The Bacterial and Fungal Compositions in the Rhizosphere of Asarum heterotropoides Fr. Schmidt var. mandshuricum (Maxim.) Kitag. in a Typical Planting Region.

Asarum is a traditional Chinese medicinal plant, and its dried roots are commonly used as medicinal materials. Research into the traits of the bacteria and fungus in the Asarum rhizosphere and how they relate to the potency of medicinal plants is important. During four cropping years and collecting months, we used ITS rRNA gene amplicon and sequencing to assess the population, diversity, and predominant kinds of bacteria and fungus in the rhizosphere of Asarum. HPLC was used to determine the three bioactive ingredients, namely asarinin, aristolochic acid I, and volatile oil. The mainly secondary metabolites of Asarum, relationships between microbial communities, soil physicochemical parameters, and possible influences on microbial communities owing to various cropping years and collecting months were all statistically examined. The cropping years and collecting months affected the abundance and diversity of rhizosphere bacteria and fungi, but the cropping year had a significant impact on the structures and compositions of the bacterial communities. The rhizosphere microorganisms were influenced by both the soil physicochemical properties and enzyme activities. Additionally, this study revealed that Trichoderma was positively correlated with the three bioactive ingredients of Asarum, while Tausonia showed entirely opposite results. Gibberella and Leptosphaeria demonstrated a significantly negative correlation with asarinin and violate oil, but they were weakly correlated with the aristolochic acid I content. This study revealed variations in the Asarum rhizosphere microorganism population, diversity, and dominant types across four cropping years and collecting months. The relationship between Asarum secondary metabolites, the soil physicochemical properties, enzyme activities, and rhizosphere microorganisms was discussed. Our results will guide the exploration of the soil characteristics and rhizosphere microorganisms' structures by regulating the microbial community to enhance Asarum quality.

Targeting neutrophils: Mechanism and advances in cancer therapy.

BACKGROUND: Cancer is a thorny problem which cannot be conquered by mankind at present and recent researchers have put their focus on tumor microenviroment. Neutrophils, the prominent leukocytes in peripheral blood that accumulate in tumours, serves as frontline cells in response to tumour progression owing to the rapid development of micro biotechnology. Hence, targeted therapy with these neutrophils has made targeting treatment a promising field in cancer therapy. MAIN BODY: We broadly summarise some studies on the phenotypes and functions of tumour-associated neutrophils as well as the unique web-like products of neutrophils that play a role in cancer progression-neutrophil extracellular traps-and the interactions between neutrophils and the tumour microenvironment. Moreover, several targeted neutrophils therapeutic studies have made some progress and provided potential strategies for the treatment of cancer. CONCLUSION: This review aims to offer a holistic perspective on therapeutic interventions targeting neutrophils to further inspire more researches on cancer therapies.

Effects of olanzapine on hippocampal CA3 and the prefrontal cortex local field potentials.

Olanzapine is an antipsychotic drug applied in psychiatry to treat psychoses, especially schizophrenia and schizoaffective disorders with similar or better improvement than haloperidol and risperidone in the treatment of depressive and negative symptoms. The effect of olanzapine on neural synchrony remains to be explored. We investigated the effects of olanzapine on gamma oscillations in the CA3 region of the hippocampus and frontal association cortex. Olanzapine reduced carbachol (CCh)-induced gamma oscillation power in CA3 slice and gamma oscillation power in the frontal association cortex in vivo. The power of theta oscillations was increased in the presence of olanzapine. The phase amplitude coupling of theta and gamma wave was strengthened by the administration of olanzapine in the frontal association cortex in vivo. Taken together, these results show that olanzapine modulates local field potential and the neuronal activity.

An assessment system for clinical and biological interpretability in ulcerative colitis.

