Integrated models of population pharmacokinetics and exposure response to optimize dosage regimen for anaprazole sodium in duodenal ulcer.

Anaprazole sodium enteric-coated tablet is a novel proton pump inhibitor which has been approved for the treatment of duodenal ulcer. The aim of this study is to provide reliable information for the design of an optimal dosage regimen. Population pharmacokinetics and exposure-response models were integrated to evaluate the pharmacokinetic parameters and covariates of Anaprazole and its metabolite M21-1, and subsequently provided dosage suggestions based on clinical trials and simulation data. A pharmacokinetic model incorporating two-compartment for the parent drug and one-compartment for the metabolite, with both first-order and zero-order mixed absorption was used to describe the pharmacokinetics of Anaprazole and M21-1. Age emerged as a significant covariate affecting the elimination rate constant of M21-1, with clearance decreasing as age advances. No correlation was observed between the pharmacokinetics of Anaprazole or M21-1 and the adverse reactions under the current dosages. BMI might be the influence factor of the mild gastrointestinal adverse reactions. Meanwhile, Anaprazole had a good healing rate (94.0 %) in duodenal ulcer patients and the exposure-response analysis indicated that the cured results were not influenced by the exposure parameters of parent drug or metabolite. In conclusion, the drug is safe when dosing between 20 and 100 mg once a day.

Chronic pancreatitis: Pain and computed tomography/magnetic resonance imaging findings.

Chronic pancreatitis (CP) is a fibroinflammatory disease characterized by irreversible destruction of pancreatic tissue. With the development of the disease, it may lead to exocrine and/or endocrine insufficiency. CP is one of the common diseases that cause abdominal pain, which will not get permanent spontaneous relief as the disease evolves. The American College of Gastroenterology clinical guidelines recommend computed tomography or magnetic resonance imaging as the first-line examination for the diagnosis of CP. CP common imaging findings include pancreatic atrophy, irregular dilatation of the pancreatic duct, calcification of pancreatic parenchyma, pancreatic duct stones, etc. In clinical practice, whether any correlations between CP-induced abdominal pain patterns (no pain/constant/intermittent pain) and corresponding imaging findings present are not well known. Therefore, this review aims to comprehensively sort out and analyze the relevant information by collecting lots of literature on this field, so as to construct a cross-bridge between the clinical manifestations and imaging manifestations of CP patients. Also, it provides an imaging basis and foundation for the classification and diagnosis of abdominal pain types in clinical CP patients.

Classification of anatomical morphology of cystic duct and its association with gallstone.

BACKGROUND: Gallstones are common lesions that often require surgical intervention. Laparoscopic cholecystectomy is the treatment of choice for symptomatic gallstones. Preoperatively, the anatomical morphology of the cystic duct (CD), needs to be accurately recognized, especially when anatomical variations occur in the CD, which is otherwise prone to bile duct injury. However, at present, there is no optimal classification system for CD morphology applicable in clinical practice, and the relationship between anatomical variations in CDs and gallstones remains to be explored. AIM: To create a more comprehensive clinically applicable classification of the morphology of CD and to explore the correlations between anatomic variants of CD and gallstones. METHODS: A total of 300 patients were retrospectively enrolled from October 2021 to January 2022. The patients were divided into two groups: The gallstone group and the nongallstone group. Relevant clinical data and anatomical data of the CD based on magnetic resonance cholangiopancreatography (MRCP) were collected and analyzed to propose a morphological classification system of the CD and to explore its relationship with gallstones. Multivariate analysis was performed using logistic regression analyses to identify the independent risk factors using variables that were significant in the univariate analysis. RESULTS: Of the 300 patients enrolled in this study, 200 (66.7%) had gallstones. The mean age was 48.10 ± 13.30 years, 142 (47.3%) were male, and 158 (52.7%) were female. A total of 55.7% of the patients had a body mass index (BMI) ≥ 24 kg/m2. Based on the MRCP, the CD anatomical typology is divided into four types: Type I: Linear, type II: n-shaped, type III: S-shaped, and type IV: W-shaped. Univariate analysis revealed differences between the gallstone and nongallstone groups in relation to sex, BMI, cholesterol, triglycerides, morphology of CD, site of CD insertion into the extrahepatic bile duct, length of CD, and angle between the common hepatic duct and CD. According to the multivariate analysis, female, BMI (≥ 24 kg/m2), and CD morphology [n-shaped: Odds ratio (OR) = 10.97, 95% confidence interval (95%CI): 5.22-23.07, P < 0.001; S-shaped: OR = 4.43, 95%CI: 1.64-11.95, P = 0.003; W-shaped: OR = 7.74, 95%CI: 1.88-31.78, P = 0.005] were significantly associated with gallstones. CONCLUSION: The present study details the morphological variation in the CD and confirms that CD tortuosity is an independent risk factor for gallstones.

