Mesenchymal stem cells-based drug delivery systems for diabetic foot ulcer: A review.

The complication of diabetes, which is known as diabetic foot ulcer (DFU), is a significant concern due to its association with high rates of disability and mortality. It not only severely affects patients' quality of life, but also imposes a substantial burden on the healthcare system. In spite of efforts made in clinical practice, treating DFU remains a challenging task. While mesenchymal stem cell (MSC) therapy has been extensively studied in treating DFU, the current efficacy of DFU healing using this method is still inadequate. However, in recent years, several MSCs-based drug delivery systems have emerged, which have shown to increase the efficacy of MSC therapy, especially in treating DFU. This review summarized the application of diverse MSCs-based drug delivery systems in treating DFU and suggested potential prospects for the future research.

Self-Appraisal of Clinical Competence in Echocardiography of Chinese Intensivists Post Basic Echocardiography Training.

Objectives To learn the echocardiography skills of intensivists after receiving a basic critical care echocardiography training course, and investigate factors that may influence their performance. Methods We completed a web-based questionnaire that assessed the skills in ultrasound scanning techniques of intensivists who took a training course on basic critical care echocardiography held in 2019 and 2020. Mann-Whitney test was used to analyze the factors which might affect their performance on image acquisition, recognizing clinical syndrome, and measuring the diameter of inferior vena cava, left ventricular ejection fraction and left ventricular outflow tract velocity-time integral.Results We enrolled 554 physicians from 412 intensive care units across China. Among them, 185 (33.4%) reported that they had 10%-30% chance of being misled by critical care echocardiography when making therapeutic decision, and 34 (6.1%) reported that the chance was greater than 30%. Intensivists who performed echocardiography under the guidance of a mentor and finished ultrasound scanning more than 10 times per week reported significant higher scores in image acquisition, clinical syndrome recognition, and quantitative measurement of inferior vena cava diameter, left ventricular ejection fraction and left ventricular outflow tract velocity-time integral than those without mentor and performing echocardiography 10 times or less per week respectively (all P < 0.05).Conclusion The skills in diagnostic medical echocardiography of Chinese intensivists after a basic echocardiographic training course remain low, and further quality assurance training program is clearly warranted.

Andrographolide ameliorates hepatic steatosis by suppressing FATP2-mediated fatty acid uptake in mice with nonalcoholic fatty liver disease.

Excessive intrahepatocellular lipid accumulation or steatosis is caused by abnormal lipid metabolism and a common character of nonalcoholic fatty liver disease (NAFLD), which may progress into cirrhosis and hepatocellular cancer. Andrographolide (Andro) is the primary active ingredient extracted from Andrographis paniculata, showing a protective role against dietary steatosis with the mechanism not fully understood. In this study, we showed that administration of Andro (50, 100, and 200 mg/kg/day for 8 weeks, respectively) attenuated obesity and metabolic syndrome in high-fat diet (HFD)-fed mice with improved glucose tolerance, insulin sensitivity, and reduced hyperinsulinemia, hyperglycemia, and hyperlipidemia. HFD-fed mice presented hepatic steatosis, which was significantly prevented by Andro. In vitro, Andro decreased the intracellular lipid droplets in oleic acid-treated LO2 cells. The selected RT-PCR array revealed a robust expression suppression of the fatty acid transport proteins (FATPs) by Andro treatment. Most importantly, we found that Andro consistently reduced the expression of FATP2 in both the oleic acid-treated LO2 cells and liver tissues of HFD-fed mice. Overexpression of FATP2 abolished the lipid-lowering effect of Andro in oleic acid-treated LO2 cells. Andro treatment also reduced the fatty acid uptake in oleic acid-treated LO2 cells, which was blunted by FATP2 overexpression. Collectively, our findings reveal a novel mechanism underlying the anti-steatosis effect of Andro by suppressing FATP2-mediated fatty acid uptake, suggesting the potential therapeutic application of Andro in the treatment of NAFLD.

Visual Rounds Based on Multiorgan Point-of-Care Ultrasound in the ICU.

Point-of-care ultrasonography (POCUS) is performed by a treating clinician at the patient's bedside, provides a acquisition, interpretation, and immediate clinical integration based on ultrasonographic imaging. The use of POCUS is not limited to one specialty, protocol, or organ system. POCUS provides the treating clinician with real-time diagnostic and monitoring information. Visual rounds based on multiorgan POCUS act as an initiative to improve clinical practice in the Intensive Care Unit and are urgently needed as part of routine clinical practice.

