[Application of mass spectrometry combined with next generation sequencing in the diagnosis of neonatal inherited metabolic diseases].

Objective: To explore the application value of mass spectrometry (MS) combined with next generation sequencing (NGS) in diagnosing neonatal inherited metabolic diseases (IMD). Methods: The clinical information, metabolites in blood and urine, and gene sequencing results of 19 neonates with IMD coming from the Department of Neonatology of Jiangxi Provincial Children's Hospital from March 2017 to September 2019 were analyzed retrospectively. The metabolites in blood were detected by liquid chromatography tandem mass spectrometry and urine were detected by gas chromatography-mass spectrometry respectively.Meanwhile, the whole bloods were dectected by neonatal genetic disease panel based on NGS. Results: Twelve neonates had the same results between MS and NGS among the 19, 2 had different results from MS to NGS, and 4 had no disease indication by MS but were diagnosed by NGS whose clinical phenotype were partially consistent with NGS results. One of them who did not carry out MS was considered as the diagnosis of IMD because of the detection of gene, and was followed up on this basis. Conclusion: MS could diagnose IMD relatively quickly to guide clinical treatment, and while NGS could verify the results of MS detection. Combination of MS and NGS would understand the cause of disease on genetic level, so as to guide further treatment and genetic consultation.

The inhibition of the breast cancer by PPARγ agonist pioglitazone through JAK2/STAT3 pathway.

Breast cancer, especially triple-negative breast cancer, is one of the deadliest cancers in women. To date, there is a lack of a good therapeutic regimen for it. PPARγ has been reported to be a tumor suppressor and could be activated by many agonists involved in cancer inhibition. Therefore, the expression of PPARγ in breast cancer was analyzed by online software UALCAN whose data were from the TCGA database. The results revealed that the PPARγ expression was reduced in breast cancer tissues. Furthermore, the methylation in the PPARγ promoter was also assayed and the results indicated that the methylation level in the PPARγ promoter in breast cancer tissue was higher than that in normal tissue. In order to verify the methylation in promoter involved in the regulation of gene PPARγ expression, the 5'-Aza and fluorescence assays were performed and the results proved that methylation in promoter participated in gene PPARγ expression regulation. Pioglitazone, a PPARγ agonist, still was not investigated in breast cancer. Therefore, the effects of pioglitazone on breast cancer cells were tested by cell viability, scratch and transwell assays, and results indicated that the pioglitazone has the inhibition effect on the proliferation and migration of breast cancer cells by PPARγ which was correlated with the JAK2/STAT3 pathway. In order to further confirm the inhibition effect of pioglitazone on breast cancer in vivo, the nude mice model was administrated by gavage with pioglitazone. And the results indicated that pioglitazone could inhibit the growth of breast cancer in the PPARγ overexpression group in vivo. In summary, the expression of gene PPARγ was decreased in breast cancer tissues, which was correlated with its methylation in the promoter region. Moreover, pioglitazone could exert its inhibition on breast cancer proliferation and migration by the JAK2/STAT3 pathway.

[Exposure to disinfection by-products during gestation and newborns' small for gestational age].

Objective: To explore the associations between exposure to chlorination disinfection by-products (CDBPs) during gestation and newborns' small for gestational age (SGA). Methods: During April 2010 to July 2012, a total of 3 903 pregnant women who lived in a district with the same water treatment plant in Wuhan, China were recruited to this perspective study. Information about demographic characteristics of pregnant women and their newborns was collected. The tap water samples were monthly collected for 28 months in 3 different sites, with 84 samples, and 4 kinds of trihalomethanes (THMs)(chloroform (TCM), bromodichloromethane (BDCM), dibromochloromethane (DBCM), and bromoform (TBM)) and 2 kinds of chlorohaloacetic acids (HAAs) (trichloroacetic acid (TCAA), dichloroacetic acid (DCAA)) were determined. The pregnant women were divided into 4 groups(Q1 to Q4) by quartile method according to their exposure level of CDBPs. Binary Logistic regression models were used to assess the associations between exposure to CDBPs during gestation and newborns' small for gestational age. Results: The average weight of all the newborns was (3 310.19±389.91) g, of which 169 (4.33%) were SGA. The median concentrations of TCM, BDCM, bromo-THMs, total THMs, TCAA, and DCAA during the whole pregnancy were 18.07, 4.93, 8.51, 26.74, 10.65, and 13.77 µg/L, respectively. Binary Logistic regression analysis showed dose-response relationships between elevated TCM and total THMs during the whole gestation and compared with Q1 group, while there was a increased risk of SGA in Q4 group, and OR(95%CI) was 1.87 (1.01-3.49) , 2.30 (1.22-4.35) , respectively (P for trend equaled to 0.044, 0.015). Compare with Q1 group, there also be positive associations between exposure to TCAA (Q4 group) during first-trimester and the whole gestation and SGA, while OR(95%CI) was 2.16 (1.19-3.91) (P for trend equaled to 0.015). Conclusion: Exposure to CDBPs during gestation might increase the risk of newborns' SGA.

