G protein regulated inducer of neurite outgrowth 1 is a potential marker for lung cancer prognosis.

Lung cancer mortality remains high, and only approximately 15% of patients with non-small cell lung cancer survive for more than five years. The purpose of this research was to investigate the prognostic value and biological functions of G protein regulated inducer of neuritis outgrowth 1(GPRIN1) in lung cancer. We used the Kaplan-Meier method to analyze the correlation between GPRIN1 and overall survival, and performed Cox regression to determine whether GPRIN1 might be an independent predictive factor for lung adenocarcinoma prognosis. qRT-PCR and Western blot assays were conducted to detect GPRIN1 expression in lung cancer cells and normal control cells. To detect the functional effects of knockdown/overexpression of GPRIN1 on lung cancer cells, we performed CCK-8, colony formation and Transwell assays. Through the Kaplan-Meier method, we found that GPRIN1 expression correlated with overall survival and adverse prognosis, and Cox regression indicated that GPRIN1 is as an independent predictive factor for lung adenocarcinoma. Furthermore, the mRNA and protein expression levels of GPRIN1 in lung cancer cells were markedly higher than those in normal cells. Downregulation of GPRIN1significantly decreased cell viability, colony formation, the number of invasive and migrating cells, and levels of epithelial-mesenchymal transition-related proteins in A549 cells. Overexpression of GPRIN1showed the opposite effect in Calu-1 cells. Together, these results indicated that GPRIN1 facilitates lung cancer proliferation and migration, possibly by affecting the epithelial-mesenchymal transition of lung cancer cells, suggesting that GPRIN1may be used as an effective target for the treatment of lung cancer.

[Estrogen and its receptors in hepatitis B virus-related hepatocellular carcinoma].

Hepatitis B virus (HBV) infection is the most common cause of hepatocellular carcinoma in China. Epidemiological surveys show that male have a much higher incidence of hepatocellular carcinoma than female. Studies have shown that estrogen and its receptors are associated to gender disparity in hepatocellular carcinoma, but the underlying molecular mechanisms has not yet been fully elucidated. This article reviews the possible mechanisms of estrogen and its receptors in the occurrence and progression of hepatitis B virus-related hepatocellular carcinoma.

[Clinicopathologic characterization of malignant mixed tumor of the skin accompanied by eccrine porocarcinoma].

Objective: To investigate the clinicopathologic features, immunophenotype, pathological diagnosis and treatment of malignant mixed tumor (MMT). Methods: Clinical and pathological features including immunohistochemical phenotypes were analyzed in a case of MMT accompanied with eccrine porocarcinoma (EP) involving both hands, diagnosed definitely in January 2018 along with review of relevant literature. Results: A 64-year-old man presented with multiple rash on both hands for 4 years. Three lesions of 0.5 to 2.2 cm were removed for pathological evaluation. The pathological changes on little finger of left and right hands were MMT with EP, whereas that removed from the right ring finger was EP. MMT showed infiltrative growth with vascular wall invasion and consisted of epithelial (glandular or tube differentiation) and mesenchymal components (mucinous and/or cartilage stroma). The endothelial cells showed moderate to severe cytological atypia, nuclear pleomorphism and increased mitotic activity. The glandular component had histological characteristics of syringocarcinoma with moderately atypical chondrocytes but without myoepithelium. EP was composed of basal cells with visible vacuoles in cytoplasm and the presence of tubular and squamous differentiation, along with obvious atypia. Immunohistochemically cavosurface epithelium of glandular differentiation of MMT showed positivity for CK7, EMA and CD117. Myoepithelium showed S-100, CK5/6 and p63 positivity and stromal cells were positive for S-100. Differential diagnoses included metaplastic carcinoma, malignant myoepithelioma and atypical mixed tumor of skin. Conclusions: MMT with EP is extremely rare.The diagnosis of MMT depends on the morphologic features. Immunohistochemical staining is helpful for differential diagnosis. Surgical excision with safety margins is the treatment of choice. Complementary radiotherapy and/or chemotherapy is still controversial. The clinical course of MMT is deemed unpredictable and long-term follow-up is necessary.