Factors associated with treatment and control of hypertension among elderly adults in Shenzhen, China: a large-scale cross-sectional study.

OBJECTIVE: Hypertension has become the leading cause of death worldwide. Data on hypertension management among Shenzhen elderly are sparse. Our study aims to investigate treated and controlled hypertension in Shenzhen elderly, and identify relevant predictors. DESIGN: A cross-sectional study. SETTING: Communities in Shenzhen, Guangdong, China. PARTICIPANTS: A cross-sectional study was conducted. We employed a convenience sampling method to select participants; 124 007 participants aged 65 years and older were recruited from January to December 2018 at local community health centres in Shenzhen. MAIN OUTCOME MEASURES: Data on treatment, control and influencing factors of hypertension were obtained from a standard questionnaire, physical measurements and biochemical analyses. RESULTS: Prevalence of hypertension was 55.8% among the sample population. Among this group of hypertensive patients, those undergoing hypertension treatment and those with hypertension under control were 54.4% and 32.3%, respectively. Employing multivariate analysis, significant associations were found between treatment and older age, junior high school education and above (OR=1.25, p＜0.05), being widowed rather than being married or cohabiting (OR=1.28, p＜0.05), engaging in physical activity (OR=1.14, p＜0.05), ex-smoker (OR=1.19, p＜0.05), habitual drinker (OR=0.72, p＜0.05), history of cardiovascular disease (CVD) (OR=2.20, p＜0.05) and comorbidities, with a higher probability for those with obesity (OR=1.89, p＜0.05), central obesity (OR=1.10, p＜0.05), diabetes (OR=1.49, p＜0.05) or dyslipidaemia (OR=1.20, p＜0.05). Male sex (OR=0.91, p＜0.05), junior high school education and above (OR=1.28, p＜0.05), engaging in physical activity (OR=1.06, p＜0.05), history of CVD (OR=1.82, p＜0.05) and individuals who had diabetes (OR=1.52, p＜0.05) or dyslipidaemia (OR=1.05, p＜0.05) were associated with increased likelihood of control. Aged 80 years and older (OR=0.93, p＜0.05), habitual drinker (OR=0.73, p＜0.05) and central obesity (OR=0.94, p＜0.05) were negatively associated with control of hypertension. CONCLUSIONS: We found a high prevalence of hypertension, but a low prevalence of treatment and control among Shenzhen elderly.

Lung ultrasound score based on the BLUE-plus protocol is associated with the outcomes and oxygenation indices of intensive care unit patients.

PURPOSE: The primary objective was to demonstrate the relationship between lung ultrasound (LUS) manifestations and the outcomes of intensive care unit (ICU) patients. The secondary objective was to determine the characteristics of LUS manifestations in different subgroups of ICU patients. METHODS: This prospective multi-center cohort study was conducted in 17 ICUs. A total of 1702 patients admitted between August 31, 2017 and February 16, 2019 were included. LUS was performed according to the bedside lung ultrasound in emergency (BLUE)-plus protocol, and LUS scores were calculated. Data on the outcomes and oxygenation indices were analyzed and compared between different primary indication groups. RESULTS: The LUS scores were significantly higher for non-survivors than for survivors and were significantly different between the oxygenation index groups, with higher scores in the lower oxygenation index groups. The LUS score was an independent risk factor for the 28-day mortality. The area under the receiver operating characteristic curve was 0.663 for prediction of the 28-day mortality and 0.748 for prediction of an oxygenation index ≤100. CONCLUSIONS: The LUS score based on the BLUE-plus protocol was an independent risk factor for the 28-day mortality and was important for the prediction of an oxygenation index ≤100. An early LUS score within 24 hours of ICU admission helps predicting the outcome of ICU patients.

The effects of UCP2 on autophagy through the AMPK signaling pathway in septic cardiomyopathy and the underlying mechanism.

