Siwu tablet attenuates high fructose-induced glomerular podocyte senescence in rats through increasing Nup155 to promote INO80 mRNA nuclear export.

ETHNOPHARMACOLOGICAL RELEVANCE: Siwu tablet (SWT), derived from a traditional Chinese medicinal formula named Siwu decoction, is widely used for blood deficiency syndrome. Siwu decoction and its derived formulas have been proven to improve renal anemia and prevent senescence. Whether SWT prevents glomerular podocyte senescence and the underlying molecular mechanism remains unknow. AIM OF THE STUDY: To elucidate the protective effect and possible mechanism of SWT on glomerular podocyte senescence. MATERIAL AND METHODS: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was performed to characterize components of SWT. Male Sprague-Dawley rats were given 10% fructose drinking water for 16 weeks. SWT (810 and 1620 mg/kg) was administered orally for the last 8 weeks. The assays of senescence-associated beta-galactosidase (SA-ß-gal) staining, immunohistochemistry, quantitative real-time polymerase chain reaction (qRT-PCR), and Western blot as well as enzyme linked immunosorbent assay were performed to evaluate rat glomerular podocyte senescence. The mRNA and protein levels of nucleoporin 155 (Nup155) and inositol requiring mutant 80 (INO80) in rat glomeruli were detected by qRT-PCR, Western blot and immunofluorescence. Foot processes and nuclear pore complexes (NPCs) of rat glomerular podocytes were visualized by transmission electron microscopy. RESULTS: One hundred and fifty-nine components were preliminarily identified in SWT. The results of animal experiments showed that SWT decreased the activity of SA-ß-gal, protein levels of p16, p21, p53 and phosphorylated histone H2AX (γ-H2AX), and mRNA levels of interleukin-1ß (IL-1ß), IL-6 and tumor necrosis factor-α (TNF-α) in glomeruli of high fructose-fed rats. As expected, SWT increased renal cortex erythropoietin mRNA expression and serum erythropoietin concentration in this animal model. SWT reduced urine albumin-to-creatinine ratio and serum levels of uric acid, creatinine and blood urea nitrogen, and recovered glomerular structure injury in high fructose-fed rats. It up-regulated mRNA and protein levels of Nup155 and the number of podocyte NPCs, and subsequently reinforced mRNA nuclear export and protein expression of INO80 in rat glomeruli under high fructose stimulation. CONCLUSIONS: SWT ameliorates glomerular podocyte senescence in high fructose-fed rats possibly by increasing Nup155 to promote INO80 mRNA nuclear export.

Bioinformatics-based drug repositioning and prediction of the main active ingredients and potential mechanisms of action for the efficacy of Dan-Lou tablet.

Drug repositioning is gaining attention as a method for developing new drugs due to its low cost, short cycle time, and high success rate. One important approach is to explore new uses for already marketed drugs. In this study, we utilized the strategy of drug repositioning, focusing on the Dan-Lou tablet. We predicted the efficacy of Dan-Lou tablet against non-small cell lung cancer based on gene expression similarity and verified it by in vitro experiments. Next, we performed further analysis and validation using network pharmacology, molecular docking and molecular dynamics. Based on the results, it was concluded that Dan-Lou tablet mainly acted through nine compounds, Quercetin, Luteolin, Scoparone, Isorhamnetin, Eugenol, Genistein, Coumestrol, Hederagenin, Succinic Acid, and mainly targeted CCL2, FEN1, TPI1, RMI2 by six pathways. This discovery not only provides a new idea for the development of Dan-Lou tablet but also provides useful predictive information for clinical treatment. The method we adopted has great development prospects as a way to predict the efficacy of new drugs and their main mechanisms of action, and it has a positive impact on the research and development of new drugs using drug repositioning and the modernization of traditional Chinese medicine.

Characteristics and real-world medication persistence of people living with HIV treated with DTG/3TC or BIC/FTC/TAF: a hospital claims database study in Japan.