Betel-nut chewing does not influence PD-L1 expression rates in recurrent/metastatic head and neck squamous cell carcinoma (HNSCC): A prospective biomarker prevalence study.

This study explored the relationship between betel-nut chewing and programmed death-ligand 1 (PD-L1) expression in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) patients in Taiwan. A total 280 R/M HNSCC patients, predominantly male, were evaluated; 75.4 % of whom chewed betel-nut. The prevalence of PD-L1 expression (combined positive score ≥1) was 94.3 % with similar PD-L1 expression rates between betel-nut-exposed and non-exposed groups. PD-L1 prevalence did not differ in those who received prior first-or second-line systemic therapy. In summary, betel-nut exposure did not notably affect PD-L1 expression rates in R/M HNSCC patients in Taiwan.

NADPH oxidase-dependent H2O2 production mediates salicylic acid-induced salt tolerance in mangrove plant Kandelia obovata by regulating Na+/K+ and redox homeostasis.

Salicylic acid (SA) is known to enhance salt tolerance in plants. However, the mechanism of SA-mediated response to high salinity in halophyte remains unclear. Using electrophysiological and molecular biological methods, we investigated the role of SA in response to high salinity in mangrove species, Kandelia obovata, a typical halophyte. Exposure of K. obovata roots to high salinity resulted in a rapid increase in endogenous SA produced by phenylalanine ammonia lyase pathway. The application of exogenous SA improved the salt tolerance of K. obovata, which depended on the NADPH oxidase-mediated H2O2. Exogenous SA and H2O2 increased Na+ efflux and reduced K+ loss by regulating the transcription levels of Na+ and K+ transport-related genes, thus reducing the Na+/K+ ratio in the salt-treated K. obovata roots. In addition, exogenous SA-enhanced antioxidant enzyme activity and its transcripts, and the expressions of four genes related to AsA-GSH cycle as well, then alleviated oxidative damages in the salt-treated K. obovata roots. However, the above effects of SA could be reversed by diphenyleneiodonium chloride (the NADPH oxidase inhibitor) and paclobutrazol (a SA biosynthesis inhibitor). Collectively, our results demonstrated that SA-induced salt tolerance of K. obovata depends on NADPH oxidase-generated H2O2 that affects Na+/K+ and redox homeostasis in response to high salinity.

PlantC2U: deep learning of cross-species sequence landscapes predicts plastid C-to-U RNA editing in plants.

In plants, C-to-U RNA editing mainly occurs in plastid and mitochondrial transcripts, which contributes to a complex transcriptional regulatory network. More evidence reveals that RNA editing plays critical roles in plant growth and development. However, accurate detection of RNA editing sites using transcriptome sequencing data alone is still challenging. In the present study, we develop PlantC2U, which is a convolutional neural network, to predict plastid C-to-U RNA editing based on the genomic sequence. PlantC2U achieves >95% sensitivity and 99% specificity, which outperforms the PREPACT tool, random forests, and support vector machines. PlantC2U not only further checks RNA editing sites from transcriptome data to reduce possible false positives, but also assesses the effect of different mutations on C-to-U RNA editing based on the flanking sequences. Moreover, we found the patterns of tissue-specific RNA editing in the mangrove plant Kandelia obovata, and observed reduced C-to-U RNA editing rates in the cold stress response of K. obovata, suggesting their potential regulatory roles in plant stress adaptation. In addition, we present RNAeditDB, available online at https://jasonxu.shinyapps.io/RNAeditDB/. Together, PlantC2U and RNAeditDB will help researchers explore the RNA editing events in plants and thus will be of broad utility for the plant research community.

