Successful management of severe hypoglycemia induced by total parenteral nutrition in patients with hepatocellular injury: Three cases reports.

BACKGROUND: Glucose imbalance is common in total parenteral nutrition (TPN). Hypoglycemia seems to be less frequent than hyperglycemia, but it influences the clinical outcome to a greater extent. Therefore, it should be effectively prevented and treated. However, there is no relevant report on how to treat hypoglycemia caused by TPN in patients with liver cell injury. CASE SUMMARY: We present three patients with liver cell injury who developed severe hypoglycemia during or after TPN infusion. The causes of severe hypoglycemia and glucose-raising strategies were discussed. According to the physiological characteristics of the hepatocellular injury, the ratio of nutrition components prescribed in TPN was appropriately adjusted for the three cases. We simultaneously reduced the dose of insulin and fat emulsion, and increased the dose of glucose in TPN. The blood glucose level was restored to normal range and clinical symptoms were eliminated. CONCLUSION: When hypoglycemia occurs during or after TPN in patients with hepatocellular injury, physicians need to simultaneously reduce insulin and fat emulsion, and increase glucose, and correct severe hypoglycemia in time to reduce its adverse consequences.

Determination of vericiguat in rat plasma by UPLC-MS/MS and its application to drug interaction.

Vericiguat (VER) is a novel soluble guanylate cyclase stimulator treating symptomatic chronic heart failure (HF), and it is a substrate of both transporters P-glycoprotein and breast cancer resistance protein (BCRP). Astragaloside IV (ASIV) is the main active ingredient in Radix Astragali (Huangqi), a traditional Chinese medicine widely used for HF treatment in China. ASIV's effect on the protein expression of P-glycoprotein and BCRP has been observed, its impact on VER metabolism remain uncertain. In the present study, male Sprague-Dawley rats were administered with 20 mg/kg ASIV and 1 mg/kg VER to study their pharmacokinetics. Blood samples were subject to liquid-liquid extraction, and riociguat was employed as the internal standard (IS). The analytical method involved a C18 column (XSelect® HSS T3 column, 2.1 × 100 mm, 2.5 µm) with a mobile phase of 0.1% formic acid and acetonitrile for gradient elution. The flow rate of the mobile phase was set at 0.2 mL/min, and 5 µL of the sample was used for analysis. The positive ion multi-response monitoring mode was utilized with a transition of m/z 427.4→109.1 for VER and m/z 423.3→109.1 for the IS. The method exhibited good linearity within the concentration range of 0.1 to 300 ng/mL (r = 0.9987), and all the validation processes were conducted in accordance with the requirements of biological analysis. The pharmacokinetic results revealed that ASIV did not significantly alter the main parameters of VER, except for Cmax, which decreased by 33.2% (P < 0.05). Overall, our study successfully established a selective, sensitive and repeatable ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis for detecting VER in rat plasma.

Anti­PD1 therapy­associated distal renal tubular acidosis: A case report.

Distal renal tubular acidosis (RTA) is a rare adverse reaction to immune checkpoint inhibitors, which only occurs in a small number of cases. To the best of our knowledge, distal RTA caused by sintilimab, a programmed cell death protein 1 (PD-1) inhibitor, has not been previously reported. In the present study, the case of a 62-year-old man with metastatic cardiac carcinoma treated with sintilimab anti-PD-1 therapy was reported. After the fourth administration of sintilimab, the treatment course was interrupted by metabolic hyperchloraemic acidosis with hypokalaemia. Following urine and blood tests, immunotherapy-induced distal RTA was suspected. Treatment with sintilimab and chemotherapy was stopped, and treatment with sodium bicarbonate and potassium citrate was started, which resulted in an adequate response. The present study provides the first case of distal RTA secondary to sintilimab treatment.

What condition leads to an unreasonable pharmaceutical price? Impact research on the effect of medical service provision on pharmaceutical price regulation based on fuss-set QCA.

Given that the pharmaceutical market has experienced severe market failures, it is necessary that we regulate pharmaceutical prices for many countries. Toward ensuring that pharmaceutical price regulation is efficient, this study investigated the antecedents that lead to an unreasonable pharmaceutical price. Based on 33 case-study countries, this study utilized QCA to analyze the conditional configuration of unreasonable pharmaceutical prices from the perspective of medical service provision. The results showed that the causes of unreasonable pharmaceutical prices are configured by medical service provision, especially cost compensation systems and payment mechanism. This study's conclusions contribute to the research on pharmaceutical price regulation and the institution of medical service provision.

Late­onset immune checkpoint inhibitor­related pneumonitis after cessation of sintilimab: A case report and literature review.

