improved ability to categorize risk.

[Diagnostic efficacy of (18)F-FDG PET-CT for focal hypermetabolic thyroid nodules].

Objective: To explore the diagnostic efficacy of by (18)F-FDG PET-CT for hypermetabolic thyroid nodules. Methods: To retrospectively analyze the clinical data of 3 192 patients underwent (18)F-FDG PET-CT in our hospital from May 2012 to October 2014. Among them, 98 patients were diagnosed with focal hypermetabolic thyroid nodules. 61 of the 98 patients were diagnosed with malignant or benign thyroid nodules using histopathological or clinical follow-up (22 malignant nodules, 39 benign nodules). The average age of these 61 patients was 61.6±12.5 years. Results: The lgSUVmax of malignant group (0.69±0.31) was significantly higher than that in benign group (0.43±0.27) (P=0.001). There was no significant difference in age, gender, nodule size, minimum diameter of nodule, lgCT, calcification, the boundary definition, density uniformity, and history of malignancy between the two groups (P>0.05). Binary Logistic regression indicated the AUC of Logistic regressive model(AUC) was 0.866±0.049 (95% CI: 0.769-0.963), and the malignant AUCs of ROC curve was 0.747±0.068 (95%CI: 0.614-0.880) which was only determined by lgSUVmax. The difference was statistically significant (P<0.01). Conclusion: (18)F-FDG PET-CT imaging can not only detect hypermetabolic thyroid nodules, but also have a certain clinical value for the identification of benign and malignant nodules.

The common variants implicated in microstructural abnormality of first episode and drug-naïve patients with schizophrenia.

Both post-mortem and neuroimaging studies have identified abnormal white matter (WM) microstructure in patients with schizophrenia. However, its genetic underpinnings and relevant biological pathways remain unclear. In order to unravel the genes and the pathways associated with abnormal WM microstructure in schizophrenia, we recruited 100 first-episode, drug-naïve patients with schizophrenia and 140 matched healthy controls to conduct genome-wide association analysis of fractional anisotropy (FA) value measured using diffusing tensor imaging (DTI), followed by multivariate association study and pathway enrichment analysis. The results showed that one intergenic SNP (rs11901793), which is 20 kb upstream of CXCR7 gene on chromosome 2, was associated with the total mean FA values with genome-wide significance (p = 4.37 × 10-8), and multivariate association analysis identified a strong association between one region-specific SNP (rs10509852), 400 kb upstream of SORCS1 gene on chromosome 10, and the global trait of abnormal WM microstructure (p = 1.89 × 10-7). Furthermore, one pathway that is involved in cell cycle regulation, REACTOME_CHROMOSOME _MAINTENANCE, was significantly enriched by the genes that were identified in our study (p = 1.54 × 10-17). In summary, our study provides suggestive evidence that abnormal WM microstructure in schizophrenia is associated with genes that are likely involved in diverse biological signals and cell-cycle regulation although further replication in a larger independent sample is needed.

[Preliminary clinical efficacy of percutaneous transcystic papilla balloon dilation for removing common bile duct stones].

Objective: To evaluate the feasibility, safety, and preliminary efficacy of percutaneous transcystic papilla balloon dilation for the common bile duct stones. Methods: A total of 11 patients with the common bile duct stones without dilatation of the intrahepatic bile ducts treated with percutaneous transcystic papilla balloon dilation in multiple center from April 2013 to May 2015 were analyzed retrospectively.In these 11 patients, there were 3 males and 8 females.And the average age was 68(52-91) years old.All patients had no obviously dilated intrahepatic bile duct, 6 patients were not suitable for endoscopic treatment or surgery, 4 patients refused endoscopic or surgical treatment and 1 patient had a history of failed endoscopic treatment.The white blood cell count, CA19-9, total bilirubin, direct bilirubin, AST, ALT and serum amylase level were recorded before the procedure, 1 week, and 1 month later.Early complications, such as cholangitis, pancreatitis, hemorrhage, and perforation were evaluated. Results: Technical success was achieved in all the 11 cases.The level of CA19-9, total bilirubin and direct bilirubin decreased significantly 1 week and 1 month after the procedure.One patient suffered from biliary tract infection.No severe complications, such as perforation of biliary or gastrointestinal tract, occurred during the follow up.Common bile duct stone recurred in 1 patient 2 years after the procedure. Conclusions: For cases who are not suitable for endoscopic treatment, surgery, or percutaneous transhepatic approach to treat the common bile duct stones, percutaneous transcystic papilla dilation is technically feasible and safe, and seems to be an appropriate alternative strategy.

Molecular cloning and differential expression of the glucocorticoid receptorgene in the estuarine tapertail anchovy Coilia nasus.

To understand the regulation of the glucocorticoid receptor gene (Gcr) during loading and transport stress in fish, the Gcr gene of Coilia nasus was cloned. Gcr in C. nasus is expressed strongly in the liver and muscle, and less stronglyin the gills, brain, spleen, intestine, trunk kidney, and head kidney. Gcr expression in both the liver and muscle was increased by loading and transport stress. NaCl reduced the death rate caused by loading and transport stress, and the expression of Gcr in liver and muscle differed significantly between the NaCl and non-NaCl groups. To investigate whether the elevated Gcr transcripts were translated into protein, proteins extracted from the liver and muscle were analyzed. In both tissues, C. nasus GCR protein expression patterns paralleled those of Gcr mRNA during stress.