Azide-free cyclization reaction access to 4-aryl-NH-1,2,3-triazoles: P-toluenesulfonyl hydrazide and sulfamic acid as nitrogen sources.

An iodine-mediated cyclization has been developed to 4-aryl-NH-1,2,3-triazoles, with p-toluenesulfonyl hydrazide and sulfamic acid used as nitrogen sources. Sulfamic acid plays a crucial role in this reaction by both acting as a substrate and providing an acidic environment. This reaction offers a metal- and azide-free strategy to access NH-1,2,3-triazoles.

Pathogenic Profile Characteristics and Clinical Risk Factor Analysis of Patients Who Died from Sepsis Combined with Pulmonary Infection by Metagenomic Next-Generation Sequencing.

Introduction: Sepsis is one of the major diseases that seriously threatens human health, and its incidence and in-hospital morbidity and mortality rates remain high. Applying metagenomic next-generation sequencing (mNGS) technology to analyze the differences in pathogenic profiles and clinical factors in patients surviving and dying from sepsis combined with pulmonary infections provides diagnostic value and application for clinical purposes. Methods: Sixty-three BALF samples from patients with sepsis combined with pulmonary infection from Fuqing Hospital Affiliated to Fujian Medical University were collected, and all of them were tested by simultaneous mNGS and conventional microbial combined test (CMT) to compare the pathogenic profiles and clinical indices of patients who survived and died of sepsis combined with pulmonary infection and to further compare the diagnostic differences between mNGS and CMT in patients who survived and died of sepsis combined with pulmonary infection. We analyzed the diagnostic value of mNGS for sepsis combined with pulmonary infection. Results: A total of 141 strains of pathogens were isolated from 63 samples of patients with sepsis combined with pneumonia at suspected infection sites, Klebsiella pneumoniae, Acinetobacter baumannii, and Stenotrophomonas maltophilia are predominant, and higher ApacheII, LAC, P and PT are all risk factors affecting the death of septic patients. Conclusion: Applying the mNGS method to patients with sepsis combined with pneumonia can improve the positive detection rate of pathogenic microorganisms and focus on death-related risk factors such as pathogenic bacteria species as well as clinical laboratory indices, which can guide clinicians to take appropriate measures to treat patients with sepsis and reduce the occurrence of death.

Golay-Encoded Ultrasound Monitoring of Simultaneous High-Intensity Focused Ultrasound Treatment: A Phantom Study.

Ultrasound (US) imaging has high potential in monitoring high-intensity focused US (HIFU) treatment due to its superior temporal resolution. However, US monitoring is often hindered by strong HIFU interference, which overwhelms the echoes received by the imaging array. In this study, a method of Golay-encoded US monitoring is proposed to visualize the imaged object for simultaneous HIFU treatment. It effectively removes HIFU interference patterns in real-time B-mode imaging and improves the metrics of image quality, such as peak signal-to-noise ratio (PSNR), structural similarity (SSIM), and contrast ratio (CR). Compared to the pulse-inversion sequence, the N -bit Golay sequence can boost the echo magnitude of US monitoring by another N times and, thus, exhibits higher robustness. Simulations show that a sinusoidal HIFU waveform can be fully eliminated using Golay decoding when the bit duration of the N -bit Golay sequence ( N is the power of 4) coincides with either odd (Case I) or even (Case II) integer multiples of the HIFU quarter period. Experimental results also show that the Golay decoding with Case II can increase the PSNR of US monitoring images by more than 30 dB for both pulse- and continuous-wave HIFU transmissions. The SSIM index also effectively improves to about unity, indicating that the B-mode image with HIFU transmission is visually indistinguishable from that acquired without HIFU transmission. Though Case I is inferior to Case II in the elimination of even-order HIFU harmonic, they together enable a more flexible selection of imaging frequencies to meet the required image resolution and penetration for Golay-encoded US monitoring.

An Improved Localization Method for the Transition between Autonomous Underwater Vehicle Homing and Docking.

