ObjectiveTo evaluate the success of Qi-deficiency model of Balb/C-nu mice established by swimming exhaustion test from the view of biomarkers and metabolic pathways by metabonomics. MethodBalb/C-nu mice were randomly divided into the normal group and Qi-deficiency group， Qi-deficiency model was established by swimming with 5% body weight metal fixed at the tail for 15 consecutive days until exhaustion （nose tip immersion time>5 s）. The urine metabonomics was analyzed by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry （UPLC-Q-TOF/MS）， and the mobile phase was acetonitrile （A）-0.1% formic acid aqueous solution （B） for gradient elution （0-1 min， 5%-8%A； 1-4 min， 8%-8.5%A； 4-5 min， 8.5%-12%A； 5-10 min， 12%-40%A； 10-12 min， 40%-100%A； 12-15 min， 100%A）， the flow rate was 0.3 mL·min^-1， the injection volume was 10 μL， electrospray ionization （ESI） in positive and negative ion modes was used in MS analysis， the MS data were acquired in full-scan mode from m/z 50-1 000. Principal component analysis （PCA）， orthogonal partial least squares-discriminant analysis （OPLS-DA）， human metabolome database （HMDB）， high collision energy ion fragments collected by MS^E and tandem MS （MS/MS） ion information were used to identify potential biomarkers. Kyoto Encyclopedia of Genes and Genomes （KEGG） database and MetaboAnalyst 5.0 were used to analyze the corresponding metabolic pathways and pathway enrichment of biomarkers. ResultEndogenous substances in urine of mice in normal group and Qi-deficiency group were obviously separated， and there were 24 biomarkers with significant difference. The metabolic pathways involved in these biomarkers were tricarboxylic acid cycle， glycolysis metabolism， amino acid metabolism， fatty acid metabolism， pyrimidine metabolism， steroid hormone biosynthesis and tryptophan metabolism. Among them， the metabolic pathways related to energy were tricarboxylic acid cycle， glycolysis metabolism， amino acid metabolism， fatty acid metabolism， pyrimidine metabolism and steroid hormone biosynthesis. ConclusionThrough the investigation of urine metabonomics， combined with the physical signs， the Qi-deficiency model established by swimming exhaustion test in Balb/C-nu mice is successfully evaluated， and it is also verified that there is a close correlation between Qi-deficiency and energy metabolism.

Systemic vasculitis (SV) is a group of heterogeneous diseases characterized by vascular wall inflammation and fibrinous necrosis of unknown causes, which can be involved in all organs and tissues of the body. All types of vasculitis can involve the intestinal tract, causing a series of digestive symptoms and even life-threatening acute abdomen. The involvement of vasculitis in the intestinal tract is difficult to distinguish from primary digestive diseases due to lack of specificity of clinical manifestations. The article mainly reviews the clinical features, diagnosis and treatment strategies of intestinal involvement in systemic vasculitis.

Objective:To explore the genetic causes of oocyte maturation arrest.Methods:A pair of sisters with primary infertility was collected in the Reproductive Medicine Center of Changhai Hospital, Naval Medical University in 2018. Two PATL2 mutations were found in the patients by second-generation whole genome sequencing. Then, for all members of the family and a healthy control person, the regions near the two mutation sites were amplified and sequenced by Sanger sequencing to verify the two mutations. Furthermore, the pathogenesis of the disease was explored through bioinformatics analysis. Results:Compound heterozygous mutations of PATL2 were identified in the two sisters: a missense mutation (p.V260M) and a splicing mutation (p.R75Vfs*21). Both mutations have been reported, and they both cause abnormal splicing of PATL2 mRNA, leading to abnormal gene function. Conclusion:Our study confirmed the correlation between PATL2 mutations and human oocyte maturation arrest, and it provided molecular biomarkers for oocyte and embryo quality assessment.

Objective:To explore the genetic causes of oocyte maturation arrest.Methods:A pair of sisters with primary infertility was collected in the Reproductive Medicine Center of Changhai Hospital, Naval Medical University in 2018. Two PATL2 mutations were found in the patients by second-generation whole genome sequencing. Then, for all members of the family and a healthy control person, the regions near the two mutation sites were amplified and sequenced by Sanger sequencing to verify the two mutations. Furthermore, the pathogenesis of the disease was explored through bioinformatics analysis. Results:Compound heterozygous mutations of PATL2 were identified in the two sisters: a missense mutation (p.V260M) and a splicing mutation (p.R75Vfs*21). Both mutations have been reported, and they both cause abnormal splicing of PATL2 mRNA, leading to abnormal gene function. Conclusion:Our study confirmed the correlation between PATL2 mutations and human oocyte maturation arrest, and it provided molecular biomarkers for oocyte and embryo quality assessment.

Systemic vasculitis (SV) is a group of heterogeneous diseases characterized by vascular wall inflammation and fibrinous necrosis of unknown causes, which can be involved in all organs and tissues of the body. All types of vasculitis can involve the intestinal tract, causing a series of digestive symptoms and even life-threatening acute abdomen. The involvement of vasculitis in the intestinal tract is difficult to distinguish from primary digestive diseases due to lack of specificity of clinical manifestations. The article mainly reviews the clinical features, diagnosis and treatment strategies of intestinal involvement in systemic vasculitis.