Immune-related adverse events following treatment with immune checkpoint inhibitors (ICIs) can occur at any time during therapy, with onset occurring most frequently during the first 3 months of treatment. However, they rarely occur after treatment cessation. An awareness of delayed immune-related events following the termination of immunotherapy is paramount for optimal tumour management. The present study reports a case of a 69-year-old male patient with right lung adenocarcinoma. He suffered from psoriasis for ~40 years and was suspected of developing immune checkpoint inhibitor-related pneumonitis (CIP) 6 months after the cessation of treatment with the anti-programmed cell death-1 receptor antibody sintilimab. The present case study is, to the best of our knowledge, the first case of late-onset CIP after the cessation of sintilimab. Subsequently, the report also reviews previously reported cases of late-onset CIP after the cessation of ICI treatment. The present report highlights the finding that CIP can develop, although rarely reported, months or even years after the termination of immunotherapy. Therefore, CIP should always be considered as one of the possibilities and addressed accordingly once the pulmonary infection is ruled out. Careful monitoring, timely diagnosis and administration of corticosteroids are essential in controlling this condition, particularly for patients with pre-existing autoimmune diseases.

Acute liver injury induced by drug interaction between dacomitinib and metoprolol due to the inhibition of CYP2D6 by dacomitinib.

INTRODUCTION: In recent years, oral antineoplastic agents are commonly used in antitumor therapy. The interaction between drugs may affect the efficacy of drugs or lead to adverse reactions. We describe the case of a patient who presented acute liver injury, possibly induced by the concomitant use of metoprolol and dacomitinib. CASE REPORT: A 62-year-old male patient with non-small cell lung cancer was admitted for anti-cancer treatment. He regularly took metoprolol tartrate 12.5 mg, 2/day for hypertension. He was treated with dacomitinib according to EGFR Exon21 L858R positive. After 3 days of dacomitinib, the patient's alanine aminotransferase (ALT) and glutathione aminotransferase (AST) increased, and the heart rate and systolic blood pressure of the patient decreased significantly. The patient was diagnosed with acute liver injury. MANAGEMENT AND OUTCOMES: Dacomitinib was discontinued and glutathione, magnesium isoglycyrrhizinate were given to treat acute liver injury. Two days after discontinued dacomitinib, the patient's heart rate increased, but the ALT and AST of the patient elevated again. Metoprolol tartrate was subsequently discontinued and the ALT and AST gradually decreased and the patient discharged from the hospital eight days later with his liver function improved. DISCUSSION: To our knowledge, this is the first case in the literature of acute liver injury possibly induced by the interaction between metoprolol and dacomitinib. The interaction most likely arose because dacomitinib is a CYP2D6 strong inhibitor and could therefore impair the metabolism of metoprolol (a CYP2D6 substrate) and increase its serum concentration. Therefore, hepatic function should be carefully monitored in patients treated with dacomitinib and metoprolol and other inhibitors or inducers of CYP2D6.

Comprehensive Evaluation of Clinical Application of Balanced Compound Amino Acid Injection.

Background: To provide a reference for hospital drug selection and rational clinical drug selection based on the evaluation of the safety, nutritional quality, and economy of 27 manufacturers of five varieties (18AA, 18AA-I, 18AA-II, 18AA-IV, 18AA-V) of balanced compound amino acids for injection and (18AA-IIoriginal research). Methods: The safety of compound amino acids for injection was evaluated by comparing the antioxidant sulfite contents. Based on the amino acid scoring standard mode and the whole egg protein mode as proposed by the Food and Agriculture Organization of the United Nations/World Health Organization (FAO/WHO) in 1973, we compared the formula. The first limiting amino acid content and the comprehensive quality of the total essential amino acid (EAA) contents of the six formulations were studied. The price/content ratio was used to evaluate their economy. Results: Similar variety produced by different manufacturers have the same formula and contents of balanced compound amino acids for injection. Safety: 18AA-IIoriginal research and 18AA-II had the lowest sulfite content. Compared with 18AA-IIoriginal research, the sulfite content of 18AA-I, 18AA, 18AA-V, and 18AA-IV were higher (10 times, 16.67 times, 16.67 times, and 33.33 times, respectively). The lower the sulfite content, the safer the product. Nutritional quality: The proportions of amino acids in the five varieties of compound amino acid injection were all suitable. The order of the first limiting amino acids for the formulations was 18AA-IIoriginal research = 18AA-II>18AA >18AA-I = 18AA-IV>18AA-V. The order of the EAA values for the formulations was 18AA-IIoriginal research = 18AA-II>18AA>18AA-I > 18AA-IV > 18AA-V. The overall effectiveness order was 18AA-IIoriginal research = 18AA-II>18AA > 18AA-I>18AA-IV>18AA-V. Economy: Among the 27 manufacturers, 12 manufacturers had a price/content ratio higher than that of 18AA-II original research manufacturers, and 15 manufacturers had a price/content ratio lower than original research manufacturers. Conclusion: Through its security, effectiveness, and economy of the comprehensive research, we recommended 18AA-II and 18AA-IIoriginal research with high safety, efficacy, and reasonable price as the first choice. 18AA and 18AA-I with better safety and reasonable price, secondary recommendation. 18AA-IV or 18AA-V with poor safety, efficacy, and economy are not recommended.

