Inflammatory caspase-11 senses and is activated by intracellular lipopolysaccharide (LPS) leading to pyroptosis that has critical role in defensing against bacterial infection, whereas its excess activation under pathogenic circumstances may cause various inflammatory diseases. However, there are few known drugs that can control caspase-11 activation. We report here that scutellarin, a flavonoid from Erigeron breviscapus, acted as an inhibitor for caspase-11 activation in macrophages. Scutellarin dose-dependently inhibited intracellular LPS-induced release of caspase-11p26 (indicative of caspase-11 activation) and generation of N-terminal fragment of gasdermin D (GSDMD-NT), leading to reduced pyroptosis. It also suppressed the activation of non-canonical nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome as evidenced by reduced apoptosis-associated speck-like protein containing a CARD (ASC) speck formation and decreased interleukin-1 beta (IL-1β) and caspase-1p10 secretion, whereas the NLRP3-specific inhibitor MCC950 only inhibited IL-1β and caspase-1p10 release and ASC speck formation but not pyroptosis. Scutellarin also suppressed LPS-induced caspase-11 activation and pyroptosis in RAW 264.7 cells lacking ASC expression. Moreover, scutellarin treatment increased Ser/Thr phosphorylation of caspase-11 at protein kinase A (PKA)-specific sites, and its inhibitory action on caspase-11 activation was largely abrogated by PKA inhibitor H89 or by adenylyl cyclase inhibitor MDL12330A. Collectively, our data indicate that scutellarin inhibited caspase-11 activation and pyroptosis in macrophages at least partly via regulating the PKA signaling pathway.

PURPOSE: The significance of neuroendocrine differentiation (NED) in gastric carcinoma (GC) is controversial, leading to ambiguous concepts in traditional classifications. This study aimed to determine the prognostic threshold of meaningful NED in GC and clarify its unclear features in existing classifications. MATERIALS AND METHODS: Immunohistochemical staining for synaptophysin, chromogranin A, and neural cell adhesion molecule was performed for 945 GC specimens. Survival analysis was performed using the log-rank test and univariate/multivariate models with percentages of NED (PNED) and demographic and clinicopathological parameters. RESULTS: In total, 275 (29.1%) cases were immunoreactive to at least 1 neuroendocrine (NE) marker. GC-NED was more common in the upper third of the stomach. PNED, and Borrmann's classification and tumor, lymph node, metastasis stages were independent prognostic factors. The cutoff PNED was 10%, beyond which patients had significantly worse outcomes, although the risk did not increase with higher PNED. Tumors with ≥10% NED tended to manifest as Borrmann type III lesion with mixed/diffuse morphology and poorer histological differentiation; the NE components in this population mainly grew in insulae/nests, which differed from the predominant growth pattern (glandular/acinar) in GC with <10% NED. CONCLUSIONS: GC with ≥10% NED should be classified as a distinct subtype because of its worse prognosis, and more attention should be paid to the necessity of additional therapeutics for NE components.
Adenocarcinoma ; Chromogranin A ; Classification ; Humans ; Immunohistochemistry ; Lymph Nodes ; Neoplasm Metastasis ; Neural Cell Adhesion Molecules ; Prognosis ; Stomach ; Stomach Neoplasms ; Synaptophysin

At present, most of the malignancies still have poor treatment and even poor prognosis .In the case of disease informing , the families of many patients with malignant tumors are inclined to conceal the disease based on the risks that may result in the patient ' s pain while patients want to know their disease diagnosis and prognosis . Telling patients the truth is helpful to promote the patients to participate in the treatment decision , cooperate with the treatment, prolong the survival time , improve the quality of life and also is the requirement of relevant laws and regulations, but it also faces many ethical conflicts in practice .Aiming at this, this paper proposed to strengthen health education , make necessary training to medical staff , design individual informative programs , cooperate rea-sonably with family members , and so on .

