Altered counts and mitochondrial mass of peripheral blood leucocytes in patients with chronic hepatitis B virus infection.

Hepatitis B virus (HBV) damages liver cells through abnormal immune responses. Mitochondrial metabolism is necessary for effector functions of white blood cells (WBCs). The aim was to investigate the altered counts and mitochondrial mass (MM) of WBCs by two novel indicators of mitochondrial mass, MM and percentage of low mitochondrial membrane potential, MMPlow%, due to chronic HBV infection. The counts of lymphocytes, neutrophils and monocytes in the HBV infection group were in decline, especially for lymphocyte (p = 0.034) and monocyte counts (p = 0.003). The degraded MM (p = 0.003) and MMPlow% (p = 0.002) of lymphocytes and MM (p = 0.005) of monocytes suggested mitochondrial dysfunction of WBCs. HBV DNA within WBCs showed an extensive effect on mitochondria metabolic potential of lymphocytes, neutrophils and monocytes indicated by MM; hepatitis B e antigen was associated with instant mitochondrial energy supply indicated by MMPlow% of neutrophils; hepatitis B surface antigen, antiviral therapy by nucleos(t)ide analogues and prolonged infection were also vital factors contributing to WBC alterations. Moreover, degraded neutrophils and monocytes could be used to monitor immune responses reflecting chronic liver fibrosis and inflammatory damage. In conclusion, MM combined with cell counts of WBCs could profoundly reflect WBC alterations for monitoring chronic HBV infection. Moreover, HBV DNA within WBCs may be a vital factor in injuring mitochondria metabolic potential.

Leucobacter triazinivorans sp. nov., a s-triazine herbicide prometryn-degrading bacterium isolated from sludge.

A Gram-stain-positive, rod-shaped, non-motile bacterial strain, designated JW-1T, was isolated from activated sludge collected from the outlet of an aeration tank in a prometryn-manufacturing plant, located in Binzhou City, Shandong province, PR China. Phylogenetic analysis, based on 16S rRNA gene sequences, indicated that strain JW-1T belongs to the genus Leucobacter and its closest neighbours are 'Leucobacter kyeonggiensis' F3-P9 (98.95 % similarity), Leucobacter celer subsp. astrifaciens CBX151T (98.62 %), Leucobacter celer subsp. celer NAL101T (98.53 %), Leucobacter chromiiresistens JG31T (97.86 %) and Leucobacter chironomi DSM 19883T (97.37 %). DNA-DNA hybridization values with the above strains were <55 %. The DNA G+C content of strain JW-1T was 72.6 mol%. The major fatty acids of strain JW-1T were iso-C16 : 0, anteiso-C15 : 0, anteiso-C17 : 0 and iso-C15 : 0. The predominant polar lipids were diphosphatidylglycerol, phosphatidylglycerol and glycolipid. The predominant menaquinone was MK-11. The cell wall amino acids were 2,4-diaminobutyric acid, alanine, glutamic acid, glycine and threonine. Based on the molecular and chemotaxonomic data, as well as the physiological and biochemical characteristics, strain JW-1T is considered to represent a novel species of the genus Leucobacter, for which the name Leucobacter triazinivorans is proposed. The type strain is JW-1T (=DSM 105188T=LMG 30083T).

Usefulness of Contrast-Enhanced Ultrasonography for Predicting Esophageal Varices in Patients with Hepatitis B Virus (HBV)-Related Cirrhosis.

