Genetic polymorphism in MDR1 C3435T is a determinant of methotrexate cerebrospinal fluid concentrations in Chinese children with acute lymphoblastic leukemia
.

AIM: This study aimed to investigate the influence of single-nucleotide polymorphism in exon 26 (C3435T) of multidrug resistance 1 (MDR1) transporter gene on the concentration of methotrexate (MTX) in Chinese childhood patients with acute lymphoblastic leukemia (ALL) receiving intravenous (IV) and intrathecal (IT) high-dose methotrexate (HDMTX) chemotherapy. MATERIALS AND METHODS: MDR1 C3435T polymorphism was investigated in 60 patients with Chinese childhood ALL. The study also compared the MDR1; polymorphism between the patients with Chinese childhood ALL and the published data on Americans, Mexicans, Caucasians, and Thais. The C3435T polymorphism was identified using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and direct sequence analysis. Cerebrospinal fluid (CSF) and plasma concentrations of MTX were measured using high-performance liquid chromatography (HPLC). MTX concentrations were compared according to MDR1 C3435T genotypes. RESULTS: The frequencies of MDR1 C3435T genotype in male and female patients with Chinese childhood ALL were significantly different (p = 0.001). For the frequencies of MDR1 C3435T genotype in Hui and Han patients with Chinese childhood ALL there was no difference (p = 0.188). The distribution of allele frequencies in patients with Chinese childhood ALL was similar to the published data on Americans, Mexican, Caucasians, and Thais (p > 0.05). The CSF concentrations of MTX were found to be significantly different between the C allele (CC + CT) carriers and TT homozygous group (p = 0.04). The plasma concentrations of MTX had no significant difference between the C allele (CC + CT) carriers and TT homozygous group (p > 0.1). CONCLUSION: This study showed that the polymorphism of MDR1 C3435T influenced the CSF concentration of MTX in patients with Chinese childhood ALL receiving IV and IT HDMTX treatment.

Efficacy of Vertebroplasty in Short-Segment Pedicle Screw Fixation of Thoracolumbar Fractures: A Meta-Analysis.

BACKGROUND Short-segment pedicle screw instrumentation provides superior outcomes in treating thoracolumbar fractures. Nevertheless, the effect of intermediate screws on the outcome of short-segment instrumentation at the fracture level has not been specifically analyzed. We performed an update meta-analysis of the effect of additional vertebroplasty on the outcome of short-segment instrumentation to determine the role of screws for patients with fractured vertebra. MATERIAL AND METHODS A systematic literature search was conducted, updated to January 2019, in terms of the efficacy of additional vertebroplasty on the outcome of short-segment instrumentation at the fracture level. After rigorous quality review, we extracted the data from qualified clinical studies. We further analyzed odds ratios (ORs) of the endpoints of interest based on the included trials. RESULTS Compared with the control group, short-segmental fixation combined with intermediate screws restored Cobb angle (P<0.001) and reduced anterior vertebral height compression (P=0.001). However, our results did not reveal statistically significant differences in operative time (P=0.28) or estimated blood loss (P=0.23). A statistically significant difference was observed in mean hospital stay (P=0.02). CONCLUSIONS Reinforcement with fracture-level screw combination can help stabilize the fractures and restore the anatomy. Nevertheless, additional trials and studies with longer follow-ups and on larger populations are warranted to confirm the current findings.

Effects of genetic polymorphisms of CYP2C19*2/*3 and MDR1 C3435T on the pharmacokinetics of lansoprazole in healthy Chinese subjects.

OBJECTIVES: To evaluate the influence of CYP2C19*2/*3 and MDR1 C3435T polymorphisms on the pharmacokinetics of lansoprazole (LPZ) in healthy Chinese subjects. METHODS: All 24 subjects were from a study of bioequivalence. Plasma concentrations of LPZ were determined by liquid chromatography/mass spectrometry. Cytochrome P450 (CYP) 2C19*2/*3 and multidrug resistance transporter gene 1 (MDR1) C3435T of the subjects were genotyped by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: Significant differences were found in the area under the concentration-time curve from predose to T (AUC(0-T)), area under the concentration-time curve from predose to infinity (AUC(0-∞), t(1/2)), and apparent oral clearance (CL/F) of LPZ between CYP2C19 extensive metabolizers and intermediate metabolizers (p < 0.05). The AUC(0-T), AUC(0-∞), maximum plasma concentration, and CL/F of LPZ were significantly different between subjects with the MDR1 C3435T C/C, C/T, and T/T polymorphisms (p < 0.05). CONCLUSION: CYP2C19*2/*3 and MDR1 C3435T polymorphisms are important determinants of LPZ pharmacokinetics.

