[Combined anluohuaxianwan and entecavir treatment significantly improve the improvement rate of liver fibrosis in patients with chronic hepatitis B virus infection].

Objective: To explore the improvement rate of liver fibrosis in patients with chronic hepatitis B virus infection who received entecavir alone or in combination with anluohuaxianwan for 78 weeks. Methods: Patients with chronic HBV infection were randomly treated with entecavir alone or in combination with anluohuaxian for 78 weeks. Ishak fibrosis score was used for blind interpretation of liver biopsy specimens. The improvement in liver fibrosis condition before and after the treatment was compared. Student's t test and non-parametric test (Mann-Whitney U-Test and Kruskal-Wallis test) were used to analyze the measurement data. The categorical variables were analyzed by Chi-square test method and Spearman's rank correlation coefficient was used to test bivariate associations. Results: Liver fibrosis improvement rate after 78 weeks of treatment was 36.53% (80/219) and the progression rate was 23.29% (51/219). The improvement of liver fibrosis was associated to the degree of baseline fibrosis and treatment methods (P < 0.05). The improvement rate of hepatic fibrosis in patients treated with anluohuaxianwan combined with entecavir at baseline F < 3 (54.74%, 52/95) was significantly higher than that in patients treated only with entecavir (33.33%, 16/48), P = 0.016 and the progression rate of hepatic fibrosis (13.68%, 13/95) was lower than that in patients treated alone (18.75%, 9/48), P = 0.466. In patients with baseline F < 3, the proportion of patients with improved and stable liver fibrosis in the combined treatment group (68.1%, 32/47) was higher than that in the treatment group alone (51.7%, 15/29). Conclusion: Combined anluohuaxianwan and entecavir treatment can significantly improve the improvement rate of liver fibrosis in patients with chronic hepatitis B virus infection. Furthermore, it has the tendency to improve the stability rate and reduce the rate of progression of liver fibrosis.

[Screening results and influencing factors of upper gastrointestinal carcinoma and precancerous lesions in Feicheng City].

Objective: To clarify the situation of the detection of upper gastrointestinal cancer and precancerous lesions in the Feicheng city and discuss the possible influencing factors. Methods: A cluster sampling method was used to determine the participants. A unified questionnaire was used to investigate the basic information including history of alcohol intake, smoking and chinese tea, as well as other eating habits, medical history of digestive tract and cancer. Endoscopy was used to to screen the patients with upper gastrointestinal cancer and precancerous lesions. Influential factors were explored by non-conditional logistic regression model. Results: 911 of 7 291participants were positive, and the total detection rate was 12.49%. The total positive detection rate of male and female was 17.94% and 8.71%, respectively (P<0.001). Multivariate logistic regression analysis showed that the sex (OR=0.527, 95%CI: 0.440-0.631), age (OR=2.037, 95%CI: 1.849-2.245), smoking (OR=1.240, 95%CI: 1.014-1.516) and alcohol consumption (OR=1.232, 95%CI: 1.012-1.500) , meat and protein intake (OR=0.794, 95%CI: 0.638-0.987) and drink tea (OR=1.233, 95%CI: 1.056-1.440) may be influencing factors of the total detection rate of upper gastrointestinal cancer and precancerosis. Conclusions: In Feicheng city, intake of meat and protein is the protective factor of the upper gastrointestinal cancer and precancerous lesions. Men, aged, smoking, drinking and tea will increase the risk of upper gastrointestinal cancer and precancerous lesions.

The effects of Forsythia suspensa extract and berberine on growth performance, immunity, antioxidant activities, and intestinal microbiota in broilers under high stocking density.

