Lipid homeostasis is considered to be related to intestinal metabolic balance, while its role in the pathogenesis and treatment of ulcerative colitis (UC) remains largely unexplored. The present study aimed to identify the target lipids related to the occurrence, development and treatment of UC by comparing the lipidomics of UC patients, mice and colonic organoids with the corresponding healthy controls. Here, multi-dimensional lipidomics based on LC-QTOF/MS, LC-MS/MS and iMScope systems were constructed and used to decipher the alteration of lipidomic profiles. The results indicated that UC patients and mice were often accompanied by dysregulation of lipid homeostasis, in which triglycerides and phosphatidylcholines were significantly reduced. Notably, phosphatidylcholine 34:1 (PC34:1) was characterized by high abundance and closely correlation with UC disease. Our results also revealed that down-regulation of PC synthase PCYT1α and Pemt caused by UC modeling was the main factor leading to the reduction of PC34:1, and exogenous PC34:1 could greatly enhance the fumarate level via inhibiting the transformation of glutamate to N-acetylglutamate, thus exerting an anti-UC effect. Collectively, our study not only supplies common technologies and strategies for exploring lipid metabolism in mammals, but also provides opportunities for the discovery of therapeutic agents and biomarkers of UC.

Objective:To explore the efficacy and influencing factors of irinotecan-loaded CalliSpheres drug-eluting bead-transcatheter arterial chemoembolization (DEBIRI-TACE) combined with regorafenib in the third-line or above treatment of unresectable colorectal cancer liver metastases.Methods:From June 2018 to June 2020, 53 patients with unresectable colorectal cancer liver metastases admitted to Linyi Cancer Hospital of Shandong Province who had failed at least second-line systemic chemotherapy were retrospectively analyzed. The patients were divided into observation group (24 cases) and control group (29 cases) according to different treatment regimes. The control group only received regorafenib monotherapy, and the observation group received regorafenib combined with DEBIRI-TACE. According to the modified Response Evaluation Criteria in Solid Tumors, the objective response rate (ORR) and disease control rate (DCR) were evaluated, and the progression-free survival (PFS) and overall survival (OS) were estimated by Kaplan-Meier method. The Cox proportional hazards model was used to analyze the OS influencing factors in the observation group. The treatment related adverse reactions were observed.Results:After 2 months of treatment, the ORR of the observation group was 75.0% (18/24) , and the DCR was 91.7% (22/24) , both were higher than those of the control group [6.9% (2/29) and 51.7% (15/29) respectively], with statistically significant differences ( χ2=25.92, P<0.001; χ2=9.94, P=0.002) . There were no statistically significant differences in the incidences of regorafenib-related adverse reactions such as hand-foot skin reaction [62.5% (15/24) vs. 65.5% (19/29) , χ2=0.05, P=0.819], fatigue [41.7% (10/24) vs. 44.8% (13/29) , χ2=0.05, P=0.817], hypertension [29.2% (7/24) vs. 34.5% (10/29) , χ2=0.17, P=0.679], diarrhea [25.0% (6/24) vs. 27.6% (8/29) , χ2=0.04, P=0.832], hoarseness [16.7% (4/24) vs. 17.2% (5/29) , χ2=0.01, P=0.956] and proteinuria [8.3% (2/24) vs. 10.3% (3/29) , χ2=0.06, P=0.803] between the two groups. The main adverse reactions related to DEBIRI-TACE in the observation group were fever, pain, nausea and vomiting, etc., which were relieved after symptomatic treatment. No serious complications such as ectopic embolism of CalliSpheres drug eluting bead occurred. By the end of the follow-up, among the 24 patients in the observation group, the median OS of patients with simultaneous liver metastases was 12 months, and that of patients with metachronous liver metastases was 22 months, with a statistically significant difference ( χ2=4.29, P=0.026) . The median OS of patients with 3-5 liver metastases was 21 months, and that of patients with more than 5 liver metastases was 14 months, with a statistically significant difference ( χ2=3.35, P=0.040) . The median OS of Child-Pugh grade A patients was 22 months, and that of Child-Pugh grade B patients was 13 months, with a statistically significant difference ( χ2=4.22, P=0.027) . The median OS was 16 months in patients with extrahepatic metastases and 23 months in patients without extrahepatic metastases, with a statistically significant difference ( χ2=7.68, P=0.013) . Cox proportional hazards model analysis showed that simultaneous liver metastases ( HR=1.59, 95% CI: 1.02-2.47, P=0.031) and extrahepatic metastases ( HR=1.61, 95% CI: 1.29-2.01, P=0.020) were independent risk factors influencing OS of patients in the observation group. The median PFS of the observation group was 9 months, and that of the control group was 5 months, with a statistically significant difference ( χ2=7.78, P=0.005) . The median OS of the observation group was 17 months, and that of the control group was 11 months, with a statistically significant difference ( χ2=16.81, P<0.001) . Conclusion:DEBIRI-TACE combined with regorafenib is effective in the third-line or above treatment of unresectable colorectal cancer liver metastases, with tolerable adverse reactions. It is a safe and feasible treatment method. The prognosis of patients with simultaneous liver metastases or extrahepatic metastases is worse.