Population structure of the greenhouse whitefly, Trialeurodes vaporariorum (Westwood), an invasive species from the Americas, 60 years after invading China.

Though the greenhouse whitefly, Trialeurodes vaporariorum (Westwood) (Hemiptera: Aleyrodidae) was introduced into China more than 60 years ago, the genetic diversity and structure of this exotic insect pest and virus vector have not been studied. To investigate the population genetic characteristics of this invasive species and to identify potential invasion routes, the genetic diversity and population structure of 17 collections of T. vaporariorum from nine provinces in China were analyzed using seven microsatellite loci. The results of the analyses indicated that the genetic diversity for the populations examined from the four provinces: Jilin, Ningxia, Guizhou and Qinghai, was lower than the genetic diversity of populations from the five provinces: Yunnan, Shandong, Shanxi, Liaoning, and Gansu. The T. vaporariorum populations analyzed in this study grouped as two distinct genetic clusters based on the analysis using STRUCTURE, whereas, 8 clusters were identified based on the BAPS analysis. Of the 136 genetic distance (Fst) values, 128 (94%) were associated with a significant exact test. However, there was no significant relationship between Fst and geographical distance. These results demonstrate that populations of T. vaporariorum in China exhibit significant genetic differentiation, indicating the likelihood that multiple introductions of T. vaporariorum into China have occurred. Also, the populations collected from the provinces of Jilin, Ningxia, Guizhou and Qinghai appear to represent secondary introductions originating from other Chinese provinces.

[Pharmacokinetics of SN-38 in rats and tissue distribution of 7-ethyl-10-hydroxycamptothecin in mice after intravenous injection of irinotecan hydrochloride nanoparticles].

The paper reported an investigation of the pharmacokinetics of SN-38 (7-ethyl-10-hydroxy-camptothecin) in rats and the tissue distribution in mice after injection of irinotecan hydrochloride nanoparticles (CPT-11) via tail veins. An LC-MS/MS method was established to determine the concentrations of SN-38 in whole blood of rats and in different tissues of mice. The pharmacokinetics and tissue distribution of SN-38 were compared after the intravenous injection of CPT-11 NPs and CPT-11 solution. Compared with irinotecan solution, the elimination half-life of SN-38 was prolonged from 2.17 h to 2.67 h after the intravenous injection of CPT-11 NPs, but its AUC had little change. After the injection of CPT-11 NPs in mice, over time, the concentrations of CPT-11-metabolized SN-38 in CPT-11 NPs were significantly higher in the whole blood, colon and lungs than those in CPT-11 solution, followed by in the spleen and liver, but those in the heart and brain had no change. However, the amount of SN-38 in the kidneys was reduced with time. CPT-11 NPs could prolong SN-38's (one of its metabolites) blood circulation time in rats and significantly increased the concentration of CPT-11-metabolized SN-38 in the whole blood, colon and lungs of mice. CPT-11 NPs made SN-38 efficiently target-bind to the colon and lungs of mice.

Development of polymorphic microsatellite markers for distylous-homostylous Primula secundiflora (Primulaceae) using HiSeq sequencing.

Primula secundiflora is an insect-pollinated, perennial herb belonging to the section Proliferae (Primulaceae) that exhibits considerable variation in its mating system, with predominantly outcrossing populations comprising long-styled and short-styled floral morphs and selfing populations comprising only homostyles. To facilitate future investigations of the population genetics and mating patterns of this species, we developed 25 microsatellite markers from P. secundiflora using next-generation sequencing and measured polymorphism and genetic diversity in a sample of 30 individuals from three natural populations. The markers displayed high polymorphism, with the number of observed alleles per locus ranging from three to 16 (mean = 8.36). The observed and expected heterozygosities ranged from 0.100 to 1.000 and 0.145 to 0.843, respectively. Twenty-one of the loci were also successfully amplified in P. denticulata. These microsatellite markers should provide powerful tools for investigating patterns of population genetic diversity and the evolutionary relationships between distyly and homostyly in P. secundiflora.