Identification of pattern recognition receptor genes in peripheral blood mononuclear cells and monocytes as biomarkers for the diagnosis of lupus nephritis.

BACKGROUND: The study aimed to investigate the diagnostic value of lupus-related pattern recognition receptors (PRRs) genes in peripheral blood mononuclear cells (PBMCs) and monocytes (MONs) for lupus nephritis (LN). METHODS: PBMCs were isolated from a cohort with 37 LN patients and 39 healthy controls (HCs), and MONs were derived from another cohort with 70 LN patients and 66 HCs. Q-PCR was used to measure the mRNA levels of CGAS, IFNB1, AIM2, IL1Β, NLRC4, NLRP3, NLRP12 and ZBP1 in the PBMCs and MONs. The Mann-Whitney U test was used to compare the data in LN patients and HCs. Eleven GEO datasets of SLE/LN were used to perform differentially expressed genes (DEGs) analysis to these PRR genes. Receiver operating characteristic (ROC) curve analysis was employed to assess the performance of individual genes or the disease prediction model established by combining multiple genes in LN diagnosis. Spearman correlation method was done to analyze the correlation between these PRRs and other clinical characteristics. RESULTS: The mRNA levels of five genes (AIM2, NLRC4, IL1B, NLRP12 and ZBP1) in PBMCs, and seven genes (CGAS, IFNB1, AIM2, IL1B, NLRP3, NLRP12 and ZBP1) in MONs of LN patients were significantly higher than those of HCs (P < 0.05). DEGs analysis based on the GEO datasets showed that ZBP1, AIM2 and IL1B were significantly increased in several datasets. The ROC curve analysis indicated that the area under curve (AUC) of the LN prediction models derived from PBMCs or MONs were 0.82 or 0.91 respectively. In addition, the expression levels of these PRRs were correlated with other clinical features in LN patients, including Anti-Sm, ESR, serum Cr, and C3. CONCLUSION: Our study suggests that these lupus-related PRRs might be served as potential biomarkers of LN.

Potential beneficial effects of long-term aspirin use on the prevalence of colorectal cancer: a population-based study of the US Nationwide Inpatient Sample.

PURPOSE: Whether long-term aspirin usage is associated with colorectal cancer (CRC) risk needs more evidence. The study evaluated the association between long-term aspirin use and prevalence of CRC in a large, nationally representative database. METHODS: Hospitalized patients aged ≥ 50 years during 2018 were identified in the United States (US) National Inpatient Sample (NIS). Patients without complete information of age, sex, race, income, and insurance status were excluded, as well as those with inflammatory bowel disease (IBD) or malignancies other than CRC. Propensity score matching (PSM) was applied to balance the characteristics between patients with and without long-term aspirin use. Logistic regressions were performed to determine the relationship between long-term aspirin use and the presence of CRC. CRC and aspirin use were identified through the administrative International Classification of Diseases (ICD) codes. RESULTS: Data from 3,490,226 patients were included, in which 688,018 (19.7%) had a record of long-term aspirin use. After 1:1 PSM, there remained 1,376,006 patients, representing 6,880,029 individuals in the US after weighting. After adjusting for confounders, long-term aspirin use was significantly associated with lower CRC odds (adjusted odds ratio [aOR] = 0.64, 95% confidence interval [CI] 0.62, 0.67). This association was not changed when stratified by age, sex, race, body mass index (BMI), and smoking. CONCLUSIONS: From a national inpatient dataset, US adults ≥ 50 years on long-term aspirin are less likely to have CRC, regardless of age, sex, race, BMI, and smoking status.

Brassinosteroid enhances salt tolerance via S-nitrosoglutathione reductase and nitric oxide signaling pathway in mangrove Kandelia obovata.

