Comparative efficacy and safety of Chinese patent medicines of iron deficiency anemia during pregnancy: A network meta-analysis.

BACKGROUND: Iron deficiency anemia (IDA) is a prevalent nutritional disorder during pregnancy. Clinical studies indicate that incorporating Chinese patent medicines (CPMs) with oral iron (OI) in treating IDA in pregnancy can reduce adverse effects and improve clinical outcomes. Nonetheless, the comparative efficacy of different CPMs remains unclear. AIM: To assess the safety and effectiveness of different CPMs for treating IDA during pregnancy using network meta-analysis. METHODS: We conducted a search for randomized controlled trials (RCTs) that combined CPM and OI for IDA treatment in pregnancy, spanning from 2013 to the present. Data analysis was performed using Rev Man 5.3 and Stata 14.0 on literature that satisfied the quality criteria. RESULTS: The analysis included 45 RCTs, encompassing 4422 pregnant patients with IDA. Six CPMs were examined, including Shengxuebao Mixture, Shengxuening Tablets (SXN), Yiqi Weixue CPMs (YQWX), Jianpi Shengxue CPMs (JPSX), Yiqi Buxue Tablets, and Compound Hongyi Buxue Oral Liquid (FFHY). Findings indicated that FFHY + OI significantly improved the clinical effective rate. SXN + OI was most effective in boosting red blood cells counts and hemoglobin levels. YQWX + OI showed superior results in improving serum ferritin, and SXN + OI was most effective in increasing serum iron levels. JPSX + OI was optimal in reducing adverse pregnancy outcomes, while YQBX + OI effectively minimized adverse events. A cluster analysis suggested that SXN + OI could be the potentially optimal therapeutic regimen for IDA in pregnancy. CONCLUSION: This study demonstrates that the combination of OI with CPMs offers better outcomes than OI alone. Based on clinical efficacy and other measured outcomes, SXN + OI emerges as the most effective treatment modality for improving the health of pregnant patients with IDA.

Enhancing drug administration flexibility: evaluation of pharmacokinetic properties of tegoprazan orally disintegrating tablet (ODT) administered via nasogastric tube or oral dosing.

Tegoprazan orally disintegrating tablet (ODT) formulation is a novel formulation to improve a convenience in comparison to taking the conventional tablet of tegoprazan, a potassium-competitive acid blocker. The purpose of this study was to evaluate the pharmacokinetic and safety profiles of tegoprazan ODT when administered via two routes: nasogastric tube or oral dosing. This study is expected to expand the administration route of tegoprazan ODT. The study was conducted in an open-label, randomized, single-dose, two-way crossover design with a 1-week washout period. Healthy subjects aged 19 to 45 years were administered 50 mg of tegoprazan ODT orally or dissolved in water via nasogastric tube. Tegoprazan, the active ingredient, was quantified using a ultra-high performance liquid chromatography tandem mass spectroscopy (UPLC-MS/MS), and pharmacokinetic parameters were determined through non-compartmental analysis. Safety was monitored throughout the study. A total of 48 subjects, successfully completed the trial. The geometric mean ratios for log-transformed Cmax and AUCt, representing the ratio of nasogastric tube group to oral dosing group, along with 90% confidence intervals, were 1.1087 (1.0243-1.2000) and 1.0023 (0.9620-1.0442), respectively. All adverse events were unrelated to tegoprazan and mild in intensity. The pharmacokinetic profiles of tegoprazan ODT were equivalent between the nasogastric tube and oral administration. Considering the demonstrated linear pharmacokinetics and concentration-dependent pharmacodynamics of tegoprazan, the administration via nasogastric tube is expected to yield effects equivalent to those of oral administration. This approach offers a viable alternative, especially beneficial for patients with oral intake difficulties.

The efficacy of levonorgestrelintrauterine system, drospirenone & ethinylestradiol tablets (II) and dydrogesterone in preventing the recurrence of endometrial polyps.