Background: As the life expectancy of people living with human immunodeficiency virus (HIV) (PLWH) has improved, chronic disease burden and polypharmacy have increased in PLWH. Simplification of the antiretroviral therapy (ART) regimen for PLWH has become crucial. The real-world treatment patterns and medication persistence of the 2-drug single-tablet regimen (STR), dolutegravir/lamivudine (DTG/3TC), compared to bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) prescribed were investigated. Methods: This retrospective, database study extracted data from a hospital-based medical claims database in Japan. The changes in ART distributions by year during the identification period between January 1, 2018 and December 31, 2021 were observed. Patients with disease record of HIV-1 infection and prescribed DTG/3TC or BIC/FTC/TAF as the first prescription of STR during the identification period were divided into two cohorts; DTG/3TC cohort and BIC/FTC/TAF cohort, respectively. Patient without medication records more than 3 months and no future data more than 6 months were excluded. Patients' characteristics were compared between the DTG/3TC cohort and the BIC/FTC/TAF cohort by Mantel-Haenszel test to adjust for age. Medication persistence was compared between the two cohorts by evaluating the continuation rates using Kaplan-Meier methods, using the log-rank test to assess the difference between the Kaplan-Meier curves. The median time-to-first prescription was compared between the two cohorts by Kaplan-Meier methods. Results: Prescriptions of DTG/3TC and BIC/FTC/TAF increased steadily from 2019 to 2021 after the release year of each STR. There was no significant difference in the time-to-first prescription (p = 0.3). A total of 959 patients were included, with 120 patients and 839 patients on DTG/3TC and BIC/FTC/TAF, respectively. The proportion of dyslipidemia at baseline was significantly higher in the DTG/3TC cohort than in the BIC/FTC/TAF cohort after adjusting for mean age (p = 0.002). There was no significant difference in medication persistence between the two cohorts (p = 0.91). Conclusion: This study showed that DTG/3TC was likely to be selected for elderly patients and those with chronic disease in real-world clinical practice, which seems in accordance with the treatment strategy recommended by guidelines. Comparable medication persistence was observed with both regimens, aligning with findings from other countries. The 2-drug single-tablet regimen DTG/3TC may be an important ART regimen for PLWH with multiple morbidities and polypharmacy in an aging society. Due to the limitations of the database, further research to assess viral loads, emergence of resistance and adverse events will be encouraged.

Tangningtongluo Tablet ameliorates pancreatic damage in diabetic mice by inducing autophagy and inhibiting the PI3K/Akt/mTOR signaling pathway.

BACKGROUND: Diabetes is a metabolic disease characterized by hyperglycaemia. Tangningtongluo Tablet (TNTL) is an inpatient formula extensively utilized to treat diabetes mellitus (DM), but the protective mechanism is not clear. This study aimed to investigate the relevant mechanisms by which TNTL affects pancreatic damage in diabetic mice and autophagy. METHODS: The impact of TNTL on pancreatic damage in diabetic mice in vitro and in vivo was investigated via glucose and lipid metabolism analyses, HE staining, CCK-8, TUNEL staining, Annexin V/PI, and Western blotting. Molecular docking and Western blotting were used to verify the results of network pharmacological analysis, which was carried out to explore the mechanism by which TNTL affects DM. The autophagosome levels were visualized via RFP-GFP-LC3 and transmission electron microscopy, and lysosomal function was evaluated via Lysotracker red staining. Western blot, immunohistochemistry and immunofluorescence staining were used to detect the expression of the autophagy proteins LC3, p62 and LAMP2. RESULTS: Compared with the model group, TNTL protected pancreas from oxidative stress, decreased the level of MDA, increased the levels of SOD and GSH-px, induced the occurrence of autophagy and decreased the levels of apoptotic factors. Moreover, TNTL inhibited the protein expression of p-PI3K, p-Akt and p-mTOR, increased the levels of LC3 and LAMP2 and decreased the level of p62, and the autophagy inhibitor CQ blocked the protective effect of TNTL on pancreatic damage in diabetic mice. CONCLUSION: These results demonstrated that TNTL ameliorated pancreatic damage in diabetic mice by inhibiting the PI3K/Akt/mTOR signaling and regulating autophagy.

A discovery in traditional Chinese medicine compatibility: Cinnabaris suppresses the Strychni Semen-induced neurotoxicity in Shang-Ke-Jie-Gu tablet.