BACKGROUND: Mitochondrial dysfunction plays an important role in the development of septic cardiomyopathy. This study aimed to reveal the protective role of uncoupling protein 2 (UCP2) in mitochondria through AMP-activated protein kinase (AMPK) on autophagy during septic cardiomyopathy. METHODS: UCP2 knockout mice via a cecal ligation and puncture (CLP) model and the H9C2 cardiomyocyte cell line in response to lipopolysaccharide (LPS) in vitro were used to study the effect. The myocardial morphological alterations, indicators of mitochondrial injury and levels of autophagy-associated proteins (pAMPK, pmTOR, pULK1, pTSC2, Beclin-1, and LC3-I/II) were assessed. In addition, the mechanism of the interaction between UCP2 and AMPK was further studied through gain- and loss-of-function studies. RESULTS: Compared with the wild-type mice, the UCP2 knockout mice exhibited more severe cardiomyocyte injury after CLP, and the AMPK agonist AICAR protected against such injury. Consistent with this result, silencing UCP2 augmented the LPS-induced pathological damage and mitochondrial injury in the H9C2 cells, limited the upregulation of autophagy proteins and reduced AMPK phosphorylation. AICAR protected the cells from morphological changes and mitochondrial membrane potential loss and promoted autophagy. The silencing and overexpression of UCP2 led to correlated changes in the AMPK upstream kinases pLKB1 and CAMKK2. CONCLUSIONS: UCP2 exerts cardioprotective effects on mitochondrial dysfunction during sepsis via the action of AMPK on autophagy.

Plasma mitochondrial DNA levels are associated with acute lung injury and mortality in septic patients.

BACKGROUND: Mitochondrial DNA (mtDNA) is a critical activator of inflammation. Circulating mtDNA released causes lung injury in experimental models. We hypothesized that elevated plasma mtDNA levels are associated with acute lung injury (ALI) in septic patients. METHODS: We enrolled 66 patients with sepsis admitted to the Department of Critical Care Medicine of Peking Union Medical College Hospital between January 2019 and October 2019. Respiratory, hemodynamic and bedside echocardiographic parameters were recorded. Plasma mtDNA, procalcitonin, interleukin 6, and interleukin 8 levels were examined. RESULTS: Plasma mtDNA levels within 24 h after admission were significantly increased in the group of septic patients with ALI [5.01 (3.38-6.64) vs 4.13 (3.20-5.07) log copies/µL, p 0.0172]. mtDNA levels were independently associated with mortality (hazard ratio, 3.2052; 95% CI 1.1608-8.8500; p 0.0253) and ALI risk (odds ratio 2.7506; 95% CI 1.1647-6.4959; p 0.0210). Patients with high mtDNA levels had worse outcomes, and post hoc tests showed significant differences in 28-day survival rates. Increased mtDNA levels were seen in patients with abdominal infection. CONCLUSIONS: Increased plasma mtDNA levels within 24 h after admission were significantly associated with ALI incidence and mortality in septic patients.

Effect of Focused Cardiac Ultrasound in Combination with Lung Ultrasound on Critically Ill Patients: A Multicenter Observational Study in China.

Objective Focused cardiac ultrasound (FCU) and lung ultrasound (LU) are increasingly being used in critically ill patients. This study aimed to investigate the effect of FCU in combination with LU on these patients and to determine if the timing of ultrasound examination was associated with treatment change. Methods This is a multicenter cross-sectional observational study. Consecutive patients admitted to the intensive care unit (ICU) were screened for enrollment. FCU and LU were performed within the first 24 h, and treatment change was proposed by the performer based on the ultrasound results and other clinical conditions. Results Among the 992 patients included, 502 were examined within 6 h of ICU admission (early phase group), and 490 were examined after 6 h of admission (later phase group). The early phase group and the later phase group had similar proportions of treatment change (48.8% vs. 49.0%, χ 2=0.003, P=0.956). In the multivariable analysis, admission for respiratory failure was an independent variable associated with treatment change, with an odds ratio (OR) of 2.357 [95% confidence interval (CI): 1.284-4.326, P=0.006]; the timing of examination was not associated with treatment change (OR=0.725, 95%CI: 0.407-1.291, P=0.275). Conclusions FCU in combination with LU, whether performed during the early phase or later phase, had a significant impact on the treatment of critically ill patients. Patients with respiratory failure were more likely to experience treatment change after the ultrasound examination.

Fluctuations of driving pressure during mechanical ventilation indicates elevated central venous pressure and poor outcomes.