Docking technology for autonomous underwater vehicles (AUVs) involves energy supply, data exchange and navigation, and plays an important role to extend the endurance of the AUVs. The navigation method used in the transition between AUV homing and docking influences subsequent tasks. How to improve the accuracy of the navigation in this stage is important. However, when using ultra-short baseline (USBL), outliers and slow localization updating rates could possibly cause localization errors. Optical navigation methods using underwater lights and cameras are easily affected by the ambient light. All these may reduce the rate of successful docking. In this paper, research on an improved localization method based on multi-sensor information fusion is carried out. To improve the localization performance of AUVs under motion mutation and light variation conditions, an improved underwater simultaneous localization and mapping algorithm based on ORB features (IU-ORBSALM) is proposed. A nonlinear optimization method is proposed to optimize the scale of monocular visual odometry in IU-ORBSLAM and the AUV pose. Localization tests and five docking missions are executed in a swimming pool. The localization results indicate that the localization accuracy and update rate are both improved. The 100% successful docking rate achieved verifies the feasibility of the proposed localization method.

Clinical Analysis of BRAFV600E Mutation and Its Correlation With Sonographic Image Characteristics in Papillary Thyroid Carcinoma in Chinese Coastal Areas.

This study analyzed the characteristics of BRAFV600E mutation in papillary thyroid carcinoma (PTC) in Chinese coastal areas. We intended to identify noninvasive methods to determine BRAFV600E status in thyroid nodules prior to surgery. BRAFV600E mutation and the sonographic characteristics of thyroid nodules were investigated in 670 PTC patients in our hospital. We aimed to determine the relationship between BRAFV600E mutation and the clinicopathological and sonographic imaging characteristics of PTC. The mutation rate of the BRAFV600E was 78.2%. BRAFV600E mutation was significantly associated with central node (univariate analyses, P = .005; multivariate analyses, P < .001, odds ratio [OR] = 10.255) and lateral node metastases (univariate analyses, P = .001; multivariate analyses, P < .001, OR = 22). It was less frequent in PTC coexisting with Hashimoto's thyroiditis (univariate analyses, P = .016; multivariate analyses, P < .001, OR = .034). Nodules without blood flow had a significantly higher mutation rate of BRAFV600E in PTC patients (univariate analyses, P = .026). BRAFV600E mutation was significantly associated with high suspicion in the Thyroid Imaging Reporting and Data System 5 (univariate analyses, P = .004; multivariate analyses, P = .014, OR = 6.456). Our results strongly suggest that BRAFV600E mutation plays a potential role in lymph node metastasis (central node metastasis, OR = 10.225; lateral node metastasis, OR = 22). Some sonographic imaging features might be helpful in estimating the status of BRAFV600E preoperatively.

A Fast Binocular Localisation Method for AUV Docking.

Docking technology plays a critical role in realising the long-time operation of autonomous underwater vehicles (AUVs). In this study, a binocular localisation method for AUV docking is presented. An adaptively weighted OTSU method is developed for feature extraction. The foreground object is extracted precisely without mixing or missing lamps, which is independent of the position of the AUV relative to the station. Moreover, this extraction process is more precise compared to other segmentation methods with a low computational load. The mass centre of each lamp on the binary image is used as matching feature for binocular vision. Using this fast feature matching method, the operation frequency of the binocular localisation method exceeds 10 Hz. Meanwhile, a relative pose estimation method is suggested for instances when the two cameras cannot capture all the lamps. The localisation accuracy of the distance in the heading direction as measured by the proposed binocular vision algorithm was tested at fixed points underwater. A simulation experiment using a ship model has been conducted in a laboratory pool to evaluate the feasibility of the algorithm. The test result demonstrates that the average localisation error is approximately 5 cm and the average relative location error is approximately 2% in the range of 3.6 m. As such, the ship model was successfully guided to the docking station for different lateral deviations.

Association Between BRAFV600E Mutation and the American College of Radiology Thyroid Imaging, Reporting and Data System in Solitary Papillary Thyroid Carcinoma.