BACKGROUND: Cinnabaris, as a commonly used mineral drugs, is a classic sedative medicine. Shang-Ke-Jie-Gu tablet is a famous Chinese patent medicine with Cinnabaris, However, the function of Cin in the prescription hasn't been clarified. PURPOSE: Our study evaluated the toxicity of Shang-Ke-Jie-Gu tablet (SK) with or without Cinnabaris, and illuminate the related mechanisms that why cinnabaris is necessary. METHODS: The toxicity of SK and Cin free Shang-Ke-Jie-Gu tablet (CFSK) was evaluated by physical and behavioral tests and histological examinations. The detoxificaion mechanism of Cin on Strychni Semen (SS)-induced neurotoxicity in SK was performed based on the analysis of intestinal absorption, liver metabolism, serum metabolomics, and gut microbiota. The mercury accumulation of SK was assayed using human hair by ICP-MS. RESULTS: Cin was found to inhibit the neurotoxicity of SS in SK. Our study shows that Cin could inhibit SS's absorption in small intestine and promote its metabolism in the liver. A serum metabolomics study showed that taurine and hypotaurine metabolism and retrograde endocannabinoid signaling pathway were associated with Cin attenuation. Association analysis with gut microbiota suggested that Cin could downregulate four key metabolites, including 12­hydroxy arachidonic acid, GM4(d18:1/18:0), C16 sphinganine, and LysoPC(18:1(11Z)/0:0), by downregulating Lachnospiraceae_NK4A136 and upregulating Prevotella to inhibit the toxic effects of SS. In addition, the danger of mercury poisoning in a longer time administration of SK was evaluated using human hair, and no visible increase in mercury was observed. CONCLUSION: As a new discovery in compatibility, Cin was proved to be capable of inhibiting the neurotoxicity not only in SK but also in Cin-SS combination, displaying vital roles in Traditional Chinese Medicines.

Comparison of the efficacy and adverse effects of oral ferrous succinate tablets and intravenous iron sucrose: a retrospective study.

OBJECTIVE: To analyse the clinical efficacy and adverse drug reactions (ADRs) of iron preparations. METHODS: A total of 374 patients with iron deficiency anaemia admitted to our hospital between 1 January and 31 December 2020 were included in this study. They were divided into 2 groups based on their medication regimens: Group A (n = 187) took oral ferrous succinate tablets, and Group B (n = 187) received intravenous iron sucrose. The remission of major symptoms, laboratory test results, ADRs and other related data were collected after 4 weeks of treatment. RESULTS: Compared with the pre-treatment baseline, haemoglobin (Hb), serum iron (SI), serum ferritin (SF) and the mean corpuscular volume (MCV) increased in both groups at 4 weeks of treatment (P < 0.05). After treatment, Group A had lower levels of Hb (108.41 ± 8.39 vs. 122.31 ± 6.04 g/L, t = 6.293, P < 0.001), SI (9.72 ± 4.24 vs. 15.62 ± 5.41 µmol/L, t = 5.482, P < 0.001) and SF (27.1 ± 10.82 vs. 39.82 ± 10.44 ug/L, t = 6.793, P < 0.001) compared with Group B. In contrast, there was no significant difference in the post-treatment level of MCV (P > 0.05). The overall response rate significantly differed between the 2 groups (78.61% vs. 90.91%, χ2 = 10.949, P < 0.001). The incidence of ADRs of both groups were similar, and the difference was not statistically significant (χ2 = 0.035, P = 0.851). CONCLUSION: Iron sucrose demonstrates favourable efficacy and safety in treating iron deficiency anaemia.

Relative bioavailability and food effect of the galectin-3 inhibitor selvigaltin (GB1211) administered as a tablet in healthy participants (GALBA-1).

PURPOSE: Overexpression of galectin-3, a ß-galactoside-binding lectin, is associated with fibrotic diseases and cancer. Selvigaltin is an oral galectin-3 inhibitor, previously administered as a 50 mg capsule. This study aimed to evaluate the relative bioavailability and food effect of selvigaltin as a 100 mg tablet in healthy volunteers. METHODS: In this single-dose, randomized, three-period, crossover study (GALBA-1; NCT05747573), participants received selvigaltin as a 100 mg tablet (under fasted and fed conditions) or as two 50 mg capsules (under fasted conditions). Primary endpoints included plasma and urine pharmacokinetic (PK) parameters. Secondary endpoints were safety and tolerability. RESULTS: Of the 13 enrolled participants, 12 completed the study. Under fasted conditions, geometric mean maximum observed plasma concentration (Cmax) and systemic exposure (AUC0─inf) of selvigaltin were 161.0% and 84.0% higher, respectively, after administration of a tablet vs. capsules. Under fed vs. fasted conditions, geometric mean Cmax of the selvigaltin tablet was 20.0% lower, whereas AUC0─inf was unaffected. Geometric mean percentage of total dose of selvigaltin excreted in urine over 0─96 h was 30.3% and 35.9% for the tablet under fasted and fed conditions, respectively, and 14.5% for the capsules. No treatment-emergent severe or serious adverse events or study discontinuations due to a treatment-emergent adverse event were reported. CONCLUSION: The tablet formulation of selvigaltin displayed higher bioavailability vs. the capsule formulation, with minimal effect of food on PK. Selvigaltin was well-tolerated during all treatments. These findings warrant further clinical development of the tablet formulation of selvigaltin without specific food restrictions. CLINICAL TRIAL REGISTRATION: NCT05747573; February 28, 2023.

