Nano Proteolysis Targeting Chimeras (PROTACs) with Anti-Hook Effect for Tumor Therapy.

Proteolysis targeting chimera (PROTAC) is an emerging pharmacological modality with innovated post-translational protein degradation capabilities. However, off-target induced unintended tissue effects and intrinsic "hook effect" hinder PROTAC biotechnology to be maturely developed. Herein, an intracellular fabricated nano proteolysis targeting chimeras (Nano-PROTACs) modality with a center-spoke degradation network for achieving efficient dose-dependent protein degradation in tumor is reported. The PROTAC precursors are triggered by higher GSH concentrations inside tumor cells, which subsequently in situ self-assemble into Nano-PROTACs through intermolecular hydrogen bond interactions. The fibrous Nano-PROTACs can form effective polynary complexes and E3 ligases degradation network with multi-binding sites, achieving dose-dependent protein degradation with "anti-hook effect". The generality and efficacy of Nano-PROTACs are validated by degrading variable protein of interest (POI) such as epidermal growth factor receptor (EGFR) and androgen receptor (AR) in a wide-range dose-dependent manner with a 95 % degradation rate and long-lasting potency up to 72 h in vitro. Significantly, Nano-PROTACs achieve in vivo dose-dependent protein degradation up to 79 % and tumor growth inhibition in A549 and LNCap xenograft mice models, respectively. Taking advantages of in situ self-assembly strategy, the Nano-PROTACs provide a generalizable platform to promote precise clinical translational application of PROTAC.

X-ray induces mechanical and heat allodynia in mouse via TRPA1 and TRPV1 activation.

Radiotherapy-related pain is a common adverse reaction with a high incidence among cancer patients undergoing radiotherapy and remarkably reduces the quality of life. However, the mechanisms of ionizing radiation-induced pain are largely unknown. In this study, mice were treated with 20 Gy X-ray to establish ionizing radiation-induced pain model. X-ray evoked a prolonged mechanical, heat, and cold allodynia in mice. Transient receptor potential vanilloid 1 and transient receptor potential ankyrin 1 were significantly upregulated in lumbar dorsal root ganglion. The mechanical and heat allodynia could be transiently reverted by intrathecal injection of transient receptor potential vanilloid 1 antagonist capsazepine and transient receptor potential ankyrin 1 antagonist HC-030031. Additionally, the phosphorylated extracellular regulated protein kinases (ERK) and Jun NH2-terminal Kinase (JNK) in pain neural pathway were induced by X-ray treatment. Our findings indicated that activation of transient receptor potential ankyrin 1 and transient receptor potential vanilloid 1 is essential for the development of X-ray-induced allodynia. Furthermore, our findings suggest that targeting on transient receptor potential vanilloid 1 and transient receptor potential ankyrin 1 may be promising prevention strategies for X-ray-induced allodynia in clinical practice.

Overexpression of Contactin 1 promotes growth, migration and invasion in Hs578T breast cancer cells.

BACKGROUND: Contactin1 (CNTN1) has been shown to play an important role in the invasion and metastasis of several tumors; however, the role of CNTN1 in breast cancer has not been fully studied. The purpose of this study is to investigate the role of CNTN1 in regulating tumor growth, migration and invasion in breast cancer. RESULTS: To investigate its function, CNTN1 was expressed in Hs578T cells. CNTN1 expression was confirmed by western blot, immunohistochemistry and real-time RT-PCR. The effect of CNTN1 overexpression on proliferation, migration and invasion of Hs578T breast cancer cells was assessed in vitro and in vivo. Our results showed that CNTN1 overexpression promoted Hs578T cell proliferation, cell cycle progression, colony formation, invasion and migration. Notably, overexpression of CNTN1 in Hs578T cells enhanced the growth of mouse xenograft tumors. CONCLUSIONS: CNTN1 promotes growth, metastasis and invasion of Hs578T breast cancer cell line. Thus, therapies targeting CNTN1 may prove efficacious for breast cancer. However, further investigation is required to understand the mechanism by which CNTN1 influences proliferation, metastasis and invasion in breast cancer.

Relationship between mammographic calcifications and the clinicopathologic characteristics of breast cancer in Western China: a retrospective multi-center study of 7317 female patients.