Modeling the cost-effectiveness of ilaprazole versus omeprazole for the treatment of newly diagnosed duodenal ulcer patients in China.

OBJECTIVES: To evaluate the cost-effectiveness of 10 mg ilaprazole once-daily vs 20 mg omeprazole once-daily to treat newly-diagnosed duodenal ulcer patients in China. METHODS: A decision tree model was constructed and the treatment impact was projected up to 1 year. The CYP2C19 polymorphism distribution in the Chinese population, the respective cure rates in the CYP2C19 genotype sub-groups, the impact of Duodenal Ulcer (DU) on utility value and drug-related side-effect data were obtained from the literature. The total costs of medications were calculated to estimate the treatment costs based on current drug retail prices in China. Expert surveys were conducted when published data were not available. Probabilistic sensitivity analysis was performed to gauge the robustness of the results. RESULTS: Ilaprazole, when compared with omeprazole, achieved a better overall clinical efficacy. For the overall population, ilaprazole achieved an incremental cost effectiveness ratio (ICER) of ¥132 056 per QALY gained. This is less than the WHO recommended threshold of 3-times the average GDP per capita in China (2014). Furthermore, sub-group analysis showed that ilaprazole is cost-effective in every province in CYP2C19 hetEM patients and in the most developed provinces in CYP2C19 homEM patients. Probabilistic sensitivity analysis suggests that the results are robust with 97% probability that ilaprozole is considered cost-effective when a threshold of 3-times China's average GDP per capita is considered. LIMITATION: This study didn't have the data of ilaprazole combined with Hp eradication therapy. Caution should be taken when extrapolating these findings to DU patients with an Hp eradication therapy. CONCLUSIONS: The cost-effectiveness analysis results demonstrated that ilaprazole would be considered a cost-effective therapy, compared with omeprazole, in Chinese DU patients based on the efficacy projections in various CYP2C19 polymorphism types.

Energy and ileal digestible amino Acid concentrations for growing pigs and performance of weanling pigs fed fermented or conventional soybean meal.

A new strategy of co-inoculating Bacillus subtilis MA139 with Streptococcus thermophilus and Saccharomyces cerevisiae was used to produce fermented soybean meal (FSBM). Three experiments were conducted to determine the concentration of digestible energy (DE) and metabolizable energy (ME) (Exp. 1), apparent ileal digestibility (AID) and standardized ileal digestibility (SID) of amino acids (AA) (Exp. 2), and feeding value (Exp. 3) of FSBM produced by this new strategy (NFSB) compared with soybean meal (SBM) and conventionally available FSBM (Suprotein). In Exp. 1, twenty-four barrows (initial body weight [BW] of 32.2 ±1.7 kg) were randomly allotted to 1 of 4 diets with 6 replicates per diet. A corn basal diet and 3 diets based on a mixture of corn and 1 of 3 soybean products listed above were formulated and the DE and ME contents were determined by the difference method. The results showed that there were no differences in DE and ME between SBM and either FSBM product (p>0.05). In Exp. 2, eight barrows (initial BW of 26.8±1.5 kg) were fitted with ileal T-cannulaes and used in a replicated 4×4 Latin square design. Three corn-starch-based diets were formulated using each of the 3 soybean products as the sole source of AA. A nitrogen-free diet was also formulated to measure endogenous losses of AA. The results showed that the SID of all AA except arginine and histidine was similar for NFSB and SBM (p>0.05), but Suprotein had greater (p<0.05) SID of most AA except lysine, aspartate, glycine and proline than NFSB. In Exp. 3, a total of 144 piglets (initial BW of 8.8±1.2 kg) were blocked by weight and fed 1 of 4 diets including a control diet with 24% SBM as well as diets containing 6% and 12% NFSB or 12% Suprotein added at the expense of SBM. During d 15 to 28, replacing SBM with 6% NFSB significantly improved average daily gain (ADG) and average daily feed intake (ADFI) (p<0.05) for nursery piglets. During the overall experiment, ADG of piglets fed diets containing 6% NFSB was significantly greater (p<0.05) than that of piglets fed SBM. In conclusion, fermentation with the new strategy did not affect the energy content or the AID and the SID of AA in SBM. However, inclusion of 6% NFSB in diets fed to nursery piglets improved performance after weaning likely as a result of better nutritional status and reduced immunological challenge.

