Targeting Toll-like receptor 4 with CLI-095 (TAK-242) enhances the antimetastatic effect of the estrogen receptor antagonist fulvestrant on non-small cell lung cancer.

PURPOSE: Estrogen plays a critical role in the invasiveness and metastasis of non-small cell lung cancer (NSCLC) through estrogen receptor ß (ERß). However, the antimetastatic effect of the ERß antagonist fulvestrant was still limited in NSCLC patients. Recently, Toll-like receptor 4 (TLR4) signaling was implicated in NSCLC metastasis. Our present study aimed to evaluate the synergistic antimetastatic effect of a combination of fulvestrant and the TLR4-specific inhibitor CLI-095 (TAK-242) on human NSCLC cells. METHODS: The expression levels of ERß and TLR4 were detected by immunohistochemical (IHC) analysis of 180 primary NSCLC and 30 corresponding metastatic lymph node samples. The association between ERß and TLR4 expression was analyzed. The aggressiveness of NSCLC cells treated with fulvestrant, CLI-095 or the drug combination and formation status of their invadopodia, invasion-associated structures, were investigated. The protein levels in NSCLC cells in different groups were determined by Western blot and immunofluorescence analyses. RESULTS: Here, a positive correlation between ERß and TLR4 expression was observed in both primary NSCLC tissue (Spearman's Rho correlation coefficient = 0.411, p < 0.001) and metastatic lymph node tissue (Spearman's Rho correlation coefficient = 0.374, p = 0.009). The protein levels of ERß in NSCLC cell lines were decreased by fulvestrant, and this suppressive effect was significantly enhanced when fulvestrant was combined with CLI-095 (p < 0.05). Both the migration and invasion of NSCLC cells were suppressed by fulvestrant or CLI-095 alone, and the combination of fulvestrant + CLI-095 showed the strongest inhibitory effect (p < 0.05). In addition, the results demonstrated that CLI-095 also helped fulvestrant restrict the formation and function of invadopodia in NSCLC cells (p < 0.05). CONCLUSIONS: Collectively, our study results suggested that CLI-095 enhances the antimetastatic effect of fulvestrant on NSCLC and provided support for further investigation of the antitumor activity of combined therapy with antiestrogen and anti-TLR4 agents in the clinic.

[Clinical analysis of seven cases of H1N1 influenza-associated encephalopathy in children].

Objective: To investigate the clinical manifestations, diagnosis, and treatment of H1N1 influenza A-associated encephalopathy (IAE) in children. Methods: The clinical manifestations, laboratory tests, cranial magnetic resonance imaging (MRI), electroencephalography (EEG) examinations and treatments of seven children with H1N1 IAE hospitalized in Guangzhou Women and Children's Medical Center from December 2018 to January 2019 were retrospectively analyzed. Results: Five of the seven children with H1N1 IAE were female. The age at admission was 4 years and 5 months (range 7 months-9 years). Neurological symptoms occurred simultaneously or early (0-3 days) after the flu-like symptom appeared. The main clinical manifestations of neurological symptoms were seizures (repeated seizures in five cases and status convulsion in two cases, including one case of unexpected fever and repeated seizures in a nine-year old girl) accompanied with altered consciousness (drowsiness in five cases and coma in two cases). Cranial MRI in three cases displayed multifocal lesions, mainly in the bilateral thalamus, brainstem and cerebellar hemisphere. MRI also showed reversible splenial lesion in the corpus callusumin in three cases. EEG tracings were characterized by diffuse slow wave activity in four cases, and status epilepticus was monitored in one case. All the 7 cases were treated with oral oseltamivir. Three cases were treated with pulsed methylprednisolone and intravenous immunoglobulin. One case was treated with intravenous immunoglobulin alone and all the patients received oral oseltamivir. All the patients survived, with three patients had minor neurological sequelae at discharge. Conclusions: The main clinical manifestations of H1N1 IAE are seizures and altered consciousness. Cranial MRI combined with EEG is helpful for early diagnosis. Intravenous immunoglobulin and (or) methylprednisolone should be considered for severe cases.

Integrative analyses of transcriptome sequencing identify novel functional lncRNAs in esophageal squamous cell carcinoma.