RATIONALE AND OBJECTIVES: The purpose of this study was to evaluate the associations between BRAFV600E mutation, the American College of Radiology (ACR) thyroid imaging, reporting and data system (TI-RADS) on ultrasound and clinicopathological characteristics in patients with a solitary papillary thyroid carcinoma (PTC). MATERIALS AND METHODS: This retrospective study included 397 patients with a solitary PTC, proved pathologically. BRAFV600E mutation status was detected in postoperative samples by real-time fluorescent polymerase chain reaction. Associations of BRAFV600E mutation with the ACR TI-RADS and clinicopathological characteristics were analyzed. RESULTS: In this study, the incidence of BRAFV600E mutation was 81.4% (323/397) in patients with a solitary PTC. Univariate analyses showed that BRAFV600E mutation was significantly associated with margin, higher ACR TI-RADS point scores, and Hashimoto's thyroiditis. In multivariate analyses, lobulated or irregular margin was independently associated with BRAFV600E mutation in total solitary PTC. Furthermore, both in total solitary PTC and papillary thyroid microcarcinoma, BRAFV600E mutation was associated with ACR TI-RADS point scores, which was positively correlated with the risk of BRAFV600E mutation. There was no significant relationship between BRAFV600E mutation and ACR TI-RADS point scores in PTC >10 mm. In addition, Hashimoto's thyroiditis had a significant negative association with BRAFV600E mutation. CONCLUSION: A lobulated or irregular margin of the thyroid nodule is independently associated with BRAFV600E mutation in patients with PTC. In addition, higher ACR TI-RADS point scores is an independent risk factor for BRAFV600E mutation, and ACR TI-RADS point scores is positively associated with the risk of BRAFV600E mutation in solitary PTC, especially in papillary thyroid microcarcinoma. Our findings may be helpful for preoperative identification and medical management of PTC patients with BRAFV600E mutation.

Epigenetic silencing of the dual-role signal mediator, ANGPTL4 in tumor tissues and its overexpression in the urothelial carcinoma microenvironment.

Urothelial carcinoma (UC) carcinogenesis has been hypothesized to occur through epigenetic repression of tumor-suppressor genes (TSGs). By quantitative real-time polymerase chain reaction array, we found that one potential TSG, angiopoietin-like 4 (ANGPTL4), was expressed at very low levels in all bladder cancer cell lines we examined. Previous studies had demonstrated that ANGPTL4 is highly expressed in some cancers, but downregulated, by DNA methylation, in others. Consequently, owing to these seemingly conflicting functions in distinct cancers, the precise role of ANGPTL4 in the etiology of UC remains unclear. In this study, using methylation-specific PCR and bisulfite pyrosequencing, we show that ANGPTL4 is transcriptionally repressed by DNA methylation in UC cell lines and primary tumor samples, as compared with adjacent noncancerous bladder epithelium. Functional studies further demonstrated that ectopic expression of ANGPTL4 potently suppressed UC cell proliferation, monolayer colony formation in vitro, and invasion, migration, and xenograft formation in vivo. Surprisingly, circulating ANGPTL4 was significantly higher in plasma samples from UC patients than normal control, suggesting it might be secreted from other cell types. Interestingly, our data also indicated that exogenous cANGPTL4 could promote cell proliferation and cell migration via activation of signaling through the Erk/focal adhesion kinase axis. We further confirmed that mouse xenograft tumor growth could be promoted by administration of exogenous cANGPTL4. Finally, immunohistochemistry demonstrated that ANGPTL4 was downregulated in tumor cells but overexpressed in tumor adjacent stromal tissues of muscle-invasive UC tissue samples. In conclusion, our data support dual roles for ANGPTL4 in UC progression, either as a tumor suppressor or oncogene, in response to microenvironmental context.

Effects of mTOR/NF-κB signaling pathway and high thoracic epidural anesthesia on myocardial ischemia-reperfusion injury via autophagy in rats.