BACKGROUND The aim of this study was to investigate the usefulness of contrast-enhanced ultrasonography (CEUS) in predicting of esophageal varices (EV) and assessing high-risk EV in patients with hepatitis B virus (HBV)-related cirrhosis. MATERIAL AND METHODS Patients with HBV-related cirrhosis who had undergone endoscopy were prospectively recruited. Hepatic dynamic CEUS was performed. Regions of interest (ROI) were drawn on the hepatic artery, hepatic vein, portal vein, and liver parenchyma to measure the corresponding features, such as arrival times. Spearman's correlation analysis was used to determine the relations between several dynamic CEUS features and the degree of EV. Receiver operating characteristics (ROC) curves were constructed to investigate the diagnostic performance of CEUS in assessing the presence of EV and high-risk EV. RESULTS Fifty-eight patients (44 men; mean age 51.3 years) were included in this study. Of these, 18 (31.0%), 12 (20.7%), 11 (19.0%), and 17 (29.3%) of patients had grade 0, 1, 2, and 3 EV, respectively. Grade 2 and grade 3 EV were considered high-risk EV. Among the CEUS features, the area under the ROC curves of intrahepatic transit time (HV-HA, i.e., the difference between hepatic vein arrival time and hepatic artery arrival time) both for assessment of the presence of EV and high-risk EV (0.883 and 0.915, respectively) were larger than the other indices. HV-HA was negatively correlated with the grade of EV. An HV-HA of under 8.2 s indicated the presence of EV and under 7 s indicated high-risk EV. CONCLUSIONS Dynamic CEUS imaging is useful in assessing the presence of EV and high-risk EV in patients with HBV-related cirrhosis.

Acoustic Radiation Force Impulse (ARFI) Elastography and Serological Markers in Assessment of Liver Fibrosis and Free Portal Pressure in Patients with Hepatitis B.

BACKGROUND The aim of this study was to investigate the feasibility of using acoustic radiation force impulse (ARFI) elastography, AST-to-platelet ratio index (APRI), and FIB-4 in assessing liver fibrosis and free portal pressure in patients with hepatitis B. MATERIAL AND METHODS We enrolled 126 patients with hepatitis B who underwent liver surgery at the General Surgery Department of the First Affiliated Hospital of Shihezi University Medical School from February 2013 to August 2015. Preoperatively, shear wave velocity (SWV) of the liver was measured with the Siemens S2000 ultrasound system to reflect liver stiffness. Serological markers were collected and fibrosis indices APRI and FIB-4 were calculated. Intraoperatively, liver tissues were harvested and free portal pressure (FPP) was measured. Postoperatively, fibrosis of liver tissues was pathologically staged. RESULTS The results of SWV, APRI, FIB-4, and FPP were all correlated with the degree of liver fibrosis (Spearman correlation coefficients: r=0.777, P<0.001; r=0.526, P<0.001; r=0.471, P<0.001; p<0.000; r=0.675, p<0.000). Receiver operating characteristic curve (ROC) analysis showed that the areas under the curve (AUC) of ARFI, APRI, and FIB-4 in diagnosing liver fibrosis were 0.830, 0.768, and 0.717, respectively, for stage F≥1; 0.861, 0.773, and 0.754, respectively, for stage F≥2; 0.941, 0.793, and 0.779, respectively, for stage F≥3; and 0.945, 0.783, and 0.754, respectively, for stage F=4. SWV, APRI, and FIB-4 were all correlated with FPP (Pearson correlation coefficients: 0.387, P<0.001; 0.446, P<0.001; 0.419, P<0.001). CONCLUSIONS ARFI, APRI, and FIB-4 can assess liver fibrosis in patients with hepatitis B when assessing the portal venous pressure. The difference in diagnostic efficacy between the 3 was not significant.

Diagnostic Accuracy of SuperSonic Shear Imaging for Staging of Liver Fibrosis: A Meta-analysis.

OBJECTIVES: The purpose of this study was to assess the performance of SuperSonic shear imaging (SuperSonic Imagine SA, Aix-en-Provence, France) for diagnosis of liver fibrosis. METHODS: Literature databases were searched to identify relevant studies from inception to February 28, 2015. Sensitivity, specificity, and other information were extracted from the studies. Pooled data were calculated by a bivariate mixed-effects binary regression model. Subgroup and sensitivity analyses were performed. Publication bias was tested by funnel plots. RESULTS: Twelve studies were included in this meta-analysis and reported on 1635 patients. The pooled sensitivity and specificity were 0.78 (95% confidence interval [CI], 0.69-0.85) and 0.95 (95% CI, 0.75-0.99), respectively, for fibrosis stages F≥1, 0.84 (95% CI, 0.81-0.86) and 0.81 (95% CI, 0.74-0.87) for F≥2, 0.89 (95% CI, 0.85-0.93) and 0.84 (95% CI, 0.77-0.89) for F≥3, and 0.88 (95% CI, 0.82-0.91) and 0.86 (95% CI, 0.81-0.90) for F=4. The areas under the summary receiver operating characteristic curves were 0.87 (95% CI, 0.84-0.90) for F≥1, 0.85 (95% CI, 0.81-0.88) for F≥2, 0.93 (95% CI, 0.91-0.95) for F≥3, and 0.93 (95% CI, 0.90-0.95) for F=4. No significant publication bias was found. CONCLUSIONS: SuperSonic shear imaging could be used for staging of liver fibrosis. Especially, it has high diagnostic accuracy for severe fibrosis and cirrhosis.