Brassinosteroid (BR) has been shown to modulate plant tolerance to various stresses. S-nitrosoglutathione reductase (GSNOR) is involved in the plant response to environment stress by fine-turning the level of nitric oxide (NO). However, whether GSNOR is involved in BR-regulated Na+ /K+ homeostasis to improve the salt tolerance in halophyte is unknown. Here, we firstly reported that high salinity increases the expression of BR-biosynthesis genes and the endogenous levels of BR in mangrove Kandelia obovata. Then, salt-induced BR triggers the activities and gene expressions of GSNOR and antioxidant enzymes, thereafter decrease the levels of malondialdehyde, hydrogen peroxide. Subsequently, BR-mediated GSNOR negatively regulates NO contributions to the reduction of reactive oxygen species generation and induction of the gene expression related to Na+ and K+ transport, leading to the decrease of Na+ /K+ ratio in the roots of K. obovata. Finally, the applications of exogenous BR, NO scavenger, BR biosynthetic inhibitor and GSNOR inhibitor further confirm the function of BR. Taken together, our result provides insight into the mechanism of BR in the response of mangrove K. obovata to high salinity via GSNOR and NO signaling pathway by reducing oxidative damage and modulating Na+ /K+ homeostasis.

A physiologically based toxicokinetic model of P-glycoprotein transporter-mediated placenta perfusion of dexamethasone in the pregnant rat.

The present dosage of Dexamethasone (DEX) administered to pregnant women may pose a risk of toxicity to their unborn offspring. We aimed to develop a maternal-fetal physiologically based toxicokinetic (PBTK) model for DEX in pregnant rats, with a specific focus on the role of the P-glycoprotein (P-gp) transporter in placenta perfusion, and finally facilitate the optimization of clinical DEX dosage. We conducted animal experiments to determine DEX concentrations in various rat tissues, and constructed the PBTK model using MATLAB software. Sensitivity analysis was performed to assess input parameters and the model stability, with fold error (FE) values serving as evaluation indices. Our results indicate the successful construction of the PBTK model, with the fitting key parameters such as the absorption rate constant (Ka), intrinsic hepatic clearance (CLh,int) and intrinsic P-gp clearance (CLint,P-gp). The median concentration of DEX in maternal plasma, fetal plasma, fetal lung, and fetal brain were determined, which allowed us to fit the tissue-to-plasma partition coefficients for the fetal lung (Kp,lung,f) and fetal brain (Kp,brain,f). After making adjustments, all calculated FE values were found to be less than 2, demonstrating the acceptability and accuracy of our model's predictions. Our model integrated external literature data and internal animal experimentation to comprehensively evaluate the maternal-fetal PK characteristics of DEX. These findings provide valuable support for the optimization of clinical DEX dosing.

Population Pharmacokinetic/Pharmacodynamic Analysis of the Glucokinase Activator PB201 in Healthy Volunteers and Patients with Type 2 Diabetes Mellitus: Facilitating the Clinical Development of PB201 in China.

PB201 is an orally active, partial glucokinase activator targeting both pancreatic and hepatic glucokinase. As the second glucokinase activator studied beyond phase I, PB201 has demonstrated promising glycemic effects as well as favorable pharmacokinetic (PK) and safety profiles in patients with type 2 diabetes mellitus (T2DM). This study aims to develop a population PK/pharmacodynamic (PD) model for PB201 using the pooled data from nine phase I/II clinical trials conducted in non-Chinese healthy volunteers and a T2DM population and to predict the PK/PD profile of PB201 in a Chinese T2DM population. We developed the PK/PD model using the non-linear mixed-effects modeling approach. All runs were performed using the first-order conditional estimation method with interaction. The pharmacokinetics of PB201 were well fitted by a one-compartment model with saturable absorption and linear elimination. The PD effects of PB201 on reducing the fasting plasma glucose and glycosylated hemoglobin levels in the T2DM population were described by indirect response models as stimulating the elimination of fasting plasma glucose, where the production of glycosylated hemoglobin was assumed to be stimulated by fasting plasma glucose. Covariate analyses revealed enhanced absorption of PB201 by food and decreased systemic clearance with ketoconazole co-administration, while no significant covariate was identified for the pharmacodynamics. The population PK model established for non-Chinese populations was shown to be applicable to the Chinese T2DM population as verified by the PK data from the Chinese phase I study. The final population PK/PD model predicted persistent and dose-dependent reductions in fasting plasma glucose and glycosylated hemoglobin levels in the Chinese T2DM population receiving 50/50 mg, 100/50 mg, and 100/100 mg PB201 twice daily for 24 weeks independent of co-administration of metformin. Overall, the proposed population PK/PD model quantitatively characterized the PK/PD properties of PB201 and the impact of covariates on its target populations, which allows the leveraging of extensive data in non-Chinese populations with the limited data in the Chinese T2DM population to successfully supported the waiver of the clinical phase II trial and facilitate the optimal dose regimen design of a pivotal phase III study of PB201 in China.