We investigated the role of mammalian target of rapamycin/nuclear factor-kappa B (mTOR/NF-κB) signaling pathway in high thoracic epidural anesthesia (HTEA) against myocardial ischemia-reperfusion (I/R) injury in rats. The rat model of myocardial I/R injury was established. Ninety rats were divided into the normal, sham, I/R, eHTEA, the PDTC, and HTEA + PDTC groups. ELISA was applied to detect cardiac function indexes. HE staining was conducted to observe histopathological changes of myocardial tissues, and TTC staining was performed to detect the myocardial infarction size. TUNEL staining was adopted to detect the cell apoptosis rate. The mRNA and protein levels of mTOR, NF-κB, Fasl, Bcl-2 and Bax, and LC3-I, LC3-II, BNIP3, and Atg5 were detected by RT-qPCR and Western blotting, respectively. The findings indicated that compared with the normal and sham groups, the I/R, PDTC, and HTEA groups showed the larger myocardial infarction size and increased cell apoptosis rate, while the results in the HTEA + PDTC group were opposite. Compared with the normal and sham groups, the I/R group showed reduced mRNA and protein levels of Bcl-2, LC3, BNIP3, and Atg5, and elevated mRNA and protein levels of mTOR, p50, p65, Bax, and Fasl, while the HTEA + PDTC group revealed the opposite results, and the PDTC and HTEA group revealed the increased mRNA and protein levels of Bcl-2, LC3, BNIP3, Atg5, mTOR, p50, p65, Bax, and Fasl. These results prove that the inhibition of mTOR/NF-κB signaling pathway potentiates HTEA against myocardial IR injury by autophagy and apoptosis in rats.

Critical Role of p53 and K-ras in the Diagnosis of Early Colorectal Cancer: a One-year, Single-center Analysis.

Background: Colorectal cancer (CRC) is strongly associated with colorectal polyps, which has become the third most common cancer in China. In the present study, we revealed the susceptible population and risk factors of colorectal polyps, and analyzed the expression of Ki-67, p53 and K-ras in the intestinal mucosa of patients with colorectal polyps in order to explore their significance in the detection and prognosis of CRC at an early stage. Materials and Methods: Total 801 cases of colorectal polyps were collected during endoscopic resection including endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD). Expression of Ki-67, p53 and K-ras in the intestinal mucosa was detected by immunohistochemistry and quantitative real-time polymerase chain reaction (qRT-PCR), respectively. Histological analysis was performed by Hematoxylin and eosin (HE) staining. Categorical variables were compared by one-way ANOVA, Pearson test, Spearman test, Kruskal-Wallis test and analysis of regression. Results: Of all patients with colorectal polyps, 90.76% of patients (n = 727) were ≥ 50 years old. 530 cases (66.17%) were males compared with 271 females (33.83%) in all 801 cases. More importantly, 1.03% patients (n = 7) underwent polypectomy and histological examination was confirmed to be the early stage of CRC. The expression of p53 was found to be significantly decreased, while K-ras was increased in tumor tissues of CRC compared with that in hyperplastic polyps and healthy controls. Conclusions: 1.03% patients (n = 7) underwent polypectomy was confirmed to be the early stage of CRC. Histological analysis for expression of p53 and K-ras can guarantee to screen the early stage of CRC.

Micro RNA-155 plays a critical role in the initiation of food allergen-related inflammation in the intestine.

The pathogenesis of food allergy (FA) is to be further investigated. Regulatory B cells (B10 cell) play a critical in the maintenance of the homeostasis in the intestine. Deregulation of B10 cell is associated with immune inflammation. Micro RNA (miR) 155 is involved in affecting immune cell function. This study tests a hypothesis that miR-155 affects the B10 cell function to facilitate the initiation of FA. In this study, BALB/c mice were sensitized to ovalbumin (OVA) to induce FA-like inflammation in the intestine. B cells were isolated from the intestine by magnetic cell sorting. The expression of miR-155 and IL-10 in B cells was assessed by real time RT-PCR. The results showed that mice sensitized to OVA showed FA-like inflammation and lower frequency of B10 cell in the intestine. B cells isolated from the intestine of FA mice showed higher levels of miR-155 and lower levels of IL-10. Although all the three T helper (Th)2 cytokines, including interleukin (IL)-4, IL-5 and IL-13, were higher in the serum, only IL-13 was positively correlated with the levels of miR-155 in the intestinal B cells. Exposure to IL-13 in the culture markedly increased the expression of miR-155 and suppressed the expression of IL-10 in B cells. Blocking miR-155 abolished the IL-13-induced IL-10 suppression in B cells and inhibited FA response in mice. In conclusion, miR-155 plays a critical role in the initiation of FA in mice. Blocking miR-155 has therapeutic potential in the treatment of FA.