[HPTLC fingerprint analysis of andrographolides from Andrographis paniculata].

OBJECTIVE: To establish the high-performance thin layer chromatography (HPTLC) fingerprint of andrographolides from Andrographis paniculata, and to valuate the fingerprint similarity of samples from different habitats, markets, used parts and so on. METHODS: Chromatographic conditions were as follows: stationary phase: precoated HPTLC GF254 silica-gel plate (20 cm x 10 cm); developing solvent system: chloroform-toluene-methanol (80:10:15); Relative humidity: 42%; Color development reagent: 5% H2SO4 ethanolic solution, heating at 105 degrees C and observing the fluorescent chromatogram in a UV cabinet at 366 nm. The common patterns of HPTLC fingerprint were obtained through CHROMAP 1.5 solution software. RESULTS: The HPTLC fingerprint of andrographolides was consisted of 9 characteristic peaks (fluorescent bands) including andrographolide, neoandrographolide and dehydroandrographolide which were chemical reference substances. The investigation and analysis of 51 batches of Andrographis paniculata showed that there were remarkable differences among different samples, so was the content of andrographolide and total lactones. CONCLUSION: This method is simple and rapid, which can serve as an effective identification and quality assessment method for Andrographis paniculata.

[Efficacy of albendazole chitosan microspheres against Echinococcus granulosus infection in mice].

OBJECTIVE: To observe the therapeutic effect of albendazole chitosan microspheres (ABZ-CS-MPs) on cystic echinococcosis in mice. METHODS: Two hundred male kunming mice were each infected by intraperitoneal inoculation of about 5 000 viable protoscoleces of Echinococcus granulosus. Another 20 mice were kept as blank control. After 12 weeks post infection, the mice were randomly divided into four groups named as infection control group (n = 20), ABZ-CS-MPs group, albendazole liposome (L-ABZ) group, and albendazole tablet group. The latter three treatment groups were then each divided into three subgroups (n = 20) by given the dose of 37.5, 75.0, and 150.0 mg/kg for three times per week, respectively. After 12 weeks of treatment, all mice were sacrificed. The weight of hydatid cysts was measured and the inhibition rate were calculated. Mouse liver was observed. The histopathological changes of E. granulosus were observed by microscopy. The concentration of albendazole sulfoxide in plasma and liver tissues was determined by high-performance liquid chromatography. RESULTS: Compared with the other treatment groups, the turbidity of contained fluid, the consolidation level and calcification level of hydatid cysts in ABZ-CS-MPs group were higher. The average weight of hydatid cysts in each treatment group was lower than that of infection control group [(3.19 +/- 2.94) g] (P < 0.05). The cyst weight in 37.5, 75.0, and 150.0 mg/kg ABZ-CS-MPs group [(0.28 +/- 0.28), (0.24 +/- 0.22), and (0.20 +/- 0.19) g, respectively] was lower than that of albendazole tablet groups [(0.77 +/- 0.74), (0.55 +/- 0.42), (0.76 +/- 0.35) g] (P < 0.05). Among the same dosage groups, the inhibition rate in ABZ-CS-MPs group (from low to high dosage sub-group: 91.1%, 92.6%, and 93.7%, respectively) was highest. In 75.0 mg/kg ABZ-CS-MPs group, there were 15 mice with class I (degeneration) and II (necrosis) pathological changes of E. granulosus hydatid. The number of mice with class I and II pathological changes in each dosage ABZ-CS-MPs sub-group and L-ABZ sub-group was more than that of albendazole tablet group (P<0.05). Plasma concentration of albendazole sulfoxide in 75.0 and 150.0 mg/kg ABZ-CS-MPs sub-groups [(0.83 +/- 0.39), (0.80 +/- 0.5) microg/ml] were higher than that of L-ABZ sub-groups [(0.34 +/- 0.03), (0.43 +/- 0.15) microg/ml] and albendazole tablet sub-groups [(0.31 +/- 0.02), (0.40 +/- 0.10) microg/ml] (P < 0.05). Compared with 37.5, 75.0, and 150.0 mg/kg albendazole tablet sub-groups [(0.04 +/- 0.02), (0.07 +/- 0.04), (0.04 +/- 0.0) microg/g], the albendazole sulfoxide concentration in liver tissue was higher in ABZ-CS-MPs sub-groups [(0.33 +/- 0.06), (0.45 +/- 0.31), (0.50 +/- 0.30) microg/g] (P < 0.05). In 37.5 mg/kg dosage sub-group, the albendazole sulfoxide concentration in liver tissue in ABZ-CS-MPs group was higher than that of L-ABZ group [(0.14 +/- 0.19) microg/g] (P < 0.05). CONCLUSION: ABZ-CS-MPs can reduce the weight of hydatid cyst and increase the concentration of al-bendazole sulfoxide in plasma and liver tissue of mice.