BACKGROUND AND PURPOSE: Limited information is available regarding the correlations between mammographic calcifications and the epidemiological features of patients with breast cancer living different lifestyles in Western China. Thus, this study aimed to investigate the relationship between mammographic calcifications and the epidemiological characteristics of female patients with breast cancer in Western China. METHODS: This was a hospital-based, retrospective, multi-center epidemiological study of patients with breast cancer. Using the Western China Clinical Cooperation Group (WCCCG) database, we obtained the records of 7317 patients (with mammographic data) diagnosed with breast cancer between March 2011 and June 2016. These patients were divided into Groups I (mass alone) and II (mass combined with calcification), and their clinical and pathological data were compared. RESULTS: A total of 4211 patients were enrolled in Group I, and 3106 patients were enrolled in Group II. The tumors in Group II were more likely to be larger (P < 0.0001), higher grade (P = 0.0029), estrogen receptor (ER)+/progesterone receptor (PR)- (P = 0.0319), and human epidermal growth factor receptor 2 (HER-2)-positive (P < 0.0001), and to have axillary lymph node metastasis (P = 0.0033) than those in Group I. Regarding treatment, patients in Group II were more likely to have undergone chemotherapy (P = 0.0108) and anti-HER2 therapy (P = 0.0102), whereas patients in Group I were more likely to have undergone endocrine therapy (P < 0.0001). CONCLUSIONS: In conclusion, mammographic calcifications in tumors were associated with distinct clinicopathologic characteristics and aggressive treatments.

Ononin promotes radiosensitivity in lung cancer by inhibiting HIF-1α/VEGF pathway.

BACKGROUND: In our previous study, we provided evidence that Astragalus mongholicus Bunge(AM) and its extracts possess a protective capability against radiation-induced damage, potentially mediated through the reduction of reactive oxygen species (ROS) and nitric oxide (NO). However, we were pleasantly surprised to discover during our experimentation that AM not only offers protection against radiation damage but also exhibits a radiation sensitization effect. This effect may be attributed to a specific small molecule present in AM known as ononin. Currently, radiation sensitizers are predominantly found in nitrazole drugs and nanomaterials, with no existing reports on the radiation sensitization properties of ononin, nor its underlying mechanism. PURPOSE: This study aims to investigate the sensitization effect of the small molecule ononin derived from AM on lung cancer radiotherapy, elucidating its specific molecular mechanism of action. Additionally, the safety profile of combining astragalus small molecule ononin with radiation therapy will be evaluated. METHODS: The effective concentration of ononin was determined through cell survival experiments, and the impact of ononin combined with varying doses of radiation on lung cancer cells was observed using CCK-8 and cell cloning experiments. The apoptotic effect of ononin combined with radiation on lung cancer cells was assessed using Hochester staining, flow cytometry, and WB assay. Additionally, WB and immunofluorescence analysis were conducted to investigate the influence of ononin on HIF-1α/VEGF pathway. Furthermore, Molecular Dynamics Simulation was employed to validate the targeted binding ability of ononin and HIF-1α. A lung cancer cell line was established to investigate the effects of knockdown and overexpression of HIF-1α. Subsequently, the experiment was repeated using tumor bearing nude mice and C57BL/6 mouse models in an in vivo study. Tumor volume was measured using a vernier caliper, while HE, immunohistochemistry, and immunofluorescence techniques were employed to observe the effects of ononin combined with radiation on tumor morphology, proliferation, and apoptosis. Additionally, Immunofluorescence was employed to examine the impact of ononin on HIF-1α/VEGF pathway in vivo, and its effect on liver function in mice was assessed through biochemistry analysis. RESULTS: At a concentration of 25 µM, ononin did not affect the proliferation of lung epithelial cells but inhibited the survival of lung cancer cells. In vitro experiments demonstrated that the combination of ononin and radiation could effectively inhibit the growth of lung cancer cells, induce apoptosis, and suppress the excessive activation of the Hypoxia inducible factor 1 alpha/Vascular endothelial growth factor pathway. In vivo experiments showed that the combination of ononin and radiation reduced the size and proliferation of lung cancer tumors, promoted cancer cell apoptosis, mitigated abnormal activation of the Hypoxia inducible factor 1 alpha pathway, and protected against liver function damage. CONCLUSION: This study provides evidence that the combination of AM and its small molecule ononin can enhance the sensitivity of lung cancer to radiation. Additionally, it has been observed that this combination can specifically target HIF-1α and exert its effects. Notably, ononin exhibits the unique ability to protect liver function from damage while simultaneously enhancing the tumor-killing effects of radiation, thereby demonstrating a synergistic and detoxifying role in tumor radiotherapy. These findings contribute to the establishment of a solid basis for the development of novel radiation sensitizers derived from traditional Chinese medicine.

