Lipidomics based on UHPLC/Q-TOF-MS to characterize lipid metabolic profiling in patients with newly diagnosed type 2 diabetes mellitus with dyslipidemia.

Dyslipidemia often accompanies type 2 diabetes mellitus (T2DM). Elevated blood glucose in patients commonly leads to high levels of lipids. Lipid molecules can play a crucial role in early detection, treatment, and prognosis of T2DM with dyslipidemia. Previous lipid studies on T2DM mainly focused on Western diabetic populations with elevated blood glucose. In this research, we investigate both high blood sugar and high lipid levels to better understand changes in plasma lipid metabolism in newly diagnosed Chinese T2DM patients with dyslipidemia (NDDD). We used a plasma lipid analysis method based on ultra-high performance liquid chromatography coupled with mass spectrometry technology (UHPLC-MS) and statistical analysis to characterize lipid profiles and identify potential biomarkers in NDDD patients compared to healthy control (HC) subjects. Additionally, we examined the differences in lipid profiles between hyperlipidemia (HL) patients and HC subjects. We found significant changes in 15 and 23 lipid molecules, including lysophosphatidylcholine (LysoPC), phosphatidylcholine (PC), phosphatidylethanolamine (PE), sphingomyelin (SM), and ceramide (Cer), in the NDDD and HL groups compared to the HC group. These altered lipid molecules are associated with five metabolic pathways, with sphingolipid metabolism and glycerophospholipid metabolism being the most relevant to glucose and lipid metabolism changes. These lipid biomarkers are strongly correlated with traditional markers of glucose and lipid metabolism. Notably, Cer(d18:1/24:0), SM(d18:1/24:0), SM(d18:1/16:1), SM(d18:1/24:1), and SM(d18:2/24:1) were identified as essential potential biomarkers closely linked to clinical parameters through synthetic analysis of receiver operating characteristic curves, random forest analysis, and Pearson matrix correlation. These lipid biomarkers can enhance the risk prediction for the development of T2DM in individuals with dyslipidemia but no clinical signs of high blood sugar. Furthermore, they offer insights into the pathological mechanisms of T2DM with dyslipidemia.

Evaluating clinical pharmacists' involvement in postoperative acute pain services: a multicenter survey in Guangdong Province, China.

Objective: Postoperative pain management is an important part of surgical pharmacy. Postoperative acute pain services in China are in their initial stages. This survey aimed to investigate the attitudes, involvement, and knowledge of clinical pharmacists in China regarding postoperative acute pain services. The results can provide valuable information to guide clinical pharmacists in developing targeted strategies to improve their postoperative acute pain service capabilities. Methods: A questionnaire was distributed to the pharmacy departments of 133 grade A tertiary hospitals in Guangdong province, and the responses were collected electronically. Results: 123 completed questionnaires were collected from clinical pharmacists. Although 95.93% of clinical pharmacists believed they should participate in postoperative pain services, only 62.6% reported substantial involvement. Overall satisfaction with the postoperative pain service was 93.5%. Understanding of non-steroidal anti-inflammatory drugs and opioid analgesics by clinical pharmacists was comparable (p > 0.05). Furthermore, 98.37% of clinical pharmacists desired systematic learning in postoperative pain management, and 40.65% expressed a strong need. Conclusion: Clinical pharmacists in China demonstrate a positive attitude toward participating in postoperative acute pain services. However, the actual level of involvement was concerning, and the lack of systematic training and well-established work protocols may be contributing factors. Efforts should be made to establish comprehensive and standardized processes and work protocols for postoperative acute pain services and provide systematic and hierarchical professional training to enhance clinical pharmacists' capabilities in postoperative acute pain services.

The effect of pharmacist-initiated perioperative multidisciplinary pharmaceutical care model and clinical pathway on pain management in patients undergoing orthopedic surgery: a before-after study.