Automatic tablet-based monoplane quantification of stroke volume and left ventricular ejection fraction: A comparative assessment against computer-based biplane and monoplane tools.

BACKGROUND: Point-of-care cardiovascular left ventricle ejection fraction (LVEF) quantification is established, but automatic tablet-based stroke volume (SV) quantification with handheld ultrasound (HAND) devices is unexplored. We evaluated a tablet-based monoplane LVEF and LV volume quantification tool (AutoEF) against a computer-based tool (Tomtec) for LVEF and SV quantification. METHODS: Patients underwent HAND scans, and LVEF and SV were quantified using AutoEF and computer-based software that utilized either apical four-chamber views (Auto Strain-monoplane [AS-mono]) or both apical four-chamber and apical two-chamber views (Auto Strain-biplane [AS-bi]). Correlation and Bland-Altman analysis were used to compare AutoEF with AS-mono and AS-bi. RESULTS: Out of 43 participants, eight were excluded. AutoEF showed a correlation of .83 [.69:.91] with AS-mono for LVEF and .68 [.44:.82] for SV. The correlation with AS-bi was .79 [.62:.89] for LVEF and .66 [.42:.81] for SV. The bias between AutoEF and AS-mono was 4.88% [3.15:6.61] for LVEF and 17.46 mL [12.99:21.92] for SV. The limits of agreement (LOA) were [-5.50:15.26]% for LVEF and [-8.02:42.94] mL for SV. The bias between AutoEF and AS-bi was 6.63% [5.31:7.94] for LVEF and 20.62 mL [16.18:25.05] for SV, with LOA of [-1.20:14.47]% for LVEF and [-4.71:45.94] mL for SV. CONCLUSION: LVEF quantification with AutoEF software was accurate and reliable, but SV quantification showed limitations, indicating non-interchangeability with neither AS-mono nor AS-bi. Further refinement of AutoEF is needed for reliable SV quantification at the point of care.

Acute Gastropathy Associated with Bowel Preparation for Colonoscopy.

Background/Aims: Utilization of low-volume preparation agents is crucial to improve patient willingness to undergo repeat colonoscopies. However, gastric safety data on preparation agents are limited. This study evaluated the acute gastropathy associated with bowel preparation agents. Methods: This retrospective study enrolled healthy subjects who underwent both esophagogastroduodenoscopy and colonoscopy screening. Baseline patient characteristics, bowel preparation success, acute gastropathy, and polyp and adenoma detection rates were evaluated for 1 L polyethylene glycol with ascorbic acid (1 L PEG/Asc) and oral sulfate tablet (OST) groups. Results: Comparison of the OST group (n=2,463) with the 1 L PEG/Asc group (n=2,060) revealed that the rates of successful cleansing and high-quality cleansing were similar between the two groups. Polyp and adenoma detection rates were significantly higher in the OST group than in the 1 L PEG/Asc group (p<0.001 and p=0.013), while the incidence of acute gastric mucosal lesion-like blood stain/clot, erosions at greater curvature side of antrum/body, multiple erosions, and overlying mucosal erythema or edema were all significantly higher in the OST group than in the 1 L PEG/Asc group (all p<0.001). Additionally, high and indeterminate probability scores of preparation agent-induced gastropathy (p=0.001) and mean Lanza scores were significantly higher in the OST group than in the 1 L PEG/Asc group (1.3 vs. 0.4, p<0.001). Conclusions: Compared with 1 L PEG/Asc, OSTs were significantly associated with acute gastropathy during bowel preparation, thus requiring careful consideration from physicians for the simultaneous screening of EGD and colonoscopy.

Feasibility of Indirect Treatment Comparisons Between Niraparib Plus Abiraterone Acetate and Other First-Line Poly ADP-Ribose Polymerase Inhibitor Treatment Regimens for Patients with BRCA1/2 Mutation-Positive Metastatic Castration-Resistant Prostate Cancer.