Four new hypogean species of the genus Triplophysa (Osteichthyes, Cypriniformes, Nemacheilidae) from Guizhou Province, Southwest China, based on molecular and morphological data.

Recently described cave species of the genus Triplophysa have been discovered in southwestern China, suggesting that the diversity of the genus is severely underestimated and that there may be many undescribed species. In this work, four new species of the genus Triplophysa are described from southwestern Guizhou Province, China, namely Triplophysacehengensis Luo, Mao, Zhao, Xiao & Zhou, sp. nov. and Triplophysarongduensis Mao, Zhao, Yu, Xiao & Zhou, sp. nov. from Rongdu Town, Ceheng County, Guizhou, Triplophysapanzhouensis Yu, Luo, Lan, Xiao & Zhou, sp. nov. from Hongguo Town, Panzhou City, Guizhou, and Triplophysaanlongensis Song, Luo, Lan, Zhao, Xiao & Zhou, sp. nov. from Xinglong Town, Anlong County, Guizhou. These four new species can be distinguished from all recognized congeners by a combination of morphological characteristics and significant genetic divergences. The discovery of these species increases the number of known cave species within the genus Triplophysa to 39, making the genus the second most diverse group of cave fishes in China after the golden-line fish genus Sinocyclocheilus. Based on the non-monophyletic relationships of the different watershed systems in the phylogenetic tree, this study also discusses the use of cave species of the genus Triplophysa to determine the possible historical connectivity of river systems.

Microarray Expression Profile of Exosomal circRNAs from High Glucose Stimulated Human Renal Tubular Epithelial Cells.

Introduction: Circular RNA (circRNAs) are a type of non-coding RNA (ncRNAs) with a wealth of functions. Recently, circRNAs have been identified as important regulators of diabetic kidney disease (DKD), owing to their stability and enrichment in exosomes. However, the role of circRNAs in exosomes of tubular epithelial cells in DKD development has not been fully elucidated. Methods: In our study, microarray technology was used to analyze circRNA expression in cell supernatant exosomes isolated from HK-2 cells with or without high glucose (HG) treatment. The small interfering RNAs (siRNA) and plasmid overexpression were used to validate functions of differentially expressed circRNAs. Results: We found that exosome concentration was higher in HG-stimulated HK-2 cells than in controls. A total of 235 circRNAs were significantly increased and 458 circRNAs were significantly decreased in the exosomes of the HG group. In parallel with the microarray data, the qPCR results showed that the expression of circ_0009885, circ_0043753, and circ_0011760 increased, and the expression of circ_0032872, circ_0004716, and circ_0009445 decreased in the HG group. Rescue experiments showed that the effects of high glucose on regulation of CCL2, IL6, fibronetin, n cadherin, e cadherin and epcam expression can be reversed by inhibiting or overexpressing these circRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) biological pathway analyses indicated that circRNA parental genes are associated with glucose metabolism, lipid metabolism, and inflammatory processes, which are important in DKD development. Further analysis of circRNA/miRNA interactions indicated that 152 differentially expressed circRNAs with fold change (FC) ≥1.5 could be paired with 43 differentially expressed miRNAs, which are associated with diabetes or DKD. Discussion: Our results indicate that exosomal circRNAs may be promising diagnostic and therapeutic biomarkers, and may play a critical role in the progression of DKD.