Prognostic impact of interstitial lung abnormalities in lung cancer: a systematic review and meta-analysis.

Background: Newly identified as a radiological concept, interstitial lung abnormalities (ILA) is emerging as a prognostic factor for lung cancer. Yet, debates persist regarding the prognostic significance of ILA in lung cancer. Our inaugural meta-analysis aimed to investigate the correlation between ILA and lung cancer outcomes, offering additional insights for clinicians in predicting patient prognosis. Methods: Articles meeting the criteria were found through PubMed, the Cochrane Library, EMBASE, and Web of Science by February 29, 2024. The outcomes evaluated were the survival rates such as overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), and cancer-specific survival (CSS). Results: A total of 12 articles with 4416 patients were included in this meta-analysis. The pooled results showed that lung cancer patients with interstitial lung abnormalities had an inferior OS (n=11; HR=2.22; 95% CI=1.68-2.95; P<0.001; I2 = 72.0%; Ph<0.001), PFS (n=3; HR=1.59; 95% CI=1.08-2.32; P=0.017; I2 = 0%; Ph=0.772), and CSS (n=2; HR=4.00; 95% CI=1.94-8.25; P<0.001; I2 = 0%; Ph=0.594) than those without, however, the ILA was not significantly associated with the DFS (n=2; HR=2.07; 95% CI=0.94-7.02; P=0.066; I2 = 90.4%; Ph=0.001). Moreover, lung cancer patients with ILA were significantly correlated with male (OR=2.43; 95% CI=1.48-3.98; P<0.001), smoking history (OR=2.11; 95% CI=1.37-3.25; P<0.001), advanced age (OR=2.50; 95% CI=1.56-4.03; P<0.001), squamous carcinoma (OR=0.42; 95% CI=0.24-0.71; P=0.01), and EGFR mutation (OR=0.50; 95% CI=0.32-0.78; P=0.002). The correlation between ILA and race, stage, ALK, however, was not significant. Conclusion: ILA was a availability factors of prognosis in patients with lung cancers. These findings highlight the importance of early pulmonary fibrosis, namely ILA for prognosis in patients with lung cancer, and provide a partial rationale for future clinical work.

Dazomet fumigation modification of the soil microorganism community and promotion of Panax notoginseng growth.

Introduction: Panax notoginseng, a medicinal herb in China, is attacked by several pathogens during its cultivation. Dazomet (DZ) is a soil fumigant that is effective in controlling soil-borne pathogens, but its long-term effects on P. notoginseng growth and soil properties are unknown. Methods: We conducted field experiments over two consecutive years to assess the impact of three concentrations of DZ fumigation (35 kg/666.7 m2, 40 kg/666.7 m2, and 45 kg/666.7 m2) on soil physicochemical properties, microbial diversity, and P. notoginseng growth. Correlation analyses were performed between microbial community changes and soil properties, and functional predictions for soil microorganisms were conducted. Results: DZ fumigation increased total nitrogen, total phosphorus, total potassium, available phosphorus, available potassium, and ammonia nitrogen levels in the soil. DZ fumigation promoted the nutrient accumulation and improvement of agronomic traits of P. notoginseng, resulted in a 2.83-3.81X yield increase, with the highest total saponin content increasing by 24.06%. And the 40 kg/666.7 m2 treatment had the most favorable impact on P. notoginseng growth and saponin accumulation. After DZ fumigation, there was a decrease in the relative abundance of pathogenic fungi such as Fusarium, Plectosphaerella, and Ilyonectria, while beneficial bacteria such as Ramlibacter, Burkholderia, and Rhodanobacteria increased. The effects of fumigation on soil microorganisms and soil physicochemical properties persisted for 18 months post-fumigation. DZ fumigation enhanced the relative abundance of bacteria involved in the biosynthesis of secondary metabolites and arbuscular mycorrhizal fungi, reduced the relative abundance of plant-animal pathogenic fungi, reduced the occurrence of soil-borne diseases. Conclusion: In conclusion, DZ fumigation enhanced soil physicochemical properties, increased the proportion of beneficial bacteria in the soil, and rebalanced soil microorganism populations, consequently improving the growth environment of P. notoginseng and enhancing its growth, yield, and quality. This study offers a theoretical foundation for DZ fumigation as a potential solution to the continuous cropping issue in perennial medicinal plants such as P. notoginseng.