A novel NF1 mutation in a Chinese patient with giant café-au-lait macule in neurofibromatosis type 1 associated with a malignant peripheral nerve sheath tumor and bone abnormality.

Neurofibromatosis type 1 (NF1; OMIM#162200) is a common neurocutaneous disorder that is characterized by multiple café-au-lait, skinfold freckling, Lisch nodules, and neurofibromas. Mutations in the NF1 gene, which encodes the neurofibromin protein, have been identified as the pathogenic gene of NF1. In this study, we present a clinical and molecular study of a Chinese patient with giant café-au-lait in NF1. The patient showed >6 café-au-lait spots on the body, axillary freckling, and multiple subcutaneous neurofibromas. He also had a malignant peripheral nerve sheath tumor and bone abnormalities. The germline mutational analysis of the NF1 gene revealed a novel missense mutation in exon 13. It is a novel heterozygous nucleotide G>A transition at position 2241 of the NF1 gene. We found no mutation in malignant peripheral nerve sheath tumor DNA from this patient. This expands the database for NF1 gene mutations in NF1. Its absence in the normal chromosomes suggests that it is responsible for the NF1 phenotype. To our knowledge, this is the first case of giant café-au-lait macule in NF1 associated with a malignant peripheral nerve sheath tumor and bone abnormality.

Determination of an economical medium for growth of Lactobacillus fermentum using response surface methodology.

AIM: Lactobacillus fermentum is a widely utilized probiotic compound fed as an alternative to antibiotics for growth promotion in a wide variety of livestock species. The objective of this research is to develop an economical and practical fermentation medium for the growth of Lact. fermentum using response surface methodology. METHODS AND RESULTS: A two-level Plackett-Burman design was used to determine which factors in the fermentation medium influence the growth of Lact. fermentum. Under our experimental conditions, peptone, urea and yeast extract were found to be major factors. Then, the steepest ascent method and the central composite design were applied to optimize the culture of Lact. fermentum. The following composition of the fermentation medium was estimated to be the most economical formula (per litre): 30 g corn syrup, 15 g glucose, 14.4 g peptone, 7 g (NH(4))(2)SO(4), 0.5 g urea, 3 g sodium acetate, 4 g sodium citrate, 0.1 g MnSO(4).4H(2)O, 0.5 g MgSO(4).7H(2)O, 7.3 g yeast extract, 0.5 g K(2)HPO(4). CONCLUSION: Based on 10 side-by-side comparisons, we found that the yield of Lact. fermentum using our fermentation medium was 64% greater than those using modified de Man, Rogosa and Sharp broth (MRS) medium (1.8 x 10(9) CFU ml(-1)vs 1.1 x 10(9) CFU ml(-1), respectively), while the cost was 89% lower than MRS. This research indicates that it is possible to increase bacterial yield by using inexpensive materials. SIGNIFICANCE AND IMPACT OF THE STUDY: It is more likely that the use of Lact. fermentum as a probiotic will increase. The low cost medium developed in this research can be used for large-scale, commercial application where economics are quite likely to be important.

Different effects of angiogenesis inhibitors IFN-alpha and TIMP-1 on lymphangiogenesis.