[Expression of steroidogenic enzymes in the rat model of polycystic ovary syndrome].

The aim of the present study was to investigate the expression changes of three steroidogenic enzymes in the polycystic ovary syndrome (PCOS). Thirty Sprague-Dawley (SD) rats were randomly divided into normal control (NC) group and PCOS group. PCOS rat model was established by DHEA injection. The serum levels of progesterone, estrogen and testosterone were measured by immunoradioassay or enzyme immunoassay. The cellular distributions of 3ß-hydroxy steroid dehydrogenase (3ß-HSD), 17ß-hydroxy steroid dehydrogenase (17ß-HSD) and cytochrome P450 aromatase (P450arom) in ovaries were detected by immunohistochemistry. The expression levels of 3ß-HSD, 17ß-HSD and P450arom were detected by RT-PCR and Western blot. The results showed that the serum levels of estrogen and testosterone of PCOS group were significantly higher than those of the NC group. There was no significant difference of serum progesterone level between the PCOS and NC groups. Compared with the NC group, the PCOS group showed increased mRNA and protein expressions of both 3ß-HSD and 17ß-HSD, as well as reduced P450arom mRNA and protein expressions. These results suggest that 3ß-HSD and 17ß-HSD, but not P450arom, may participate in the ovarian hormonal regulation in the present rat model of PCOS.

An In Vivo Self-Assembled Bispecific Nanoblocker for Enhancing Tumor Immunotherapy.

Anti-PD-L1 monoclonal antibody has achieved substantial success in tumor immunotherapy by T-cells activation. However, the excessive accumulation of extracellular matrix components induced by unsatisfactory T-cells infiltration and poor tumor penetration of antibodies make it challenging to realize efficient tumor immunotherapy. Herein, a peptide-based bispecific nanoblocker (BNB) strategy is reported for in situ construction of CXCR4/PD-L1 targeted nanoclusters on the surface of tumor cells that are capable of boosting T-cells infiltration through CXCR4 blockage and enhancing T-cells activation by PD-L1 occupancy, ultimately realizing high-performance tumor immunotherapy. Briefly, the BNB strategy selectively recognizes and bonds CXCR4/PD-L1 with deep tumor penetration, which rapidly self-assembles into nanoclusters on the surface of tumor cells. Compared to the traditional bispecific antibody, BNB exhibits an intriguing metabolic behavior, that is, the elimination half-life (t1/2 ) of BNB in the tumor is 69.3 h which is ≈50 times longer than that in the plasma (1.4 h). The higher tumor accumulation and rapid systemic clearance overcome potential systemic side effects. Moreover, the solid tumor stress generated by excessive extracellular matrix components is substantially reduced to 44%, which promotes T-cells infiltration and activation for immunotherapy efficacy. Finally, these findings substantially strengthen and extend clinical applications of PD-1/PD-L1 immunotherapy.

Lactobacillus Intestinalis Primes Epithelial Cells to Suppress Colitis-Related Th17 Response by Host-Microbe Retinoic Acid Biosynthesis.

Gut microbiome is integral to the pathogenesis of ulcerative colitis. A novel probiotic Lactobacillus intestinalis (L. intestinalis) exerts a protective effect against dextran sodium sulfate-induced colitis in mice. Based on flow cytometry, colitis-associated Th17 cells are the target of L. intestinalis, which is supported by the lack of protective effects of L. intestinalis in T cell-null Rag1-/- mice or upon anti-IL-17-A antibody-treated mice. Although L. intestinalis exerts no direct effect on T cell differentiation, it decreases C/EBPA-driven gut epithelial SAA1 and SAA2 production, which in turn impairs Th17 cell differentiation. Cometabolism of L. intestinalis ALDH and host ALDH1A2 contributed to elevated biosynthesis of retinoic acid (RA), which accounts for the anti-colitis effect in RAR-α -mediated way. In a cohort of ulcerative colitis patients, it is observed that fecal abundance of L. intestinalis is negatively associated with the C/EBPA-SAA1/2-Th17 axis. Finally, L. intestinalis has a synergistic effect with mesalazine in alleviating murine colitis. In conclusion, L. intestinalis and associated metabolites, RA, have potential therapeutic effects for suppressing colonic inflammation by modulating the crosstalk between intestinal epithelia and immunity.