A 42-d experiment was conducted with 276 Arbor Acres broilers (1 d of age, weighing 41.1 ± 1.5 g) to determine the effects of Forsythia suspensa extract (FSE) and berberine (BE) on growth performance, immunity, antioxidant activities, and intestinal microbiota stocked at high stocking density (28 kg of BW/m(2) as the normal density, 46 kg of BW/m(2) as the high density). The feeding program consisted of a starter diet from d 1 to 21 of age and a finisher diet from d 22 to 42. Dietary treatments included (1) negative control group (NC), stocked at high density; (2) positive control group (PC), stocked at normal density; (3) FSE, NC + 100 mg/kg of FSE; (4) BE, NC + 100 mg/kg of BE; and (5) FSE + BE, NC + 100 mg/kg of FSE + 100 mg/kg of BE. Birds had free access to diets and water. Body weight and feed intake were measured at d 21 and 42. Blood, spleen and bursa, and intestinal contents were collected at d 42 for analysis. The results showed that growth performance did not differ among treatments in the starter period; however, in the finisher and overall periods, birds in FSE + BE, FSE, BE, and PC had greater final BW, ADG, and ADFI than the birds in NC (P < 0.05). The birds in FSE + BE, FSE, BE, and PC had greater bursa weight, bursa weight/BW ratio, serum total antioxidant capacity, and superoxide dismutase activity than birds in NC (P < 0.05). The FSE + BE, FSE, and BE birds had lower serum malondialdehyde level than NC birds (P < 0.05). The FSE + BE, FSE, BE, and PC birds had lower counts of Escherichia coli but greater Lactobacillus in the cecum than that of NC birds (P < 0.05). Dietary supplementation with FSE, BE, or both can improve the growth performance possibly by enhancing immunity, reducing oxidative stress, and promoting intestinal colonization by healthy microbiota of broilers under high stocking density.

IPCS: an integrated process control system for enhanced in-situ bioremediation.

To date, there has been little or no research related to process control of subsurface remediation systems. In this study, a framework to develop an integrated process control system for improving remediation efficiencies and reducing operating costs was proposed based on physical and numerical models, stepwise cluster analysis, non-linear optimization and artificial neural networks. Process control for enhanced in-situ bioremediation was accomplished through incorporating the developed forecasters and optimizers with methods of genetic algorithm and neural networks modeling. Application of the proposed approach to a bioremediation process in a pilot-scale system indicated that it was effective in dynamic optimization and real-time process control of the sophisticated bioremediation systems.

An integrated numerical and physical modeling system for an enhanced in situ bioremediation process.

Groundwater contamination due to releases of petroleum products is a major environmental concern in many urban districts and industrial zones. Over the past years, a few studies were undertaken to address in situ bioremediation processes coupled with contaminant transport in two- or three-dimensional domains. However, they were concentrated on natural attenuation processes for petroleum contaminants or enhanced in situ bioremediation processes in laboratory columns. In this study, an integrated numerical and physical modeling system is developed for simulating an enhanced in situ biodegradation (EISB) process coupled with three-dimensional multiphase multicomponent flow and transport simulation in a multi-dimensional pilot-scale physical model. The designed pilot-scale physical model is effective in tackling natural attenuation and EISB processes for site remediation. The simulation results demonstrate that the developed system is effective in modeling the EISB process, and can thus be used for investigating the effects of various uncertainties.

[1.4 kb 5' flanking region of class I patatin directs tuber-specific gus expression in potato (Solanum tuberosum L.)].

Binary vectors pPATIs (with partial signal sequence) and pPATI (without signal sequence) were constructed by fusing 1.4 kb 5' flanking regions of Class I patatin gene with GUS. Transient GUS expression was observed in in vitro tuber slices bombarded with pPATI. These constructs were then introduced into potato (cv. Desiree) via Agrobacterium tumefaciens transformation. Transgenic potato plants were confirmed by X-Gluc staining and PCR. Using in vitro tuberization system, GUS activities were assayed by fluorescence. It was shown that, in plants transformed with PATI-GUS, GUS specific activities were about 10-20 fold higher in tubers than in stems. Increased sucrose concentration could not induce PATI-GUS expression, but light enhanced PATI-GUS expression in cultured shoots.

Dual role for nitric oxide in dynorphin spinal neurotoxicity.