INTRODUCTION: Poly(ADP-ribose) polymerase inhibitors (PARPi) are a novel option to treat patients with metastatic castration-resistant prostate cancer (mCRPC). Niraparib plus abiraterone acetate and prednisone (AAP) is indicated for BRCA1/2 mutation-positive mCRPC. Niraparib plus AAP demonstrated safety and efficacy in the phase 3 MAGNITUDE trial (NCT03748641). In the absence of head-to-head studies comparing PARPi regimens, the feasibility of conducting indirect treatment comparisons (ITC) to inform decisions for patients with first-line BRCA1/2 mutation-positive mCRPC has been explored. METHODS: A systematic literature review was conducted to identify evidence from randomized controlled trials on relevant comparators to inform the feasibility of conducting ITCs via network meta-analysis (NMA) or population-adjusted indirect comparisons (PAIC). Feasibility was assessed based on network connectivity, data availability in the BRCA1/2 mutation-positive population, and degree of within- and between-study heterogeneity or bias. RESULTS: NMAs between niraparib plus AAP and other PARPi regimens (olaparib monotherapy, olaparib plus AAP, and talazoparib plus enzalutamide) were inappropriate due to the disconnected network, differences in trial populations related to effect modifiers, or imbalances within BRCA1/2 mutation-positive subgroups. The latter issue, coupled with the lack of a common comparator (except for olaparib plus AAP), also rendered anchored PAICs infeasible. Unanchored PAICs were either inappropriate due to lack of population overlap (vs. olaparib monotherapy) or were restricted by unmeasured confounders and small sample size (vs. olaparib plus AAP). PAIC versus talazoparib plus enzalutamide was not possible due to lack of published arm-level baseline characteristics and sufficient efficacy outcome data in the relevant population. CONCLUSION: The current randomized controlled trial evidence network does not permit robust comparisons between niraparib plus AAP and other PARPi regimens for patients with 1L BRCA-positive mCRPC. Decision-makers should scrutinize any ITC results in light of their limitations. Real-world evidence combined with clinical experience should inform treatment recommendations in this indication.

Guizhitongluo Tablet inhibits atherosclerosis and foam cell formation through regulating Piezo1/NLRP3 mediated macrophage pyroptosis.

BACKGROUND: Atherosclerosis (AS) is the main pathological basis for the development of cardiovascular diseases. Vascular inflammation is an important factor in the formation of AS, and macrophage pyroptosis plays a key role in AS due to its unique inflammatory response. Guizhitongluo Tablet (GZTLT) has shown clinically effective in treating patients with AS, but its mechanism is elusive. PURPOSE: This study was to determine the effects of GZTLT on atherosclerotic vascular inflammation and pyroptosis and to understand its underlying mechanism. MATERIALS AND METHODS: The active constituents of GZTLT were analysed by means of UPLC-HRMS. In vivo experiments were performed using ApoE-/- mice fed a high fat diet for 8 weeks, followed by treatment with varying concentrations of GZTLT orally by gavage and GsMTx4 (GS) intraperitoneally and followed for another 8 weeks. Oil red O, Haematoxylin-eosin (HE) and Masson staining were employed to examine the lipid content, plaque size, and collagen fibre content of the mouse aorta. Immunofluorescence staining was utilised to identify macrophage infiltration, as well as the expression of Piezo1 and NLRP3 proteins in aortic plaques. The levels of aortic inflammatory factors were determined using RT-PCR and ELISA. In vitro, foam cell formation in bone marrow-derived macrophages (BMDMs) was observed using Oil Red O staining. Intracellular Ca2+ measurements were performed to detect the calcium influx in BMDMs, and the expression of NLRP3 and its related proteins were detected by Western blot. RESULTS: The UPLC-HRMS analysis revealed 31 major components of GZTLT. Our data showed that GZTLT inhibited aortic plaque formation in mice and increased plaque collagen fibre content to stabilise plaques. In addition, GZTLT could restrain the expression of serum lipid levels and suppress macrophage foam cell formation. Further studies found that GZTLT inhibited macrophage infiltration in aortic plaques and suppressed the expression of inflammatory factors. It is noteworthy that GZTLT can restrain Piezo1 expression and reduce Ca2+ influx in BMDMs. Additionally, we found that GZTLT could regulate NLRP3 activation and pyroptosis by inhibiting Piezo1. CONCLUSION: The present study suggests that GZTLT inhibits vascular inflammation and macrophage pyroptosis through the Piezo1/NLRP3 signaling pathway, thereby delaying AS development. Our finding provides a potential target for AS treatment and drug discovery.

Posaconazole gastro-resistant tablets for preventing invasive fungal disease after haematopoietic stem cell transplantation: a propensity-matched cohort study.