[Effects of Panax notoginseng saponins on pneumocyte apoptosis and c-Jun N-terminal kinase in lung ischemia/reperfusion injury].

The aim of the present study is to investigate the effects of Panax notoginseng saponins (PNS) on pneumocyte apoptosis and apoptosis-related protein, as well as c-Jun N-terminal kinase (JNK) in lung ischemia/reperfusion (I/R) injury. Thirty Wistar rats were randomly divided into control group, I/R group and PNS group. The unilateral lung I/R model was replicated by obstruction of left lung hilus for 30 min and reperfusion for 120 min in vivo. The rats in PNS group were given intraperitoneal injection of PNS at 60 min before ischemia and 10 min before reperfusion. Some lung tissues sampled at the end of the experiment were assayed for wet/dry weight ratio (W/T). The expressions of phosphorylated JNK (p-JNK) and JNK protein were detected by Western blot. The expressions of Bcl-2, Bax and Caspase-3 protein were detected by immunocytochemistry techniques. The pneumocyte apoptotic index (AI) was detected by terminal deoxynuleotidy1 transferase mediated dUTP nick end labeling (TUNEL). The morphological and ultrastructure changes were observed under light microscope and electron microscope, and the injured alveolus rate (IAR) was counted as well. The results showed that compared to control group, I/R group showed increased expressions of p-JNK, Bcl-2, Bax and Caspase-3 protein (all P < 0.01), decreased ratio of Bcl-2/Bax (P < 0.05), and increased values of AI, W/T and IAR (all P < 0.01). Moreover, light microscope and electron microscope showed serious morphological and ultrastructure injury in I/R group. Compared to I/R group, PNS group showed markedly decreased expressions of p-JNK, Bax and Caspase-3 protein (all P < 0.01), increased expression of Bcl-2 protein and ratio of Bcl-2/Bax (both P < 0.01), and lower values of AI, W/T and IAR (all P < 0.01). Meanwhile, light morphological and ultrastructure injury was found to be alleviated in PNS group. These results suggest that PNS can protect lung tissue from I/R injury, and the mechanism may correlate with suppressing JNK signal pathway, up-regulating the ratio of Bcl-2/Bax which results in inhibition of Caspase-3 dependent apoptosis.

[The protective function and mechanism of notoginsenoside Rb1 against hypoxia hypercapnia-induced pulmonary vasoconstriction].

OBJECTIVE: To explore the protective function and mechanism of notoginsenoside Rb1 against hypoxia hypercapnia-induced pulmonary vasoconstriction (HHPV). METHODS: The pulmonary artery smooth muscle cells of healthy male SD rats were primarily cultured and the second to the fifth subcultured cells were incubated with 8, 40, and 100 mg/L notoginsenoside Rb1 respectively under the hypoxia-hypercapnia condition (1% O2 and 6% CO2). The cells were harvested for 24 h. The phosphated extracellular signal-regulated kinase (p-ERK) protein expression of the cells was detected by Western blot. The mRNA expressions of ERK1 and ERK2 were detected using half quantitative reverse transcription polymerase chain reaction (RT-PCR). RESULTS: The expression of p-ERK protein, the mRNA expressions of ERK1 and ERK2 were weakly positive in the control group. Their expressions in the hypoxia-hypercapnia group were obviously enhanced (P < 0.01). After intervention of Rb1 at different concentrations, their expressions were obviously lowered (P < 0.05, P < 0.01) in a dose-dependent manner. The optimal effects were obtained at the dose of 100 mg/L. The expression of p-ERK protein was significantly positively correlated with mRNA expressions of ERK1 and ERK2 in notoginsenoside Rbl-treated groups (r = 0.500, P < 0.01; r = 0.977, P < 0.01). CONCLUSIONS: ERK1/2 pathway might play a role in the rat HHPV. Notoginsenoside Rb, could alleviate HHPV by inhibiting the ERK1/2 pathway.

A multiple detection method for distinguishing gene mutations based on melting curves of extended quenching probes.