Protective Effects of Microrna-22 Against Endothelial Cell Injury by Targeting NLRP3 Through Suppression of the Inflammasome Signaling Pathway in a Rat Model of Coronary Heart Disease.

BACKGROUND/AIMS: This study aimed to identify the role of microRNA-22 (miR-22) in endothelial cell (EC) injury in coronary heart disease (CHD) by targeting NLRP3 through the inflammasome signaling pathway. METHODS: A total of 24 healthy male Sprague-Dawley (SD) rats were divided into normal and atherosclerosis groups. The atherosclerosis rats were assigned into blank, negative control (NC), miR-22 mimic, miR-22 inhibitor and miR-22 inhibitor + siNLRP3 groups. A luciferase reporter gene assay was used to detect the relationship between miR-22 and NLRP3. MiR-22 expression as well as NLRP3 and caspase-1 mRNA and protein expression were measured using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. The activity and apoptosis of coronary arterial endothelial cells (CAECs) were determined by MTT and Hoechst 33258. CAEC lumen formation was detected by a lumen formation assay. An enzyme-linked immunosorbent assay (ELISA) was used to detect IL-1ß, IL-6, IL-10 and IL-18 levels. RESULTS: The results indicated that the atherosclerosis group significantly decreased miR-22 expression but increased NLRP3 and caspase-1 mRNA and protein expression. The cell survival rate was significantly increased in the miR-22 mimic group and significantly reduced in the miR-22 inhibitor group. The miR-22 mimic group displayed a lower apoptosis rate and more cells with obvious lumen walls and numerous tubular structures, while cells in the miR-22 inhibitor group were unable to form lumen walls and had a scattered distribution compared to the blank group. The ELISA showed that IL-1ß, IL-6 and IL-18 levels were markedly decreased, while IL-10 was clearly increased in the miR-22 mimic group. In contrast, in the miR-22 inhibitor group, IL-1ß, IL-6 and IL-18 levels were significantly increased, and IL-10 levels were decreased. CONCLUSION: Our findings indicated that miR-22 could lower the levels of pro-inflammatory cytokines by inhibiting the NLRP3 inflammasome pathway, which suppresses CAEC apoptosis and protects CAECs in rats with CHD.

[Effects of mesangial cell on proliferation and function of osteoblast in vitro].

OBJECTIVE: To explore the effects and mechanism of mesangial cell (MC) on proliferation and function of osteoblast in vitro from growth factors. METHODS: Osteoblast cultured in vitro were divided into normal blood serum group and MC group and cultured supernatant fluid by 10% serum culture medium and 20% MC culture medium. MTF was used to checked the proliferation of osteoblast at the end of 24, 48, 72, 120 h; Expression of BGP and OPN were tested 72 h and 144 h after culture; Expression of IGF-alpha and TGF-beta were tested 144 h after culture. RESULTS: The proliferation of osteoblast in MC group was obviously higher than normal blood serum group in different times (P < 0.05); The level of BGP and OPN of osteoblast was obviously higher than normal blood serum group (11.3%, 16.4%, 55.0% and 39.6%); and the level of IGF-alpha and TGF-beta of osteoblast was obviously higher than normal blood serum group (10.1% and 47.7%). CONCLUSION: MC can directly act on osteoblast, promote the proliferation and function of osteoblast by promoting secretion of TGF-beta.