OBJECTIVES: To evaluate posaconazole (POS) gastro-resistant tablets for preventing invasive fungal disease (IFD) in haematopoietic stem cell transplantation (HSCT) patients and analyse POS plasma concentrations. METHODS: A single-arm trial was designed with a historical cohort as a control. Patients aged 13 years and older undergoing HSCT at the HSCT Center of Blood Diseases Hospital, Chinese Academy of Medical Sciences between December 2020 and May 2022 were enrolled, prospectively taking POS gastro-resistant tablets orally from day 1 to day 90 post-transplant and monitoring plasma concentrations. We also identified a retrospective cohort treated with alternative antifungal prophylaxis between January 2018 and December 2020, matched using propensity score methods. The primary outcome was the cumulative incidence of IFD at day 90 post-transplant. RESULTS: The prospective study involved 144 patients receiving POS gastro-resistant tablets for IFD prevention, contrasting with 287 patients receiving non-POS tablets. By day 90 post-transplant, the POS tablet group exhibited a significantly lower cumulative incidence of IFD (2.81%; 95% CI, 0.09-5.50% vs. 7.69%; 95% CI, 4.60-10.78%; p 0.044). Adverse events were comparable between the groups with liver changes in 33/144 (22.92%) vs. 84/287 (29.27%) (p 0.162), and renal injuries in 15/144 (10.41%) vs. 37/287 (12.89%) (p 0.457). Mean POS plasma concentrations on days 4, 8, 15, and 22 post-administration were 930.97 ng/mL, 1143.97 ng/mL, 1569.8 ng/mL, and 1652.57 ng/mL, respectively. DISCUSSION: Patients administered POS gastro-resistant tablets for antifungal prophylaxis experienced a lower cumulative incidence of IFD. POS plasma concentrations in HSCT patients stabilized by day 15 of medication.

A Systematic Review of Tablet-Based Interactive Distraction as a Preoperative Anxiolytic in Pediatric Patients Undergoing Same-Day Procedures.

Evidence shows tablet-based interactive distraction (TBID) is effective as a preoperative anxiolytic in pediatric patients. TBID involves age-appropriate video games that have been preloaded onto a tablet (TAB) and subsequently given to a pediatric patient before the administration of anesthesia. The purpose of this study is to provide a comprehensive analysis of previous studies that have investigated the use of TBID to minimize preoperative anxiety. The literature criteria for this systematic review included randomized controlled trials and prospective studies that used TBID as a method to reduce preoperative anxiety in pediatric patients aged 1-12 years. Data extraction concentrated on the patient population to which the TABs were introduced, the method of TAB administration, how anxiety was evaluated, who completed the evaluations, and the results of each publication. This chosen data set is to systematically understand if TBID is effective and to identify the most practical ways to implement TBID. Collected data from the selected publications were entered into a table. For this systematic review, 27 publications from 2006 to 2023 were screened for eligibility. These studies were selected using a combination of MeSH terms and a Title-Abstract filter in PubMed, Embase, and Scopus. These data represented 475 total patients (T) and 249 patients who implemented TAB use. The other 226 patients were used as various control groups. The outcome of each study is summarized and placed into a table. This study is expected to provide an overall assessment of the effectiveness of TBID and proposed guidelines for clinicians to incorporate TAB use into preoperative protocols. The time to give the TAB to the children impacts its efficiency. This review accentuates the effectiveness of utilizing TBID to mitigate preoperative anxiety in pediatric patients based on a comprehensive analysis of multiple prior studies conducted in diverse healthcare settings, including pediatric hospitals and surgical centers. TAB use demonstrated an effective reduction in perioperative anxiety, emergence of delirium, and time to discharge, increasing parental satisfaction compared to midazolam. These results are likely replicable across a broader range of clinical settings, provided the intervention parameters, such as the timing of TAB introduction and the personalization of content to patient interests, are carefully adapted to each situation. The anxiety evaluations of patients using TBID varied based on the evaluator. Therefore, future research should analyze if perceived anxiety in patients using TABs is consistent or not among the evaluators. The impact of this TBID review has the potential to set a new benchmark for managing pediatric preoperative anxiety, with significant implications for healthcare quality and patient satisfaction.

A smart tablet-phone-based high-performance pancreatic cancer cell biosensing system for drug screening.

Exploring more efficient pancreatic cancer drug screening platforms is of significant importance for accelerating the drug development process. In this study, we developed a high-sensitivity bioluminescence system based on smartphones and smart tablets, and constructed a pancreatic cancer drug screening platform (PCDSP) by combining the pancreatic cancer cell sensing model (PCCSM) on the multiwell plates (MTP). A smart tablet was used as the light source and a smartphone as the colorimetric sensing device. The smartphone dynamically controls the color and brightness displayed on the smart tablet to achieve lower LOD and wider detection ranges. We constructed PCCSM for 24 h, 48 h, and 72 h , and performed colorimetric experiments using both PCDSP and a commercial plate reader (CPR). The results showed that the PCDSP had a lower LOD than that of CPR. Moreover, PCDSP even exhibited a lower LOD for 24 h PCCSM testing compared to CPR for 48 h PCCSM testing, effectively shortening the drug evaluation process. Additionally, the PCDSP offers higher portability and efficiency compared with CPR, making it a promising platform for efficient pancreatic cancer drug screening.