This study was designed to examine the effects of angiogenesis inhibitors IFN-alpha and TIMP-1 on lymphangiogenesis. We cultured lymphatic endothelial (LE) cells from pig thoracic ducts and performed morphological observations using light microscopy, TEM, and confocal microscopy to confirm their lymphatic origin. We tested these cells for growth inhibition by angiogenesis inhibitors IFN-alpha and TIMP-1 using both the scraping line and MTT methods. In addition, we analyzed apoptosis using the Hoechst and Caspase staining methods. Finally, we tested IFN-alpha and TIMP-1 using in vivo inhibitory assays. By morphological observations, all LE cells in vivo and in vitro were found to be of very similar morphology. Both in vitro inhibitory assays of scraping line and MTT showed significant differences for the IFN-alpha treatment (p < 0.01) and no significant difference for TIMP-1. Hoechst and Caspase apoptosis assays demonstrated that IFN-alpha could induce apoptosis of LE cells, and TIMP-1 had little effect. IFN-alpha and TIMP-1 inhibitory in vivo assays showed a lack of healing following IFN-alpha treatment compared to control and TIMP-1 treatment. In summary, these different angiogenesis inhibitors have different effects on lymphangiogenesis. IFN-alpha inhibits proliferation and migration of LE cells in a dose-dependent fashion and induces apoptosis of LE cells while TIMP-1 has no significant inhibitory effects on proliferation, migration, or inducing apoptosis.

Effects of enzyme supplementation on performance, nutrient digestibility, gastrointestinal morphology, and volatile fatty acid profiles in the hindgut of broilers fed wheat-based diets.

A growth trial and a metabolism trial were conducted as 2 experiments to investigate the effects of dietary enzyme supplementation (primarily xylanase and beta-glucanase) on performance, nutrient digestibility, intestinal morphology, digestive organ size, and volatile fatty acid profiles in the hindgut of broiler chickens fed wheat-based diets. The experimental diets in both trials consisted of a wheat-based control diet supplemented with 0, 200, 400, 600, 800, or 1,000 mg/kg enzyme. Diets were given to the birds from d 7 to 42 of age. In the growth trial, enzyme supplementation improved performance of the broilers; daily gain and feed conversion increased linearly (P < 0.01) with increasing levels of enzyme supplementation. Enzyme inclusion decreased the size of the digestive organs and the gastrointestinal tract to some extent. The relative length of each intestinal segment decreased linearly (P < 0.05). The relative weight of the anterior intestine on d 21 and ileum on d 42 also decreased linearly (P < 0.01). On d 21 and 42, there were negative linear (P < 0.05) relationships between increasing enzyme supplementation and the relative weight of the liver and pancreas, respectively. Furthermore, there was a linear (P < 0.01) increase in total volatile fatty acid content in ileum on d 21 and in the cecum on d 21 and 42. During each period of the metabolism trial, apparent crude protein digestibility increased linearly (P < 0.05), whereas no differences were detected (P > 0.05) in AME.

Influence of cultivating conditions on the alpha-galactosidase biosynthesis from a novel strain of Penicillium sp. in solid-state fermentation.

AIMS: The work is intended to achieve optimum culture conditions of alpha-galactosidase production by a mutant strain Penicillium sp. in solid-state fermentation (SSF). METHODS AND RESULTS: Certain fermentation parameters involving incubation temperature, moisture content, initial pH value, inoculum and load size of medium, and incubation time were investigated separately. The optimal temperature and moisture level for alpha-galactosidase biosynthesis was found to be 30 degrees C and 50%, respectively. The range of pH 5.5-6.5 was favourable. About 40-50 g of medium in 250-ml flask and inoculum over 1.0 x 10(6) spores were suitable for enzyme production. Seventy-five hours of incubation was enough for maximum alpha-galactosidase production. Substrate as wheat bran supplemented with soyabean meal and beet pulp markedly improved the enzyme yield in trays. CONCLUSIONS: Under optimum culture conditions, the alpha-galactosidase activity from Penicillium sp. MAFIC-6 indicated 185.2 U g(-1) in tray of SSF. SIGNIFICANT AND IMPACT OF THE STUDY: The process on alpha-galactosidase production in laboratory scale may have a potentiality of scaling-up.

Genomic analysis reveals RhoC as a potential marker in hepatocellular carcinoma with poor prognosis.