The pharmacological effects of nitric oxide synthase (NOS) inhibitors, NO donor, and NOS substrate on dynorphin(Dyn) A(1-17) spinal neurotoxicity were studied. Intrathecal (i.t.) pretreatment with both 7-nitroindazole 1 micromol, a selective neuronal constitutive NOS (ncNOS) inhibitor, and aminoguanidine 1 micromol, a selective inducible NOS (iNOS) inhibitor, 10 min prior to i.t. Dyn A(1-17) 20 nmol significantly ameliorated Dyn-induced neurological outcome. Both 7-nitroindazole and aminoguanidine significantly antagonized the increases of cNOS and iNOS activities measured by conversion of 3H-L-arginine to 3H-L-citrulline in the ventral spinal cord, and blocked the Dyn-induced increases of ncNOS-immunoreactivity in the ventral horn cells 4 h after i.t. Dyn A(1-17) 20 nmol. Pretreatment with Nomega-nitro-L-arginine methyl ester (L-NAME) 1 micromol, a cNOS inhibitor nonselective to both ncNOS and endothelial NOS (ecNOS), did not antagonize Dyn A(1-17) 20 nmol-induced permanent paraplegia but aggravated Dyn A(1-17) 10 nmol-induced transient paralysis and caused permanent paraplegia. Pretreatment with L-NAME 1 micromol 10 min before i.t. Dyn A(1-17) 1.25 and 2.5 nmol, which produced no significant motor dysfunction alone, induced transient paralysis in seven out of 12 and five out of seven rats, respectively. L-NAME 1 micromol plus Dyn A(1-17) 10 nmol induced ncNOS-immunoreactivity expression in ventral horn cells. Both low and high doses of aminoguanidine (0.2-30 micromol) did not affect spinal motor function, but high doses of L-NAME (5-20 micromol) induced dose-dependent hindlimb and tail paralysis associated with spinal cord injury in normal rats. Pretreatment with low-dose Spermine NONOate, a controlled NO releaser, 0.1 and 0.5 micromol 10 min before i.t. Dyn A(1-17) 20 nmol, significantly prevented Dyn spinal neurotoxicity, and high-dose Spermine NONOate 2 micromol i.t. per se induced transient and incomplete paraplegia. But pretreatment with L-Arg 10 micromol 10 min before Dyn A(1-17) 20 nmol produced only partial blockade of Dyn-induced paraplegia. These results demonstrated that relatively specific inhibition of ncNOS and iNOS block Dyn-induced increases in cNOS and iNOS activities and ncNOS-immunoreactivity in ventral spinal cord, but nonspecific inhibition of ncNOS and ecNOS aggravated Dyn spinal neurotoxicity. It suggested that both ncNOS and iNOS play an important role, but ecNOS might be beneficial in Dyn spinal neurotoxicity. Moderate production of NO (at vascular level) has an apparently neuroprotective effect, and overproduction of NO (at cellular level) induces neurotoxicity.

Huperzine-A in capsules and tablets for treating patients with Alzheimer disease.

AIM: To compare the efficacy and safety between huperzine-A (Hup) in capsules and tablets for treating patients with Alzheimer disease (AD). METHODS: Using multicenter, prospective, double-blind, double-mimic, parallel, positive controlled and randomized methods, 60 patients meeting with the NINCDS-ARDRA criteria of AD were divided into 2 equal groups. Patients in the capsule group received 4 capsules of Hup (each contains 50 micrograms) and 4 tablets of placebo (lactose and starch inside); while the tablet group received 4 tablets of Hup (each contains 50 micrograms) and 4 capsules of placebo, p.o., twice a day for 60 d. All the patients were evaluated with a lot of related ranting scales, and physiological and laboratory examination. RESULTS: There were significant differences (P < 0.01) on all the psychological evaluations between 'before' and 'after' the 60-d trial of 2 groups, but there was no significant difference between 2 groups by group t test (P > 0.05). The changes of oxygen free radicals in 2 groups showed marked improvement. No severe side effect besides moderate to mild nausea was found in both groups. CONCLUSION: There is equal efficacy and safety between Hup in capsule and tablet for treating patients with AD, and Hup can reduce the pathological changes of the oxygen free radicals in the plasma and erythrocytes of patients with AD.

Do nutritional supplements lower the risk of stroke or hypertension?