[Pharmacokinetic interaction of pioglitazone hydrochloride and atorvastatin calcium in Beagle dogs].

The object of this study is to investigate the pharmacokinetic interaction of pioglitazone hydrochloride and atorvastatin calcium in healthy adult Beagle dogs following single and multiple oral dose administration. A randomized, cross-over study was conducted with nine healthy adult Beagle dogs assigned to three groups. Each group was arranged to take atorvastatin calcium (A), pioglitazone hydrochloride (B), atorvastatin calcium and pioglitazone hydrochloride (C) orally in the first period, to take B, C, A in the second period, and to take C, A, B in the third period for 6 days respectively. The blood samples were collected at the first and the sixth day after the administration, plasma drug concentrations were determined by LC-MS/MS, a one-week wash-out period was needed between each period. The pharmacokinetic parameters of drug combination group and the drug alone group were calculated by statistical moment method, calculation of C(max) and AUC(0-t) was done by using 90% confidence interval method of the bioequivalence and bioavailability degree module DAS 3.2.1 software statistics. Compared with the separate administration, the main pharmacokinetic parameters (C(max) and AUC(0-t)) of joint use of pioglitazone hydrochloride and atorvastatin calcium within 90% confidence intervals for bioequivalence statistics were unqualified, the mean t(max) with standard deviation used paired Wilcoxon test resulted P > 0.05. There was no significant difference within t1/2, CL(int), MRT, V/F. Pioglitazone hydrochloride and atorvastatin calcium had pharmacokinetic interaction in healthy adult Beagle dogs.

[Pharmacokinetics and tissue distribution of irinotecan hydrochloride nanoparticles].

To investigate the pharmacokinetics of irinotecan hydrochloride (CPT-11) in rats and the tissue distribution of CPT-11 in mice after injection of irinotecan hydrochloride nanoparticles (CPT-11 NPs) via tail veins, separately, a LC-MS/MS method was established to determine the concentration of CPT-11 in whole blood of rats and in different tissues of mice. The pharmacokinetics and tissue distribution of CPT-11 were compared after the intravenous injection of CPT-11 NPs and CPT-11 solution. Compared with CPT-11 solution, the elimination half-life of CPT-11 was prolonged from 2.28 h to 3.95 h after the intravenous injection of CPT-11 NPs, and its AUC was 1.47 times than that of CPT-11 solution. After the injection of CPT-11 NPs in mice, the concentrations of CPT-11 loaded in CPT-11 NPs were significantly higher in the whole blood, colon and lungs than those in CPT-11 solution, but lower in the spleen, liver, kidney and heart, but the least in brain. CPT-11 NPs could improve CPT-11 's AUC, and help CPT-11 to reach long circulation activity.

[The modification of apoptosis correlated gene, protein and protein activity in rat hippocampus induced by benzo[a] pyrene sub-chronic exposure].