Conventional PCR methods can detect only a few targets simultaneously and do not fulfill most clinical requirements, especially those for detecting plasma circulating DNA. By designing characteristic universal fluorescent probes, combining multiplex PCR with the invasive reaction, and analyzing the resulting differences in the melting curves formed by extension with double-stranded probes, we developed a new method to distinguish between three mutations in the same fluorescent channel and nine mutations in three fluorescent channels in a single tube. After optimization, this method was used to distinguish between 27 mutations using only three reactions, and mutations representing as low as 0.2%-0.5% of DNA could be detected, even when up to nine mutations were present at the same time. Testing of nine clinical samples, including three L858R-positive, four 19 del-positive, and two L861Q-positive samples, showed consistent results with digital PCR tests. Compared with the conventional PCR method, our method expands the capabilities of fluorescence detection by achieving multiplex detection in a single-tube, thereby providing a simple, low-cost tool for clinical applications.

Release estimation of pollutants in river by the variational analysis approach.

After accidental release of pollutants in rivers, the release estimation of the pollutant is necessary for the dealing of this accident. With the increase of people's attention to river pollution, the monitoring data of river pollution will become more and more abundant and diversified. At this point, data assimilation approaches will be more advantageous. In this paper, a new model called variational analysis inverse model (VAIM) based on the variational data assimilation is proposed to solve the pollutant release estimation problem. In the framework of the variational analysis, the conjugate gradient method and one-dimensional imprecise line search Wolfe-Powell conditions are combined to solve this problem. The implicit finite difference scheme is adopted to solve the one-dimensional advection-dispersion equation. Some synthetic cases are conducted to evaluate the robustness of the proposed model under the effect of the observational error and the effect of initial estimates for release rates in the iteration. Results show that VAIM successfully recovers the accurate release. There are only slight differences among estimated releases by VAIM under different initial estimates. Field tracer experiments are used to evaluate the practicability of VAIM. Results show that the relative error between the estimated release and the real release in the field tracer experiment is only 1.2%. In conclusion, VAIM is a release estimation method with high accuracy and will play an important role in river pollution management.

The effects of sacubitril/valsartan on heart failure with preserved ejection fraction: a meta-analysis.

BACKGROUND: Compared with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, Sacubitril/Valsartan has been reported to have superior results. However, the effects of sacubitril/valsartan on heart failure with preserved ejection fraction (HFpEF) are still in dispute. OBJECTIVES: This study aims to evaluate the effects of sacubitril/valsartan on the treatment of HFpEF patients. METHODS: PubMed, Embase, Web of Science, Cochrane Library, and Clinicaltrials.gov were used to search for randomised controlled trials of sacubitril/valsartan in HFpEF patients from inception to 7 December 2020. RESULTS: Four studies, with a total of 7739 participants, met the inclusion criteria. The present meta-analysis results showed that compared with the control group, sacubitril/valsartan reduced the hospitalisation rate of HF in HFpEF patients [Risk Ratio(RR): 0.85; 95% confidence interval (CI): 0.79-0.93; p = 0.0002). Regarding all-cause mortality, cardiovascular mortality, and the improvement in NYHA class, sacubitril/valsartan did not show apparent advantages. Although sacubitril/valsartan was linked to increasing the risk of symptomatic hypotension (RR: 1.44; 95% CI: 1.25-1.66; p﹤0.00001), there was no evidence supporting the incidence of renal function worsening and hyperkalemia. CONCLUSION: Our study shows that compared with valsartan or individualised medical therapy (IMT), there were not different between the two groups except for the hospitalisation rate which was favoured by Sacubitril/Valsartan treatment group for HFpEF patients.

Comparative clinical studies of primary chemoradiotherapy versus S-1 and nedaplatin chemotherapy against stage IVb oesophageal squamous cell carcinoma: a multicentre open-label randomised controlled trial.

