Mapping metabolite change in the mouse brain after esketamine injection by ambient mass spectrometry imaging and metabolomics.

Ketamine is a new, fast, and effective antidepression treatment method; however, the possible dissociation effects, sensory changes, abuse risk, and the inability to accurately identify whether patients have a significant response to ketamine limit its clinical use. Further exploration of the antidepressant mechanisms of ketamine will contribute to its safe and practical application. Metabolites, the products of upstream gene expression and protein regulatory networks, play an essential role in various physiological and pathophysiological processes. In traditional metabonomics it is difficult to achieve the spatial localization of metabolites, which limits the further analysis of brain metabonomics by researchers. Here, we used a metabolic network mapping method called ambient air flow-assisted desorption electrospray ionization (AFADESI)-mass spectrometry imaging (MSI). We found the main changes in glycerophospholipid metabolism around the brain and sphingolipid metabolism changed mainly in the globus pallidus, which showed the most significant metabolite change after esketamine injection. The spatial distribution of metabolic changes was evaluated in the whole brain, and the potential mechanism of esketamine's antidepressant effect was explored in this research.

Development of a UPLC-MS/MS method for the determination of active ingredients of Shuang Hu in rat blood and its application in pharmacokinetics.

A simple and sensitive method using in vivo microdialysis coupled with UPLC-MS/MS was established to evaluate the pharmacokinetics of Shuang Hu tincture (SHZTN). Xevo TQ-S was used to analyze the active ingredients of mesaconitine, hypaconitine, 4-hydroxycinnamic acid, ferulic acid and N-(2, 3-dimethyl phenyl)-2- aminobenzoic acid of SHZTN. Samples were prepared using a methanol precipitation method and the internal standards lannaconitine and p-hydroxybenzoic acid were added. The method validation was conducted according to the guidelines of the Pharmacopoeia of China. A good linear range was obtained in the range of 1-2,000 ng/ml. The intra-day and inter-day precisions were less than 14.7%, and the accuracy range of all the analytes was -10.5-9.3%. The recovery of each analyte was over 95.5%, and matrix effects can be neglected. After a single dose of 20 mg/kg SHZTN, the area under the curve and peak concentration of the five active ingredients were significantly increased by transdermal compared with oral administration, which indicated the high bioavailability of SHZTN. The time to peak concentration of all compounds was <3.4 h, and the half-life was <15.4 h, which indicated that the five compounds have the best absorption and rapid elimination. The method was successfully developed and applied to the pharmacokinetic study of SHZTN.

Impact of Helicobacter pylori eradication on the gastric microbiome.

BACKGROUND: Helicobacter pylori (Hp) eradication has been used for many years. Yet, the impact of this eradication on the normal gastric microflora is not well understood. In this study, we explored the effect of eradication on the stomach microbial community and its recovery after successful Hp eradication. METHODS: Among the 89 included patients, 23, 17, 40, and 9 were included in the Hp-negative, Hp-positive, successful eradication, and failed eradication groups, respectively. Four subgroups were further determined according to disease status (Hp-negative chronic gastritis [N-CG], Hp-negative atrophic gastritis [N-AG], successful-eradication chronic gastritis [SE-CG], and atrophic gastritis with successful eradication [SE-AG]). During the endoscopic examination, one piece of gastric mucosa tissue was obtained from the lesser curvature side of the gastric antrum and gastric corpus, respectively. In addition, 16S rDNA gene sequencing was used to analyze the gastric mucosal microbiome. RESULTS: In the Hp-negative group, the gastric microbiota was dominated by five phyla: Firmicutes, Proteobacteria, Actinobacteria, Bacteroidetes, and Fusobacteria. After successfully eradicating Hp, the bacterial flora in the stomach recovered to a considerable extent. In the failed eradication group, the flora was similar to the flora in Hp-positive subjects based on the alpha and beta diversities. Among the groups, Curvibacter and Acinetobacter were enriched in the presence of Hp (i.e., failed eradication and Hp-positive groups), suggesting that these two genera could be used as biomarkers in the symbiotic flora in the presence of Hp. SE-CG was characterized by an increase in Firmicutes taxa and a decrease in Proteobacteria taxa compared with N-CG. SE-AG was characterized by a decrease in Firmicutes relative to N-AG. Finally, no differences were found in the pairwise comparisons of nitrate and nitrite reductase functions of the microflora among the four subgroups. CONCLUSIONS: After Hp infection, the diversity and relative abundance of gastric microflora were significantly decreased. Yet, gastric microbiota could be partially restored to the Hp-negative status after eradication. Still, this effect was incomplete and might contribute to the long-term risks.