Between 1986 and 1991, 29,584 persons took part in a randomized nutritional intervention trial in Linxian, China, an area whose residents had chronically low intakes of several nutrients and high rates of esophageal and gastric cardia cancer as well as stroke. Using a one-half replicate of a 2(4) factorial design, we randomized individuals to one of eight groups which received combinations of four supplements: retinol and zinc (factor A); riboflavin and niacin (factor B); vitamin C and molybdenum (factor C); and beta-carotene, alpha-tocopherol (vitamin E), and selenium (factor D). Deaths that occurred during 5 years of supplementation were ascertained and classified according to cause. At the end of the supplementation period, we measured blood pressure readings and determined the prevalence of hypertension. Participants who received factor D had reductions in total mortality (9%) and total cancer mortality (13%). These individuals also had the largest reduction in stroke mortality (relative risk = 0.91; 95% confidence interval = 0.76-1.07). End-of-trial hypertension, however, was not less prevalent among those receiving factor D. Our findings contrast with the larger reductions in stroke death and hypertension found in a parallel trial of Linxian subjects with esophageal dysplasia who received a multivitamin/mineral supplement, suggesting an effect largely derived from nutrients other than those received in the present study.

Lowered risks of hypertension and cerebrovascular disease after vitamin/mineral supplementation: the Linxian Nutrition Intervention Trial.

A total of 3,318 men and women from a region in rural China were randomized to receive daily either a multiple vitamin/mineral supplement or a placebo. Deaths that occurred in the participants were ascertained and classified according to cause over the 6-year period from 1985 to 1991. At the end of supplementation, blood pressure readings were taken, and the prevalence of hypertension was determined. There was a slight reduction in overall mortality in the supplement group (relative risk (RR) = 0.93, 95 percent confidence interval (CI) 0.75-1.16), with the decreased relative risk most pronounced for cerebrovascular disease deaths (RR = 0.63, 95 percent CI 0.37-1.07). This benefit was greater for men (RR = 0.42, 95 percent CI 0.19-0.93) than for women (RR = 0.93, 95 percent CI 0.44-1.98). Among the survivors, the presence of elevations in both systolic and diastolic blood pressures was less common in those who received the supplement (RR for men = 0.43, 95% CI 0.28-0.65; RR for women = 0.92, 95 percent CI 0.68-1.24). This study indicates that supplementation with a multivitamin/mineral combination may have reduced mortality from cerebrovascular disease and the prevalence of hypertension in this rural population with a micronutrient-poor diet.

Effect of nutrition intervention on intermediate endpoints in esophageal and gastric carcinogenesis.

A nutrition intervention trial involving > 3000 participants was conducted in Linxian, China, where the esophageal and stomach cancer mortality rates are among the highest in the world and suspicion exists that chronic deficiencies of multiple nutrients are etiologically involved. The trial was randomized, double-blind, and placebo-controlled and tested the effect of multivitamin and multimineral supplements in reducing cancer incidence and mortality in adults with cytologically detected esophageal dysplasia. Endoscopic and cytologic examinations of samples of trial participants during the intervention allowed evaluation of intermediate endpoints in esophageal and gastric carcinogenesis, including asymptomatic histologic precancerous lesions and early invasive cancer, epithelial proliferation, and cytologic abnormalities. Results from these ancillary studies suggest that multivitamin and multimineral supplementation may decrease proliferation and enhance cytologic reversion to nondysplasia.

Effects of vitamin/mineral supplementation on the proliferation of esophageal squamous epithelium in Linxian, China.

Abnormalities of epithelial proliferation have been proposed as an early step in gastrointestinal carcinogenesis. To determine whether micronutrient supplementation may reduce squamous epithelial proliferation in the esophagus, we evaluated proliferation in subjects participating in a randomized nutrition intervention trial in Linxian, China, where esophageal cancer rates are among the highest in the world. After 30 months of intervention involving daily supplementation with multiple vitamins and minerals, an endoscopic survey was performed and squamous biopsies from 512 subjects were labeled with tritiated thymidine and autoradiographed. Analysis showed no treatment effect on the overall amount of squamous epithelial proliferation measured by the total labeling index. However, a measure of the vertical distribution of labeled cells showed lower values with supplementation: a 14% reduction in all subjects (P = 0.29), and a 29% reduction in nonsmokers (P = 0.03). These results suggest a potential modest benefit for short-term intervention with multiple vitamins and minerals on squamous epithelial cell proliferation of the esophagus in this high-risk population.

Effects of vitamin/mineral supplementation on the prevalence of histological dysplasia and early cancer of the esophagus and stomach: results from the General Population Trial in Linxian, China.