[Effects of anti-osteopontin antibody on expression of MMP-2 and TGF-beta1 in hepatic alveolar hydatid tissue of gerbil].

OBJECTIVE: To observe the effect of anti-osteopontin antibody on the level of matrix metalloproteinase (MMP-2) and TGF-beta1 in gerbils infected with Echinococcus multilocularis. METHODS: One hundred and eighty gerbils were infected with Echinococcus protoscoleces (approximately 400 for each gerbil) by abdominal opening inoculation in liver. The gerbils were randomly divided into three groups: anti-osteopontin antibody experiment group (group A), rabbit serum injection group (group B), and model group (group C). Gerbils in groups A and B were injected with antiosteopontin antibodies and rabbit serum (0.15 mi/gerbil) via tail vein, respectively. Ten gerbils from each group were sacrificed at 20, 60, 100, 140, 180, and 220 days post-infection, respectively. The liver tissue with hydatid cysts were collected and the expression of MMP-2 and TGF-beta1 was observed by immunohistochemistry staining (SP method). RESULTS: E. multilocularis hydatid tissue spreader over the liver and abdominal cavity. There was no significant difference in the number of MMP-2-positive gerbils among the three groups (P > 0.05). At 100, 140, and 180 days post-infection, the number of TGF-beta1-positive gerbils in group A (3, 2, and 2) was considerably less than that of group B (8, 8, and 9) and group C (8, 9, and 9) (P < 0.05). CONCLUSION: Anti-osteopontin antibody can reduce the expression of TGF-beta1 in hepatic alveolar hydatid tissue of gerbils at certain time, but have no effect on MMP2.

A randomized, controlled trial to investigate cognitive behavioral therapy in prevention and treatment of acute oral mucositis in patients with locoregional advanced nasopharyngeal carcinoma undergoing chemoradiotherapy.

Purpose: Oral mucositis is a common side effect of concurrent chemoradiotherapy (CCRT). This study aimed to determine whether cognitive behavioral therapy (CBT) could help prevent oral mucositis during chemoradiation therapy for locoregional advanced nasopharyngeal carcinoma (LA-NPC). Methods and materials: Between July 15, 2020, and January 31, 2022, a randomized controlled phase II trial was conducted. Eligible patients (N=282, 18-70 years old) with pathologically diagnosed LA-NPC were randomly assigned to receive CBT or treatment as usual (TAU) during CCRT (computer-block randomization, 1:1). The primary endpoints were the incidence and latency of oral mucositis. Results: The incidence of oral mucositis was significantly lower in the CBT group (84.8%; 95% confidence interval [CI], 78.7%-90.9%) than in the TAU group (98.6%; 95% CI, 96.6%-100%; P<0.001). The median latency period was 26 days and 15 days in the CBT and TAU groups, respectively (hazard ratio, 0.16; 95% CI, 0.12-0.22; P<0.001). CBT significantly reduced ≥ grade 3 oral mucositis (71.9% vs. 22.5%, P<0.001), dry mouth (10.8% vs. 3.7%, P=0.021), dysphagia (18% vs. 5.1%, P=0.001), and oral pain (10% vs. 3.6%, P=0.034) compared with TAU. Patients receiving CBT and TAU during CCRT had similar short-term response rates. Conclusions: CBT reduced the occurrence, latency, and severity of oral mucositis in patients with LA-NPC during CCRT.