Colon cancer-related anemia (CCRA) is mainly caused by systemic inflammation, intestinal bleeding, iron deficiency and chemotherapy-induced myelosuppression in colon cancer. However, the best therapeutic schedule and related mechanism on CCRA were still uncertain. Studies on blood enrichment and anti-tumor effects of combined Danggui Buxue Decoction (DBD), Fe and rhEPO based on CCRA and gut microbiota modulation were conducted in this paper. Here, CCRA model was successfully induced by subcutaneous inoculation of CT-26 and i.p. oxaliplatin, rhEPO + DBD high dosage + Fe (EDF) and rhEPO + DBD high dosage (ED) groups had the best blood enrichment effect. Attractively, EDF group also showed antitumor activity. The sequencing results of gut microbiota showed that compared to P group, the relative abundances of Lachnospiraceae and opportunistic pathogen (Odoribacter) in ED and EDF groups were decreased. Interestingly, EDF also decreased the relative abundances of cancer-related bacteria (Helicobacter, Lactococcus, Alloprevotella) and imbalance-inducing bacteria (Escherichia-Shigella and Parabacteroides) and increased the relative abundances of butyrate-producing bacteria (Ruminococcaceae_UCG-014), however, ED showed the opposite effects to EDF, this might be the reason of the smaller tumor volume in EDF group. Our findings proposed the best treatment combination of DBD, rhEPO and Fe in CCRA and provided theoretical basis and literature reference for CCRA-induced intestinal flora disorder and the regulatory mechanism of EDF.

ObjectiveTo investigate the characteristics of polysomnography （PSG） in depression patients complicating moderate-to-severe obstructive sleep apnea hypopnea syndrome （OSAHS）. MethodsA retrospective analysis was conducted on the outpatients， inpatients and physical examination population who completed overnight PSG monitoring in the sleep medicine center of Suzhou Guangji Hospital from December 2017 to October 2019. Four groups of subjects were finally enrolled， including depression patients with moderate-to-severe OSAHS （n=31）， depression patients without OSAHS （n=79）， moderate-to-severe OSAHS patients （n=96） and normal control group （n=32）. The sleep process related indicators （total sleep time， sleep latency， number of awakenings）， sleep structure related indicators （N1， N2， N3， percentage of REM sleep， REM latency， REM sleep duration）， sleep-related respiratory variables （oxygen reduction index） and other polysomnographic parameters of the four groups were compared. ResultsIn terms of sleep process， the total sleep time， sleep latency and number of awakenings yielded significant differences among the four groups （F=2.874， 3.959， 12.291， P<0.05 or 0.01）. In terms of sleep structure， the percentage of total sleep time in N2 and N3 stages demonstrated significant differences among the four groups （F=13.885， 48.013， P<0.01）. The REM latency， REM sleep duration and percentage of REM sleep manifested significant differences among the four groups （F=41.492， 11.827， 10.552， P<0.01）. In terms of sleep-related respiratory variables， the oxygen reduction index exhibited significant differences among the four groups （F=170.585， P<0.05）. ConclusionDepression patients complicating moderate-to-severe OSAHS suffer from severe sleep process and structural disturbances， accompanied by quite frequent and severe sleep-related respiratory events.