Objective To investigate the effects of citric acid on the related indexes of salivary secretion under acid loading in or‐der to optimize the citric acid load method .Methods The saliva samples were collected from 10 young healthy volunteers at 1-90 s before ,at 91-120 s during and at 121-210 s after citric acid loading .The indexes were detected in saliva with mixed loading and after loading .The salivary alpha‐amylase(sAA ) activity ,pH value ,saliva flow rate ,total protein concentration in various groups were detected .The ratio values before and after the acid loading were compared among the groups .Results (1)The sAA activity , saliva pH value and total protein concentrations after acid loading were significantly increased compared before loading (P<0 .05) , moreover the ratio of after loading and before loading was greater than 1(P<0 .05);(2) however in the citric acid mixing ,the sAA activity ,saliva pH value and total protein concentration were decreased compared with before acid loading ,its ratio was less than 1 (P<0 .05) .Conclusion Citric acid affects the secretion result of acid loading saliva secretion ,it is suggested that the saliva under acid loading is separated treated and analyzed .

Objective To analyze the indoor radon level and distribution characteristic in different geological background by studying the indoor radon level in three typical areas in Zhuhai City.Methods The region of investigation includes three districts:granite area in Zhuhai District,granite area in Doumen District and the Quaternary sedimentary area in Doumen District.Activated charcoal adsorption method was used to measure the indoor radon concentrations.In some sampling sites,solid state nuclear track detectors were used at the same time for the indoor radon measurement.Results The average indoor radon level included 80 buildings was (66.0 ± 49.8) Bq/m3 using activated charcoal adsorption method and the maximum value was 1078.5 Bq/m3.The results of 23 sampling sites show that the average indoor radon level using solid state nuclear track detectors was (88.8 ± 49.1) Bq/m3,and (69.5 ± 37.7) Bq/m3 by activated charcoal adsorption method.The indoor radon concentration was (73.6 ± 61.0),(87.5 ± 58.3) and (48.6 ± 22.6) Bq/m3 in granite area in Zhuhai District,granite area in Doumen District and the Quaternary sedimentary area in Doumen District,respectively.Conclusions The surface lithology of an area has a certain impact on the indoor radon level.The indoor radon level in granite area in Zhuhai District and Doumen District is apparently higher than that in the Quaternary sedimentary area in Doumen District.The study of indoor radon level and distribution characteristic should be discussed in combination with geological background of area.

Objective To compare the differences of temperature results between mercury thermometer and infrared thermometer. Methods The temperature of three parts was recorded respectively by mercury thermometer in axilla and infrared thermometer in forehead and earlobe on the same patient, totally 98 patients were recorded in ICU. Results There was statistical difference of three parts' temperature in 98 cases. It could be assumed that axilla temperature ＞ earlobe temperature ＞ forehead temperature;There was no statistical difference of three parts' temperature in 17 cases with temperature 38.0～38.9 ℃ by mercury thermometer, but the difference had clinical significance. It could be assumed that axilla temperature ＞ earlobe temperature ＞ forehead temperature; There was statistical difference of three parts' temperature in 30 cases with temperature at 37.0～37.9 ℃ by mercury thermometer. It could be assumed that axilla temperature ＞ earlobe temperature ＞ forehead temperature. There was no statistical difference of three parts'temperature in 51 cases with temperature at 35.0～36.9 ℃ by mercury thermometer. Conclusions Temperature of the patients with normal axilla temperature could be monitored by infrared thermometer instead of mercury thermometer,but it is not applicable to the patients with fever.

Objective To investigate the clinical features and microsurgical resection techniques of cerebellopontine angle cholesteatoma. Methods Clinical features, surgical approach and techniques, results and complications were analyzed in 30 cases of cerebellopontine angle cholesteatoma. Results Total resection in 26 cases, subtotal resection in 4 cases ,no operative mortality. Post-operative complications was aseptic encephalitis which was most common after treatment, and all recovered. Conclusion Cerebellopontine angle cholesteatoma was a third category of common tumors, CT, MRI examination can provide diagnosis. According to cholesteatoma involving the site ,selecting a good surgical approach and making good use of microsurgical technique could improve surgical total removal rate and reduce postoperative complications.