[The value of lung ultrasound score for therapeutic effect assessment of ventilator-associated pneumonia].

To study the value of lung ultrasound score (LUS) in assessing the clinical outcome of patients with ventilator-associated pneumonia(VAP). A total of 99 VAP patients were enrolled in a prospective study. All patients met the diagnostic criterion of VAP based on the 2013 guidelines and admitted into our ICU from Jun 2013 to Jun 2015. All parameters were recorded on the diagnostic day (day 1) and day 5, including LUS, clinical pulmonary infection score (CPIS), chest X ray (CXR), Acute Physiology and Chronic Health Evaluation Ⅱ (APACHEⅡ) score, Sequential Organ Failure Assessment(SOFA) score, etc. According to the CPIS, patients were divided into 2 groups(CPIS less than 6 and more or equal to 6). CPIS and LUS were similar on day 1 between two groups (P>0.05). However, on day 5, significant differences of CPIS and LUS were found between groups with CPIS<6 and CPIS≥6 (P=0.019 and P<0.001 respectively). LUS decreased on day 5 in CPIS<6 group and increased in CPIS≥6 group. In CPIS<6 group, there was a positive correlation between LUS and CPIS on day 1(r=0.375, P=0.003) and day 5 (r=0.590, P<0.001). CPIS≥6 groupshowed the same trend on day 1 (r=0.484, P=0.002) and day 5 (r=0.407, P=0.011). LUS can be used to dynamically evaluate the clinical outcome of VAP.

A computational method to predict carbonylation sites in yeast proteins.

Several post-translational modifications (PTM) have been discussed in literature. Among a variety of oxidative stress-induced PTM, protein carbonylation is considered a biomarker of oxidative stress. Only certain proteins can be carbonylated because only four amino acid residues, namely lysine (K), arginine (R), threonine (T) and proline (P), are susceptible to carbonylation. The yeast proteome is an excellent model to explore oxidative stress, especially protein carbonylation. Current experimental approaches in identifying carbonylation sites are expensive, time-consuming and limited in their abilities to process proteins. Furthermore, there is no bioinformational method to predict carbonylation sites in yeast proteins. Therefore, we propose a computational method to predict yeast carbonylation sites. This method has total accuracies of 86.32, 85.89, 84.80, and 86.80% in predicting the carbonylation sites of K, R, T, and P, respectively. These results were confirmed by 10-fold cross-validation. The ability to identify carbonylation sites in different kinds of features was analyzed and the position-specific composition of the modification site-flanking residues was discussed. Additionally, a software tool has been developed to help with the calculations in this method. Datasets and the software are available at https://sourceforge.net/projects/hqlstudio/ files/CarSpred.Y/.

Primary intraosseous ganglioneuromatous paraganglioma of the sacrum with immunopositivity for cytokeratin.

BACKGROUND: Paragangliomas are derived from neurosecretory cells believed to be of neural crest origin. A spinal location of paraganglioma is rare and usually presents as an intradural mass. PATIENT AND METHODS: A primary intraosseous paraganglioma of sacrum is extremely unusual, and only 6 cases were reported. In this study, we report a rare case of a 44-year-old man with the complaint of low back pain and lower extremity weakness. Imaging workup, including computerized tomography (CT), and magnetic resonance imaging (MRI) presented an intraosseous sacral lesion with invasion of sacrum in the S1-S3 vertebrae, and extension to L4-L5 spinal canal. The patient underwent subtotal tumor resection, followed by radiation therapy. RESULTS: The morphological and immunohistochemical studies revealed a composite tumor of paraganglioma and ganglioneuroma components, with immunopositivity for cytokeratin. CONCLUSIONS: To the best of our knowledge, this is the first report in the literature demonstrating an intraosseous sacral paraganglioma with these 2 pathological features.

A meta-analysis of pemetrexed-based doublet compared with pemetrexed alone for the second-line treatment of advanced non-small-cell lung cancer.