BACKGROUND: Poor pain control is common in perioperative orthopedic surgeries. However, there is a lack of exploration of the clinical pharmacy practice model for this population. AIM: To construct a perioperative pharmaceutical care model and clinical pathway for patients undergoing orthopedic surgeries and assess their impact on pain management. METHOD: This historical before-and-after study was conducted in the Department of Orthopedics of a tertiary hospital in Guangdong Province, China. The control group was surgical patients who received routine diagnosis and treatment. The intervention group received pain management from a multidisciplinary team based on a pharmacist-initiated pharmaceutical care practice model and clinical pathways for medication management. The primary outcome measures were postoperative pain at rest (PAR) and movement-evoked pain (MEP) scores, number of breakthrough pains, and length of hospital stay. RESULTS: A total of 320 orthopedic surgery patients were included. Among patients with expected moderate or severe postoperative pain (82.5%), significantly lower PAR and MEP scores were observed in the intervention group 24 h after surgeries compared to the control group (p < 0.05). Compared to the control group, hospital stay in the intervention group was shortened by 2.3 days (p < 0.001). However, there were no significant differences in the control of breakthrough pain and the incidence of adverse drug reactions (p > 0.05). CONCLUSION: Multidisciplinary perioperative pain management practice models and clinical pathways initiated by pharmacists could improve outcome indicators related to pain management and support the role and value of pharmacists.

Lipidomics of the erythrocyte membrane and network pharmacology to explore the mechanism of mangiferin from Anemarrhenae rhizoma in treating type 2 diabetes mellitus rats.

Mangiferin, a natural C-glucoside xanthone, is one of the major bioactive ingredients derived from the dry rhizome of Anemarrhenae rhizome, which has been reported to exhibit various pharmacological effects, including anti-oxidant, anti-inflammatory, anti-fatty liver, anti-metabolic syndrome, and anti-diabetic. However, the precise molecular mechanisms underlying its impact on phospholipid metabolism in the erythrocyte membrane of type 2 diabetes mellitus (T2DM) remain unclear. The present research aimed to evaluate the effects of mangiferin on glucose and lipid metabolism in T2DM model rats and discuss the relationship between lipid metabolites and potential targets involved in the hypoglycemic effects by integrating lipidomics and network pharmacology method. After 8 consecutive weeks of treatment with mangiferin, the T2DM model rats exhibited significant improvements in several biochemical indices and cytokines, including fasting blood glucose (FBG) levels after 12 h of fasting, fasting insulin level (FINS), total cholesterol (T-CHO), triacylglycerols (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), homeostasis model assessment of insulin resistance (HMOA-IR), TNF-α and IL-6. A total of 22 differential lipid metabolites were selected from erythrocyte membrane phospholipids, which were closely associated with the processes of T2DM. These metabolites mainly belonged to glycerophospholipid metabolism and sphingolipid metabolism. Based on network pharmacology analysis, 22 genes were recognized as the potential targets of mangiferin against diabetes. Moreover, molecular docking analysis revealed that the targets of TNF, CASP3, PTGS2, MMP9, RELA, PLA2G2A, PPARA, and NOS3 could be involved in the modulation of inflammatory signaling pathways and arachidonic acid (AA) metabolism to improve IR and hyperglycemia. The combination of immunohistochemical staining and PCR showed that mangiferin could treat T2DM by regulating the expression of PPARγ protein and NF-κB mRNA expression to impact glycerophospholipids (GPs) and AA metabolism. The present study showed that mangiferin might alleviate IR and hyperglycemia of T2DM model rats via multiple targets and multiple pathways to adjust their phospholipid metabolism, which may be the underlying mechanism for mangiferin in the treatment of T2DM.

Surgical Pharmacy for Optimizing Medication Therapy Management Services within Enhanced Recovery after Surgery (ERAS®) Programs.

Drug-related problems (DRPs) are common among surgical patients, especially older patients with polypharmacy and underlying diseases. DRPs can potentially lead to morbidity, mortality, and increased treatment costs. The enhanced recovery after surgery (ERAS) system has shown great advantages in managing surgical patients. Medication therapy management for surgical patients (established as "surgical pharmacy" by Guangdong Province Pharmaceutical Association (GDPA)) is an important part of the ERAS system. Improper medication therapy management can lead to serious consequences and even death. In order to reduce DRPs further, and promote the rapid recovery of surgical patients, the need for pharmacists in the ERAS program is even more pressing. However, the medication therapy management services of surgical pharmacy and how surgical pharmacists should participate in ERAS programs are still unclear worldwide. Therefore, this article reviews the main perioperative medical management strategies and precautions from several aspects, including antimicrobial agents, antithrombotic agents, pain medication, nutritional therapy, blood glucose monitoring, blood pressure treatment, fluid management, treatment of nausea and vomiting, and management of postoperative delirium. Additionally, the way surgical pharmacists participate in perioperative medication management, and the relevant medication pathways are explored for optimizing medication therapy management services within the ERAS programs. This study will greatly assist surgical pharmacists' work, contributing to surgeons accepting that pharmacists have an important role in the multidisciplinary team, benefitting medical workers in treating, counseling, and advocating for their patients, and further improving the effectiveness, safety and economy of medication therapy for patients and promoting patient recovery.