Hepatocellular carcinoma (HCC) is one of the most malignant human tumours because of its high incidence of metastasis. The mechanisms underlying the metastasis of HCC, however, remain poorly understood. In this study, we performed cDNA microarray analysis to profile gene expression patterns in two subtypes of HCC, solitary large HCC (SLHCC) and nodular HCC (NHCC), which differ significantly in the incidence of metastasis. Among 668 genes that were differentially expressed, we focused on RhoC, whose expression was significantly decreased in SLHCC compared to NHCC. The expression of RhoC in HCC and pericarcinomatous liver tissues (PCLT) was analysed at both the mRNA and protein levels by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting. In addition, immunohistochemistry was also performed on 94 cases of HCC with follow-up information. Collectively, our data indicate that the expression of RhoC significantly increased in HCC compared to PCLT; extrahepatic metastatic lesions expressed significantly higher levels of RhoC than the corresponding intrahepatic HCC tissues. There is a highly significant correlation of the RhoC expression levels with tumour vein invasion, number of tumour nodes and the status of differentiation. Significantly, the HCC patients with RhoC-positive expression had shorter survival than those with RhoC-negative expression. Together, our findings suggest a strong correlation between the expression of RhoC and HCC metastasis, implicating RhoC as a potential prognosis marker and therapeutic target for HCC.

Effects of glycaemic control on cardiovascular disease in diabetic American Indians: the Strong Heart Study.

AIMS: Diabetes increases the risk of cardiovascular disease (CVD). Only part of this excess risk is explained by diabetes-associated hypertension, obesity, and lipid disorders. Poor glycaemic control may help explain the residual CVD risk. The aim of this study was to determine whether variations in glycaemic control are associated with CVD risk in diabetic individuals. METHODS: We examined longitudinal data from the Strong Heart Study, a population-based study of CVD and its risk factors among American Indians (a population with a high prevalence of diabetes). Diabetes was defined using the 1998 World Health Organization criteria: fasting plasma glucose >/= 126 mg/dl or 2-h plasma glucose >/= 200 mg/dl. American Diabetes Association guidelines for glycaemic control were used: good, A(1c) < 7%; fair, 7-7.9%; and poor, >/= 8%. The analysis was based on data from diabetic individuals with no CVD at baseline. RESULTS: During 9 years of follow-up, 494 of the 2011 diabetic participants developed CVD. Although Cox multivariate regression modelling showed dose-response effects of glycaemic control on overall CVD and coronary heart disease (CHD) incidence, the relationships were weakened when adjusted for confounding variables. Kaplan-Meier analysis, however, showed that diabetic individuals with poor baseline glycaemic control had significantly increased proportions of overall CVD and CHD (P = 0.001) during the 9 years of follow-up, compared with those who had good or fair control. CONCLUSIONS: These findings highlight the importance of risk factors, such as high blood pressure and dyslipidaemia, in increasing CVD risk in those with diabetes.

Effects of isomalto-oligosaccharides on broiler performance and intestinal microflora.

Dose effects of dietary isomalto-oligosacchrides (IMO) on broiler growth performance and characteristics of the intestinal microflora were compared. Three hundred sixty male broilers were randomly allotted to five treatments, with eight replicate pens per treatment and nine chicks per pen. Chicks were fed either a basal diet (control) or the basal diet plus 0.3, 0.6, 0.9, or 1.2% IMO. All chicks had access to feed and water ad libitum during the 7-wk experiment. At the end of the experiment, eight chicks per treatment were randomly chosen to measure the thymus index. Additionally, six birds per treatment were randomly selected to determine viable bacterial counts of Lactobacillus, Escherichia coli, and total aerobes in the digestive tract. The digesta of all the killed birds were also used to measure short-chain fatty acid (SCFA) levels. The results indicate that IMO enhanced growth performance during the initial 3 wk, but no further effects were detected during the latter 4 wk of the experiment. Isobutyrate level in crop content and acetate level in duodenum digesta were decreased by supplementation with IMO (P < 0.05). Isovalerate level in duodenum digesta was decreased in the 0.3 and 0.6% IMO groups (P < 0.001), whereas the jejunum butyrate and isobutyrate levels of the 0.3% IMO group were higher than in other groups (P < 0.05). The facultative microflora of the crop and cecum were not affected by IMO supplementation. However, the thymus index was increased significantly in chicks consuming diets containing 0.3% IMO.