Integrated Network Pharmacology and Experimental Approach to Investigate the Protective Effect of Jin Gu Lian Capsule on Rheumatoid Arthritis by Inhibiting Inflammation via IL-17/NF-κB Pathway.

Purpose: This study aimed to investigate the main pharmacological action and underlying mechanisms of Jin Gu Lian Capsule (JGL) against rheumatoid arthritis (RA) based on network pharmacology and experimental verification. Methods: Network pharmacology approaches were performed to explore the core active compounds of JGL, key therapeutic targets, and signaling pathways. Molecular docking was used to predict the binding affinity of compounds with targets. In vivo experiments were undertaken to validate the findings from network analysis. Results: A total of 52 targets were identified as candidate JGL targets for RA. Sixteen ingredients were identified as the core active compounds, including, quercetin, myricetin, salidroside, etc. Interleukin-1 beta (IL1B), transcription factor AP-1 (JUN), growth-regulated alpha protein (CXCL1), C-X-C motif chemokine (CXCL)3, CXCL2, signal transducer and activator of transcription 1 (STAT1), prostaglandin G/H synthase 2 (PTGS2), matrix metalloproteinase (MMP)1, inhibitor of nuclear factor kappa-B kinase subunit beta (IKBKB) and transcription factor p65 (RELA) were obtained as the key therapeutic targets. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed that the efficacy of JGL was functionally involved in regulating immune-mediated inflammation, in which IL-17/NF-κB signaling was recommended as one of the main pathways. Molecular docking suggested that the core active compounds bound strongly to their respective targets. Experimentally, JGL treatment mitigated inflammation, showed analgesic activity, and ameliorated collagen-induced arthritis. Enzyme-linked immunosorbent assay showed that JGL effectively reduced the serum levels of cytokines, chemokines, and MMPs. Immunohistochemistry staining showed that JGL markedly reduced the expression of the targets in IL-17/NF-κB pathway including IL-17A, IL-17RA, NF-κB p65, C-X-C motif ligand 2, MMP1 and MMP13. Conclusion: This investigation provided evidence that JGL may alleviate RA symptoms by partially inhibiting the immune-mediated inflammation via IL-17/NF-κB pathway.

[Gender differences in antidepressant effect of raw Rehmanniae Radix].

For the first time, this study evaluated the gender differences and mechanisms of the antidepressant effects of raw Rehmanniae Radix(RRR) based on the classic depression model with traditional Chinese medicine syndrome of Yin deficiency and internal heat. The depression model with Yin deficiency and internal heat was established by the widely recognized and applied method of thyroxine induction of the classic depression model with Yin deficiency and internal heat(chronic unpredictable mild stress). Male and female mice were simultaneously treated with RRR. The study analyzed indicators of nourishing Yin and clearing heat, conventional antidepressant efficacy test indicators, and important biomolecules reflecting the pathogenesis and prevention and treatment mechanisms of depression, and conducted a correlation analysis of antidepressant efficacy, Yin-nourishing and heat-clearing efficacy, and biological mechanism in different genders, thereby comprehensively assessing the antidepressant effects of RRR on depression of Yin deficiency and internal heat, as well as its gender differences and mechanisms. RRR exhibited antidepressant effects in both male and female mouse models, and its antidepressant efficacy showed gender differences, with a superior effect observed in females. Moreover, the effects of RRR on enhancing or improving hippocampal neuronal pathology, nucleus-positive areas, postsynaptic dense area protein 95, and synaptophysin protein expression were more significant in females than in males. In addition, RRR significantly reversed the abnormal upregulation of nuclear factor(NF)-κB/cyclooxygenase 2(COX2)/NOD-like receptor thermal protein domain associated protein 3(NLRP3) pathway proteins in the hippocampus of both male and female mouse models. The antidepressant effects of RRR were more pronounced in depression female mice with Yin deficiency and internal heat syndrome, possibly due to the improvement of neuronal damage and enhancement of neuroplasticity. The antidepressant mechanisms of RRR for depression with Yin deficiency and internal heat syndrome may be associated with the downregulation of the NF-κB/COX2/NLRP3 pathway to reduce neuronal damage and enhance neuroplasticity.