[Research Progress and Prospect of Herbicide Residue Characteristics in Black Soil Region of China].

Food security is the top priority of a country. As an important granary in China, the northeast black land is a "ballast" to ensure national food security. However, the long-term and high-intensity application of herbicides in black land farmland has led to the accumulation and migration of herbicides in the soil, which affects soil quality, crop yield, and quality and hinders sustainable agricultural development in the black soil. To solve the problem of herbicide residues in black land farmland, it is necessary to control the application of herbicides from the source, as well as to elucidate the current situation, spatial and temporal evolution, and driving factors of herbicide residues, in order to achieve scientific prevention and control and precise policy implementation. The main contents of this study were as follows:1systematically summarize the application status and problems of herbicides in the farmland of black soil in China, suggesting that there are currently problems such as irregular application and insufficient product innovation of herbicides in the farmland of black soil; 2 comprehensively analyze the current status of herbicide residues, identify the deficiencies in recent studies on herbicide residue characteristics, spatial distribution, and pollution diagnosis in the farmland of black soil, and clarify the gaps in the research on the residue characteristics of herbicides in the farmland of black soil; and 3 propose the research prospect and key orientation for the herbicide residue diagnosis and risk management in the farmland of the black soil region of China. The results of this study can provide science and technology support for guaranteeing soil health, food security, and ecosystem security of black land farmland in China.

[Effect of anti-osteopontin antibody on expression of IL-2 and IL-5 in hepatic alveolar hydatid tissue of gerbil].

OBJECTIVE: To observe the effect of anti-osteopontin antibody on the level of IL-2 and IL-5 in the liver of gerbil infected with Echinococcus multilocularis (Em). METHODS: 180 gerbils were infected with echinococcus protoscoleces (approximately 400 for each gerbil) by abdominal opening inoculation in liver. The gerbils were randomly divided into three groups with 60 each: experiment group (group A, with anti-osteopontin antibody interference), control group (group B, with normal rabbit serum injection) and model group (group C, with no interference). Ten gerbils from each group were sacrificed at 20, 60, 100, 140, 180, and 220 days post-infection respectively. The liver tissue with hydatid cysts was collected and the expression of IL-2 and IL-5 was observed after immunohistochemistry staining (SP method). RESULTS: E. multilocularis hydatid tissue spreaded over the liver and abdominal cavity. The positive expression rate of IL-2 in the tissue showed no statistical difference among the three groups (P > 0.05). On the days 140 and 180, however, the positive expression rate of IL-5 in group A was 40% and 20% respectively, considerably lower than that in group B (100% and 90%) and group C (90% and 80% respectively). CONCLUSION: The anti-osteopontin antibody can reduce Th2 type cytokine response in the Em-infected gerbils, which may strengthen the immunity of the host.

[The correlation between osteopontin and metastasis of hepatic Echinococcus multilocularis infection].

OBJECTIVE: To investigate the expression and distribution of osteopontin (OPN) in Echinococcus multilocularis cyst, and explore the role of OPN in the metastasis of hepatic E. multilocularis infection. METHODS: Forty gerbils were infected with 20% E. multilocularis suspension (0.1 ml per gerbil) through abdominal opening injection in liver. Gerbils were sacrificed at 100 days postinfection for observing the growth and metastasis of hepatic echinococcus cyst. The liver, hepatic echinococcus cyst and metastasis tissue were observed on HE stain; the expression of OPN were measured by immunohistochemistry staining (SP method). RESULTS: E. multilocularis were spread over the liver and abdominal cavity. Expression of OPN was found at different degree in echinococcus cysts. The positive expression rate of OPN in echinococcus cysts was 70% (28/40). OPN was mainly distributed in the germinal layer, inflammatory cells and some liver cells. 60% (24/40) occurred thoracic lymph node metastases. The OPN expression rate in hepatic echinococcus cysts with thoracic lymph node metastases (83%, 20/24) was significantly higher than that of hepatic echinococcus cysts without thoracic lymph node metastases (50%, 8/16) (P < 0.05). The positive expression of OPN in lymph node metastases (92%, 22/24) was higher than that of hepatic echinococcus cyst (70%, 28/40) (P < 0.05). CONCLUSION: Osteopontin mainly distributes in the germinal layer of hepatic echinococcus cyst and inflammatory cells, which might be involved in metastasis of hepatic E. multilocularis infection.