Inappropriate mechanical ventilation may induce hemodynamic alterations through cardiopulmonary interactions. The aim of this study was to explore the relationship between airway pressure and central venous pressure during the first 72 h of mechanical ventilation and its relevance to patient outcomes. We conducted a retrospective study of the Department of Critical Care Medicine of Peking Union Medical College Hospital and a secondary analysis of the MIMIC-III clinical database. The relationship between the ranges of driving pressure and central venous pressure during the first 72 h and their associations with prognosis were investigated. Data from 2790 patients were analyzed. Wide range of driving airway pressure (odds ratio, 1.0681; 95% CI, 1.0415-1.0953; p < 0.0001) were independently associated with mortality, ventilator-free time, intensive care unit and hospital length of stay. Furthermore, wide range of driving pressure and elevated central venous pressure exhibited a close correlation. The area under receiver operating characteristic demonstrated that range of driving pressure and central venous pressure were measured at 0.689 (95% CI, 0.670-0.707) and 0.681 (95% CI, 0.662-0.699), respectively. Patients with high ranges of driving pressure and elevated central venous pressure had worse outcomes. Post hoc tests showed significant differences in 28-day survival rates (log-rank (Mantel-Cox), 184.7; p < 0.001). In conclusion, during the first 72 h of mechanical ventilation, patients with hypoxia with fluctuating driving airway pressure have elevated central venous pressure and worse outcomes.

Induction and deduction in sepsis-induced cardiomyopathy: five typical categories.

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. The heart is one of the most important oxygen delivery organs, and dysfunction significantly increases the mortality of the body. Hence, the heart has been studied in sepsis for over half a century. However, the definition of sepsis-induced cardiomyopathy is not unified yet, and the conventional conception seems outdated: left ventricular systolic dysfunction (LVSD) along with enlargement of the left ventricle, recovering in 7 to 10 days. With the application of echocardiography in intensive care units, not only LVSD but also left ventricular diastolic dysfunction, right ventricular dysfunction, and even diffuse ventricular dysfunction have been seen. The recognition of sepsis-induced cardiomyopathy is gradually becoming complete, although our understanding of it is not deep, which has made the diagnosis and treatment stagnate. In this review, we summarize the research on sepsis-induced cardiomyopathy. Women and young people with septic cardiomyopathy are more likely to have LVSD, which may have the same mechanism as stress cardiomyopathy. Elderly people with ischemic cardiomyopathy and hypertension tend to have left ventricular diastolic dysfunction. Patients with mechanical ventilation, acute respiratory distress syndrome or other complications of increased right ventricular afterload mostly have right ventricular dysfunction. Diffuse cardiac dysfunction has also been shown in some studies; patients with mixed or co-existing cardiac dysfunction are more common, theoretically. Thus, understanding the pathophysiology of sepsis-induced cardiomyopathy from the perspective of critical care echocardiography is essential.

Study on Image Acquisition of Transthoracic Echocardiography in Mechanically Ventilated ICU Patients.

Objective This study aimed to determine which parameters in transthoracic echocardiography (TTE) are more likely to be affected when applied in a critical care setting with mechanical ventilation.Methods Ninety mechanically ventilated ICU patients were enrolled into the study group. The control group consisted of 90 patients who underwent interventional therapy. All patients had bedside TTE for parametric measurements including the right ventricular size, septal kinetics and left ventricular ejection fraction (LVEF) by eyeballing (visual assessment), the tricuspid annular plane systolic excursion (TAPSE), mitral annular plane systolic excursion (MAPSE) by M-mode sonography, the right ventricular outflow tract velocity-time integral (RVOT VTI) and left ventricular outflow tract velocity-time integral (LVOT VTI) by pulse-Doppler, the right ventricular fraction of area change (FAC) and left ventricular ejection fraction (LVEF Simpson) by endocardium tracing. We compared the differences in the frequency of optimal image acquisition in assessments of these parameters between the two groups, as well as the differences in acquisition rates of parameter measurements in ventilated ICU patients.Results There were significantly fewer patients in the study group than in the control group who had optimal images acquisitions for parameter assessments with M-mode method, pulse Doppler method and endocardium-tracing method (P<0.05); no significant difference was obsered in the number of patients with optimal images for RV eyeballing and LVEF eyeballing between the two groups. In the study group, significantly fewer optimal images were acquired for FAC than for TAPSE (22.2% vs. 72.2%, χ2=45.139, P<0.001) and RVOT VTI (22.2% vs. 71.1%, χ2=43.214, P<0.001); there were also fewer optimal images acquired for LVEF Simpson than for MAPSE (37.8% vs. 84.4%, χ2=41.236, P<0.001) and LVOT VTI (37.8% vs. 85.6%, χ2=43.455, P<0.001).Conclusions Images acquisition of optimal TTE images tend to be difficult in mechanically ventilated ICU patients, but eyeballing method for functional evaluation could be an alternative method. For quantitative parameters measurements, M-mode based longitudinal function evaluation and pulse Doppler-based VTI were superior to the endocardium-tracing based parameter assessments.