Studies on the in vivo and in vitro mutagenicity and the lipid peroxidation of chlorinated surface (drinking) water in rats and metabolically competent human cells.

In the present study, DNA damaging and mutagenic effects of chlorinated drinking water (CDW) extracts obtained from polluted raw water resources were examined in metabolically competent human Hep G2 hepatoma cells using the in vitro micronucleus assay and the single cell gel electrophoresis (SCGE, comet assay). Additionally, the in vivo induction of micronuclei (MN) was studied in polychromatic erythrocytes (PCEs) derived from bone marrow of CDW-treated Wistar rats. Furthermore, we examined the influence of CDW on the lipid peroxidation (LpO) in blood, liver, kidney and testicle of rats. The results demonstrated significant increases of micronucleated PCEs in the bone marrow of rats fed with relatively low CDW doses (33.3ml/kg body weight per day). Similar effects, i.e. increases of MN frequencies, were found in Hep G2 hepatoma cells after CDW treatment (41 MN/1000 binucleated cells (BNCs) for 167ml CDW) in comparison to the vehicle control (24 MN/1000 BNC). Additionally, DNA damages caused by CDW were observed in the comet assay. As a product of LpO, the levels of malondialdehyde (MDA) were significantly enhanced almost in all animals and organs tested after CDW treatment. In livers and serum of rats dose-dependent increases of MDA were observed. The data indicated that extracts from CDW obtained from polluted raw water were able to cause oxidative damages and to induce various biological effects in mammalian cells in vivo and in vitro, i.e. clastogenicity and/or aneugenicity, DNA strand breaks and/or alkali-labile damages. The consistency of the results among the various biological systems and endpoints led to the conclusion that the consumption of chlorinated drinking water obtained from polluted raw water may enhance the body burden with mutagenic and/or carcinogenic substances and therefore, means a potential genetic hazard for human health.

A case-control study of hepatitis B and C virus infection as risk factors for hepatocellular carcinoma in Henan, China.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common cancers in the world and is particularly prevalent in China. China is also a hyperendemic area for hepatitis B virus (HBV) infection. Although a strong association between HBV infection and HCC has been established previously, the role of hepatitis C virus (HCV) infection and the interaction between HBV and HCV in the development of HCC has not been adequately explored. The major objective of this study is to determine the relationship between HBV or HCV infection and HCC by use of case-control study in Henan, China. METHOD: In all, 152 HCC patients and 115 control patients were collected from four hospitals in Henan, China between January 1994 and October 1995. The demographic characteristics of the two groups were comparable. In further analysis, a 1:1 pair-matched case-control study was performed. Of 152 HCC patients, 113 were randomly selected to be pair-matched by sex and age (+/-5 years) to controls with non-hepatic disease. All the cases and controls were interviewed during hospitalization by two specially trained interviewers using a standard questionnaire. All sera were tested for HBV and HCV markers. Odds ratios (OR) and 95% CI for HCC risk factors were calculated by logistic regression model controlling for possible confounding factors such as sex and age. The multivariate analysis was done on the basis of the univariate analysis. RESULTS: The results of this study indicated that the prevalence of hepatitis B surface antigen (HBsAg) and antibody to HCV (anti-HCV) were much higher in HCC patients (63.2% and 11.2% respectively) than in the control patients (5.2%, 3.5%). The difference between two groups was significant (P < 0.05). Risk factor analysis revealed that both HBV and HCV infection were important factors for HCC in Henan, China and HBV appeared to have a key role in the development of HCC. Odds ratios of HBsAg and HBV infection were 28.82 (95% CI: 11.18-78.78) and 31.22 (95% CI: 13.86-72.15), respectively. Moreover, the risk of developing HCC increased significantly and showed an additive effect when both viral markers of HBV and HCV infection were considered (OR = 42.85). Results from the 1:1 pair-matched case-control study also showed that HBV infection was an important risk factor for HCC, which was consistent with the results from the group-matched case-control study. CONCLUSION: This is the first reported case-control study of HCC in Henan, China. This study provides further evidence that chronic HBV infection is strongly associated with the development of HCC among this population. Our results have demonstrated that HCV and HBV infection are independent and probably additive risk factors for HCC.