PURPOSE: This meta-analysis investigated pemetrexed-based doublet compared with pemetrexed alone as second-line therapy for patients with advanced non-small cell lung cancer. METHODS: Randomized controlled trials which compared pemetrexed-based doublet with single-agent pemetrexed in patients as second-line treatment of advanced non-small cell lung cancer were searched. Overall survival (OS) was the primary end point, while secondary end points included progression-free survival, overall response rate, 1-year survival rate, and grade 3 or 4 toxicity. RESULTS: Four eligible randomized clinical trials including 1,084 patients were selected. Meta-analysis demonstrated that pemetrexed-based doublet arm significantly improved the overall response rate (OR=2.70, 95% CI: 1.76-4.15, p=0.000), compared with docetaxel alone group, while there were no significant differences in overall survival (HR=0.88, 95% CI: 0.74-1.04, p=0.132), progression-free survival (HR=0.91, 95% CI: 0.73-1.15, p=0.443), and 1-year survival rate (OR=1.43, 95% CI: 0.85-2.40, p=0.178) between the two arms. However, there were more frequencies of grade 3-4 leucopenia (OR=2.86, 95% CI: 1.32-6.20, p=0.008), neutropenia (OR=2.69, 95% CI: 1.55-4.68, p=0.000) and thrombocytopenia (OR=6.92, 95% CI: 2.51-19.07, p=0.000) in pemetrexed-based doublet group. Grade 3-4 anemia (OR=0.62, 95% CI: 0.33-1.18, p=0.144) and fatigue (OR=1.15, 95% CI: 0.73-1.79, p=0.550) had equivalent incidences in the two groups. CONCLUSIONS: This is the first meta-analysis to compare pemetrexed-based doublet with single-agent pemetrexed in second-line therapy of non-small cell lung cancer. Our meta-analysis suggested that pemetrexed combination chemotherapy was not superior to single-agent arm and was not recommended as the second-line chemotherapy for patients with non-small cell lung cancer (Tab. 2, Fig. 6, Ref. 20).

Traditional Chinese medicine and related active compounds: a review of their role on hepatitis B virus infection.

Since the significant public health hazard of Hepatitis B virus (HBV) infection and obvious drug resistance and dose-dependent side effects for common antiviral agents (e.g., interferon α, lamivudine, and adefovir), continuous development of agents to treat HBV infection is urgently needed. Traditional Chinese medicine (TCM) is an established segment of the health care system in China. Currently, it is widely used for chronic hepatitis B (CHB) in China and many parts of the world. Over a long period of time in clinical practice and in basic research progress, the effectiveness and beneficial contribution of TCM on CHB have been gradually known and confirmed. Based upon our review of related papers and because of our prior knowledge and experience, we have selected some Chinese medicines, including Chinese herbal formulas (e.g., Xiao-Chai-Hu-Tang, Xiao-Yao-San, and Long-Dan-Xie-Gan-Tang), single herbs (e.g., Phyllanthus niruri, Radix astragali, Polygonum cuspidatum, Rheum palmatum, and Salvia miltiorrhiza) and related active compounds (e.g., wogonin, artesunate, saikosaponin, astragaloside IV, and chrysophanol 8-O-beta-Dglucoside) and Chinese medicine preparations (e.g., silymarin, silibinin, kushenin, and cinobufacini), which seem effective and worthy of additional and indepth study in treating CHB, and we have given them a brief review. We conclude that these Chinese herbal medicines exhibit significant anti-HBV activities with improved liver function, and enhanced HBeAg and HBsAg sero-conversion rates as well as HBV DNA clearance rates in HepG2 2.2.15 cells, DHBV models, or patients with CHB. We hope this review will contribute to an understanding of TCM and related active compounds as an effective treatment for CHB and provide useful information for the development of more effective antiviral drugs.

Acceptable warm ischemia time of tracheal grafts from non-heart-beating donors in rats.