Clinically significant endoscopic findings in patients of dyspepsia with no warning symptoms: A cross-sectional study.

BACKGROUND: Dyspepsia is one of the commonest clinical disorder. However, controversy remains over the role of endoscopy in patients with dyspepsia. No studies have evaluated the diagnostic value of endoscopy in patients with no warning symptoms according to the Rome IV criteria. AIM: To study the diagnostic value of endoscopy in dyspeptic patients with no warning symptoms. METHODS: This cross-sectional study included dyspeptic patients with no warning symptoms who met the inclusion and exclusion criteria at The First Affiliated Hospital, Zhejiang Chinese Medical University from April 2018 to February 2019. The clinical data were collected using questionnaires, including dyspeptic information, warning symptoms, other diseases, family history and basic demographic data. Based on dyspeptic symptoms, patients can be divided into epigastric pain syndrome, postprandial distress syndrome or overlapping subtypes. RESULTS: A total of 1016 cases were enrolled, 304 (29.9%) had clinically significant findings that were detectable by endoscopy. The endoscopy findings included esophageal lesions in 180 (17.7%) cases, peptic ulcers in 115 (11.3%) cases and malignancy in 9 (0.89%) patients. Multivariate logistic regression analysis showed that males [odds ratio (OR) = 1.758, P < 0.001], body mass index > 25 (OR = 1.660; P = 0.005), epigastric pain (OR = 1.423; P = 0.019) and Helicobacter pylori infection (OR = 1.949; P < 0.001) were independently associated with risk factors for the presence of clinically significant findings on endoscopy. CONCLUSION: Chinese patients with dyspepsia with no warning symptoms should undergo endoscopy, particularly males, patients with body mass index > 25, epigastric pain or Helicobacter pylori infection.

Efficacy of short-term moderate or high-dose statin therapy for the prevention of contrast-induced nephropathy in high-risk patients with chronic kidney disease: systematic review and meta-analysis.

Although previous studies have indicated that statin therapy can effectively prevent the development of CIN, this observation remains controversial, especially in high-risk patients. A meta-analysis was performed to evaluate the efficacy of statin pretreatment for preventing the development of CIN in patients with chronic kidney disease (CKD) and to determine its effectiveness in various subgroups. We searched the online databases PubMed, EMBASE, and the Cochrane Library. RCTs that involved the comparison of the short-term moderate or high-dose statin pretreatment with placebo for CIN prevention in CKD patients undergoing angiography were included. The primary outcome was CIN prevalence. Seven RCTs comprising 4256 participants were investigated in this analysis. The risk of developing CIN in patients pretreated with statins was significantly lower than that in patients pretreated with placebo (RR=0.57, 95%CI=0.43-0.76, p=0.000). The SCr values of the statin group, when analyzed 48h after angiography were lower than those of the placebo group ((SMD=-0.15, 95% CI=-0.27 to -0.04, p=0.011). In the subgroup analysis, statin pretreatment could decrease the risk of CIN in CKD patients with DM (RR=0.54, 95% CI=0.39-0.76, p=0.000), but not in CKD patients without DM (RR=0.84, 95% CI=0.44-1.60, p=0.606). The efficacy of atorvastatin for preventing CIN was consistent with that observed with the use of rosuvastatin. The risk ratios (RR) were 0.51 (95% CI=0.32-0.81, p=0.004) and 0.60 (95% CI=0.41-0.88, p=0.009), respectively. Our study demonstrated that statin pretreatment could prevent the development of CIN in CKD patients. However, subgroup analysis demonstrated that statin pretreatment, despite being effective in preventing CIN in patients with CKD and DM, was not helpful for CKD patients without DM. Rosuvastatin and atorvastatin exhibited similar preventive effects with respect to CIN.