PIP: One of the most common cancers in the world, hepatocellular carcinoma (HCC) is particularly prevalent in China. China is also a hyperendemic area for hepatitis B virus (HBV) infection. Findings are presented from a case-control study conducted in Henan, China, to determine the relationship between HBV or hepatitis C virus (HCV) infection and HCC. 152 HCC patients and 115 control patients were recruited from 4 hospitals in Henan between January 1994 and October 1995. In further analysis, 113 of the 152 HCC patients were randomly selected to be 1:1 pair-matched by sex and age to controls with nonhepatic disease. All cases and controls were interviewed and had their sera tested for HBV and HCV markers. The prevalences of hepatitis B surface antigen (HBsAg) and antibody to HCV (anti-HCV) were 63.2% and 11.2%, respectively, in HCC patients, and 5.2% and 3.5%, respectively, in the controls. Risk factor analysis found that both HBV and HCV infection were important factors for HCC, with HBV appearing to have a central role in the development of HCC. Odds ratios of HBsAg and HBV infection were 28.82 and 31.22, respectively. The risk of developing HCC increased significantly and showed an additive effect when the viral markers of both HBV and HCV infection were considered. Results from the 1:1 pair-matched case-control study also showed HBV infection to be an important risk factor for HCC, consistent with the results from the group-matched case-control study.

[Studies on the effects of low-dose selenium and high-dose cadmium on myocardial injury].

The effects of low-dose selenium and high-dose cadmium on myocardial injury were studied in weanling S.D. rats fed with feed containing controlled levels of selenium and cadmium. Results indicated low-dose selenium and high-dose cadmium could injure heart and myocardial cell membrane system to a certain extent, and cause focal necrosis and reduction in activities of glutathione peroxidase and cytochrome oxidase of heart muscle in rats. It suggested there were certain factors in the grain produced in the areas where Keshan disease was prevalent, which injured heart muscle in rats. So, selenium supplement could prevent from myocardial injury caused by the grain grown in those areas.

[Influence of the blight of Morinda officinalis How on microscopic structure and constituents of the host].

The results showed that microscopic structure in biennial roots, the contents of B and Mn in nutritive organ and beta-sitosterol content in roots, stems of Morinda officinalis were affected markedly. The total sugar content in the roots and aerial stems was decreased by 5.42%-15.29%.

Effects of glutathione depletion using buthionine sulphoximine on the cytotoxicity in mammalian cells and human tumor cells in vitro.

An inhibitor of glutathione biosynthesis, buthionine sulphoximine (BSO), was used to deplete the endogenous thiols in mammalian cells in vitro. In this study, the cytotoxicity of BSO and BSO combined with the hypoxic cell radiosensitizer misonidazole (MISO) was investigated. Both aerobic and hypoxic cytotoxicity of MISO was found to be increased. The concentration of BSO required to reduce the colony forming ability to 50% (Cc) for the chronic cytotoxicity on V79 cells was 0.03 mmol/L under aerobic condition, while the Cc for the acute cytotoxicity on V79 cells under hypoxic and aerobic conditions was 0.4 and 0.5 mmol/L. The growth inhibition rate of human tumor cells K562 and SGC-7901 by BSO was 6.89-26.06% and 12.01-55.69%, respectively. Enhanced cytotoxicity activity was observed when BSO was used in combination with cis-dichlorodiamino Pt(II) or 5-fluorouracil.

Isolation, characterization, and immunological detection of neutrophil-activating peptide 2: a proteolytic degradation product of platelet basic protein.

Neutrophil-activating peptide 2 (NAP-2), corresponding to platelet basic protein fragment 25-94, was prepared by chymotryptic digestion of its precursors, low affinity platelet factor 4 or beta-thromboglobulin, followed by purification by high performance liquid chromatography. NAP-2 (0.1-1.5 microns) caused the release of human granulocyte elastase from cytochalasin B-treated neutrophils in a dose-dependent manner. In the same system, beta-thromboglobulin, human platelet factor 4, S-pyridylethyl NAP-2, and platelet basic protein C-terminal fragment (77-94) were inactive, whereas platelet basic protein fragment 22-89 had low, but significant, activity. Sensitive immunological identification of NAP-2 based on nonequilibrium isoelectric focusing and immunoblotting is described.