OBJECTIVES: Warm ischemia (WI)-induced airway complications are common in clinical lung transplantation. However, the acceptable WI time of tracheal grafts from non-heart-beating donors (NHBDs) is unknown. The purpose of this study was to determine the acceptable WI time by observing tracheal epithelial regeneration among NHBD. METHOD: Forty-eight rats were randomly divided into four groups (each with 12 rats): WI-0 minutes (group A), WI-30 minutes (group B), WI-45 minutes (group C), and WI-60 minutes (group D). In each group, the tracheas from 6 rats were imbedded in the greater omentum of 6 other rats. Fourteen days later, the transplanted trachea was obtained from the recipient to evaluate epithelial thickness and regeneration. Six tracheas were obtained from living donors as a control group. RESULTS: There were no significant differences in tracheal transplantation time (mean, 17.66±1.21 minutes). There were no significant differences in epithelial thickness and regeneration between the controls and groups A, B, and C (P<.05). Group D showed no normal epithelial structure of the trachea only with monolayer cells. CONCLUSIONS: The time limits of tolerance to WI of tracheal grafts from NHBDs may be 45 minutes.

Radiosensitization and anti-tumour effects of cytosine deaminase and thymidine kinase fusion suicide gene in human adenoid cystic carcinoma cells.

Herpes simplex virus thymidine kinase (HSV-TK) and Escherichia coli cytosine deaminase (CD) can convert innocuous prodrugs into cytotoxic metabolites and are being investigated for use in gene therapy for cancer. Human adenoid cystic carcinoma (ACC-2) cells transduced with a CD/HSV-TK fusion gene (ACC-2/CD-TK cells) were found to be more sensitive to radiation than ACC-2 cells when exposed to 5-fluorocytosine (5-FC; 40 microg/ml) plus ganciclovir (0.1 microg/ml) for 48 h before irradiation. Analysis of radiation survival curves for cells exposed to 5-FC plus ganciclovir before irradiation showed that ACC-2 cells had a higher capacity for sublethal damage repair (D(q) value) and greater cellular radiosensitivity (D(0) value) than ACC-2/CD-TK cells. Colony formation rate after 2 Gy of irradiation was significantly greater for ACC-2 than for ACC-2/CD-TK cells when cells were treated with 5-FC plus ganciclovir before irradiation. This study, therefore, indicates that addition of radiation might substantially improve the therapeutic potential of CD-TK fusion gene therapy of human adenoid cystic carcinomas.

[Effects of baicalin on hepatocyte apoptosis induced by TNF-alpha and act D in rats].

OBJECTIVE: To study the effects of baicalin on rat hepatocyte apoptosis induced by tumor necrosis factora (TNF-alpha) and actinomycin D (Act D) in vitro. METHODS: Hepatocytes were cultured with different concentrations of baicalin and the cell apoptosis was induced by TNF-alpha and Act D in vitro. After culturing for 24 h, the activity of hepatocysts was examined by MTT assay and the function of hepatocytes for secreting albumin was detected by bromocresolum Viride method. Agarose gelelectrophoresis and flow cytometric analysis were used to determine the apoptotic cells. RESULTS: The actively of the hepatocyte (A) and content of albumin (ALB) in the supernatant of cultured cells in the groups of 0.2 microgram.ml-1 and 2.0 micrograms.ml-1 of baicaline were significantly higher than those in apoptotic model group (A: P < 0.01; ALB: P < 0.01); respectively Even the ALB value in the group of 0.2 microgram.ml-1 baicalin was higher that of black control group (P < 0.01); The clear "ladder-like" streak-band of DNA fragments was found only in the apoptosis model group by the agarose gel electrophoresis. The flow cytometry showed that all the apoptosis rates in the three baicalin groups were lower than that of the apoptotic model group (P < 0.01). CONCLUSION: Baicaline can restrain rat hepatocyte apoptosis induced by TNF-alpha and ActD in vitro.

Prospective comparison of whole-blood- and plasma-based hepatitis C virus RNA detection systems: improved detection using whole blood as the source of viral RNA.