OBJECTIVE: To observe the effects of subchronic exposure to benzo[a]pyrene (B[a]P) on the mRNA and protein expression levels of apoptosis-related genes (bax, bcl-2, caspase-3, caspase-6, and caspase-9) and the activities of Caspase-3, Caspase-6, and Caspase-9 in the hippocampal neurons of rats and to investigate the neurotoxic mechanism by which B[a]P induces the apoptosis of neurons. METHODS: Fifty-two healthy SD rat were randomly divided into five groups according to preliminary neurobehavioral test results: blank control group, solvent control group, and 1.0, 2.5, and 6.25 mg/kg B[a]P exposure groups; the rats in exposure groups were intraperitoneally injected with B[a]P every other day for 90 days. The Morris water maze was used to test the learning and memory ability of rats; flow cytometry was used to measure the apoptosis ratio of hippocampal neurons; real-time quantitative PCR and Western blot were used to measure the mRNA and protein expression levels of apoptosis-related genes; spectrophotometry was used to measure the activities of their en-coded proteins. RESULTS: Compared with the blank control group, solvent control group, and 1.0 mg/kg B[a]P exposure group, the 2.5 and 6.25 mg/kg B[a]P exposure groups hada significantly longer mean escape latency period (P < 0.05) and a significantly increased number of times of platform crossing (P < 0.05), and the 6.25 mg/kg B[a]P exposure group had significantly lower length and percentage of time spent in the platform quadrant (P < 0.05). The early apoptosis ratio rose as the dose of B[a]P increased (P trend < 0.05); the early apoptosis ratios of 1.0, 2.5, and 6.25 mg/kg B[a]P exposure groups were significantly higher than those of blank control group and solvent control group (P < 0.05). Compared with the blank control group, solvent control group, and 1.0 and 2.5 mg/kg B[a]P exposure groups, the 6.25 mg/kg B[a]P exposure group had significantly increased Bax expression (P < 0.05) and significantly decreased Bcl-2 expression and Bcl-2/Bax ratio (P < 0.05). The 2.5 and 6.25 mg/kg B[a]P exposure groups had significantly higher expression levels of Caspase-3 and Caspase-6 than the blank control group, solvent control group, and 1.0 mg/kg B[a]P exposure group (P < 0.05). The activities of Caspase-3, Caspase-6, and Caspase-9 were significantly higher in the 2.5 and 6.25 mg/kg B[a]P exposure groups than in the blank control group and solvent control group (P < 0.05). There was a positive correlation between the activities of Caspase-3, Caspase-6, and Caspase-9 and early apoptosis ratio of hippocampal neurons in rats (r = 0.793, P = 0.019; r = 0.886, P = 0.006; r = 0.773, P = 0.025). There were no significant differences in the mRNA expression of Bax, Bcl-2, Caspase-3, Caspase-6, and Caspase-9 among these groups (P > 0.05). CONCLUSION: Subchronic exposure to B[a]P can induce apoptosis of hippocampal neurons; its mechanism may be related to the fact that B[a]P can induce upregulated expression of Bax, inhibit expression of Bcl-2, lead to decrease in Bcl-2/Bax ratio, induce upregulated expression of Caspase-3 and Caspase-6, and cause increase in the activities of Caspase-3, Caspase-6, and Caspase-9.

The role of symbiotic fungi in the life cycle of Gastrodia elata Blume (Orchidaceae): a comprehensive review.

Gastrodia elata Blume, a fully mycoheterotrophic perennial plant of the family Orchidaceae, is a traditional Chinese herb with medicinal and edible value. Interestingly, G. elata requires symbiotic relationships with Mycena and Armillaria strains for seed germination and plant growth, respectively. However, there is no comprehensive summary of the symbiotic mechanism between fungi and G. elata. Here, the colonization and digestion of hyphae, the bidirectional exchange of nutrients, the adaptation of fungi and G. elata to symbiosis, and the role of microorganisms and secondary metabolites in the symbiotic relationship between fungi and G. elata are summarized. We comprehensively and deeply analyzed the mechanism of symbiosis between G. elata and fungi from three perspectives: morphology, nutrition, and molecules. The aim of this review was to enrich the understanding of the mutualistic symbiosis mechanisms between plants and fungi and lay a theoretical foundation for the ecological cultivation of G. elata.

Genomic and in-vitro characteristics of a novel strain Lacticaseibacillus chiayiensis AACE3 isolated from fermented blueberry.