Efficacy of short-term moderate or high-dose statin therapy for the prevention of contrast-induced nephropathy in high-risk patients with chronic kidney disease: systematic review and meta-analysis

Although previous studies have indicated that statin therapy can effectively prevent the development of CIN, this observation remains controversial, especially in high-risk patients. A meta-analysis was performed to evaluate the efficacy of statin pretreatment for preventing the development of CIN in patients with chronic kidney disease (CKD) and to determine its effectiveness in various subgroups. We searched the online databases PubMed, EMBASE, and the Cochrane Library. RCTs that involved the comparison of the short-term moderate or high-dose statin pretreatment with placebo for CIN prevention in CKD patients undergoing angiography were included. The primary outcome was CIN prevalence. Seven RCTs comprising 4256 participants were investigated in this analysis. The risk of developing CIN in patients pretreated with statins was significantly lower than that in patients pretreated with placebo (RR=0.57, 95%CI=0.43-0.76, p=0.000). The SCr values of the statin group, when analyzed 48h after angiography were lower than those of the placebo group ((SMD=-0.15, 95% CI=-0.27 to -0.04, p=0.011). In the subgroup analysis, statin pretreatment could decrease the risk of CIN in CKD patients with DM (RR=0.54, 95% CI=0.39-0.76, p=0.000), but not in CKD patients without DM (RR=0.84, 95% CI=0.44-1.60, p=0.606). The efficacy of atorvastatin for preventing CIN was consistent with that observed with the use of rosuvastatin. The risk ratios (RR) were 0.51 (95% CI=0.32-0.81, p=0.004) and 0.60 (95% CI=0.41-0.88, p=0.009), respectively. Our study demonstrated that statin pretreatment could prevent the development of CIN in CKD patients. However, subgroup analysis demonstrated that statin pretreatment, despite being effective in preventing CIN in patients with CKD and DM, was not helpful for CKD patients without DM. Rosuvastatin and atorvastatin exhibited similar preventive effects with respect to CIN.

Emerging relationship between RNA helicases and autophagy.

RNA helicases, the largest family of proteins that participate in RNA metabolism, stabilize the intracellular environment through various processes, such as translation and pre-RNA splicing. These proteins are also involved in some diseases, such as cancers and viral diseases. Autophagy, a self-digestive and cytoprotective trafficking process in which superfluous organelles and cellular garbage are degraded to stabilize the internal environment or maintain basic cellular survival, is associated with human diseases. Interestingly, similar to autophagy, RNA helicases play important roles in maintaining cellular homeostasis and are related to many types of diseases. According to recent studies, RNA helicases are closely related to autophagy, participate in regulating autophagy, or serve as a bridge between autophagy and other cellular activities that widely regulate some pathophysiological processes or the development and progression of diseases. Here, we summarize the most recent studies to understand how RNA helicases function as regulatory proteins and determine their association with autophagy in various diseases.

[Risk Factors of Acute Kidney Injury Complicating Adult Primary Nephrotic Syndrome].

Objective To explore the risk factors of acute kidney injury(AKI)in adult primary nephrotic syndrome(PNS). Methods Totally 185 patients with PNS were divided into AKI group(n=51)and non-AKI group(n=134).The demographic data and clinical and histological features at admission were compared between the two groups.The independent risk factors for AKI were evaluated by Logistics regression analysis. Results In 51 PNS patients with AKI,the common pathological types of AKI included minor glomerular abnormalities(29.4%),IgA nephropathy(25.5%),and membranous nephropathy(17.6%).The incidences of renal tubular casts and epithelial vacuoles in the AKI group were significantly higher than those in the non-AKI group(P=0.004,P=0.030).Males were more likely to suffer from AKI than females(P=0.000).Patients in AKI group had significantly lower albumin level(P=0.015)and higher levels of random urine protein,serum creatinine,uric acid,urea nitrogen,and triglyceride than non-AKI group(P=0.030,P=0.000,P=0.000,P=0.000,and P=0.006),and polyserous and oliguria occurred more often in the AKI group(P=0.000,P=0.002).The AKI group had significantly higher incidences of high blood pressure and infections(P=0.035,P=0.000).Multivariate logistics regression analysis showed albumin(<25 g/L),serum creatinine(>96 µmol/L),urea nitrogen(≥6.8 mmol/L),uric acid(≥400 µmol/L),diabetes,infection,and renal tubular casts were the independent risk factors for AKI. Conclusions AKI complicating PNS is associated with a variety of factors.Its independent risk factors include the levles of albumin,serum creatinine,urea nitrogen,and uric acid,diabetes,infections,and renal tubular casts.

Factors and Outcome of Renal Osteodystrophy-Associated Initial Fragility Fracture in End-Stage Renal Disease Patients.

