[Advances in clinical studies of chronic cough].

Chronic cough is a common complaint in respiratory specialist clinics, with a significant impact on cough-specific quality of life and psychophysiological health. The diagnosis, treatment and management of chronic cough remains a major challenge. We summarized a series of recent advances from clinical studies in the epidemiology, diagnosis and management of chronic cough over the past year.

[Transthoracic ultrasonographic features of typical high-resolution computed tomography signs of interstitial lung diseases].

Objective: To investigate the accuracy of bedside transthoracic lung ultrasonography (TLU) in different typical high resolution computed tomography (HRCT) signs of interstitial lung diseases (ILDs). Methods: Fifty patients first diagnosed with ILDs were enrolled from January 2016 to December 2018. There were 21 males and 29 females. The mean age was (56±14) years(rang 42-73 years). TLU was performed in inspiration for the characters of A-lines and B-lines as well as pleural at anterior, lateral and dorsal chest walls, respectively. HRCT was selected at three levels according to the upper, middle, and lower lung fields. The range of each level needing to be evaluated corresponded to the TLU scanning field one by one, and recording the signs of HRCT. Early change of ILDs was definite as the HRCT score was no more than 1 and no honeycomb was present. The correlation between A-lines, B-lines, pleural abnormal and HRCT signs was evaluted. Spearman's correlation coefficient was used to evaluate the relationship between B-lines and HRCT score. Results: The sensitivity and specificity of A-lines for HRCT normality were 83.9% and 84.9%, respectively. Coincidence rate was 84.6%. The sensitivity and specificity of B-lines for HRCT abnormality were 84.9% and 83.9%, respectively. Coincidence rate was 84.6%. Interlobular septal thickening shadow had fewer B-lines and narrower interval than other HRCT signs, while the other HRCT signs had no differences in B-lines. And the sensitivity and specificity of B-lines for detection the early change of HRCT in ILDs were 89.5% and 89.2%, respectively. Coincidence rate was 89.3%. A positive correlation was found between the number of B-lines and HRCT scores (R=0.827, P<0.001), and the width of B-lines and HRCT score (R=0.951, P<0.001). Meanwhile, a negative correlation was found between the interval of B-lines and HRCT score (R=-0.831, P<0.001). The sensitivity and specificity of TLU for HRCT pleural abnormality were 100.0% and 90.0%, respectively. Coincidence rate was 93.6%. Conclusions: TLU showed high sensitivity and specificity in finding interstitial changes of the lung. It gives a new view on the diagnostic possibilities of ILDs and may be used to evaluate the severity and the therapeutic effect of treatment. However, TLU could not differentiate HRCT signs of ILDs.

Circular RNA circRNA_0000285 promotes cervical cancer development by regulating FUS.

OBJECTIVE: Recently, the vital role of circular RNAs (circRNAs) in human diseases has attracted much attention. The aim of this research was to verify the potential role of circRNA_0000285 in the development of cervical cancer (CC). PATIENTS AND METHODS: CircRNA_0000285 expression in both CC cells and tissue samples was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Functional experiments were performed, including cell counting kit-8 (CCK-8) assay, cell cycle assay and transwell assay. Meanwhile, the underlying mechanism was explored through qRT-PCR and Western blot assay, respectively. In addition, the function of circRNA_0000285 was identified in vivo. RESULTS: CircRNA_0000285 expression level was significantly higher in CC samples than that of corresponding normal tissues. Moreover, the growth and migration abilities of CC cells were significantly inhibited after circRNA_0000285 was knocked down in vitro. Furthermore, the expression of FUS was remarkably down-regulated after knockdown of circRNA_0000285. Subsequent results indicated that the expression level of FUS was positively correlated with the expression of circRNA_0000285 in CC tissues. In addition, the knockdown of circRNA_0000285 significantly inhibited the formation and metastasis of CC in nude mice. CONCLUSIONS: CircRNA_0000285 could enhance the proliferation and metastasis of CC by up-regulating FUS, which might be a potential therapeutic target for CC treatment.