Ulcerative colitis (UC) is a serious inflammatory bowel disease (IBD) with high morbidity and mortality worldwide. As the traditional diagnostic techniques have various limitations in the practice and diagnosis of early ulcerative colitis, it is necessary to develop new diagnostic models from molecular biology to supplement the existing methods. In this study, we developed a machine learning-based synthesis to construct an artificial intelligence diagnostic model for ulcerative colitis, and the correctness of the model is verified using an external independent dataset. According to the significantly expressed genes related to the occurrence of UC in the model, an unsupervised quantitative ulcerative colitis related score (UCRScore) based on principal coordinate analysis was established. The UCRScore is not only highly generalizable across UC bulk cohorts at different stages, but also highly generalizable across single-cell datasets, with the same effect in terms of cell numbers, activation pathways and mechanisms. As an important role of screening genes in disease occurrence, based on connectivity map analysis, 5 potential targeting molecular compounds were identified, which can be used as an additional supplement to the therapeutic of UC. Overall, this study provides a potential tool for differential diagnosis and assessment of bio-pathological changes in UC at the macroscopic level, providing an opportunity to optimize the diagnosis and treatment of UC.

Bioactivity and Component Analysis of Water Extract of Sophora japonica against Hyperuricemia by Inhibiting Xanthine Oxidase Activity.

Hyperuricemia (HUA) is a metabolic condition caused by excessive production or low excretion of uric acid (UA) in the body. Xanthine oxidase (XOD) is the key enzyme in the process of metabolism purines to generate UA. In this study, the in vitro inhibitory effect of water extract of the flower bud of Sophora japonica (WESJ) on XOD was investigated by ultraviolet spectrophotometry. A mice model of HUA was constructed to explore the effect of WESJ on UA levels and the mechanism of action on renal function. Based on Box-Behnken design, the optimal extraction process of WESJ was determined to extract Sophora japonica twice with 8 times of water, 0.5 h each time. Pharmacological results showed that low, medium, and high doses of WESJ (200, 400, 600 mg/kg) could significantly reduce serum UA level, inhibit the activity of XOD in blood and liver, and have a protective effect on kidney damage caused by high UA. Through UPLC-Q-TOF-MS/MS analysis, 214 compounds were identified in WESJ, including flavonoids, polyphenols, triterpenoids, organic acids, and others. The rat serum of WESJ was analyzed, and 23 prototype components entering the blood were identified, including 15 flavonoids and polyphenols, which may be the main bioactive components. In conclusion, flavonoids and polyphenols in WESJ may reduce the level of UA and alleviate kidney damage by inhibiting the activity of XOD. WESJ is expected to be used as a plant-based food and dietary supplement for the treatment of HUA.

Isorhamnetin, the xanthine oxidase inhibitor from Sophora japonica, ameliorates uric acid levels and renal function in hyperuricemic mice.

Hyperuricemia is a metabolic condition closely linked to xanthine oxidase (XOD) function, which is involved in the production of uric acid (UA). In this study, XOD was used as a target to construct an in vitro and in vivo activity screening and verification system. The XOD inhibition ability of the main components from the water extract of Sophorae Flos (WSF), an unopened dry flower bud of Sophora japonica, was screened by HPLC. Isorhamnetin (IRh) was identified as a major flavonoid XOD inhibitor from WSF, and we characterized its effects and potential mechanism in ameliorating UA levels and renal function in hyperuricemia model mice. Hyperuricemia was induced by oral administration of potassium oxonate (PO) and hypoxanthine to mice for 7 days. The biochemical index results showed that treatments with low, medium, and high doses of IRh (50, 100, and 150 mg kg-1) significantly reduced serum UA levels and inhibited XOD activity in serum and in the liver. Additionally, IRh effectively decreased the levels of serum creatinine and blood urea nitrogen, suggesting that it possessed nephroprotective effects in hyperuricemic mice. Furthermore, histopathological results showed that nuclear lesions and renal tubule dilatation in the kidneys of IRh-treated hyperuricemic mice were reduced, suggesting that IRh may alleviate renal injury. Molecular docking results showed that IRh combined well with XOD and is an effective XOD inhibitor. In conclusion, IRh from Sophora japonica may reduce the UA levels and alleviate renal injury by inhibiting XOD activity. It potentially functions as a therapeutic drug and dietary supplement to treat hyperuricemia.

Quantitation of vistusertib by UHPLC-MS/MS in rat plasma and its application to a pharmacokinetic study.