BACKGROUND: Renal osteodystrophy has caused increased risk of fragility fracture in end-stage renal disease (ESRD) patients. However, risk factors and outcome of ESRD patients with fragility fracture remain uncharacterized. We aimed to assess these parameters in ESRD patients. SUMMARY: This retrospective case-control study analyzed 354 ESRD patients (initial fragility fracture [FF] group, n = 59; control group, n = 295). Pre-dialysis blood hemoglobin, serum albumin, lipid, calcium, phosphorus, alkaline phosphatase (ALP), and intact parathyroid hormone (iPTH) were collected. All procedures performed involving human participants were in accordance with the ethical standards of the institutional committee of The First Affiliated Hospital of Chongqing Medical University (IRB approval number 216-82), and informed consent was obtained from all participants. There were higher prevalence rates of primary hypertension and diabetes, higher serum ALP, corrected calcium, and lower serum total cholesterol, low-density lipoprotein, lipoprotein-α, and iPTH in the FF group. Fractures were more likely to occur in the higher level of corrected calcium as well as in the lower iPTH group. High corrected calcium (p = 0.010, OR = 11.308, 95% CI: 1.770-72.242) and serum ALP (p = 0.000, OR = 1.007, 95% CI: 1.004-1.011) were independent risk factors of fragility fracture. The incidence of all-cause mortality and cardiovascular (CV) events in ESRD patients with fragility fracture was higher than in those without fracture. KEY MESSAGES: Patients with hypertension, diabetes, excessive suppression of PTH, and poor nutritional status are more prone to fractures. Serum corrected calcium and ALP were independent risk factors of fragility fracture. Patients with initial fragility fracture had more CV events and higher mortality.

[A new triterpenic acid from the roots of Rosa laevigata].

This study was designed to investigate triterpenoids from the roots of Rosa laevigata Michx. The silica gel column chromatography was used to separate the chemical constituents from the roots of Rosa laevigata Michx. HPLC was used to analyze its purity and chemical constitution. Spectroscopy methods were used to determine their structures. Five constituents were isolated and identified as19α-OH-3ß-E-feruloyl corosolic acid (1), 23-hydroxy-tormentic acid (2), 2α, 3ß, 19α, 23- tetrahydroxy-12-en-28-oleanolic acid (3), 2α, 3α, 20ß- trihydroxyurs-13 (18)-en-28-oic-acid (4), 2α, 3ß, 20ß-trihydroxyurs-13 (18)-en-28-oic-acid (5). Compound 1 was assigned as a new compound, compounds 4, 5 were obtained from the genus Rosa for the first time.

[Triterpenoids from roots of Rosa laevigata].

To study the triterpenoids from the roots of Rosa laevigata. The silica gel column chromatography was used to separate the chemical constituents from the roots of Rosa laevigata Michx. HPLC was used to analyze its purity, chemical and spectroscopy methods were used to determine their structures. 12 constituents were isolated and identified as(2R, 19R)methyl 2-acetyloxy-19- hydroxyl-3-oxo-urs-12-en-28-carboxylate(1), pomonic acid (2), 18, 19-seco, 2α, 3α-dihydroxy-19-oxo-urs-11, 13(18)-dien-28-oic acid(3), swinhoeic acid (4), myrianthic acid(5), 2α, 3ß, 19α-trihydroxy-24-oxo-urs-12-en-oic acid (6), tormentic acid(7), arjunic acid (8), 1ß-hydroxyeuscaphic acid(9), quadranoside Ⅷ (10), alpinoside(11), rubuside B (12). Compounds 1-4, 6, 9, 11-12 were obtained from this plant for the first time. Compounds 2-4, 6, 11-12 were obtained from the genus Rosa for the first time.

[Triterpene constituents from Rosa cymosa Tratt].

The constituents in 95% ethanol extract of the root of Rosa cymosa Tratt were purified by column chromatography techniques, leading to isolation of eleven triterpenes. Their structures were elucidated by spectroscopic data as pomolic acid (1), fupenzic acid (2), ursolic acid (3), euscaphic acid (4), arjunic acid (5), tomentic acid (6), 3ß-E-feruloyl corosolic acid (7), 1ß-hydroxyeuscaphic acid (8), myrianthic acid (9), cecropiacic acid (10), and ilexoside B (11). Among them, compounds 3, 6-8, 10 and 11 were obtained from this plant for the first time, and compounds 7 and 10 were obtained from this genus for the first time.