Protective effect of excitatory amino acids on cold-restraint stress-induced gastric ulcers in mice: role of cyclic nucleotides.

Previous studies have shown that excitatory amino acids (EAAs) and their receptors may play important roles in the mammalian enteric system. In this study, we investigated whether EEAs, including L-glutamate (L-Glu) and subtypes N-methyl-D-aspartate (NMDA), kainic acid (KA), and quisqualic acid (QA), reduce cyclic AMP (cAMP) levels and play a role in protecting gastric lesions in cold-restraint stress (CRS) mice. First, we found that dose-dependent administration of four selected EAAs significantly attenuated the increase of cAMP content and exhibited a protective effect on the development of gastric lesions induced by CRS. Second, CRS treatment exhibited a decrease of cGMP content and an increase of cAMP content with marked time-dependent changes, and a high cAMP/cGMP ratio in mice gastric mucosa. Third, pretreatment with 0.25 microg/kg or 0.5 microg/kg dibutyryl cGMP (db-cGMP) exhibited protective effects on CRS-induced gastric lesions, with preventive ratios of 24.61% and 35.32%, respectively. Moreover, db-cGMP at 0.5 microgg/kg significantly attenuated the increase in both cAMP content and the cAMP/cGMP ratio in CRS-treated gastric mucosa. In contrast, db-cAMP exhibited no protective effect, and significantly decreased cGMP content and increased the cAMP/cGMP ratio. These results suggest that EAAs significantly reduce CRS-induced gastric ulcers in mice. The possible mechanism of the antiulcer activity of EAAs may be related to a decrease in the cAMP content in the gastric mucosa of mice. In addition, an increase of the cAMP/cGMP ratio significantly involved in CRS-induced gastric ulcer formation in mice.

Potent induction of long-term CD8+ T cell memory by short-term IL-4 exposure during T cell receptor stimulation.

An important goal of vaccination is to achieve long-term survival of functional memory T cells. Using a MHC-compatible adoptive transfer system, we show here that a short, 3-day IL-4 but not IL-2 or IL-12 exposure during in vitro T cell receptor stimulation of naive CD8(+) T cells induced long-lasting in vivo memory. Such long-term memory CD8(+) T cells expressed antigen-specific cytotoxicity and the potential for IFN-gamma and IL-4 production. Our results support the concept that functional T cell longevity can be regulated by cytokines during initial antigen encounter and provide a rational foundation for vaccine development. They also may have implications in formulating optimal therapeutic regimens of ex vivo expanded autologous cancer- and HIV-specific CD8(+) T cells. In addition, the availability of large numbers of memory CD8(+) T cells generated through our high-efficiency system should facilitate progress in the molecular dissection of CD8(+) T cell memory development.

Prostate cancer: localization with three-dimensional proton MR spectroscopic imaging--clinicopathologic study.

PURPOSE: To assess the efficacy of combined magnetic resonance (MR) imaging and three-dimensional (3D) proton MR spectroscopic imaging in the detection and localization of prostate cancer. MATERIALS AND METHODS: MR imaging and 3D MR spectroscopic imaging examinations were performed in 53 patients with biopsy-proved prostate cancer and subsequent radical prostatectomy with step-section histopathologic examination. The prostate was divided into sextants. At MR imaging, the presence or absence of cancer in the peripheral zone of each sextant was assessed independently by two readers (readers 1 and 2) unaware of the findings at 3D MR spectroscopic imaging and histopathologic examination. At 3D MR spectroscopic imaging, cancer was diagnosed as possible if the ratio of choline plus creatine to citrate exceeded 2 SD above population norms or as definite if that ratio exceeded 3 SDs above the norm. RESULTS: On the basis of sextants, sensitivity and specificity, respectively, for MR imaging were 77% and 61% (reader 1) and 81% and 46% (reader 2) with moderate interreader agreement (kappa = 0.43). The 3D MR spectroscopic imaging diagnosis of definite cancer had significantly higher specificity (75%, P < .05) but lower sensitivity (63%, P < .05). Receiver operating characteristic analysis showed significantly (P < .001) improved tumor localization for both readers when 3D MR spectroscopic imaging was added to MR imaging. High specificity (up to 91%) was obtained when combined MR imaging and 3D MR spectroscopic imaging indicated cancer, whereas high sensitivity (up to 95%) was obtained when either test alone indicated a positive result. CONCLUSION: The addition of 3D MR spectroscopic imaging to MR imaging provides better detection and localization of prostate cancer in a sextant of the prostate than does use of MR imaging alone.