[Inhibition of invasive growth and metastasis of hepatic alveolar echinococcosis by anti-osteopontin antibody].

OBJECTIVE: To observe the inhibitive effect on invasive growth and metastasis of Echinococcus multilocularis by exogenous anti-osteopontin (OPN) antibody. METHODS: 180 gerbils were infected with 20% E. multilocularis suspension (approximately 400 protoscoleces in 0.1 ml per gerbil) through abdominal opening injection in liver, and then divided into model group, experiment group and control group. Experiment group and control group each with 60 gerbils were injected via the tail vein with 0.15 ml of anti-OPN antibody (1:32) and rabbit serum, respectively. All gerbils in the two groups received injections, with 2-day interval for the first seven injections, and then at 7-day interval for the remaining injections. Model group were without any treatment. The three groups were subdivided into six groups each with 10 gerbils. The gerbils from each group were sacrificed on day 1, 20, 40, 60, 80, and 100 after infection, respectively. Hepatic echinococcus cyst and metastasis tissue were observed. The expression of OPN was measured by immunohistochemistry staining (SP method). Serum samples were collected at 100 d post-infection, and the content of OPN in sera was measured by ELISA. RESULTS: There were no significant difference in cyst weight and metastatic rate of thoracic lymph node among the three groups at 1, 20, 40, 60, and 80d post-infection (P > 0.05), while at 100 d postinfection, cyst weight and metastatic rate of thoracic lymph node in experiment group [(7.28 +/- 0.38) g, 20%] were lower than that of control group [(9.70 +/- 0.61) g, 70%] and model group [(932 +/- 0.73) g, 70%] (P < ). Expression of OPN was found at different levels in echinococcus cysts. OPN was located in the cytoplasm, and mainly distributed in the germinal layer. The OPN positive expression levels were not significantly different between experiment group and other groups on day 1, 20, 40, 60, and 80 afer infection ( >0 . 05). At 100d post-infection, OPN positive expression rate and serum OPN content in experimental group [20% and (30.90 +/- 2.25) ng/.l micro respectively] was lower than that of control group [80% and (41.03.2 +/- 76) nWng/micro and model group [80% and (42.39 +/- 2.85) nWng/micro (PdL < 0.). CONCLUSION: Anti-osteopontin antibody can reduce OPN concentration in hepatic echinococcus cyst and serum, and inhibit the invasive growth and metastasis of E. multilocularis.

Evaluation of the bitter components of bamboo shoots using a metabolomics approach.

Bamboo shoots, most of which are bitter in taste, are a traditional vegetable eaten in Asia. However, our understanding of the components responsible for this bitterness is limited. In this study, we used metabolomic and phytochemical analyses to scientifically study bamboo shoot bitterness. Based on oral evaluation, 16 common bamboo shoots were categorized into four bitterness groups. The most bitter species was Pleioblastus amarus. Thus, we isolated and performed a detailed spectroscopic analysis of 14 main compounds from this species. The correlation between the concentration of these components and bitterness in four representative bamboo shoot species was then analyzed by UPLC-MRM-MS and PLS-DA. It appears that bamboo shoot bitterness is largely due to l-phenylalanine, uridine, l-omithine, l-tryptophan, and adenine, with l-phenylalanine being the greatest contributor. In addition to identifying the primary component involved in bamboo shoot bitterness, this study also outlines a novel method for evaluating the bitterness of natural foods.