Aim: The present study aimed to develop a UHPLC-MS/MS method for determination of vistusertib in biological matrix, and to describe the pharmacokinetic behavior of vistusertib in SD rats. Methodology & results: After protein precipitation with acetone and acetonitrile (1:1), the chromatographic separation was achieved on an Agilent Poroshell 120 EC-C18 column and detected with a SCIEX QTRAP 4500 mass spectrometer under positive ionization mode. The developed UHPLC-MS/MS method showed an excellent linearity within the range of 1.0-3000 ng/ml with good accuracy and precision. Vistusertib showed a rapid absorption and reached the maximum concentration of 3532.2 ± 678.0 ng/ml 20-30 min after oral administration in Sprague-Dawley rats. Conclusion: The established analytical method was fast, sensitive and robust, and successfully applied to describe the pharmacokinetic behavior of vistusertib following an oral administration in rats.

A review on the fruit components affecting uric acid level and their underlying mechanisms.

Uric acid (UA) is produced in the liver and excreted through the kidneys and intestines. If UA is overproduced or its excretion reduces, the concentration of UA increases, leading to hyperuricemia and gout. The high concentration of UA is also related to cardiovascular disease, hypertension, obesity, and other diseases. Fruits are healthy foods. However, fruits contain fructose and small amounts of purine, and the product of their metabolism is UA. Therefore, theoretically, eating fruits will increase the concentration of serum UA. Fruit components are numerous, and their effects on serum UA are complex. According to the current research, fructose, purine, polyphenols, vitamin C, dietary fiber, and minerals present in fruits influence serum UA concentrations. In addition to the UA synthesized by fructose and purine metabolism, the mechanisms by which other components affect the concentration of serum UA can be summarized as follows: (a) inhibiting xanthine oxidase; (b) reducing reabsorption of UA; and (c) improving the excretion of UA. In this review, we comprehensively discussed the fruit components that affect serum UA concentrations, and explained their mechanisms for the first time, which references for patients with hyperuricemia to take fruits. PRACTICAL APPLICATIONS: With the rising prevalence, hyperuricemia and gout have become public health problems that endanger our daily life. The key to the treatment of hyperuricemia is to control the level of serum UA within the normal range. Fruits are healthy foods. However, fruit components are numerous, and their effects on serum UA are complex. According to the current research, fructose, purine, polyphenols, vitamin C, dietary fiber, and minerals present in fruits influence serum UA concentrations. In this review, we comprehensively discussed the fruit components that affect serum UA concentrations. We also explained their mechanisms, which references for patients with hyperuricemia to take fruits.

A brief review of urate transporter 1 (URAT1) inhibitors for the treatment of hyperuricemia and gout: Current therapeutic options and potential applications.

Hyperuricemia is a common metabolic condition, cause by increased levels of serum urate (SUA). Reduced excretion of uric acid is reported as the key factor of primary hyperuricemia, accounting for approximately 90% of the cases. Urate transporter 1 (URAT1) is a major protein involved in uric acid reabsorption (about 90%). Therefore, URAT1 inhibitors are considered to be a highly effective and promising class of uricosuric agents for treating hyperuricemia. This review summarizes the development of URAT1 inhibitors for the treatment of hyperuricemia, including approved URAT1 inhibitors, URAT1 inhibitors under development in clinical trials, substances with URAT1 inhibitory effects from derivatives and natural products, and conventional drugs with new uses. This review provides new ideas regarding research on URAT1 inhibitors by introducing the structure, properties, and side effects of chemical drugs, as well as the sources and categories of natural drugs. We also discuss new mechanisms of classic drugs, which may provide guidance to many practicing clinicians. The research and discovery of new inhibitors remain in full swing, and tremendous developments are expected in the field.

Development of a validated LC-MS/MS method for quantification of phosphoinositide 3 kinase inhibitor GSK2636771: Application to a pharmacokinetic study in rat plasma.