Peroxisome proliferation, adipocyte determination and differentiation of C3H10T1/2 fibroblast cells induced by humic acid: induction of PPAR in diverse cells.

Humic acid, a high-molecular-weight polyphenolic compound, exists abundantly in soil, natural water, and various terrestrial and aquatic environments. Humic acid causes peroxisome proliferation in mouse liver and induces the expression of peroxisome proliferator activated receptor (PPAR) in BNL CL.2 cells. Both cytotoxicity and flow cytometry show that humic acid inhibits the growth of C3H10T1/2 cells at G1 phase. C3H10T1/2 fibroblast cells express PPARgamma and the adipocyte P2 (aP2) genes which convert into adipocytes after being treated with humic acid. Our findings may provide a unique model for studying the molecular control of determination and differentiation of mesodermal cell lineages.

Effects of L-glutamic acid on acid secretion and mucosal blood flow in the rat stomach.

The effect of intravenous administration of L-glutamic acid (L-Glu) on gastric acid secretion and gastric mucosal blood flow (GMBF) in anesthetized rats were investigated. Infusion with synthetic L-Glu alone had no effect on spontaneous acid secretion. However, L-Glu reduced histamine- (2 mg/kg/hr) or oxotremorine- (1 microg/kg/hr) stimulated acid secretion, whereas L-Glu had no effect on acid secretion induced by pentagastrin (8 microg/kg/hr). Furthermore, this inhibitory effect of L-Glu on histamine- or oxotremorine-stimulated acid secretion was blocked by 6,7-dinitroquinoxaline-2,3-dione (DNQX), a non-NMDA receptor antagonist. The effect of L-Glu on gastric mucosal microcirculation in the anesthetized rats was evaluated by using Laser Doppler Flowmetry (LDF). The results showed that L-Glu did not significantly reduce both mucosal and serosal blood flow in stomach. No significant modulatory effect on histamine- or oxotremorine-stimulated increase in GMBF was noted after infusion with L-Glu. It is concluded that L-glutamic acid is capable of the modulating of gastric acid secretion via ionotropic non-NMDA receptors, but do not affect on GMBF. However, L-glutamic acid showed no effect on acid secretion by itself.

Localizing prostate cancer in the presence of postbiopsy changes on MR images: role of proton MR spectroscopic imaging.