Magnetic resonance imaging for acute pancreatitis in type 2 diabetes patients.

Type 2 diabetes mellitus (T2DM) and its complications have significantly increased the burden of mortality and disability globally, making diabetes one of the most dangerous and prevalent chronic diseases. Acute pancreatitis (AP) is one of the most frequent gastrointestinal causes for hospital admission, which is a common exocrine pancreatic inflammatory disease that can cause severe abdominal pain and multiple organ dysfunction. There is an inseparable relationship between AP and diabetes. Diabetes is a high risk factor of AP, and patients with AP can develop pancreatogenic diabetes. In T2DM patients, the incidence rate of AP is significantly higher than that of the general population, and the clinical symptoms are more severe, with the majority of cases being moderate to severe AP. This review briefly introduces the pathogenesis and clinical features of AP in T2DM patients, focusing on the magnetic resonance imaging (MRI) manifestations of AP in T2DM patients. Our aim is to evaluate the severity of AP in patients with T2DM by MRI, so as to help clinicians assess the patient's condition and prognosis.

Case report: Giant atypical granular cell tumor of the median nerve.

Granular cell tumors are extremely uncommon soft tissue neoplasms that mostly occur in the head and neck regions. Granular cell tumors are generally benign, asymptomatic, and rarely involve the median nerve. Due to the lack of awareness about granular cell tumors, they are easily misdiagnosed and mistreated in primary hospitals. Here, we report a giant atypical granular cell tumor located on the median nerve, approximately 12 cm in size, with unusual symptoms of median nerve damage. Magnetic resonance imaging revealed a fusiform mass that was hyperintense on T2-weighted images and iso-hypointense on T1-weighted images. The mass was subsequently biopsied and found to be a granular cell tumor. The tumor was resected, and a pathological examination was performed. Pathological examination revealed necrotic foci, abundant eosinophilic granules, pustular ovoid bodies, and multiple mitoses. Immunohistochemical staining revealed that the tumor cells were positive for S-100, CD68, SMA, SOX-10, Calretinin, and TFE3. The integrated diagnosis was an atypical granular cell tumor. To the best of our knowledge, this is the first report of an atypical granular cell tumor involving the median nerve. Furthermore, we comprehensively reviewed the existing literature to provide a concise summary of the diagnostic criteria, imaging findings, and pathological features of granular cell tumors. Given the high recurrence and metastasis rates of this disease, granular cell tumors of the median nerve should be considered when a patient presents with symptoms of median nerve impairment. The diagnosis of atypical granular cell tumors relies on pathological examination. In addition, extensive resection and long-term follow-up are necessary to improve prognosis.

PEGylated exenatide injection (PB-119) improves beta-cell function and insulin resistance in treatment-naïve type 2 diabetes mellitus patients.

Objective: PB-119, a PEGylated exenatide injection, is a once-weekly glucagon-like peptide-1 receptor agonist. In the present study, we aimed to evaluate the effects of PB-119 on insulin resistance and beta-cell function in Chinese patients with type 2 diabetes mellitus (T2DM) to uncover its antidiabetic characteristics. Methods: A total of 36 Chinese T2DM patients were randomized to receive 25 µg and 50 µg PB-119 once weekly and exenatide (5-10 µg injected under the skin 2 times a day adjusted by the doctor) for 12 weeks. Oral mixed meal tolerance tests were conducted before the study and on Day 79. The data were fitted to estimate beta-cell function and insulin sensitivity parameters using the SAAM II package integrating the oral minimal model (OMM), which was compared with Homeostatic Model Assessment (HOMA) analysis results. Results: Exenatide or PB-119 treatment, compared with their baseline, was associated with higher beta-cell function parameters (φb, φs and φtot), disposition index, insulin secretion rates, and a lower glucose area under the curve. High-dose PB-119 also has a higher insulin resistance parameter (SI) than the baseline, but HOMA-IR did not. For the homeostatic model assessment parameters, HOMA-IR showed no statistically significant changes within or between treatments. Only high-dose PB-119 improved HOMA-ß after 12 weeks of treatment. Conclusion: After 12 weeks of treatment, PB-119 decreased glycemic levels by improving beta-cell function and insulin resistance.