Major histocompatibility complex (MHC) tetramer technology offers a powerful means to study specific T cell populations of interest. To investigate the immune response of H-2Db-restricted CD8+ T cells in immunotherapy, we prepared the H-2Db tetramer and verified its effectiveness in enumerating the CD8+ T cells specific for the lymphocytic choriomeningitis virus (LCMV). First, the cDNA encoding H-2Db heavy chain was cloned by RT-PCR from the spleen of a C57BL/6 mouse. The expression vector for H-2Db-BSP, i.e. the ectodomain of H-2Db fused to a BirA substrate peptide (BSP), was constructed and overexpressed in E. coli BL21(DE3). Then, the denatured H-2Db-BSP was refolded in the presence of human beta2-microglobulin as well as the GP33-41 peptide (KAVYNFATC, KAV) of LCMV. The biotinylated H-2Db/KAV molecules were purified, then bound to streptavidin-PE and tetramerized. Finally, the prepared H-2Db KAV tetramer reagent was verified by detecting the CD8+ T cells specific for HCMV in KAV peptide vaccinated C57BL/6 mouse, with a mouse receiving subcutaneous injection of only adjuvant as negative control. The results showed that the tetramer positive rates were 0.27%, 0.11%, and 0.24% within the CD8+ T cell populations in the peripheral blood, draining lymph nodes, and spleen of vaccinated mouse, respectively. There was only very low background staining (< or = 0.01%) of those samples from the control mouse. Beside, the best results were achieved in the staining of the peripheral blood sample. In conclusion, the established procedure of preparing H-2Db tetramer will facilitate the study of the immune responses of antigen-specific CD8+ T cells in the experimental immunotherapy on the mice with H-2Db allele background.
Animals ; Antibody Specificity ; CD8-Positive T-Lymphocytes ; immunology ; H-2 Antigens ; genetics ; Histocompatibility Antigens Class I ; genetics ; Immunologic Techniques ; Lymphocytic choriomeningitis virus ; immunology ; Male ; Mice ; Mice, Inbred C57BL ; T-Cell Antigen Receptor Specificity ; immunology

OBJECTIVE:To study the pharmacokinetics and bioequivalence of both domestic ranitidine hydrochloride capsules and imported ranitidine hydrochloride tablets.METHODS:20healthy volunteers were randomized into groups,whose plasma concentrations of ranitidine were determined at different time after single oral dose of300mg ranitidine hydrochloride capsule or ranitidine hydrochloride tablets300mg by own control by a RP-HPLC method,the pharmacokinetic parameters were computed and which were experienced variance analysis and two-way t-tests and one-way t-tests.RESULTS:The respective pharmacokinetic parameters of ranitidine hydrochloride tablets and ranitidine hydrochloride capsuless were as fol?lows,the C max were(1247.1?547.5)?g/L and(1294.8?613.2)?g/L;t max were(2.98?0.73)h and(2.73?0.80)h;t 1/2 were(3.17?0.36)h and(3.33?0.42)h;AUC 0～t were(5805.9?1403.5)(?g?h)/L and(5941.2?1526.3)(?g?h)/L;AUC 0～∞ were(6163.8?1456.4)(?g?h)/L and(6351.8?1652.7)(?g?h)/L;The relative bioavailability of the ranitidine hydrochloride capsules to ranitidine hydrochloride tablets was(104.3?24.3)%.CONCLUSION:Ranitidine hydrochloride capsules and the ranitidine hydrochloride tablets were bioequivalent.

AIM: Peripheral blood mononuclear cells (PBMC) were cultured in vitro to study the effect of gossypol, a polyphenolic antifertility agent, on the activation of normal human T cells. METHODS: Double fluorescent staining together with flow cytometry was adopted to analyze the influence of gossypol on expression of the early activation antigen CD69 on T-lymphocytes under stimulation of mitogen or phorbol ester. RESULTS: Analysis of T cell activation in vitro revealed that preincubation of PBMC with 100 μmol/L gossypol could completely inhibit the expression of early activation marker CD69 on CD3+ T cells in response to 10　mg/L PHA, and block T cell activation by 10-7 mol/L PDB as well. The suppression of CD69 expression was dose-dependent and IC50 of gossypol on PDB and PHA were (35.7±2.9) μmol/L and (32.8±1.5) μmol/L(眘), respectively. Besides, gossypol had similar inhibitory effect on CD69 expression of CD3- lymphocytes. However, it did not have any significant effect on T cell surface molecule CD3 down-regulation. CONCLUSION: Gossypol could inhibit T cell activation in vitro in response to polyclonal activators, both PHA and PDB, suggesting that its action site may be at PKC or its downstream and that gossypol possessed potential immuno-regulatory effect.