Numerous different species of LAB are used in different fields due to their unique characteristics. However, Lacticaseibacillus chiayiensis, a newly established species in 2018, has limited microorganism resources, and lacks comprehensive evaluations of its properties. In this study, L. chiayiensis AACE3, isolated from fermented blueberry, was evaluated by genomic analysis and in vitro assays of the properties. The genome identified genes associated with biofilm formation (luxS, ccpA, brpA), resistance to oxidative stress (tpx, trxA, trxB, hslO), tolerance to acidic conditions (dltA, dltC), resistance to unfavorable osmotic pressure (opuBB, gbuA, gbuB, gbuC), and adhesion (luxS, dltA, dltC). The AACE3 showed 112 unique genes, relative to the other three L. chiayiensis strains. Among them, the presence of genes such as clpP, pepO, and feoA suggests a possible advantage of AACE3 over other L. chiayiensis in terms of environmental adaptation. In vitro evaluation of the properties revealed that AACE3 had robust antibacterial activity against eight common pathogens: Streptococcus agalactiae, Staphylococcus aureus, Escherichia coli, Salmonella enteritidis, Salmonella choleraesuis, Shigella flexneri, Pseudomonas aeruginosa, and Klebsiella pneumoniae. In addition, AACE3 showed more than 80% survival rate in all tests simulating gastrointestinal fluid, and it exhibited high antioxidant capacity. Interestingly, the cell culture supernatant was superior to intact organisms and ultrasonically crushed bacterial extracts in all tests of antioxidant capacity. These results suggested that the antioxidant capacity may originate from certain metabolites and extracellular enzymes produced by AACE3. Moreover, AACE3 was a moderate biofilm producer due to the self-agglomeration effect. Taken together, L. chiayiensis AACE3 appears to be a candidate strain for combating the growing incidence of pathogen infections and antioxidant production.

Nano-Calcium Carbonate Affect the Respiratory and Function Through Inducing Oxidative Stress: A Cross-sectional Study Among Occupational Exposure of Workers and a Further Research for Underlying Mechanisms.

OBJECTIVE: The aim of the study is to investigate whether nano-calcium carbonate (nano-CaCO 3 ) occupational exposure could induce adverse health effects in workers. METHODS: A cross-sectional study was conducted in a nano-CaCO 3 manufacturing plant in China. Then, we have studied the dynamic distribution of nano-CaCO 3 in nude mice and examined the oxidative damage biomarkers of subchronic administrated nano-CaCO 3 on Sprague-Dawley rats. RESULTS: The forced vital capacity (%) and the ratio of FEV1 to FVC is the rate of one second of workers were significantly decreased than unexposed individuals. Dynamic imaging in mice of fluorescence labeled nano-CaCO 3 showed relatively high uptake and slow washout in lung. Similar to population data, the decline in serum glutathione level and elevation in serum MDA were observed in nano-CaCO 3 -infected Sprague-Dawley rats. CONCLUSIONS: We found that nano-CaCO 3 exposure may result in the poor pulmonary function in workers and lead to the changes of oxidative stress indexes.

Efficacy and Safety of Gegen Qinlian Decoction for Pediatric Diarrhea: A Systematic Review and Meta-Analysis.

Objective: To evaluate the clinical efficacy and safety of Gegen Qinlian decoction in the treatment of pediatric diarrhea. Methods: A search for relevant RCTs was performed from which a systematic review and meta-analysis was conducted. This meta-analysis was registered at INPLASY (reference number ID: INPLASY202180105). Results: (1) Eleven trials involving 1126 patients were included in the meta-analysis. (2) Two trials recorded the adverse events. (3) The meta-analysis showed that compared with the control group, the experimental group has a significantly shorter duration of diarrhea in children (MD = -18.64, 95% CI (-23.76, -13.52), P < 0.00001), duration of fever (MD = -19.43, 95% CI (-25.76, -13.11), P < 0.00001), duration of vomiting [MD = -22.51, 95% CI (-29.92, -15.09), P < 0.00001], duration of correcting dehydration (MD = -23.35, 95% CI (-35.48, -11.22), P=0.0002), and the effective rate (OR = 4.64, 95% CI (3.12, 6.90), P < 0.00001). Conclusion: There were significant differences in the clinical efficacy in the treatment of pediatric diarrhea between the experimental and control groups. Thus, Gegen Qinlian decoction may have certain advantages in the treatment of pediatric diarrhea. In addition, we conclude the following: (1) the application of Gegen Qinlian decoction to treat this disease is recommended for >5 days. (2) We recommend conducting multicenter RCTs to avoid the impact of regional differences on the results. (3) We recommend using the unmodified Gegen Qinlian decoction, which may have better efficacy.