A cross-sectional study of acute cor pulmonale in acute respiratory distress syndrome patients in China.

BACKGROUND: Increased right ventricle afterload during acute respiratory distress syndrome (ARDS) may induce acute cor pulmonale (ACP), which is associated with a poor clinical outcome. Echocardiography is now considered as a rapid and non-invasive tool for diagnosis of ACP. The aims of this study were to investigate the morbidity and mortality rates of ACP in ARDS patients in intensive care units (ICUs) across the mainland of China and to determine the severity and prognosis of ACP in ARDS patients through an ultrasound protocol (TRIP). And the association between ACP related factors and the ICU mortality will be revealed. METHODS: This study is a multicenter and cross-sectional study in China which will include ICU participants when diagnosed as ARDS. The ultrasound protocol, known as the TRIP, is proposed as severity assessment for ACP, which includes tricuspid regurgitation velocity (T), right ventricular size (R), inferior vena cava diameter fluctuation (I), and pulmonary regurgitation velocity (P). The 28-day mortality, ICU/hospital mortality, the length of stay in ICU, mechanical ventilation days, hemodynamic parameters and lab parameters of liver function and kidney function are all recorded. DISCUSSION: This large-scale study would give a sufficient epidemic investigation of ACP in ARDS patients in China. In addition, with the TRIP protocol, we expect that we could stratify ACP with more echocardiography parameters. TRIAL REGISTRATION: NCT03827863, https://clinicaltrials.gov/ct2/show/NCT03827863.

Early initiation renal replacement therapy for fluid management to reduce central venous pressure is more conducive to renal function recovery in patients with acute kidney injury.

BACKGROUND: Acute kidney injury (AKI) is a serious complication in critically ill patients with septic shock treated in the intensive care unit. Renal replacement therapy (RRT) is a treatment for severe AKI; however, the time of initiation of RRT and factors that affect the recovery of kidney function remains unclear. This study was to explore whether early initiation of RRT treatment for fluid management to reduce central venous pressure (CVP) can help to improve patients' kidney function recovery. METHODS: A retrospective analysis of septic patients who had received RRT treatment was conducted. Patients received RRT either within 12 h after they met the diagnostic criteria of renal failure (early initiation) or after a delay of 48 h if renal recovery had not occurred (delayed initiation). Parameters such as patients' renal function recovery at discharge, fluid balance, and levels of CVP were assessed. RESULTS: A total of 141 patients were eligible for enrolment: 40.4% of the patients were in the early initiation group (57 of 141 patients), and 59.6% were in the delayed initiation group (84 of 141 patients). There were no significant differences in the characteristics at baseline between the two groups, and there were no differences in 28-day mortality between the two groups (χ = 2.142, P = 0.143); however, there was a significant difference in the recovery rate of renal function between the two groups at discharge (χ = 4.730, P < 0.001). More importantly, early initiation of RRT treatment and dehydration to reduce CVP are more conducive to the recovery of renal function in patients with AKI. CONCLUSION: Compared with those who received delayed initiation RRT, patients who received early-initiation RRT for dehydration to reduce CVP have enhanced kidney function recovery.

Microcirculation dysfunction in endotoxic shock rabbits is associated with impaired S-nitrosohemoglobin-mediated nitric oxide release from red blood cells: a preliminary study.

BACKGROUND: Microcirculation dysfunction with blood flow heterogeneity is an important characteristic in sepsis shock. We hypothesized that impaired ability of red blood cells to release nitric oxide resulted in microcirculation dysfunction in sepsis shock. METHODS: 4,4'-Diisothiocyanatostilbene-2,2'-disulfonic acid disodium salt hydrate (DIDS), an inhibitor of band3 protein, was used to inhibit S-nitrosohemoglobin-mediated nitric oxide release. Rabbits were randomly divided into four groups: control (n = 6), lipopolysaccharide (LPS) (n = 6), LPS + DIDS (n = 6), and control + DIDS group (n = 6). Macrocirculation (cardiac output and mean arterial pressure) and microcirculation (microvascular flow index and flow heterogeneity index) parameters were recorded. At 2-h time point, arterial and venous S-nitrosohemoglobin concentrations were measured. RESULTS: The arterial-venous difference for S-nitrosohemoglobin in the LPS group was lower than the control group (27.3 ± 5.0 nmmol/L vs. 40.9 ± 6.2 nmmol/L, P < 0.05) but was higher than the LPS + DIDS group, with a statistically significant difference (27.3 ± 5.0 nmmol/L vs. 16.0 ± 4.2 nmmol/L, P < 0.05). Microvascular flow index for the LPS group at 2 h was lower than the control group (1.13 ± 0.16 vs. 2.82 ± 0.08, P < 0.001) and higher than the LPS + DIDS group (1.13 ± 0.16 vs. 0.84 ± 0.14, P < 0.05). Flow heterogeneity index for the LPS group at 2 h was higher than the control group (1.03 ± 0.27 vs. 0.16 ± 0.06, P < 0.001) and lower than the LPS + DIDS group (1.03 ± 0.27 vs. 1.78 ± 0.46, P < 0.001). CONCLUSIONS: In endotoxic shock rabbits, the ability of S-nitrosohemoglobin-mediated nitric oxide release from RBC was impaired, and there was an association between the ability and microcirculation dysfunction especially increased blood flow heterogeneity.