PURPOSE: To assess whether magnetic resonance (MR) spectroscopic imaging with MR imaging can improve prostate cancer localization in postbiopsy hemorrhage cases. MATERIALS AND METHODS: Records of 175 patients with prostate cancer were retrospectively reviewed; 42 patients (135 hemorrhagic sites) had spatially correlated biopsy data. Patients underwent both phased-array coil-endorectal coil MR imaging and three-dimensional MR spectroscopic imaging within 180 days after transrectal ultrasound (US)-guided biopsy. High-signal-intensity hemorrhage on T1-weighted images and corresponding high- or low-signal-intensity areas on T2-weighted images and the metabolic ratio (choline + creatine)/citrate were recorded. Cancer was identified as a low-signal-intensity area at T2-weighted MR imaging or a metabolite ratio greater than 3 standard deviations above normal at MR spectroscopic imaging. MR imaging, spectroscopic, and biopsy findings were compared. RESULTS: Forty-nine patients had postbiopsy hemorrhage. On T2-weighted images, a higher (P < .01) percentage of hemorrhagic sites demonstrated low signal intensity (80% [108 of 135 sites]), which is similar to the signal intensity seen with cancer. The addition of MR spectroscopic imaging to MR imaging resulted in a significant increase (P < .01) in the accuracy (52% to 75%) and specificity (26% to 66%) of tumor detection. CONCLUSION: The addition of MR spectroscopic imaging to MR imaging significantly improves the ability to determine the presence of prostate cancer and spatial extent when postbiopsy changes hinder interpretation with MR imaging alone.

Design of a high-flux and high-resolution VUV bending-magnet beamline.

A high-flux and high-resolution VUV beamline (4-40 eV) has been designed and is under construction at SRRC. This beamline, which collects 50 mrad of horizontal radiation, uses a 6 m cylindrical-grating monochromator with an incident angle of 70 degrees instead of the conventional normal-incidence-monochromator (NIM) design. Special features, such as movable entrance slit, bendable vertical focusing mirror and movable curved exit slit, are employed to enhance greatly the beamline performance. With both slit openings set at 10 micro m, the energy-resolving power can reach as high as 70000. Photon fluxes of 1 x 10(13) and 1 x 10(10) photons s(-1) are calculated for energy-resolving powers of 1000 and 40000, respectively. The best image size at the sample position is smaller than 0.45 x 0.2 mm.

Improved water and lipid suppression for 3D PRESS CSI using RF band selective inversion with gradient dephasing (BASING).

A T1 insensitive solvent suppression technique-band selective inversion with gradient dephasing (BASING)-was developed to suppress water and lipids for 1H magnetic resonance spectroscopy (MRS). BASING, which consists of a frequency selective RF inversion pulse surrounded by spoiler gradient pulses of opposite signs, was used to dephase stopband resonances and minimally impact passband metabolites. Passband phase linearity was achieved with a dual BASING scheme. Using the Shinnar-Le Roux algorithm, a highpass filter was designed to suppress water and rephase the lactate methyl doublet independently of TE, and water/lipid bandstop filters were designed for the brain and prostate. Phantom and in vivo experimental 3D PRESS CSI data were acquired at 1.5 T to compare BASING with CHESS and STIR suppression. With BASING, the measured suppression factor was over 100 times higher than with CHESS or STIR causing baseline distortions to be removed. It was shown that BASING can be incorporated into a variety of sequences to offer improved suppression in the presence of B1 and T1 inhomogeneites.

Cloning and expression of CD24 gene in human hepatocellular carcinoma: a potential early tumor marker gene correlates with p53 mutation and tumor differentiation.

To search for genes related to hepatocarcinogenesis, the differential display technique for eukaryotic mRNA was conducted. We have cloned a gene that encodes the CD24 protein from the cDNA library of human hepatocellular carcinoma (HCC). A single 2.1-kb mRNA was identified in HCC specimens and the HuH-7 HCC cell line but only rarely in small amounts in nontumor livers. In 79 unicentric HCC, CD24 mRNA was overexpressed in 52 cases (66%), found in trace amounts in 11, and not detectable in 16 (20%). In 12 cases of multicentric HCC, CD24 mRNA was overexpressed in 21 (68%) of 31 tumor nodules and was helpful for the determination of tumor clonal origin. There was an increased frequency of CD24 mRNA overexpression in patients younger than 50 years with HCC (86% versus 59%, P < 0.025), in serum hepatitis B surface antigen-positive individuals (74% versus 48%, P < 0.023), in those with an elevated serum alpha-fetoprotein level (82%, versus 56%, P < 0.04), and in HCC with alpha-fetoprotein mRNA expression (82% versus 56%, P < 0.04). There was a strong correlation of CD24 mRNA overexpression with p53 gene mutation in HCC (91% versus 46%, P < 0.0005) and poorly differentiated HCC (82% versus 53%, P < 0.0008). Despite its correlation with p53 mutation and the unfavorable outcome of HCC with p53 mutation, the CD24 mRNA expression did not correlate with tumor size, tumor invasiveness, or patient's prognosis. Thus, the CD24 gene expression appears to be a common event in HCC and may serve as an early but not prognostic biomarker for malignant transformation of hepatocytes.