We previously demonstrated that whole blood contains significantly more hepatitis C virus (HCV) RNA than plasma. To validate the whole-blood-based HCV RNA detection method, a prospective comparison of HCV RNA detection in whole blood and plasma from 50 patients with chronic liver disease was undertaken. Whole-blood and plasma aliquots were independently tested for HCV RNA by reverse transcriptase (RT) PCR assay, and plasma was tested by the Roche Amplicor assay. HCV RNA was detected in 35 of 50 (70%) whole-blood samples by RT-PCR but in only 26 of 50 (52%) plasma samples tested by the Amplicor assay (P < 0.01). HCV RNA was detected in 85% of HCV antibody-positive patients by the whole-blood method compared with 74% of plasma samples by the Amplicor method. The five HCV antibody-positive subjects who were negative by whole-blood-based RT-PCR assay were all receiving interferon therapy and had normal transaminases at the time of testing. HCV RNA was detected in 38% of HCV antibody-negative subjects by the whole-blood-based RT-PCR assay compared with 6.25% of these patients by the Amplicor assay (P < 0. 05). There were nine samples in which HCV RNA was detected in whole blood but the Amplicor test was negative. Eight of the nine RNAs prepared from these whole-blood samples tested positive in the Amplicor assay, thus confirming the specificity of our results. This study demonstrates that whole-blood-based HCV RNA detection is more sensitive than currently available commercial tests and that whole-blood RNA is suitable for use in commercial assays.

Recombinant hepatitis A virus antigen: improved production and utility in diagnostic immunoassays.

Hepatitis A virus (HAV) immunoassays use cell culture-derived HAV antigen to detect HAV-specific antibodies. The current method of production of HAV antigen in tissue culture is time-consuming and expensive. We previously expressed the HAV open reading frame in recombinant vaccinia viruses (rV-ORF). The recombinant HAV polyprotein was accurately processed and was assembled into subviral particles. These particles were bound by HAV-neutralizing antibodies and were able to elicit antibodies which were detected by commercial immunoassays. The present investigation compared the production of HAV antigen by standard tissue culture methods to the production of HAV antigen with the recombinant vaccinia virus system. In addition, HAV and rV-ORF antigens were assessed for their utility in diagnostic immunoassays. Serum or plasma samples from HAV antibody-positive and antibody-negative individuals were evaluated by immunoassay that used either HAV or rV-ORF antigen. All samples (86 of 86) in which HAV antibody was detected by a commercial enzyme-linked immunosorbent assay (ELISA) also tested positive by the recombinant antigen-based immunoassay (VacRIA). Similarly, all samples (50 of 50) that were HAV antibody negative also tested negative by the VacRIA. The lower limit of detection of HAV antibody was similar among immunoassays with either HAV or rV-ORF antigen. Thus, in the population studied, the sensitivity and specificity of the VacRIA were equivalent to those of the commercial ELISA. Since production of recombinant antigen is faster and less expensive than production of traditional HAV antigen, the development of diagnostic HAV antibody tests with recombinant HAV antigen appears warranted.

[Clinical study of combined Chinese herbal medicine with move stripe field radiation in treating primary hepatocellular carcinoma].

OBJECTIVE: To find a more effective treatment of primary hepatocellular carcinoma by using combined therapy of Chinese herbal medicine with radiotherapy. METHODS: Prospective study was conducted with double-blind method on prognosis of patients treated with combined therapy of Xuefu Zhuyu decoction and move stripe field radiation on entire liver. A control group was established and treated with placebo and radiotherapy. RESULTS: The 1-, 3- and 5-year survival rates of the test group were higher than those of the control group by 20.0%, 23.4% and 16.6% respectively. The remote metastatic rate of the two groups were not different significantly. CONCLUSIONS: Xuefu Zhuyu decoction showed coordinative effect with radiotherapy on antitumor, it could enhance the radiosensitivity of liver cancer cells, increase the radiation tolerance of normal hepatocytes and reduce the side effect of radiotherapy.

Distribution of hepatitis C virus (HCV) RNA in whole blood and blood cell fractions: plasma HCV RNA analysis underestimates circulating virus load.