Utility of in vitro and in vivo systems for studying the permeability of capsaicin and nonivamide through different intestinal regions.

1. The present study determined and compared the permeability of capsaicin and nonivamide along the length of the intestine in rats. Accordingly, the purpose was to evaluate this synthetic analog as a clinical substitute for capsaicin.. 2. Permeabilities of capsaicin and nonivamide were measured in experiments utilizing Ussing chambers and in vivo methods. Capsaicin concentrations were examined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). 3. Both capsaicin (0.80 × 10-6 cm/s) and nonivamide (0.22 × 10-6 cm/s, p > 0.05) had poor permeabilities across the jejunal membrane. The permeability of nonivamide (10.12 × 10-6 cm/s) was significantly greater than that of capsaicin (5.34 × 10-6 cm/s, p < 0.05) across the iliac membrane. In contrast, the permeability of nonivamide (8.42 × 10-6 cm/s) across the colonic membrane was markedly lower than that of capsaicin (14.48 × 10-6 cm/s, p < 0.05). In accordance with the in vitro study, the drug concentration-time curve of nonivamide was significantly higher in the ileum (F = 14.18, p < 0.05) but lower in the colon (F = 11.86, p < 0.05) compared with capsaicin. 4. The results demonstrate that capsaicin and nonivamide exhibit varying permeabilities across several different intestinal tissues. The relevance of such extended investigations to healthcare is underscored by the lower cost of nonivamide versus capsaicin, along with potential application in prevention and management of the disease.

Metabolomics approach based on ultra-high-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry to identify the chemical constituents of the Traditional Chinese Er-Zhi-Pill.

Er-Zhi-Pill, which consists of Ligustri lucidi fructus and Ecliptae prostratae herba, is a classical traditional Chinese medicinal formulation widely used as a liver-nourishing and kidney-enriching tonic. To identify the bioactive ingredients of Er-Zhi-Pill and characterize the variation of chemical constituents between co-decoction and mix of individually decocted L. lucidi fructus and E. prostratae herba, a novel metabolomics approach based on ultra high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry in both positive and negative ion modes, was established to comprehensively analyze chemical constituents and probe distinguishable chemical markers. In total, 68 constituents were unambiguously or tentatively identified through alignment of accurate molecular weights within an error margin of 5 ppm, elemental composition and fragmentation characteristics, including eight constituents, which were confirmed by comparing to reference standards. Furthermore, principal component analysis and partial least squares discriminant analysis using Simca-p+ 12.0 software were applied to investigate chemical differences between formulations obtained by co-decoction and a mixture of individual decoctions. Global chemical differences were found in samples of two different decoction methods, and 16 components, including salidroside, specneuzhenide and wedelolactone, contributed most to the observed differences. This study provides a basic chemical profile for the quality control and further mechanism research of Er-Zhi-Pill.

In vitro characterization and inhibition of the interaction between ciprofloxacin and berberine against multidrug-resistant Klebsiella pneumoniae.