What factors determine brand communication? A hybrid brand communication model from utilitarian and hedonic perspectives.

Introduction: With the advancement of new media, brand communication has been taken into consideration by lots of firms. Apparently, customer affection plays a significant role in brand communications, though few studies have determined how the twofold of information function works in this communication mechanism. Based on this research gap and practical background, this paper proposes a hybrid model of communication comprising the utilitarian and hedonic aspects. Methods: For this study, 575 questionnaires were collected, followed by the structural equation modeling of the derived data to test the research model. Results: The results of statistical analysis show that the brand communication can be improved in terms of both utilitarian and hedonic aspects. Moreover, psychological contract and customer engagement play a chain mediation role in this mechanism. Discussion: These findings contribute to the research of brand communication mechanism in digital era. Likewise, the findings offers several practical implications to the brand management.

Four new myrsinol diterpenes from Euphorbia prolifera.

Four new myrsinol diterpenes, euphorbialoids K-N (1-4), have been isolated from the roots of Euphorbia prolifera. Their structures were elucidated on the basis of extensive 1D and 2D NMR (COSY, HMQC, HMBC, and NOESY) and mass (ESI-MS and HR-ESI-MS) spectroscopic data analyses.

Three new myrsinol diterpenes from Euphorbia prolifera and their neuroprotective activities.

Three new myrsinol diterpenes were isolated from the roots of Euphorbia prolifera. Their structures were elucidated as 2α-O-isobutyryl-3ß,5α,7ß,10,15ß-penta-O-acetyl-14α-O-benzoyl-10,18-dihydromyrsinol (1), 2α-O-isobutyryl-3ß-O-propion-yl-5α,7ß,10,15ß-tetra-O-acetyl-10,18-dihydromyrsinol (2), and 2α,14α-di-O-benzoyl-3ß,5α,7ß,10,15ß-penta-O-acetyl-10,18-dihydromyrsinol (3) on the basis of spectroscopic data analyses (IR, ESI-MS, HR-ESI-MS, and 1D and 2D NMR). Their neuroprotective activities were evaluated and compounds 1 and 2 showed neuroprotective effects against MPP+ -induced neuronal cell death in SH-SY5Y cells.

Isolation, characterization, and NO inhibitory activities of sesquiterpenes from Blumea balsamifera.

Blumea balsamifera belongs to the family Compositae, and its leaves have been used as a flavoring ingredient and a tea. A phytochemical investigation of the aerial parts of B. balsamifera led to the isolation of 10 new (1-10) and 1 known (11) sesquiterpenes. Their structures were elucidated on the basis of extensive one- and two-dimensional nuclear magnetic resonance (heteronuclear multiple-quantum coherence, heteronuclear multiple-bond correlation, (1)H-(1)H correlation spectroscopy, and nuclear Overhauser effect spectrometry) spectroscopic data analyses, and the structure of compound 1 was confirmed by X-ray crystallography. The inhibitory activities on lipopolysaccharide-induced NO production in murine microglial BV-2 cells of these sesquiterpenes were evaluated, and all of the compounds showed inhibitory effects.

Iridoids from the roots of Valeriana jatamansi.

Two new iridoids, jatamanvaltrates N (1) and O (2), together with four known compounds (3-6), were isolated from the roots of Valeriana jatamansi. Their structures and relative configurations were elucidated by spectroscopic methods (IR, ESI-MS, HR-ESI-MS, 1D, and 2D NMR) and by comparison of their NMR spectral data with those of related compounds. All the isolated compounds were evaluated for their neuroprotective effects, and only compound 1 showed weak neuroprotective activities.

Iridoids from the roots of Valeriana jatamansi and their biological activities.

A new iridoid, jatamandoid A (1), and four known analogues (2-5) were isolated from the roots of Valeriana jatamansi. Their structures were elucidated on the basis of extensive spectroscopic analysis (IR, ESI-MS, HR-ESI-MS, 1-D and 2-D NMR). Five compounds were evaluated and compounds 1, 2 and 5 showed moderate neuroprotective effects against MPP(+)-induced neuronal SH-SY5Y cell death.

Bioactive myrsinol diterpenoids from the roots of Euphorbia prolifera.

Ten myrsinol diterpenes, euphorbiaproliferins A-J (1-10), along with nine known analogues (11-19) were isolated from the roots of Euphorbia prolifera. Their structures were elucidated by spectroscopic data analysis (IR, ESIMS, HRESIMS, 1D and 2D NMR), and the structure of 1 was confirmed by X-ray crystallography. The diterpenes showed neuroprotective effects against MPP+-induced neuronal cell death in SH-SY5Y cells.