Enrichment of trace bioactive constituents and metabolites from complex biological samples is chal-lenging. This study presented a one-pot synthesis of magnetic polydopamine nanoparticles (Fe3O4@-SiO2@PDA NPs) with multiple recognition sites for the magnetic dispersive solid-phase extraction (MDSPE) of ginsenosides from rat plasma treated with white ginseng. The extracted ginsenosides were characterized by combining an ultra-high-performance liquid chromatography coupled to a high-resolution mass spectrometry with supplemental UNIFI libraries. Response surface methodology was statistically used to optimize the extraction procedure of the ginsenosides. The reusability of Fe3O4@-SiO2@PDA NPs was also examined and the results showed that the recovery rate exceeded 80％ after recycling 6 times. Furthermore, the proposed method showed greater enrichment efficiency and could rapidly determine and characterize 23 ginsenoside prototypes and metabolites from plasma. In com-parison, conventional methanol method can only detect 8 ginsenosides from the same plasma samples. The proposed approach can provide methodological reference for the trace determination and charac-terization of different bioactive ingredients and metabolites of traditional Chinese medicines and food.

An untargeted urinary metabonomics method based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry ( UPLC-Q-TOF-MS ) has been established to investigate the mechanism of Schisandra chinensis in treating diabetes and its complications. The urinary biomarkers related to the therapeutic effects of Schisandra chinensis on the diabetes rats were analyzed. In urine, 28 kinds of endogenous metabolites were identified as potential biomarkers, including 13 endogenous metabolites in positive ion mode, 15 endogenous metabolites in negative ion mode, and hippuric acid detected both in positive and negative ion modes. The results revealed that Schisandra chinensis mainly affected the pathways of pentose and glucuronate interconversions, riboflavin metabolism, pantothenate and CoA biosynthesis, arginine and proline metabolism, intestinal bacteria metabolism, ascorbate and aldarate metabolism and tryptophan metabolism in diabetic rats. Combined with biological analysis of these pathways, the therapeutic mechanism of Schisandra chinensis on diabetes and its complications was verified. Based on the biological function of each pathway, the effect of Schisandra chinensis on diabetic nephropathy is stronger. Moreover, it also has the effects of protecting liver, decreasing fat and antioxidant activity.

Phenylketonuria (PKU) is a newborn inherited metabolic disorder caused by the genetic deficiency of hepatic enzyme phenylalanine hydroxylase (PAH) which thus in metabolic disorder of phenylalanine. In this study, ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was used to analyze the accurate amount of coenzyme Q10 (CoQ10) and the relative amount of CoQ9 in newborn dried blood spot (DBS) collected from 5 PKU newborns (3 and 30 days after birth, respectively) and 20 healthy newborns. The content of CoQ10 was (122.1±24.9 ng/mL) and (59.0±12.0 ng/mL) in DBS from healthy newborns and PKU newborns, respectively. The relative contents of cholesterol and glucose in the DBS were determined by gas chromatography-mass spectrometry (GC-MS). In comparison with healthy newborn group, the levels of CoQ10, CoQ9, cholesterol and glucose were all significantly decreased in PKU newborns. The increased content of Phe and the decreased content of CoQ10 showed significant inverse correlation in the DBS from PKU. This study provides references for diet therapy of PKU newborns.

The brain pharmacokinetics of hyperoside and 1 , 5-dicaffeoylquinic acid and the effects of acanthopanax senticosus leaves on neurotransmitters in cerebral ischemic rat brain were investigated. In the study, acute incompleteness cerebral ischemia model was developed by ligating the bilateral common carotid arteries of rats. The differences of brain pharmacokinetics of hyperoside and 1,5-dicaffeoylquinic acid between control and cerebral ischemic rats were determined by online microdialysis coupled with MS/MS method. At the same time, the contents of glutamic acid (Glu), aspartic acid (Asp), γ-aminobutyric acid (GABA), serotonin (5-HT) , dopamine ( DA) , and acetylcholine( Ach) in rat hippocampus among different groups were determined simultaneously in MRM mode. ACE 5 C18-AR column was used for separation. Results showed that the online analytical method had excellent linearity (R2>0. 99). The accuracy and precision could meet the analysis requirement. Besides, the hyperoside and 1,5-dicaffeoylquinic acid penetrated the blood-brain barrier successfully and metabolized quickly, but the absorption reduced and elimination became faster in cerebral ischemic rats; the contents of Glu, Asp, GABA and DA in brain issue of cerebral ischemic rats decreased significantly ( p<0 . 01 ) and the level of Ach increased remarkably ( p<0 . 05 ) after a preventive medication with the extract of acanthopanax senticosus leaves for one week.

A serumal metabonomics method based on UPLC/Q-TOF-MS was established to investigate the mechanism of Schisandra chinensis to treating diabetic nephropathy. The diabetic model was established by feeding with high-fat and high-sucrose chow and streptozotocin intraperitoneal injection. After intragastric administration for 12 weeks, the content of protein and creatinine in rat urine was detected. The results showed that Schisandra chinensis could reduce the content of protein in urine of diabetic rat ( p<0 . 05 ) and ameliorate the condition of diabetic nephropathy. The serum metabolic profiling was analysed by using UPLC/Q-TOF-MS and partial least squares-discriminated analysis ( PLS-DA) was used for data analysis. The score of PLS-DA showed that there was significant difference among the metabolic profile of control group, model group and Schisandra chinensis group ( WWZ ) . Potential biomarkers of Schisandra chinensis ameliorating diabetic nephropathy were selected by orthogonal partial least squares ( OPLS)-DA model. According to the results of OPLS-DA, the MS/MS data of each compound which provided greater contribution to separation of each group were searched from the HMDB databases. Seven endogenous metabolites were identified as potential biomarkers such as xanthurenic acid, palmitic amide, oleamide, uric acid, 5-hydroxyhexanoic acid, p-cresol sulfate, and p-cresol glucuronide. The results revealed that Schisandra chinensis mainly affected the pathways of tryptophan metabolism, gut microbiota metabolism, purine metabolism and fatty acid metabolism to treating type 2 diabetes mellitus. The gut microbiota metabolism and purine metabolism was an important pathway on diabetic nephropathy.