Comparison of subperiosteal or subgaleal drainage and subdural drainage in patients with chronic subdural hematoma: A systematic review and meta-analysis.

BACKGROUND: Chronic subdural hematoma (CSDH) is a relatively common disease, especially in the elderly, for which there is no clear standard of treatment available. The authors systematically evaluated the efficacy of various surgical procedures for the treatment of chronic subdural hematoma. METHODS: Electronic databases of PubMed, EmBase, Web of Science, Medicine, and the Cochrane Library were searched systematically. Based on the PRISMA template, we finally selected and analyzed 13 eligible papers to evaluate the effect of different drainage methods on CSDH. The primary outcomes were recurrence and clinical outcomes. Secondary outcomes were mortality and postoperative complications and other parameters. RESULTS: The meta-analysis included 3 randomized controlled trials and 10 retrospective studies (non-randomized controlled trials) involving 3619 patients. The pooled results showed no statistically significant difference between non-subdural drainage (NSD) and subdural drainage (SD) in mortality and complication rates (P > 0.05). Additionally, overall pooled results showed that the use of NSD (10.9%) has a lower recurrence rate than the use of SD (11.7%), but the results were not statistically significant (relative risk ratio [RR] = 0.98; 95% confidence interval [CI] = 0.70-1.45; I2 = 47%; P = .92). However, the difference between NSD and SD in postoperative bleeding rate reached statistical significance (RR = 2.39; 95% CI = 1.31-4.36; I2 = 0 %; P = .004). Subgroup analysis showed that SD was associated with similar recurrent CSDH (RR = 0.75; 95% CI = 0.52-1.09; I2 = 0%; P = .14), good recovery (RR = 0.98; 95% CI = 0.93-1.04; I2 = 0%; P = .50), and mortality (RR = 0.98; 95% CI = 0.37-2.57; I2 = 0%; P = .96), compared to NSD. CONCLUSIONS: These results suggest that NSD and SD are equally effective in the treatment of patients with CSDH, with no difference in final clinical characteristics and radiologic outcomes. However, in patients with limited subdural space after evacuation of a hematoma, NSD may be the preferred strategy to avoid iatrogenic brain injury.

Application of national early warning score in assessing postoperative illness severity in elderly patients with gastrointestinal illnesses.

BACKGROUND: Population aging is a social problem that is being faced in most countries. OBJECTIVE: To apply the National Early Warning Score (NEWS) for an early warning on the vital signs and consciousness of elderly patients who are hospitalized in the gastrointestinal surgical department and to provide a reference for early detection of changes in illness severity in elderly patients by studying the correlation between NEWS value and changes in illness severity. METHODS: We enrolled 528 elderly patients who were hospitalized in the gastrointestinal surgical department of a tertiary grade A hospital in Guizhou Province between June 2020 and May 2021, to analyze how NEWS max value correlates with illness severity and obtain the optimal NEWS cutoff value for both potentially critically ill and critically ill elderly patients using the receiver operating characteristic (ROC) curve. RESULTS: There were statistically significant differences in NEWS values between elderly patients with various illness severities (P< 0.05). NEWS values correlated positively with illness severity (r= 0.605, P< 0.001). Based on the ROC curve, early warning trigger values for NEWS to identify potentially critically ill, critically ill and terminally ill elderly patients were 6, 7 and 8, respectively. The area under the curve (AUC) for potentially critically ill, critically ill and terminally ill elderly patients was 0.907, 0.921 and 0.939, respectively. NEWS performed better in detecting patient illness severity than Modified Early Warning Score (MEWS) in AUC, sensitivity, specificity, and Youden's index, with statistically significant differences (P< 0.05). CONCLUSION: An early warning on the vital signs and consciousness of hospitalized elderly patients using NEWS can facilitate advanced detection of changes in illness severity of elderly patients by medical staff and enable timely treatment, thus significantly lowering the risks of illness deterioration.