OBJECTIVE: To analyze the efficacy of levonorgestrelintrauterine system, Drospirenone & ethinylestradiol tablets (II), and dydrogesterone in preventing the recurrence of endometrial polyps after hysteroscopic endometrial polypectomy. METHODS: One hundred seventy patients who underwent hysteroscopic endometrial polypectomy in the Gynecology Department of Tianmen First People's Hospital in Hubei Province from January 2022 to June 2023 were randomly divided into the levonorgestrelintrauterine system group, Drospirenone & ethinylestradiol tablets (II) group, dydrogesterone group, and a control group. The recurrence rates, endometrial thickness, and menstrual volume changes at 6 and 12 months post-operation were compared among these four groups. RESULTS: The recurrence rates in the levonorgestrelintrauterine system group, Drospirenone & ethinylestradiol tablets (II) group, and dydrogesterone group were lower than the control group, with statistical significance (P < 0.01), with the levonorgestrelintrauterine system group having the lowest recurrence rate. The endometrial thickness at 6 and 12 months post-operation in the levonorgestrelintrauterine system group, Drospirenone & ethinylestradiol tablets (II) group, and dydrogesterone group was thinner than that of the control group and thinner than pre-operation, with statistical significance (P < 0.01). The menstrual volume at 3 months post-operation in the levonorgestrelintrauterine system group, Drospirenone & ethinylestradiol tablets (II) group, and dydrogesterone group was significantly less than the control group, and less than the pre-operation volume. CONCLUSION: Dydrogesterone, drospirenone & ethinylestradiol tablets (II), and levonorgestrelintrauterine system all play a role in preventing the recurrence of endometrial polyps, but levonorgestrelintrauterine system is significantly better than dydrogesterone and Drospirenone & ethinylestradiol tablets (II) in terms of postoperative recurrence rate, endometrial thickness, menstrual changes, and compliance, and is worth promoting in clinical application.

Fabrication and characterization of cocoa butter-based caffeine fast-melting tablets.

Aim: The objective of this study was to develop and characterize the physical properties of fast-melting tablets (FMTs) using cocoa butter as the base and caffeine as the model drug. Method: The simple refrigerator freezing method was employed to prepare caffeine-loaded, FMTs from cocoa butter bases. Results: The F3 chosen formulation achieved a disintegration time of 1.20 min ± 0.035, which falls within the specified limit set by the European Pharmacopoeia. The cumulative drug release data of F3, was 88.52 and 94.08% within 60 and 75 min, respectively (NLT 85% as per US FDA requirement). All the other physical test standards for FMTs met the pharmacopeial specifications. Conclusion: Based on the findings, the simple refrigerator freezing method could be used to formulate FMTs.

Patient-friendly natural caffeine-loaded cocoa butter-based fast-melting tablets with rapid disintegration, affordability, safety and biocompatibility are an efficient base for drug delivery.

Dan-Lou tablets reduce inflammatory response by inhibiting the activation of NLRP3 inflammasome for coronary heart disease.

BACKGROUND: The activation of the NLRP3 inflammasome has recently been revealed as a novel pathological mechanism of coronary heart disease (CHD). The Dan-Lou tablets (DLT) is widely used in the clinical treatment of CHD and prescription characterized by multi-component and multi-target regulation. However, the anti-inflammatory mechanism of DLT in the treatment of CHD remains unclear. PURPOSE: This study aimed to evaluate the effect of DLT in the treatment of CHD on the priming and activation of the NLRP3 inflammasome and to investigate the underlying anti-inflammatory mechanisms. METHODS: First, CHD rats model were established by a high-fat diet combined with left anterior coronary artery ligation (LADCA) followed by DLT intervention. The therapeutic effect of DLT was evaluated according to cardiac function, lipid level, and cardiac histopathology. Next, data-independent acquisition (DIA) proteomics was used to identify the key differential proteins of DLT intervention in CHD rats, and bioinformatics analysis was performed. Finally, the differentially expressed proteins in the NOD-like signaling pathway were verified based on bioinformatics results, and the priming and activation steps of the NLRP3 inflammasome were detected. RESULTS: In this study, a high-fat diet combined with LADCA was utilized to generate a CHD model, and DLT alleviated myocardial ischemia injury by inhibiting lipid deposition and inflammatory response. Proteomic studies observed that the RNF31, TXN2, and GBP2 of the NOD-like receptor signaling pathway were verified as the key targets of DLT in inhibiting myocardial injury in CHD rats. Furthermore, DLT in the treatment of CHD rats may function through the downregulation of P2X7R expression, thereby interfering with the priming (TLR4/MyD88/NF-κB) and activation (NLRP3/ASC/Caspase-1) of the NLRP3 inflammasome regulated by HSP90, and may then reduce the release of the IL-1ß and IL-18 inflammatory factors to play an anti-myocardial injury effect. CONCLUSION: Our findings elucidate a novel mechanism of DLT and provide some new drug evaluation targets and therapeutic strategies for CHD. This study innovatively proposed that DLT further exerts an anti-myocardial injury effect by inhibiting P2X7R expression, thereby interfering with the priming (TLR4/MyD88/NF-κB) and activation (NLRP3/ASC/Caspase-1) of the NLRP3 inflammasome regulated by HSP90, and then downregulates the release of the IL-1ß and IL-18 inflammatory factors.