Prolongation of the gastric residence time of caffeine after administration in fed state: Comparison of effervescent granules with an extended release tablet.

The aim of the present study was to investigate the gastroretentive capacity of different formulation principles. This was indirectly determined by the absorption behavior of caffeine from the dosage forms. A slow and continuous appearance of caffeine in the saliva of healthy volunteers was used as a parameter for a prolonged gastric retention time. For this purpose, a four-way study was conducted with twelve healthy volunteers using the following test procedures: (1) Effervescent granules with 240 mL of still water administered in fed state, (2) effervescent granules with 20 mL of still water in fed state, (3) extended release (ER) tablet with 240 mL of still water in fed state, and (4) effervescent granules with 240 mL of still water in fasted state. The initial rise of the caffeine concentrations was more pronounced after the intake of the effervescent granules in the fed state compared to that of the ER tablets. However, tmax tended to be shorter in the fed study arms following administration of the ER tablet compared to the granules. Overall, the application of active pharmaceutical ingredients formulated as effervescent granules seems to be a promising approach to increase their gastric residence time after intake in fed state.

Yiwei Xiaoyu granules for treatment of chronic atrophic gastritis with deficiency syndrome of the spleen and stomach.

BACKGROUND: The Correa sequence, initiated by Helicobacter pylori (H. pylori), commonly progresses to gastric cancer through the stage of chronic atrophic gastritis (CAG). Although eradication of H. pylori only reduces the risk of gastric cancer, it does not eliminate the risk for neoplastic progression. Yiwei Xiaoyu granules (YWXY) are a commonly used composite preparation in Chinese clinics. However, the pursuit of excellence in clinical trials and the establishment of standardized animal experiments are still needed to contribute to full understanding and application of traditional Chinese medicine in the treatment of CAG. AIM: To demonstrate the effectiveness of YWXY in patients with CAG and spleen-stomach deficiency syndrome (DSSS), by alleviating histological scores, improving response rates for pathological lesions, and achieving clinical efficacy in relieving DSSS symptoms. METHODS: We designed a double-blind, randomized, controlled trial. The study enrolled seventy-two H. pylori-negative patients (mean age, 52.3 years; 38 men) who were randomly allocated to either the treatment group or control group in a 1:1 ratio, and treated with 15 g YWXY or 0.36 g Weifuchun (WFC) tablet combined with the respective dummy for 24 wk. The pre-randomization phase resulted in the exclusion of 72 patients: 50 participants did not meet the inclusion criteria, 12 participants declined to participate, and 10 participants were excluded for various other reasons. Seven visits were conducted during the study, and histopathological examination with target endoscopic biopsy of narrow-band imaging was requested before the first and seventh visits. We also evaluated endoscopic performance scores, total symptom scores, serum pepsinogen and gastrin-17. RESULTS: Six patients did not complete the trial procedures. Treatment with YWXY improved the Operative Link on Gastric Intestinal Metaplasia Assessment (OLGIM) stage, compared with WFC (P < 0.05). YWXY provided better relief from symptoms of DSSS and better improvement in serum gastric function, compared with WFC (P < 0.05). CONCLUSION: YWXY compared with WFC significantly reduced the risk of mild or moderate atrophic disease, according to OLGIM stage, significantly relieved symptoms of DSSS, and improved serum gastric function.

Selection of lubricant type and concentration for orodispersible tablets.

Lubricants are essential for most tablet formulations as they assist powder flow, prevent adhesion to tableting tools and facilitate tablet ejection. Magnesium stearate (MgSt) is an effective lubricant but may compromise tablet strength and disintegratability. In the design of orodispersible tablets, tablet strength and disintegratability are critical attributes of the dosage form. Hence, this study aimed to conduct an in-depth comparative study of MgSt with alternative lubricants, namely sodium lauryl sulphate (SLS), stearic acid (SA) and hydrogenated castor oil (HCO), for their effects on the tableting process as well as tablet properties. Powder blends were prepared with lactose, sodium starch glycolate or crospovidone as the disintegrant, and a lubricant at different concentrations. Angle of repose was determined for the mixtures. Comparative evaluation was carried out based on the ejection force, tensile strength, liquid penetration and disintegratability of the tablets produced. As the lubricant concentration increased, powder flow and tablet ejection improved. The lubrication efficiency generally decreased as follows: MgSt > HCO > SA > SLS. Despite its superior lubrication efficacy, MgSt is the only lubricant of four evaluated that reduced tablet tensile strength. Tablet disintegration time was strongly determined by tensile strength and liquid penetration, which were in turn affected by the lubricant type and concentration. All the above factors should be taken into consideration when deciding the type and concentration of lubricant for an orodispersible tablet formulation.