Effects of Zhishi Daozhi Decoction on the intestinal flora of nonalcoholic fatty liver disease mice induced by a high-fat diet.

Background and aims: Nonalcoholic fatty liver disease (NAFLD) is the most common type of chronic liver disease with a high incidence, and the situation is not optimistic. Intestinal flora imbalance is strongly correlated with NAFLD pathogenesis. Zhishi Daozhi Decoction (ZDD) is a water decoction of the herbs used in the classical Chinese medicine prescription Zhishi Daozhi Pills. Zhishi Daozhi Pills has shown promising hepatoprotective and hypolipidemic properties, but its specific mechanism remains unclear. Methods: Mice were fed on a high fat-rich diet (HFD) for ten weeks, and then the animals were administrated ZDD through oral gavage for four weeks. The serum liver function and blood lipid indexes of the mice were then tested using an automatic biochemical analyzer. H&E and Oil Red O staining were used to observe the pathological conditions of mice liver tissue, and 16S rRNA sequencing technology was used to analyze the changes in intestinal flora of mice. The concentration of short-chain fatty acids (SCFAs) in the gut of mice was analyzed by gas chromatography-mass spectrometry (GC-MS). The expression of tight junction (TJ) proteins between ileal mucosal epithelial cells was analyzed using the immunofluorescence technique. Results: ZDD was found to reduce the bodyweight of NAFLD mice, reduce serum TG, CHO, ALT, and AST levels, reduce fat accumulation in liver tissue, make the structure of intestinal flora comparable to the control group, and increase the concentration of intestinal SCFAs. It was also found to increase the expression of TJ proteins such as occludin and ZO-1, making them comparable to the control group. Conclusions: ZDD has a therapeutic effect on NAFLD mice induced by HFD, which may act by optimizing the intestinal flora structure.

Individual and combined effects of GSTM1, GSTT1, and GSTP1 polymorphisms on lung cancer risk: A meta-analysis and re-analysis of systematic meta-analyses.

ABSTRACT: Thirty-five previous meta-analyses have been reported on the individual glutathione S-transferase M1 (GSTM1) present/null, glutathione S-transferase T1 (GSTT1) present/null, and glutathione S-transferase P1 (GSTP1) IIe105Val polymorphisms with lung cancer (LC) risk. However, they did not appraise the credibility and explore the combined effects between the 3 genes and LC risk.We performed a meta-analysis and re-analysis of systematic previous meta-analyses to solve the above problems.Meta-analyses of Observational Studies in Epidemiology guidelines were used. Moreover, we employed false-positive report probability (FPRP), Bayesian false discovery probability (BFDP), and the Venice criteria to verify the credibility of current and previous meta-analyses.Significantly increased LC risk was considered as "highly credible" or "positive" for GSTM1 null genotype in Japanese (odds ratio (OR) = 1.30, 95% confidence interval (CI) = 1.17-1.44, I2 = 0.0%, statistical power = 0.997, FPRP = 0.008, BFDP = 0.037, and Venice criteria: AAB), for GSTT1 null genotype in Asians (OR = 1.23, 95% CI = 1.12-1.36, I2 = 49.1%, statistical power = 1.000, FPRP = 0.051, BFDP = 0.771, and Venice criteria: ABB), especially Chinese populations (OR = 1.31, 95% CI = 1.16-1.49, I2 = 48.9%, Statistical power = 0.980, FPRP = 0.039, BFDP = 0.673, and Venice criteria: ABB), and for GSTP1 IIe105Val polymorphism in Asians (Val vs IIe: OR = 1.28, 95% CI = 1.17-1.42, I2 = 30.3%, statistical power = 0.999, FPRP = 0.003, BFDP = 0.183, and Venice criteria: ABB). Significantly increased lung adenocarcinoma (AC) risk was also considered as "highly credible" or "positive" in Asians for the GSTM1 (OR = 1.35, 95% CI = 1.22-1.48, I2 = 25.5%, statistical power = 0.988, FPRP < 0.001, BFDP < 0.001, and Venice criteria: ABB) and GSTT1 (OR = 1.36, 95% CI = 1.17-1.58, I2 = 30.2%, statistical power = 0.900, FPRP = 0.061, BFDP = 0.727, and Venice criteria: ABB) null genotype.This study indicates that GSTM1 null genotype is associated with increased LC risk in Japanese and lung AC risk in Asians; GSTT1 null genotype is associated with increased LC risk in Chinese, and GSTP1 IIe105Val polymorphism is associated with increased LC risk in Asians.