[Multi-center phase II clinical trial of humanized anti-epidermal factor receptor monoclonal antibody h-R3 combined with radiotherapy for locoregionally advanced nasopharyngeal carcinoma].

OBJECTIVE: To evaluate the efficacy and safty of the humanized anti-epidermal factor receptor monoclonal antibody h-R3 in combination with radiotherapy for locoregionally advanced nasopharyngeal carcinoma. METHODS: Totally, 137 patients from 7 medical center around China were randomly divided into combined therapy group or control group. There was no difference in Karnofsky performance score between two groups. All patients in both groups received radical conventionally fractionated radiotherapy to the total dose of D(T) 70-76 Gy. For the combined therapy group, h-R3 was added at a dose of 100 mg i.v. weekly for 8 weeks started at the beginning of radiotherapy. RESULTS: Of the 137 eligilbe patients, 70 were in the combined therapy group treated by h-R3 plus radiotherapy and 67 in the control group by radiotherapy alone. The intent-to-treat (ITT) population consisted of 130 patients, while the per-protocol (PP) population was composed of 126 patients. The efficacy was assessed respectively at three point of time: the end of treatment, the 5th- and 17th-week after treatment. The complete response (CR) of the combined therapy group was significantly higher than that of the control group in both ITT and PP (ITT: 65.63%, 87.50%, 90.63% versus 27.27%, 42.42%, 51.52%; PP: 67.21%, 90.16%, 93.44% versus 27.69%, 43.08%, 52.31%; P < 0.05, respectively). The most common h-R3-related adverse reactions were fever (4.3%), hypotension (2.9%), nausea (1.4%), dizziness (2.9%) and rash (1.4%), which could be reversible if treated properly. Radiotherapy combined with 100 mg h-R3 i. v. weekly was tolerable and did not aggravate the side effects of radiation. The quality of life in the combined therapy group was comparable to that in the control group. CONCLUSION: This phase 1 multicenter clinical trial shows that h-R3 in combination with radiotherapy is effective and well-tolerated for the treatment of locoregionally advanced nasopharyngeal carcinoma.

In-vitro bioaccessibility of five pyrethroids after human ingestion and the corresponding gastrointestinal digestion parameters: A contribution for human exposure assessments.

Bioaccessibility is a crucial parameter in assessing the absorption of contaminants during the human digestive process, but few studies have involved the differences in the bioaccessibilities of pesticides. To investigate the mode of using the in vitro bioaccessibility to refine estimates of dietary exposure to pesticide residues, this study measured the bioaccessibilities of five pyrethroids in apples, and then, it modelled physicochemical predictors (gastrointestinal pH, digestive times, and the solid-liquid (S/L) ratio) of the bioaccessibilities of pyrethroids. Apple samples of gastric and intestinal phase digestive juices were obtained from an in vitro simulated digestion model. Our survey of in vitro digestion models found that the bioaccessibilities ranged from 4.42% to 31.22% and 10.58%-35.63% in the gastric and intestinal phases, respectively. A sharp trend similar to a normal distribution was observed between the bioaccessibilities and pH values. The bioaccessibility reached its highest value at a pH of 1.91 in the simulated gastric juice and did not significantly change with an increase of the digestive time. A significant negative correlation occurred between the bioaccessibility and S/L ratio, which followed a logarithmic equation. The correlation coefficients (R2) ranged from 0.9259 to 0.9831 and 0.9077 to 0.9960 in the simulated gastric and intestinal juice, respectively, suggested that both the pH value and S/L ratio were the main factors affecting the bioaccessibility. Furthermore, a combination of the acceptable daily intake (ADI) and bioaccessibility for human exposure assessments indicated the implication that traditional risk assessment using ADI may seriously overestimate the actual risk.

Factors Affecting Transfer of Pyrethroid Residues from Herbal Teas to Infusion and Influence of Physicochemical Properties of Pesticides.