3D printing of multi-unit gastro-retentive tablets for the pulsatile release of artesunate.

Pulsatile drug delivery is hardly achieved by conventional gastro-retentive dosage forms. Artesunate as a typical anti-malaria medicine needs oral pulsatile release. Here, artesunate-loaded pulsatile-release multi-unit gastro-retentive tablets (APGTs) were prepared with a semi-solid extrusion three-dimensional (3D) printing method. An APGT was composed of three units: artesunate-loaded immediate and delayed release units and a block unit. The matrix of the immediate/delayed release units consisted of polyvinylpyrrolidone (PVP) K30 and croscarmellose sodium, which improved the rapid release of artesunate when contacting water. The block unit consisted of octadecanol, hydroxypropyl methyl cellulose K15M, PVP K30, and poloxamer F68. APGTs showed multi-phase release in simulated gastric liquids (SGLs). The first immediate release phase continued for 1 h followed by a long block phase for 7 h. The second rapid release phase was initiated when the eroded holes in the block unit extended to the inner delayed release unit, and this phase continued for about 14 h. Low-density APGTs could ensure their long-term floating in the stomach. Oral APGTs remained in the rabbit stomach for about 20 h. 3D printing provides a new strategy for the preparation of oral pulsatile-release tablets.

Venetoclax Clinical Pharmacokinetics After Administration of Crushed, Ground or Whole Tablets.

PURPOSE: Venetoclax is a potent, orally bioavailable BCL-2 inhibitor used in the treatment of some hematological malignancies. Crushing tablets may be necessary to help with the administration of venetoclax to patients with swallowing difficulties or patients requiring nasogastric tube feeding. The study was conducted to assess the bioavailability of crushed and finely ground venetoclax tablets relative to whole tablets. METHODS: An open-label, randomized, 3-way, crossover study in 15 healthy adult females was conducted. Venetoclax tablets were administered orally in a crushed, ground or intact form on Day 1 of each period with water following a high-fat breakfast. Pharmacokinetic samples were collected up to 72 hours postdosing. FINDINGS: The crushed and ground tablets met the bioequivalence criteria (0.80-1.25) relative to the intact tablets with respect to area under the concentration-time curve to time of the last measurable concentration (AUCt) and to infinite time (AUCinf) but exhibited a slightly lower maximum plasma concentration (Cmax). This was not considered clinically significant as only venetoclax overall exposure (AUC) has been shown to correlate with clinical efficacy. There was no change in the physical appearance and the evaluated physicochemical properties of crushed and ground venetoclax tablets after 72 hours of storage at 25°C/60% relative humidity. IMPLICATIONS: Crushing or grinding venetoclax tablets before administration could be considered as a viable alternative method of administration for patients who have difficulty swallowing whole venetoclax tablets or patients requiring nasogastric tube feeding. GOV IDENTIFIERS: NCT05909553, registered June 12, 2023.

Effect of Jianpi Shengxue Tablet on Iron Metabolism and Nutritional Status in Patients with Renal Anemia: A Prospective, Randomized, Open, Parallel Controlled and Multicenter Clinical Study.

OBJECTIVE: This study aimed to analyze the clinical efficacy of the Jianpi Shengxue tablet for treating renal anemia. METHODS: A total of 200 patients with renal anemia from December 2020 to December 2022 were enrolled and randomly divided into two groups. Patients in the control group were treated with polysaccharide-iron complex, and those in the experimental group were administered Jianpi Shengxue tablet. After 8 weeks of continuous treatment, the therapeutic outcomes regarding anemia were compared between the two groups. RESULTS: After treatment, the red blood cell (RBC) count, hematocrit (HCT), reticulocyte percentage (RET), ferritin (SF), serum iron (SI), transferrin saturation (TSAT), and serum albumin (ALB) all increased (P<0.01), and the clinical symptom score and total iron binding capacity decreased (P<0.01) in the experimental group. Moreover, the improvements in RBC, HCT, RET, SF, SI, TAST, ALB, and clinical symptoms (fatigue, anorexia, dull skin complexion, numbness of hands and feet) in the experimental group were significantly greater than those in the control group (P<0.05). The total effective rate for treating renal anemia was significantly higher in the experimental group than in the control group (P<0.01). CONCLUSION: The Jianpi Shengxue tablet demonstrates efficacy in treating renal anemia, leading to significant improvements in the laboratory examination results and clinical symptoms of patients with renal anemia.