[Pollution Characteristics and Risk Assessment of Organophosphate Esters in Rivers and Water Body Around Taihu Lake].

To explore the pollution characteristics, potential sources, and ecological and health risk of organophosphate eaters (OPEs) in the surface water of Taihu Lake, water samples from 18 surrounding rivers were collected, as well as 11 water samples from Taihu Lake. The concentrations of 13 OPEs in the water were determined using UPLC-MS/MS, and the spatial distribution of the OPEs in surface water of Taihu Lake basin was further analyzed. The results indicate that, in addition to tripropyl phosphate (TPrP), 2-ethylhexyl diphenyl phosphate (EHDPP), and tricresyl phosphate (TCrP), ten OPEs were detected in all the water samples, the total concentration (ΣOPEs) ranged from 152.5 ng·L-1 to 2524 ng·L-1, and the concentration median value was 519.2 ng·L-1. Tri(chloropropyl) phosphate (TCPP) and tri(2-chloroethyl) phosphate (TCEP) were the dominant OPEs, with the concentration ranges of 73.7-1753.9 ng·L-1 (medium value:204.6 ng·L-1) and 43.9-313.5 ng·L-1 (medium value:131.3 ng·L-1), respectively. The ΣOPEs decreased from the northwest region to the southeast, which corresponds to the economic and industrial development. The results of the source identification reveal that the wastewater discharge from electronics and textile enterprises, construction materials, and vehicular and marine traffic emissions may be the principal sources of the OPEs in Taihu Lake. The ecological risk assessment results indicate that only TCPP, tri(dichloropropyl) phosphate (TDCP), and triphenyl phosphate (TPhP) in some sites had a low risk. The health risk assessment reveals that there were no risks based on water intake, but the long-term risk of OPEs to the aquatic ecosystem and surrounding residents still need attention.

4-(3-Fluoro-4-meth-oxy-phen-yl)-1-(4-meth-oxy-phen-yl)-5-(3,4,5-trimeth-oxy-phen-yl)-1H-imidazole.

In the title mol-ecule, C(26)H(25)FN(2)O(5), the fluoro-meth-oxy-, meth-oxy- and trimeth-oxy-substituted benzene rings form dihedral angles of 12.65 (2), 84.15 (2) and 55.67 (2)°, respectively, with the imidazole ring. The crystal structure is stabilized weak inter-molecular C-H⋯F and C-H⋯O hydrogen bonds.

Association between the combined effects of GSTM1 present/null and CYP1A1 MspI polymorphisms with lung cancer risk: an updated meta-analysis.

BACKGROUND: Many studies have been performed to explore the combined effects of glutathione-S-transferase M1 (GSTM1) present/null and cytochrome P4501A1 (CYP1A1) MspI polymorphisms with lung cancer (LC) risk, but the results are contradictory. Two previous meta-analyses have been reported on the issue in 2011 and 2014. However, several new articles since then have been published. In addition, their meta-analyses did not valuate the credibility of significantly positive results. OBJECTIVES: We performed an updated meta-analysis to solve the controversy following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. METHODS: False-positive report probability (FPRP), Bayesian false discovery probability (BFDP), and the Venice criteria were used to verify the credibility of meta-analyses. RESULTS: Twenty-three publications including 5734 LC cases and 7066 controls met the inclusion criteria in the present study. A significantly increased risk of LC was found in overall analysis, Asians and Indians. However, all positive results were considered as 'less-credible' when we used the Venice criteria, FPRP, and BFDP test to assess the credibility of the positive results. CONCLUSION: These positive findings should be interpreted with caution and results indicate that significant associations may be less-credible, there are no significantly increased LC risk between the combined effects of GSTM1 present/null and CYP1A1 MspI polymorphisms.