Cystine is the primary source material for the synthesis of glutathione.However,the pharmacokinetics and tissue distribution of cystine are largely unknown.A surrogate analyte D4-cystine was employed to generate calibration curves for the determination of levels of D4-cystine and endogenous cystine in mice by liquid chromatography-tandem mass spectrometry(LC-MS/MS).Validation assessments proved the sensitivity,specificity and reproducibility of the method with a lower limit of quantification(LLOQ)of 5 ng/mL over 5-5000 ng/mL in plasma.The pharmacokinetics of D4-cystine were evaluated after administering injections and oral solutions,both of which minimally impacted endogenous cystine levels.The absolute bioavailability of cystine was 18.6％,15.1％and 25.6％at doses of 25,50 and 100 mg/kg,respectively.Intravenously injected D4-cystine resulted in dramatically high plasma levels with reduced levels in the brain and liver.Intragastrically administered D4-cystine resulted in high levels in the plasma and stomach with relatively low levels in the lung,kidney,heart and brain.

Identification of components and metabolites of traditional Chinese medicines (TCMs) employing liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-Q-TOF MS) techniques with information-dependent acquisition (IDA) approaches is increasingly frequent. A current drawback of IDA-MS is that the complexity of a sample might prevent important compounds from being triggered in IDA settings. Sequential window acquisition of all theoretical fragment-ion spectra (SWATH) is a data-independent acquisition (DIA) method where the instrument deterministically fragments all precursor ions within the predefined m/z range in a systematic and unbiased fashion. Herein, the superiority of SWATH on the detection of TCMs' components was firstly investigated by comparing the detection ef-ficiency of SWATH-MS and IDA-MS data acquisition modes, and sanguisorbin extract was used as a mode TCM. After optimizing the setting parameters of SWATH, rolling collision energy (CE) and variable Q1 isolation windows were found to be more efficient for sanguisorbin identification than the fixed CE and fixed Q1 isolation window. More importantly, the qualitative efficiency of SWATH-MS on sanguisorbins was found significantly higher than that of IDA-MS data acquisition. In IDA mode, 18 kinds of sangui-sorbins were detected in sanguisorbin extract. A total of 47 sanguisorbins were detected when SWATH-MS was used under rolling CE and flexible Q1 isolation window modes. Besides, 26 metabolites of sangui-sorbins were identified in rat plasma, and their metabolic pathways could be deduced as decarbonylation, oxidization, reduction, methylation, and glucuronidation according to their fragmental ions acquired in SWATH-MS mode. Thus, SWATH-MS data acquisition could provide more comprehensive information for the component and metabolite identification for TCMs than IDA-MS.

Objective To evaluate the efficacy and safety of anticoagulant therapy with warfarin for hemodialysis patients with atrial fibrillation.Methods A cohort of 118 hemodialysis patients with atrial fibrillatio were enrolled.The patients were divided into two groups:in warfarin group (n=53) the standard medication of warfarin was given for at least 3 months by adjusting the INR between 2.0 and 3.0;while no anticoagulants were given after discharge in non-warfarin group (n=65).Patients were followed up regularly,the events of stoke,death and bleeding were documented and compared between two groups.Results There were no significant differences in age,sex,underlying disease,predictive score of stroke risk in patients with non-valvular atrial fibrillation (CHA2DS2-VASc),predictive score of bleeding risk in patients with non-valvular atrial fibrillation (HAS-BLED) and dialysis frequency between the two groups (P＞0.05).There were no significant differences in events of ischemic stroke [11％(6/53) vs.12％(8/65),x2=0.027,P=0.87],bleedings [(9％(5/53) vs.5％(3/65),P=0.46] and gastrointestinal bleeding events [6％(3/53) vs.3％ (2/65),P=0.66] between two groups.There were no significant differences in the death event [15％(10/53) vs.22％(14/65),x2=0.129,P=0.72] and cardiac death [9％(5/53) vs.11％(7/65),x2=0.057,P=0.81] between two groups.Conclusion This study suggests that warfarin may not prevent ischemic stroke in hemodialysis patients with chronic atrial fibrillation,further studies are needed to determine the risks and benefits of anticoagulation therapy in these patients.