[GTW-induced abnormal expressions of testicular reproduction-related genes and intervention with kidney-tonifying Chinese herbs].

OBJECTIVE: To explore the abnormal expressions of testicular reproduction-related genes induced by glycosides of Tripterygium wilfordii (GTW) and the intervention with kidney-tonifying Chinese herbs. METHODS: Adult Balb/C male mice were fed on GTW at 30 mg per kg per d for 3 weeks to establish a model of reproductive dysfunction. The model mice were divided into different groups to receive intragastrical administration of saline (0.25 ml/d), GTW (30 mg per kg per d), Cistanche (10 g per kg per d), Rehmannia (10 g per kg per d), and Rehmannia + Cistanche (20 g per kg per d), respectively, once a day for 3 weeks. And a Cistanches pretreatment group was treated with GTW (30 mg per kg per d) and Cistanche (10 g per kg per d) for the same length of time. Then we detected the changed expressions of testicular reproduction-related genes Dzip1, Fas, c-jun and Wnt4 in each group. RESULTS: The model mice showed an obviously down-regulated expression of the Y chromosome microdeletion-related gene Dzip1, and up-regulated expressions of the germ cell apoptosis-related gene Fas, proto-oncogene c-jun, and signal transduction-related gene Wnt4. Intervention with Chinese herbs achieved different degrees of improvement of the mice's reproductivity, and the most obvious efficacy was observed with the combined use of kidney-yang tonifying Cistanche and kidney-yin nourishing Rehmannia. CONCLUSION: GTW exerts significant impact on reproduction-related genes. Both the kidney-yang tonifying drug Cistanche and kidney-yin nourishing drug Rehmannia can counteract some of the reproductive toxicity of GTW, while the combination of the two can further enhance the effect.

Efficient in vitro siRNA delivery and intramuscular gene silencing using PEG-modified PAMAM dendrimers.

Although siRNA techniques have been broadly applied as a tool for gene knockdown, substantial challenges remain in achieving efficient delivery and in vivo efficacy. In particular, the low efficiency of target gene silencing in vivo is a critical limiting step to the clinical application of siRNA therapies. Poly(amidoamine) (PAMAM) dendrimers are widely used as carriers for drug and gene delivery; however, in vivo siRNA delivery by PAMAM dendrimers remains to be carefully investigated. In this study, the effectiveness of G5 and G6 PAMAM dendrimers with 8% of their surface amines conjugated to MPEG-5000 was studied for siRNA delivery in vitro and for intramuscular in vivo delivery in mice. The results from the PEG-modified dendrimers were compared to the results from the parent dendrimers as well as Lipofectamine 2000 and INTERFERin. Both PEG-modifed dendrimers protect the siRNA from being digested by RNase and gave high transfection efficiency for FITC-labeled siRNA in the primary vascular smooth muscle cells (VSMC) and mouse peritoneal macrophages. The PEG-modified dendrimers achieved knockdown of both plasmid (293A cells) and adenovirus-mediated green fluorescence protein (GFP) expression (Cos7 cells) in vitro with efficiency similar to that shown for Lipofectamine 2000. We further demonstrated in vivo that intramuscular delivery of GFP-siRNA using PEG-modified dendrimer significantly suppressed GFP expression in both transiently adenovirus infected C57BL/6 mice and GFP transgenic mice.

[Summarization of Chinese rhubarb recorded by the Westerners in China in the Ming and Qing dynasties].

The westerners in China in the Ming and Qing dynasties, such as travellers, missionaries, archaeologists and explorers etc., left many records of Chinese rhubarb, among which included botanical characteristics, rhubarb trade and the preparation method and usage of rhubarb. These records reflected the evolution of cognition on Chinese rhubarb of the Westerners in China as well as the constant in-depth cognition on Chinese rhubarb, and also reflected the situation of sino-foreign medical exchange from one angle. Sifting the records of Chinese rhubarb by the Westerners who came to China in the Ming and Qing dynasties will contribute to further relevant research on rhubarb as well as sino-foreign medical exchanges.