Resuscitation of Septic Patients with Target-and-endpoint Protocol: A Retrospective Study from a Chinese Tertiary Hospital ICU.

Objective To investigate the effect of target-and-endpoint protocol on the resuscitation of septic patients.Methods This is a retrospective study performed at the Peking Union Medical College Hospital Intensive Care Unit. We enrolled 545 septic patients who needed vasopressors on at least the first day of ICU admission. The general characteristics, blood lactate level, mean arterial pressure (MAP), central venous pressure (CVP) and saturation of central venous oxygen (ScvO2) at admission and 6, 24 hours after admission were collected. The parameters at different time points were compared. Lactate clearance rate and in-hospital mortality were analyzed.Results The 6-hour lactate clearance rate was 21.6% (IQR, 8.6%-39.0%), and in-hospital mortality was 9.4%. For patients with low CVP values (<8 mm Hg, 1 mm Hg=0.133 kPa) at admission, CVP increased significantly at 6 hours after admission (5.4±1.6 mm Hg vs. 7.7±2.6 mm Hg, P<0.001). For patients with low MAP (<75 mm Hg) at admission, the MAP values increased significantly at 6 hours (64.2±7.1 mm Hg vs. 82.2±13.1 mm Hg, P<0.001). For patients with low ScvO2 value (<70%) at admission, the ScvO2 value increased significantly at 6 hours (61.9%±7.0% vs. 71.9%±7.8%, P<0.001). No difference was found between the values at 6 hours and the corresponding values at 24 hours after admission. For patients with high CVP values (≥8 mm Hg) at admission, CVP decreased significantly at 6 hours (11.3±4.0 mm Hg vs. 10.3±2.9 mm Hg, P<0.001). For patients with high MAP (≥75 mm Hg) at admission, the MAP values decreased significantly at 6 hours (94.2±13.9 mm Hg vs. 89.4±11.4 mm Hg, P<0.001). For patients with high ScvO2 value (≥70%) at admission, the ScvO2 values decreased significantly at 6 hours (76.8%±4.2% vs. 72.9%±7.3%, P<0.001). No difference was found between the values at 6 hours and the corresponding values at 24 hours.Conclusions This study suggested that in the resuscitation of sepsis and septic shock patients in the ICU, the target values did not need to be within the "normal range" recommended by early-goal directed therapy. The "target-and-endpoint" protocol, which aimed for personalized goals, deserves more consideration.

Rapid characterization of the absorbed chemical constituents of Tangzhiqing formula following oral administration using UHPLC-Q-TOF-MS.

Tangzhiqing formula, a Chinese herbal formula, is used for the treatment of type II diabetes and prediabetes. Although its effectiveness has been certified by clinical use, its absorbed chemical constituents are not comprehensively represented. Thence, in order to reveal potential bioactive components and metabolism of Tangzhiqing formula, an ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry method was developed. A total of 86 absorbed components, including 38 prototype compounds and 48 metabolites, were identified in rat plasma, urine, and feces after oral administration of Tangzhiqing formula. This was the first systematic study on the chemical constituents and metabolic profiling of Tangzhiqing formula. The results indicated that alkaloids and flavonoids were main absorbed components, and glucuronidation and sulfation were the major metabolites. Moreover we concluded that alkaloids and flavonoids first underwent demethylation and hydrolysis reactions before biotransformed to phase II metabolites. This study provided valuable data for safety estimation of Tangzhiqing formula, which will be advantageous for clinical application.