The transfer of pesticide residues from herbal teas to their infusion is a subject of particular interest. In this study, a multi-residue analytical method for the determination of pyrethroids (fenpropathrin, beta-cypermethrin, lambda-cyhalothrin, and fenvalerate) in honeysuckle, chrysanthemum, wolfberry, and licorice and their infusion samples was validated. The transfer of pyrethroid residues from tea to infusion was investigated at different water temperatures, tea/water ratios, and infusion intervals/times. The results show that low amounts (0-6.70%) of pyrethroids were transferred under the different tea brewing conditions examined, indicating that the infusion process reduced the pyrethroid content in the extracted liquid by over 90%. Similar results were obtained for the different tea varieties, and pesticides with high water solubility and low octanol-water partition coefficients (log Kow) exhibited high transfer rates. Moreover, the estimated values of the exposure risk to the pyrethroids were in the range of 0.0022-0.33, indicating that the daily intake of the four pyrethroid residues from herbal tea can be regarded as safe. The present results can support the identification of suitable tea brewing conditions for significantly reducing the pesticide residue levels in the infusion.

Factors Affecting the Bioaccessibility and Intestinal Transport of Difenoconazole, Hexaconazole, and Spirodiclofen in Human Caco-2 Cells Following in Vitro Digestion.

This study examined how gastrointestinal conditions affect pesticide bioaccessibility and intestinal transepithelial transport of pesticides (difenoconazole, hexaconazole, and spirodiclofen) in humans. We used an in vitro model combining human gastric and intestinal digestion, followed with Caco-2 cell model for human intestinal absorption. Bioaccessibility of three tested pesticides ranged from 25.2 to 76.3% and 10.6 to 79.63% in the gastric and intestinal phases, respectively. A marked trend similar to the normal distribution was observed between bioaccessibility and pH, with highest values observed at pH 2.12 in gastric juice. No significant differences were observed with increasing digestion time; however, a significant negative correlation was observed with the solid-liquid (S/L) ratio, following a logarithmic equation. R2 ranged from 0.9198 to 0.9848 and 0.9526 to 0.9951 in the simulated gastric and intestinal juices, respectively, suggesting that the S/L ratio is also a major factor affecting bioaccessibility. Moreover, significant dose- and time-response effects were subsequently observed for intestinal membrane permeability of difenoconazole, but not for hexaconazole or spirodiclofen. This is the first study to demonstrate the uptake of pesticides by human intestinal cells, aiding quantification of the likely effects on human health and highlighting the importance of considering bioaccessibility in studies of dietary exposure to pesticide residues.

[Analysis on the anatomic features of 47 cases of hepatic hydatidosis complicated with biliary fistula].

OBJECTIVE: To propose a criterion and its significance of clinical classification of hepatic hydatidosis complicated with biliary fistula. METHODS: 47 hepatic hydatidosis with biliary fistula cases who were given a subadventitial pericystectomy were observed from 2000 to 2005 in a retrospective study. The methods included observation of the different anatomic features of hepatic hydatidosis complicated with biliary fistula during the surgical operation and evaluation of the curative effect. RESULTS: All the 47 patients recuperated successfully and had no complication. Based on the anatomic features of hepatic hydatidosis complicated with biliary fistula, a criterion on clinical classification was proposed as three types: tangential, transfixional and terminal types. CONCLUSIONS: Hepatic hydatidosis complicated with biliary fistula can be classified as three types according to its anatomic features.

[Expression of osteopontin in the pericystic layer of hepatic hydatid cyst].

OBJECTIVE: To investigate the expression and distribution of osteopontin (OPN) in the pericystic layer of Echinococcus granulosus cyst. METHODS: 60 surgically excised cysts were studied with HE and immunohistochemistry staining by using antibodies specific for OPN. Immunofluorescence double labeling technique and Media Cybernetics Image (Pro Plus 5.1 software) were used to appraise the relationship between the OPN and macrophages (CD68). RESULTS: Expression of OPN was found at various degree in hydatid cysts, 75% (45/60) was distributed in the intra-layer at the parasite side, 8.3% (5/60) distributed in the extra-layer near the side of liver parenchyma ("exocyst"-layer vs "adventitia"-layer, P<0.01). Macrophages were identified between the intra-layer and extra-layer, and OPN was observed in most of the macrophages. Meanwhile, OPN was concurrently found with the deposit of calcium in a similar distribution in the hydatid cyst. CONCLUSION: Osteopontin mainly distributes in the intra-pericystic layer of hepatic hydatid cyst.