Long non-coding RNAs (lncRNAs) have a critical role in cancer initiation and progression, and thus may mediate oncogenic or tumor suppressing effects, as well as be a new class of cancer therapeutic targets. We performed high-throughput sequencing of RNA (RNA-seq) to investigate the expression level of lncRNAs and protein-coding genes in 30 esophageal samples, comprised of 15 esophageal squamous cell carcinoma (ESCC) samples and their 15 paired non-tumor tissues. We further developed an integrative bioinformatics method, denoted URW-LPE, to identify key functional lncRNAs that regulate expression of downstream protein-coding genes in ESCC. A number of known onco-lncRNA and many putative novel ones were effectively identified by URW-LPE. Importantly, we identified lncRNA625 as a novel regulator of ESCC cell proliferation, invasion and migration. ESCC patients with high lncRNA625 expression had significantly shorter survival time than those with low expression. LncRNA625 also showed specific prognostic value for patients with metastatic ESCC. Finally, we identified E1A-binding protein p300 (EP300) as a downstream executor of lncRNA625-induced transcriptional responses. These findings establish a catalog of novel cancer-associated functional lncRNAs, which will promote our understanding of lncRNA-mediated regulation in this malignancy.

Novel methylene blue staining technique for localizing small esophageal leiomyomas during thoracoscopic enucleation.

The treatment of choice for leiomyoma, the most common benign esophageal tumor, is thoracoscopic enucleation. One of the most difficult aspects of thoracoscopic enucleation is the precise localization of small tumors (≤1.5 cm) and tumors without external protrusion. No simple, feasible solutions to this problem are available. We developed a novel methylene blue staining technique to localize small esophageal leiomyomas and evaluated the feasibility of our technique. Between January 2013 and July 2014, eight patients with small esophageal leiomyomas (≤1.5 cm) underwent thoracoscopic enucleation in Tongji Hospital. Preoperative endoscopic ultrasonography was performed in all patients. The leiomyomas were located in the middle (n = 5) and lower (n = 3) thirds of the esophagus. We preoperatively injected 0.5-1.0 mL methylene blue in the submucosa adjacent to the tumors under standard gastroscope guidance. The entire staining process took about 10 minutes. Staining was successful in all patients. The unstained tumor was exposed after the blue-stained mediastinal pleura, and overlying muscle were incised longitudinally. All procedures were successfully completed without conversion to open surgery. No abnormalities were detected in the esophageal mucosa. The median operating time was 60 minutes (range, 40-90 minutes). Postoperative histopathology confirmed leiomyoma in all patients. The median postoperative hospital stay was 6 days (range, 5-7 days). No major complications, such as esophageal leakage or esophageal diverticulum, occurred. Endoscopic methylene blue staining is safe and feasible for localizing small esophageal leiomyomas during thoracoscopic enucleation. This method will enable precise and easy enucleation.

Accuracy of cast posts and cores using a new investigative method.

Generally, two techniques are used to fabricate a cast post and core (CPC): direct and indirect. To date, research has made no clear indication as to a comparative level of accuracy between the techniques. Therefore, the purpose of the current study was to compare the accuracy of two techniques to produce CPCs for posterior teeth using a new method. Nine endodontically treated human premolars were used for fabricating CPCs using the direct and indirect methods. A total of 18 CPCs were produced, two for each tooth, cast in high noble type IV gold. A silicone impression material was inserted into the root canals, followed by the CPCs. The remaining material in the space between the canal wall and the CPC was weighed using an electronic precision balance. By evaluating the weight of the silicon specimens, the accuracy and intimacy of fit were obtained. Since the number of samples was small, a Student t-test was used for statistical evaluation at a 90% confidence interval. The CPCs obtained by using each method were independently examined by two clinicians for proper fit. Power analysis indicated that for a 90% confidence interval and 0.8 power value, nine specimens would be necessary to achieve a statistically meaningful test. The mean value for the weight of the nine specimens obtained using the direct method was 10.3 ± 2.6 mg, while the mean value for the corresponding specimens obtained using the indirect method was significantly smaller, 7.4 ± 2.3 mg. The Student t-test value was P = 0.006. The indirect method provided CPCs with a better fit and higher accuracy. The Student t-test demonstrated a significant difference between the direct and indirect procedures. The indirect method is a valuable technique for the dental practitioner when multiple posterior cast posts and cores are necessary or interocclusal space is limited.