A simple and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) coupled with one-step protein precipitation extraction method was developed and validated for determination of GSK2636771, a phosphoinositide 3 kinase (PI3K) inhibitor in rat plasma. After protein precipitation with acetonitrile, the chromatographic separation was carried out on a CORTECS UPLC C18 column, with acetonitrile and 0.1 % formic acid in water as mobile phase at a flow rate of 0.30 mL·min-1. The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring (MRM) mode via electrospray ionization (ESI) source, with target quantitative ion pairs of m/z 434.2→416.2 for GSK2636771, and 411.2→367.2 for BKM120 (internal standard). The calibration curve was linear over the range of 2.0-8000 ng·mL-1, and the LLOQ was evaluated to be 2.0 ng·mL-1. The accuracy (relative error, RE %) ranged from -3.4 % to 4.7 %, and the intra- and inter-day precision were within 15 %, and with the mean extraction recovery 82.1-89.3 %. The validated method described a quantification method of GSK2636771 in detail for the first time and applied to a pharmacokinetic study after oral administration of GSK2636771 at low, medium and high doses in rats. The mean plasma concentration versus time profiles of GSK2636771 showed a dose-dependent relationship at different doses.

Pre-operative to post-operative serum carcinoembryonic antigen ratio is a prognostic indicator in colorectal cancer.

We explored the prognostic significance of the pre-operative-to-post-operative serum carcinoembryonic antigen (pre-post-CEA) ratio in colorectal cancer (CRC). We detected pre- and post-operative CEA levels in 2035 CRC patients surgically treated at First Affiliated Hospital of Zhengzhou University between June 2001 and June 2011. Univariate analysis revealed the pre-post-CEA ratio is associated with distant metastasis and degree of tumor differentiation (both P < 0.05). Multivariate analysis showed that the pre-post-CEA ratio is associated with lymphatic and distant metastasis, tumor-node-metastasis (TNM) stage and degree of tumor differentiation (all P < 0.01). The pre-CEA levels, pre-post-CEA ratios, distant metastasis, TNM stage and degree of tumor differentiation were all associated with 5-yr overall survival (all P < 0.05) based on multivariate analysis. Consequently, pre-CEA levels, pre-post-CEA ratios, distant metastasis and TNM stage are independent risk factors for CRC. We have thus demonstrated that the pre-post-CEA ratio is a prognostic indicator for CRC patients.

[Efficacy comparison of robotic and laparoscopic radical surgery in the treatment of middle-low rectal cancer].

OBJECTIVE: To compare the clinical efficacy of robotic and laparoscopic radical surgery in the treatment of middle-low rectal cancers. METHODS: From January 2015 to March 2016, intra-operative and postoperative follow-up data of 30 patients with middle-low rectal cancers who underwent robotic radical resection(robot group) and 32 patients with middle-low rectal cancers who underwent laparoscopic radical resection (laparoscopy group)n in our department were retrospectively collected. The distance from cancer to anal margin was less than 10 cm in both two groups and advanced rectal cancers were confirmed by preoperative colonoscopy biopsy. Associated data were compared between two groups. RESULTS: There were 13 males and 17 females in robot group with age of 27 to 85 (mean 59.7) years, disease course of 3 to 12 (mean 6.2) months and clinical stage T2-3N0-1. There were 16 males and 16 females in laparoscopic group with age of 32 to 79 (mean 60.3) years, disease course of 2 to 10(mean 5.9) months and clinical stage T2-3N0-1. The baseline data of two groups were not significantly different (all P>0.05). All the patients in two groups completed operations successfully without conversion to open operation. Compared with laparoscopic group, the blood loss was less [(100.3±43.7) ml vs. (150.3±68.2) ml, t=3.413, P=0.001], the first flatus time [(49.3±12.4) h vs. (58.6±12.5) h, t=2.838, P=0.006] and urinary catheter removal time [(3.0±0.7) d vs. (4.8±0.9) d, t=5.491, P=0.000] were shorter, while the operation time [(217.3±57.8) min vs. (187.9±23.1) min, t=2.772, P=0.009] was longer in robot group. No cancer tissue was observed in resection margin of two groups. Number of harvested lymph node per case (15.2±7.4 vs. 13.9±4.9, t=-0.764, P=0.448), distance from anal margin to tumor distal edge [(7±3) cm vs. (6.5±3) cm, t=-1.952, P=0.056] and postoperative hospital stay [(13.6±1.3) d vs. (13.8±1.8) d, t=0.925, P=0.359] were not significantly different between two groups. No serious complications occurred in two groups during intra-operative and postoperative period. During following up of 3 to 12 (average 8.7) months, 1 case of anastomotic fistula occurred in each group and was cured by conservative treatment without significant difference [3.3%(1/30) vs. 3.1%(1/32), P=1.000]. No sexual dysfunction was found in either groups. Two cases in laparoscopic group presented relapse and metastasis, but no recurrence and metastasis was observed in robot group. There was no death in two groups. CONCLUSION: Robotic radical surgery in the treatment of middle-low rectal cancers is safe and effective with the advantages of less trauma, less bleeding, rapid recovery of intestinal function and urinary function.