INTRODUCTION: Oesophageal squamous cell carcinoma (OSCC) is one of the most commonly occurring devastating tumours worldwide, including in China. To date, the standard care of patients with stage IV OSCC is systemic chemotherapy and palliative care, which results in poor prognosis. However, no consensus has been established regarding the role of radiotherapy in targeting the primary tumour in patients with stage IVa OSCC. Thus, the aim of this study is to assess the effectiveness of primary radiotherapy combined with S-1 and nedaplatin (NPD) chemotherapy in the patients with stage IV OSCC. METHODS AND ANALYSIS: The study is a multicentre, open-label, randomised controlled trial. A total of 180 eligible patients with stage IV OSCC will be randomised into a study group (90 patients) and a control group (90 patients). Patients in the study group will receive radiotherapy to the primary tumour at a dose of 50.4 Gy combined with 4-6 cycles of S-1 and NPD chemotherapy. In the control group, patients will only receive 4-6 cycles of S-1 and NPD chemotherapy. The primary and secondary outcomes will be measured. The differences between the two groups will be statistically analysed with regard to overall survival, the progression-free survival and safety. All outcomes will be ascertained before treatment, after treatment and after the follow-up period.The results of this study will provide evidence on the role of radiotherapy in patients with stage IV OSCC in China, which will show new options for patients with advanced oesophageal cancer. ETHICS AND DISSEMINATION: This study was approved by the Institutional Ethics Committee of The First Hospital Affiliated of Zhengzhou University (approval number: SS-2018-04). TRIAL REGISTRATION: The trial has been registered at the Chinese Clinical Trial Registry (ChiCTR1800015765) on 1 November 2018; retrospectively registered, http://www.chictr.org.cn/index.aspx.

Antagonistic effect of atipamezole, flumazenil and naloxone following anaesthesia with xylazine, tramadol and tiletamine/zolazepam combinations in pigs.

OBJECTIVE: To evaluate the antagonistic effects of atipamezole (ATI), flumazenil (FLU) and naloxone (NAL) alone and in various combinations following administration of tiletamine-zolazepam-xylazine-tramadol. STUDY DESIGN: Prospective, experimental, randomized cross-over study. ANIMALS: Eight Chinese miniature pigs (three females and five males) mean age 8 (range 7-10) months and bodyweight 57.5 (52.4-62.1) kg. METHODS: All animals were anaesthetized with tiletamine/zolazepam (3.0 mg kg(-1)), xylazine (1.2 mg kg(-1)) and tramadol (1.6 mg kg(-1)) given intramuscularly (IM). Thirty minutes later, one of eight treatments was administered IM: saline control, ATI (0.12 mg kg(-1)), FLU (0.1 mg kg(-1)), NAL (0.03 mg kg(-1)), ATI-FLU, FLU-NAL, ATI-NAL or ATI-FLU-NAL. After injection of antagonists the following times were recorded: to recovery of the palpebral, pedal and tail clamp reflexes, to head movement, sternal recumbency, standing and walking. Posture, sedation, analgesia, jaw relaxation and auditory response were scored at set times until 120 minutes after injection of antagonists. Heart rates, respiratory rates and rectal temperature were measured at those times. Data were analyzed by anova for repeated measures, followed by the Tukey's test to compare differences between means, or by Kruskal-Wallis test as appropriate. RESULTS: FLU, NAL alone, or FLU-NAL did not effectively antagonize anaesthesia induced by tiletamine/zolazepam-xylazine-tramadol. ATI, ATI-FLU, ATI-NAL and ATI-FLU-NAL produced an immediate and effective recovery from anaesthesia. The combination of ATI-FLU-NAL was the most effective combination in antagonizing the anaesthetic effect. Adverse effects such as tachycardia, tachypnoea, excitement and muscle tremors were not observed during this study. CONCLUSION AND CLINICAL RELEVANCE: ATI-FLU-NAL is the most effective combination for antagonizing tiletamine/zolazepam-xylazine-tramadol anaesthesia in pigs. However, ATI alone or in various combinations also provides effective antagonism.

[The diagnostic value of MSCT multi-dimensional reconstructions for congenital vascular ring with tracheal stenosis].