A randomized nutrition intervention trial was conducted among 29,584 adult residents of Linxian, China, to examine the effects of vitamin/mineral supplementation on the occurrence of esophageal/gastric cardia cancer in this high-risk population. A fractional factorial study design allowed evaluations of four different combinations of nutrients: (A) retinol and zinc; (B) riboflavin and niacin; (C) vitamin C and molybdenum; and (D) beta-carotene, vitamin E, and selenium. During the 5.25-year intervention, significant reductions in total mortality, total cancer mortality, and stomach cancer mortality occurred among those receiving beta-carotene, vitamin E, and selenium. At the end of intervention, an endoscopic survey was carried out in a sample of subjects to see if the nutritional supplements had affected the prevalence of clinically silent precancerous lesions and early invasive cancers of the esophagus or stomach. Endoscopy was performed on 391 individuals from two study villages. The prevalences of esophageal and gastric dysplasia and cancer were compared by nutrient factor. Cancer or dysplasia was diagnosed in 15% of the participants. No statistically significant reductions in the prevalence of esophageal or gastric dysplasia or cancer were seen for any of the four vitamin/mineral combinations. The greatest reduction in risk (odds ratio, 0.38; P = 0.09) was seen for the effect of retinol and zinc on the prevalence of gastric cancer. Although no significant protective effects were seen in this endoscopic survey, there was a suggestion that supplementation with retinol and zinc may protect against the development of gastric neoplasia in this high-risk population. Additional studies with larger numbers of endpoints will be needed to further evaluate this possibility.

Effects of vitamin/mineral supplementation on the prevalence of histological dysplasia and early cancer of the esophagus and stomach: results from the Dysplasia Trial in Linxian, China.

Linxian, China has some of the highest rates of esophageal/gastric cardia cancer in the world, and epidemiological evidence suggests that chronically low intake of micronutrients may contribute to these high cancer rates. To examine whether supplementation with multiple vitamins and minerals can affect the occurrence of esophageal/gastric cardia cancer in this population, a two-arm randomized nutrition intervention trial was conducted among 3318 Linxian residents with cytological evidence of esophageal dysplasia. During the 6-year intervention, esophageal/gastric cardia cancer mortality was 8% lower among those receiving the active supplements. After 30 and 72 months of intervention, endoscopic surveys were carried out to see if the nutritional supplements had affected the prevalence of clinically silent precancerous lesions and early invasive cancers of the esophagus and stomach. In the first survey, in 1987, 833 subjects were endoscoped; in the second survey, in 1991, 396 subjects were examined. The histological diagnoses from each survey were compared by treatment group. Cancer or dysplasia was diagnosed in 28% of the subjects endoscoped in 1987 and 24% of those examined in 1991. The odds ratio for subjects in the treatment group (versus those in the placebo group) having esophageal or gastric dysplasia or cancer was 0.84 (95% confidence interval, 0.61-1.15) in 1987 and 0.86 (0.54-1.38) in 1991. Although modest protective effects on worst overall diagnosis were seen in the supplemented group in both surveys, none of the results was statistically significant, and the findings must be considered inconclusive.(ABSTRACT TRUNCATED AT 250 WORDS)

Nutrition intervention trials in Linxian, China: supplementation with specific vitamin/mineral combinations, cancer incidence, and disease-specific mortality in the general population.