Main source of drinking water and familial aggregation of Kashin-Beck disease: a population based on case-control family study.

PURPOSE: Kashin-Beck disease (KBD) is an osteoarthropathy affecting 2.5 million of 30 million residents of China's KBD-endemic regions. This study assesses the etiologic role of river water as a main source of drinking water, its impact on and interaction with KBD familial aggregation. METHODS: From 2006-2007, we conducted a population-based case-control study of familial KBD in Linyou County, Shaanxi Province, China. Study subjects included 212 case families (1,951 individuals) and 212 control families (1,897 individuals). Using conditional logistic regression to analyze case-control data and second-order generalized estimating equation (GEE2) to examine family data, we adjusted for age and gender in all marginal regression analyses. RESULTS: The odds ratio (OR) for river water intake's association with KBD was 5.97 (95% confidence interval [CI]), 3.32-10.72). Compared with relatives of controls, proband relatives had a higher risk of disease, with a conditional OR = 2.35 (95% CI, 1.05-5.24). When river water was controlled in the analyses, association parameters among first- and second-degree relatives were no longer statistically significant. CONCLUSION: Collective river water intake among relatives was likely and predominantly responsible for familial KBD aggregation in southwestern China.

[Logistic regression of the environmental risk factors in areas with Kashin-Beck disease].

OBJECTIVE: In order to find the factors influencing the prevalence of KBD, the possible nosogenetic factors of the family in Kashin-Beck disease (KBD) areas were analyzed. METHODS: The possible nosogenetic factors in mild, middle, high prevalence KBD areas were analyzed by logistic regression. The differences of the factors between three kinds of KBD areas were compared. RESULTS: Univariate analysis found sanitary conditions and meat-egg-mild were associated with KBD prevalence in all kinds KBD areas. Binary logistic analysis of multivariate suggested the possible nosogenetic factors were different in the different kind of KBD areas. It was wheat in mild prevalence area, sanitary conditions and meat-egg-mild in middle prevalence area, and sanitary conditions, rice and meat-egg-mild in high prevalence area. CONCLUSION: The risk factors are associated with the kind of KBD areas. The different preventive methods should be taken according to the kind of KBD areas, which will improve the effect of prevention.

[Epidemiological characters of Kashin-Beck disease in nuclear families].

OBJECTIVE: To understand the epidemiological characters of Kashin-Beck disease (KBD) in nuclear families, and to probe the pathogenetic mechanism and its etiology. METHODS: Clinical diagnosis was used to identify nuclear families in KBD areas. Based on the clinical manifestation of parents in the nuclear families, 4938 nuclear families were divided into four types. According to the seriousness in KBD areas, prevalence of offspring and family aggregation in low, middle and high prevalence areas were formed and data was analyzed. RESULTS: (1) Type of nuclear family was associated to the degree of disease seriousness in the areas. (2) There was an aggregation of disease among the offsprings in the nuclear families of medium and high prevalence diseased areas. (3) There was an aggregation of offspring in the nuclear family of both parents or father alone who were suffered from KBD. (4) The prevalence of offspring in nuclear family of both parents with KBD was obviously higher than that in the nuclear family with single parent or neither having KBD. CONCLUSION: The degree of diseased areas seemed to influence the seriousness of KBD in individuals. The prevalence of parents in nuclear families might play a role in the pathogenesis of KBD.