Objective To investigate the efficacy and prognostic factors of transcatheter arterial chemoembolization (TACE),and radiofrequency ablation (RFA) combined with intensity modulated radiotherapy (IMRT) for hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT).Methods Sixtythree cases of HCC with PVTT were retrospectively analyzed.All of them received 1-3 time(s) of TACE therapy followed by RFA.IMRT was finally performed to PVTT.Both the therapeutic effects of HCC and PVTT were observed in 6 to 8 weeks after IMRT therapy.The long-run efficacy was observed by analyzing the 1-3 year(s) survival rate,and the hazards to prognosis were analyzed.Results The CR,PR,SD,PD numbers and rates in PVTT were 9 cases (15.0％),36 cases (60.0％),10 cases (16.6％),and 5 cases (8.3％).The effective rate in PVTT was 75.0％.Meanwhile the CR,PR,SD,PD numbers and rates in HCC were 19 cases (31.6％),30 cases (50.0％),6 cases (10.0％),and 5 cases (8.3％).The effective rate in HCC was 81.6％.The 1,2 and 3 year survival rates were 73.3％,45.0％ and 27.0％,respectively.ECOG score (x2 =53.046,P =0.000),history of hepatitis (x2 =6.472,P =0.030),tumor size (x2 =7.293,P =0.026),the number of tumor(x2 =24.382,P =0.000),the types of tumor thrombus (x2 =28.085,P =0.000) and Child-Pugh class (x2 =6.184,P =0.040) were independent hazardous factors for survivals.Conclusion TACE combined with RFA is effective treatment for HCC with PVTT patients with low frequency of severe complications and high rate of tumor response.ECOG score,history of hepatitis,the size and number of tumor,the types of tumor thrombus,Child-Pugh class are the factors that influence the long curative effect.

The aim of the study is to evaluate the effects of the single and mixed decoction of Thallus laminariae (kelp) and Glycyrrhiza glabra (licorice) on the metabolism and their difference. The mixed decoction of kelp and licorice and the single decoction were made and intragastrically administered to the SD rats. The effect on system metabolism, the toxicity of liver and kidney were assessed by GC-MS profiling of the endogenous molecules in serum, routine biochemical assays and histographic inspection of tissues from SD rats, separately. The mixed decoction of kelp and licorice induced more obvious pathological abnormalities in SD rats than a single decoction of kelp, while the extracts of licorice did not show any pathological change. Neither the mixed, nor the single decoction showed abnormal histopathology. After intragastric administration of extracts for 5 days, the mixed decoction induced a decrease of ALT (no significant change in the groups of single decoction) and an increase of BUN (so did the single decoction of kelp). Metabolomic profile of the molecules in serum revealed that the metabolic patterns were all obviously affected for the three groups, i.e., the mixed and single decoction of kelp and licorice. The rats given with the single decoction of kelp showed a similar pattern to that of the mixed decoction, indicating that the kelp primarily contributed the perturbation of metabolism for the mixed decoction. All three groups induced a decrease of branched chain amino acids, TCA cycle intermediates and glycolysis intermediates (e.g., pyruvic acid and lactic acid) and an increase of 3-hydroxybutyric acid. Kelp decoction showed stronger potential in reducing TCA cycle intermediates and glycolysis intermediates than the other two groups, while the levels of branched chain amino acids were the lowest after licorice extracts were given. These results suggested that the effect of the mixed decoction on metabolism was closely associated with both kelp and licorice. The continuous administration of single decoction of kelp and the mixed decoction of licorice and kelp resulted in pathological abnormalities in kidney of SD rats. The mixed decoction of kelp and licorice distinctly perturbed sera molecules and hence system metabolism, which showed associated with those of kelp and licorice. Although the metabolic effect was associated with both kelp and licorice, the results suggested kelp contributed to it primarily.

The pharmacokinetic translation from bench to bedside has been an important component in translational research. Based on non-clinical pharmacokinetic research results, scale factor allometric model and physiology- based pharmacokinetic model were used to investigate the translational method of pharmacokinetic parameters from quantitative pharmacology perspective. The method includes the reasonable extrapolation of translation for inter-species and analysis of in vivo-in vitro differences. The pharmacokinetic translation model from bench to bedside will help to optimize clinical administration into simulation study.