Boronated metalloporphyrins: a novel approach to the diagnosis and treatment of cancer using contrast-enhanced MR imaging and neutron capture therapy.

Porphyrins are a unique class of metal chelating agents that have shown specific affinity for neoplasms. The water-soluble free-base derivative, tetrakiscarborane carboxylate ester of 2,4-(alpha,beta-dihydroxyethyl) deuteroporphyrin IX (BOPP), an agent designed for neutron capture therapy, has previously demonstrated selective localization and retention in a C6 murine glioma. In the present work, the authors demonstrate that the manganese chelate of BOPP also selectively localizes in a rat 9L gliosarcoma and preferentially enhances the tumor-normal brain contrast of T1-weighted images for at least 92 hours. The data indicate a maximal enhancement of contrast between tumor and normal brain at 24 hours after injection, compared with 5 minutes for manganese (III) tetraphenylporphine sulfonate (TPPS4). The results also indicate that Mn-BOPP may have a slower uptake in the 9L glioma than Mn-TPPS4 but a longer retention in the tumor. Mn-BOPP is unique in that it represents, to the authors' knowledge, the first example of a single agent that can enhance contrast between tumor and normal tissue and be potentially effective as an agent for boron neutron capture therapy.

[Studies on the chemical constituents of Glycyrrhiza pallidiflora Maxim].

A species of the genus Glycyrrhiza, G. pallidiflora Maxim, growing in Jiangsu and Hebei Provices of China, has been little studied before on its chemical constituents. This paper reports the isolation and chemical elucidation of five compounds from this plant, one of them is a new compound named glypallichalcone (P-2). Their chemical structures were elucidated by means of chemical and spectrometric analysis (UV, IR, MS, 1HNMR and 13CNMR) and were first reported to be present in this plant. Glypallichalcone (P-2), was found to be 4-hydroxy-2,4'-dimethoxy-chalcone. The known compounds were identified to be 4'-O-methylcoumestrol (P-1), N-acetyl-glutamic acid (P-3), formononetin and beta-sitosterol (P-5).

[The structure of glyeurysaponin].

A species of the genus Glycyrrhiza, G. eurycarpa P.C. Li recently reported as a new species growing in Gansu Province Xinjiang Autonomous Region has rarely been studied before on its chemical constituents. This paper reports the isolation and chemical elucidation of two triterpene glucosides named glyeurysaponin (K-4) and uralsaponin B (K-3) from this species collected in Jinta County, Gansu Province. Their chemical structures were elucidated by means of chemical and spectrometric analysis (UV, IR, MS, 1HNMR and 13CNMR) and were first reported to be present in this plant. Glyeurysaponin (K-4), C42H62O16 was obtained as white crystals, mp 288 degrees C (d), [alpha]18D + 22.5 degrees (c 0.62,60%MeOH). Its structure was found to be be 3 beta-hydroxy-11-oxo-olean-12-en-30-oic acid-3-O-beta-D-glucuronopyranosyl-(1----4)-beta-D-glucuronopyr anoside. Glyeurysaponin is a new triterpenoid saponin. The known saponin was identified to be 3 beta-hydroxy-11-oxo-olean-12-en-30-oic acid-3-O-beta-D-glucuronopyranosyl-(1----3)-beta-D-glucuronopyr anoside, uralsaponin B.