Ciprofloxacin is a quinolone antibiotic used to treat Klebsiella pneumoniae infections in the clinic. Previous studies have demonstrated that berberine exhibits antibacterial activity and less acquired resistance related to efflux pumps. The multidrug efflux pump acrAB-tolC can be stimulated to expel as much toxic material as possible from the cells, but a detrimental effect can be produced owing to an overcrowded periplasm with excess expression products, which inhibits bacterial growth. In this study, the in vitro antibacterial activities of ciprofloxacin in combination with berberine were evaluated and compared with those of ciprofloxacin and berberine alone by evaluating the MIC, MBC and summation fractional IC against 20 clinical multidrug-resistant K. pneumoniae isolates, 1 quality control bacterium and 1 induced-resistance bacterium. Susceptibility tests showed that the MIC for the combination of berberine and ciprofloxacin was 1/2 that of the individual agents or less. Antimicrobial activities of 18.18% synergy and 77.27% additivity were found. Furthermore, synergism was verified through a time-kill assay, which suggested that the synergistic antibacterial effect of the two-drug combination may, to some extent, be related to the high expression of the acrAB-tolC and acrR multidrug efflux pumps. Indeed, the expression of these genes was increased >14-fold in the isolates affected by ciprofloxacin-berberine combination synergism.

Diabetes mellitus may induce cardiovascular disease by decreasing neuroplasticity.

Neuroplasticity has been defined "the ability of the nervous system to respond to intrinsic or extrinsic stimuli by reorganizing its structure, function and connections". The nervous system monitors and coordinates internal organ function. Thus neuroplasticity may be associated with the pathogenesis of other diseases besides neuropsychiatric diseases. Decreased neuroplasticity is associated with cardiovascular disease (CVD) and a disease related to decreased neuroplasticity may confer a greater CVD risk. Diabetes mellitus (DM) is related to CVD and DM induces decreased neuroplasticity, which is manifested as depression, Alzheimer's disease and diabetic neuropathy. Therefore we conclude that DM may induce CVD by decreasing neuroplasticity.

Pharmacist-led medication education in cancer pain control: a multicentre randomized controlled study in Guangzhou, China.

OBJECTIVE: To evaluate clinical pharmacist-led pain-medication education in patients with cancer. METHODS: A controlled study was conducted prospectively at six tertiary hospitals in China. In-patients with cancer were randomized to receive conventional treatment plus medication education or no education (controls). Education consisted of access to information booklets and eight 30-min face-to-face counselling sessions given by clinical pharmacists over 4 weeks. Patients completed pain- and analgesic-knowledge assessments and a Brief Pain Inventory, pre- and post-study. RESULTS: A total of 123 and 114 patients in the education and control groups, respectively, completed follow-up. At the end of the study, patient knowledge regarding cancer pain and pain control was significantly increased in both groups; pain and analgesic knowledge scores were significantly higher in the education group compared with controls. In the control group, the increase in total pain-related knowledge was significantly greater in analgesic-naïve patients compared with those who were using/had used analgesics. Pain intensity scores and pain interference of daily activities were significantly reduced in the education group compared with controls. CONCLUSIONS: Clinical pharmacist-led medication education resulted in improved pain control in patients with cancer.

[Relationship between the genetic polymorphism of CYP3A5 gene and the clinical response to bicyclol in chronic hepatitis B].

OBJECTIVE: To investigate the relationship between the genetic polymorphisms of CYP3A5 and the clinical effectiveness of Bicyclol on patients with chronic hepatitis B to make individual medication possible. METHODS: 34 cases of chronic hepatitis B were treated by bicyclol tablets for 24 weeks. Liver function indexes (ALT and AST) were determined before and after treatment. Blood CYP3A5 genotyping of each patient was determined by the PCR-RFLP analysis. RESULTS: All subjects were genotyped for the CYP3A5*3 gene and divided into different group. The groups comprised subjects with CYP3A5*3 carriers (n=18) and CYP3A5*1 carriers (n=16) which include CYP3A5*1/*1 (n=2) and CYP3A5*1/*3 (n=14). Compared with pre-treatment, the serum ALT and AST levels were decreased obviously in all patients. The mean percentage reduction of serum ALT and AST levels were significantly greater in subjects with CYP3A5*3 carriers (79.73% and 74.76%) than in those with CYP3A5*1 carriers (65.90% and 49.63%; P < 0.05) The recovery rates of ALT and AST were significantly highter in CYP3A5*3 carriers than those in CYP3A5*1 carriers (P < 0.05). CONCLUSION: CYP3A5 genotype has an impact on the therapeutic effects of Bicyclol. The subjects with CYP3A5*3 carriers is more effective than the subjects with CYP3A5*1 carriers. CYP3A5 genotyping may be helpful in predicting therapeutic effects of Bicyclol especially in the terms of decreasing ALT and AST.