OBJECTIVE: To evaluate the diagnostic value of multi-slice CT (MSCT) reconstructions for congenital vascular rings together with tracheal stenosis. METHODS: 9 cases of children with congenital vascular ring and tracheal stenosis confirmed by surgery were collected in the study, all cases had undergone thin slice CT contrast enhancement, the MSCT data were transmitted to the workstation for multiplanar reconstruction (MPR), volume rendering technique (VRT) and VR transparency reconstruction. With the surgical results as the gold standard, the imaging characteristics of echocardiography (UCG) and MSCT were comparatively analyzed. RESULTS: In 9 cases, there were 4 cases of pulmonary artery sling, 3 cases of right aortic arch combination with left aberrant subclavian artery, 1 case of double aortic arch, 1 case of innominate artery compression syndrome. In this group, 5 cases were accompanied with other cardiac malformations (tetralogy of Fallot in 2 cases, double outlet right ventricle with patent ductus arteriosus and ventricular septal defect in 1 case, ventricular septal defect in 1 case, double superior vena cava in 1 case), 1 case of tetralogy of Fallot demonstrated many tortuous collateral arteries around aorta. All malformations were well displayed by VRT, MPR. VR transparency reconstruction can stereoscopically display trachea and bronchial compression condition, the main trachea was compressed in 6 cases, the main trachea and left main bronchus was compressed in 2 cases, the main trachea and left main bronchus was compressed in 1 cases, UCG detected all intracardiac malformations, 1 case of pulmonary artery sling was misdiagnosed as patent ductus arteriosus, 8 cases of vascular rings, tracheal and bronchial stenosis were missed. CONCLUSION: MSCT reconstruction technology is a noninvasive, rapid diagnostic method, it can clearly show the congenital vascular rings abnormalities and the degree of tracheal stenosis, it has important significance for clinic treatment.

[Left ventricular longitudinal rotation changes in patients with dilated cardiomyopathy detected by two-dimensional speckle tracking imaging].

OBJECTIVE: To assess the left ventricular longitudinal rotation (LR) in patients with dilated cardiomyopathy (DCM). METHODS: Conventional echocardiography (GE-Vivid7) was performed in 35 healthy subjects and 42 DCM patients. Left atrial diameter was measured by M-mode echocardiography, left ventricular end-systolic, end-diastolic volume and left ventricular ejection fraction (LVEF) were calculated by bi-plane simpson's method. The peak velocity during early diastole (Ve) and late diastole (Va) of anterior mitral valve were measured by pulse-waved doppler, and the ratio Ve/Va was calculated. The peak radial systolic strain, strain rate in systolic, early and late diastolic periods were measured. Segmental LR and global LR were assessed using two-dimensional speckle tracking imaging (2D-STI). RESULTS: The peak radial systolic strain, strain rate in systolic, early and late diastolic periods in DCM group were significantly lower than in healthy subjects, the rotation degrees of the middle and base lateral, the apex and the base septum walls were significantly lower than those of the healthy subjects. A prominent counterclockwise LR (0.76° ± 2.63°) was shown in healthy subjects while prominent clockwise LR (-1.58° ± 3.42°) was present in DCM patients. The time delay between the left ventricular lateral wall and the base septum wall in DCM patients significantly correlated with the peak LR of the left ventricular (r = 0.409, P < 0.01; r = 0.396, P < 0.01). CONCLUSIONS: 2D-STI can be used to assess the LR in DCM patients and a clockwise LR is present in DCM patients which might be caused by the time delay between the left ventricular lateral wall and the base-septum wall.

Spider Mites Singly Infected With Either Wolbachia or Spiroplasma Have Reduced Thermal Tolerance.

Heritable symbionts play an essential role in many aspects of host ecology in a temperature-dependent manner. However, how temperature impacts the host and their interaction with endosymbionts remains largely unknown. Here, we investigated the impact of moderate (20°C) and high (30 and 35°C) temperatures on symbioses between the spider mite Tetranychus truncatus and two maternally inherited endosymbionts (Wolbachia and Spiroplasma). We found that the thermal tolerance of mites (as measured by survival after heat exposure) was lower for mites that were singly infected with either Wolbachia or Spiroplasma than it was for co-infected or uninfected mites. Although a relatively high temperature (30°C) is thought to promote bacterial replication, rearing at high temperature (35°C) resulted in losses of Wolbachia and particularly Spiroplasma. Exposing the mites to 20°C reduced the density and transmission of Spiroplasma but not Wolbachia. The four spider mite strains tested differed in the numbers of heat shock genes (Hsps) induced under moderate or high temperature exposure. In thermal preference (Tp) assays, the two Wolbachia-infected spider mite strains preferred a lower temperature than strains without Wolbachia. Our results show that endosymbiont-mediated spider mite responses to temperature stress are complex, involving a combination of changing endosymbiont infection patterns, altered thermoregulatory behavior, and transcription responses.