Prevalence of Mycoplasma suis (Eperythrozoon suis) infection in swine and swine-farm workers in Shanghai, China.

OBJECTIVE: To determine the prevalence of Mycoplasma suis infection in swine, swine-farm workers, and swine veterinarians in Shanghai, China. SAMPLE POPULATION: 172 swine and 65 workers and veterinarians from 19 commercial swine farms. PROCEDURES: Blood samples were collected from all study subjects. Blood samples were examined for the presence of M suis by means of compound and scanning electron microscopy. A species-specific PCR assay was developed for detection of M suis DNA extracted from blood samples. Relationships between infection status of swine and sex, age, geographic location, and clinical signs of disease were evaluated by use of a C(2) test. The phylogenetic relationship between partial 16S ribosomal RNA (rRNA) sequences from swine and human isolates of M suis was determined. RESULTS: 86% (148/172) of swine and 49% (32/65) of humans had positive PCR assay results for M suis infection. Swine infection status was not associated with any variable, with the exception of pyrexia and subcutaneous bleeding. The partial 16S rRNA sequences from human and swine isolates of M suis were 98% homologous and in the same phylogenetic cluster as a previously identified swine isolate of M suis. CONCLUSIONS AND CLINICAL RELEVANCE: A large proportion of swine and humans in close contact with those swine were infected with M suis in Shanghai, China. The close phylogenetic relationship between swine and human isolates of M suis suggested possible interspecies transmission; however, additional research is required to better assess that possibility.

Modeling translocation of particles on one-dimensional polymer lattices.

We introduce a general random walk model that is an extension of the random walk model proposed by Berg. The model can be used to describe a particle's translocation along a polymeric lattice with a nonuniform distribution of obstacles. These obstacles are representative of DNA-bound proteins, of drugs, and of a DNA packing environment. Using this model in the bacteriophage replication process, we show the effects of random obstacles on an ATP-driven particle's translocation along single-stranded DNA. The principal finding is that the average statistical time of the translocation process decreases with the increase of an obstacle's strength. We also find an interesting relation between the average statistical time and the DNA chain length. Our results can be used to explain some physiological phenomena. They show the usefulness of our model in an analysis of the effect of random obstacles on particles' translocation along one-dimensional polymer lattices.

Optical correlator that uses cesium vapor.

We obtain the correlation pattern between two amplitude-modulated input images of 36 and 280 random black and white pixels, using the standard degenerate four-wave-mixing geometry of 852-nm optical beams in a 1-mm-thick cesium-vapor cell. The total optical input power is 3.2 mW to obtain 0.4 nW of power in the correlation pattern. We verified that the buildup time of the four-wave-mixing signal is ~30 ns. Using the random patterns, we analyze the performance of the cesium optical correlator in terms of the number of pixels that can be processed and the number of photons per pixel used. We show how to scale our experimental results for the efficiency of the cesium correlator to images containing a larger number of pixels.

Low-intensity degenerate four-wave mixing at the cesium D1 resonance in thin cells.

We observed low-intensity cw degenerate four-wave mixing at the D1 resonance in a 10-microm-thick cesium-vapor cell. Normal population depletion caused by optical pumping is alleviated by frequent atom-wall collisions. The reflectivity at the D1 resonance is approximately equal in magnitude to that observed at the D2 cycling transition under similar conditions.

High-pressure apparatus for dielectric measurements in high frequency.

The present article describes an experimental apparatus for the measurement of low-loss dielectric material under conditions of high pressures (maximum pressure 1500 bars) and high frequencies (1-15 MHz.) The measurements of these losses are based on the classical method of the Q-meter with a general Radio type 1690-A sample holder, located in a high-pressure bomb. All the manual operations made on the holder during the measurements are controlled by dc motors. The first results have shown that the dielectric losses of polyethylene (PE) vary with the pressure. This apparatus will later be used in the measurement of the dielectric losses of the insulating materials used for submarine telecommunication cables.