Previous experiments using a cationic surfactant to detect hepatitis C virus (HCV) RNA in whole blood (WB) suggested that WB was a more plentiful source of viral RNA than was plasma. The relative HCV RNA titers in WB, plasma, peripheral blood mononuclear cells (PBMC), neutrophils, and red blood cells (RBC)/platelets from 10 patients with chronic HCV infection were compared. WB contained significantly more HCV RNA than plasma, which contained more HCV RNA than PBMC, neutrophils, or RBC/platelets (P < .001). To determine if this increased sensitivity was clinically relevant, results of WB and plasma HCV RNA assays were compared with commercial quantitative and qualitative plasma HCV RNA assay results obtained for patients receiving interferon therapy. WB was significantly more sensitive than commercial plasma reverse transcription-polymerase chain reaction for detecting HCV RNA (P < .005). These data indicate that a significant proportion of HCV RNA in peripheral blood is not identified by standard plasma RNA detection methods.

[Clinical study on effect of combined treatment of fuchunpian with radiotherapy on nasopharyngeal carcinoma].

The study based on the clinical prospective trial of 60 cases of nasopharyngeal carcinoma treated with combined treatment of radiotherapy and Fuchunpian in our hospital from September, 1988 to January, 1990. Results of clinical data of 5 years follow-up showed that Fuchunpian not only couldn't enhance the radiosensitivity of patients, but also increase the blood metastatic potency, the metastatic rate of patients treated with Fuchunpian (36.7%) was 2.67 times higher than that without it (10.0%). Therefore, it was considered that use Fuchunpian as a routine either administrated alone or combined with radiotherapy in treatment of nasopharyngeal carcinoma is not suitable.

A minority group and China's one-child policy: the case of the Koreans.

This report describes the participation in the one-child certificate program by Koreans living in China, using data from a household survey conducted in 1986 in Yanbian Korean Autonomous Prefecture, Jilin Province. Although the Koreans and all other minorities are exempt from China's strict one-child family policy, by pledging not to have more than one child they receive the one-child incentives. The total minority population in China is nearly 70 million and their combined population growth rate is much higher than that of the Han majority. The Korean minority, however, has had a growth rate lower than that of the Han. Nevertheless, the level of acceptance of the one-child certificate among Korean couples is only about 10 percent of those who currently have one child--one-fourth of the 1982 national figure. Life-table analysis indicates that fewer than 9 percent of Korean women would accept the certificate within a six-year period after their first birth. In the meantime, a second child would be born to 60 percent of the women. Among eight factors considered, three--place of residence, occupation of husband, and sex of the living child--significantly affected the rate of acceptance of the certificate, according to the hazards model.

[Clinical and ultrastructural observations of juvenile periodontitis].

In this study, clinical data of 7 cases of juvenile periodontitis were analyzed in company with electron microscopic observations. It consisted of 6 females, and 1 male, aged from 12 to 18 years old. TEM showed chronic inflammation of the pocket walls, marked plasma cell and lymphocyte infiltration. Plasma cells revealed abundant dilated rough endoplasmic reticulum and were classified into three types. Numerous bacteria were found in lamina propria in one case, without any signs of phagocytosis. The collagen fibers were fragmented, dissolved and arranged out of order. The characteristics of clinical history, and the ultrastructural changes of the periodontal pocket were analyzed and discussed.

[Clinical use of a rotation cheek flap].

The inverse triangular skin defect between lower eyelid and up lip can be repaired by cheek rotation flap. In order to preventing lower eyelid eversion, the author designed a triangular flap in the lateral canthal area which can change force bearing direction in this area. The flap can repair the defect as wide as 8 X 5 cm when the combination of bilobate flap of the posterior auricular flap and cheek flap was used. This technique was performed in 23 cases in last three years.

An analysis of prognostic factors in cirrhosis.

To develop a more comprehensive index for predicting the prognous of liver cirrhosis. 300 consecutive patients with cirrhosis were studied in terms of survival from 1975 to 1986. Median follow-up period was 5.3 years. A multivariable survival analysis (Cox's regression model) using clinical biochemical data obtained at admission disclosed eight factors of value in predicting prognosis: age, frequency of previous GI bleeding, ascites, hepatic encephalopathy, serum albumin, serum bilirubin, hemoglobin and prothrombin time. A prognostic index was constructed for the calculation of the estimated survival probability.