BACKGROUND: Epidemiologic evidence indicates that diets high in fruits and vegetables are associated with a reduced risk of several cancers, including cancers of the esophagus and stomach. Vitamins and minerals in these foods may contribute to the reduced cancer risk. The people of Linxian County, China, have one of the world's highest rates of esophageal/gastric cardia cancer and a persistently low intake of several micronutrients. PURPOSE: We sought to determine if dietary supplementation with specific vitamins and minerals can lower mortality from or incidence of cancer as well as mortality from other diseases in Linxian. METHODS: Individuals of ages 40-69 were recruited in 1985 from four Linxian communes. Mortality and cancer incidence during March 1986-May 1991 were ascertained for 29,584 adults who received daily vitamin and mineral supplementation throughout this period. The subjects were randomly assigned to intervention groups according to a one-half replicate of a 2(4) factorial experimental design. This design enabled testing for the effects of four combinations of nutrients: (A) retinol and zinc; (B) riboflavin and niacin; (C) vitamin C and molybdenum; and (D) beta carotene, vitamin E, and selenium. Doses ranged from one to two times U.S. Recommended Daily Allowances. RESULTS: A total of 2127 deaths occurred among trial participants during the intervention period. Cancer was the leading cause of death, with 32% of all deaths due to esophageal or stomach cancer, followed by cerebrovascular disease (25%). Significantly (P = .03) lower total mortality (relative risk [RR] = 0.91; 95% confidence interval [CI] = 0.84-0.99) occurred among those receiving supplementation with beta carotene, vitamin E, and selenium. The reduction was mainly due to lower cancer rates (RR = 0.87; 95% CI = 0.75-1.00), especially stomach cancer (RR = 0.79; 95% CI = 0.64-0.99), with the reduced risk beginning to arise about 1-2 years after the start of supplementation with these vitamins and minerals. No significant effects on mortality rates from all causes were found for supplementation with retinol and zinc, riboflavin and niacin, or vitamin C and molybdenum. Patterns of cancer incidence, on the basis of 1298 cases, generally resembled those for cancer mortality. CONCLUSIONS: The findings indicate that vitamin and mineral supplementation of the diet of Linxian adults, particularly with the combination of beta carotene, vitamin E, and selenium, may effect a reduction in cancer risk in this population. IMPLICATIONS: The results on their own are not definitive, but the promising findings should stimulate further research to clarify the potential benefits of micronutrient supplements.

Nutrition intervention trials in Linxian, China: multiple vitamin/mineral supplementation, cancer incidence, and disease-specific mortality among adults with esophageal dysplasia.

BACKGROUND: A number of vitamins and minerals have been shown to influence carcinogenesis in experimental animals. In humans, epidemiologic evidence suggests that intake of fruits and vegetables may reduce risk of esophageal and other cancers. Vitamins and minerals in these foods may contribute to the reduced cancer risk. The people of Linxian, China, have persistently low intake of multiple nutrients and exhibit one of the world's highest rates of esophageal/gastric cardia cancer, with an exceptionally high risk of esophageal dysplasia. PURPOSE: To determine whether supplementation with multiple vitamins and minerals may reduce esophageal/gastric cardia cancer among persons with esophageal dysplasia, we conducted a 6-year prospective intervention trial in Linxian. METHODS: Mortality and cancer incidence were ascertained from May 1985 through May 1991 for 3318 persons with cytologic evidence of esophageal dysplasia who were randomly assigned to receive, throughout that period, daily supplementation with 14 vitamins and 12 minerals or placebo. Doses were typically two to three times U.S. Recommended Daily Allowances. Compliance was assessed by counting unused pills monthly for all trial participants and by assaying nutrient levels in blood collected from samples of individuals randomly selected without replacement every 3 months throughout the trial. Cancers were identified through routine surveillance and by special cytology and endoscopy screenings after 2 1/2 years and 6 years. RESULTS: A total of 324 deaths occurred during the 6-year intervention period; 167 occurred in the control (placebo) group and 157 occurred in the supplement group. Cancer was the leading cause of death (54% of all deaths); 18% were due to cerebrovascular diseases and 29% to other causes. Cumulative esophageal/gastric cardia death rates were 8% lower (relative risk [RR] = 0.92; 95% confidence interval [CI] = 0.67-1.28) among individuals receiving supplements rather than placebo, a nonsignificant (P > .10) difference. Risk of total mortality was 7% lower (RR = 0.93; 95% CI = 0.75-1.16; P > .10), total cancer 4% lower (RR = 0.96; 95% CI = 0.71-1.29; P > .10), cerebrovascular disease 38% lower (RR = 0.62; 95% CI = 0.37-1.06; P = .08), and other diseases 12% higher (RR = 1.12; 95% CI = 0.74-1.69; P > .10) among the treated group. Cumulative cancer incidence rates were nearly the same in the two groups. CONCLUSIONS: No substantial short-term beneficial effect on incidence or mortality for this type of cancer occurred following daily supplementation with multiple vitamins and minerals among adults with precancerous lesions of the esophagus. IMPLICATIONS: Although no statistically significant short-term benefits were observed, longer follow-up should be more informative about the effectiveness of this 6-year supplementation on cancer and other diseases among individuals with esophageal dysplasia.