Clinical and biological predictors of Cladribine effectiveness in Multiple Sclerosis: A real-world, single Centre study considering a two-year interval from year-2 dosing.

OBJECTIVES: Cladribine tablets (CLAD) for adult patients with highly active relapsing multiple sclerosis (RMS) have been available in Italy since 2018. We aimed to assess predictors of no-evidence-of-disease-activity-3 (NEDA-3) status after 24 months of the last dose of CLAD. RESULTS: We included 88 patients (70.5% female, mean age at CLAD start 35.4 ± 11.4). Eighteen patients were treatment naïve, 48 switched to CLAD from a First line Disease Modifying Drug (DMD), and 22 from Second line DMDs. All patients were observed for a median follow-up time of 2.4 (1-4) years after the last dose of CLAD. Forty-nine patients (55.7%) showed NEDA at the last available follow-up. Naïve patients (p = 0.001), those with a lower number of previous DMDs (p < 0.001) and, even though not significantly, those switching from first line DMDs (p = 0.069) were more likely NEDA3 at the last available follow-up. In a subgroup of 30 patients (34%), Serum Light Neurofilaments (sNFL) levels showed a decrease from baseline to the 24 months of follow-up, statistically significant from baseline to the sixth month, and from the first to the second year detection. sNFL levels at 12th month showed a strong inverse correlation with the time to NEDA3 loss. CONCLUSIONS: Our experience provides information for the 2-years after the last dose of CLAD, confirming a higher effectiveness of CLAD when placed early in the treatment algorithm. Given the ongoing expansion of the therapeutic landscape in MS, sNfL could support individualized decision-making, used as blood-based biomarker for CLAD responses in clinical practice.

Development and Evaluation of a Prototype Mobile Application for Intravenous Drug Dose Calculation in Overweight and Obese Thai Children: Precision Dosing in Practice.

Background: Medication dosing in overweight and obese children often involves complex weight-based calculations, leading to higher dosing errors, particularly with intravenous drugs. Currently, tools to aid in dosage calculations are lacking for these patients, especially in Thai population. Objective: This study aimed to develop a mobile application with the intent of utilizing it as a tool to enhance the efficiency and accuracy of dosing calculations required for obese and overweight Thai children. Methods: The performance of the application was assessed in 3 key aspects using a sample of 30 healthcare professionals. These key aspects included: 1) the accuracy of dosage calculations, assessed through pre- and posttests comparing manual calculations to app-based calculations using a 10-item questionnaire, 2) the time taken for calculations before and after app usage, 3) user satisfaction, which was measured through a questionnaire. Results: The integration of applications into the calculation demonstrated a significant improvement when compared to the manual calculation in both accuracy (6.10 vs 9.33 out of 10, P < .001) and efficiency (10.40 vs 8.53 minutes per 10 questions, P = .008). Also, the application elicited high levels of satisfaction among users, as reflected by an overall mean satisfaction score of 4.57 on a 5-point scale. Conclusion: The integration of this application to assist in dosage calculations for overweight and obese pediatric Thai patients has yielded favorable outcomes concerning accuracy, efficiency, and user satisfaction. Further development should be pursued within a larger cohort, with an emphasis on real-world implementation in clinical settings.

In-situ monitoring of in vitro drug release processes in tablets using optical coherence tomography.

Film-coated modified-release tablets are an important dosage form amenable to targeted, controlled, or delayed drug release in the specific region of the gastrointestinal (GI) tract. Depending on the film composition and interaction with the GI fluid, such coated products can modulate the local bioavailability, systemic absorption, protection as an enteric barrier, etc. Although the interaction of a dosage form with the surrounding dissolution medium is vital for the resulting release behavior, the underlying physicochemical phenomena at the film and core levels occurring during the drug release process have not yet been well described. In this work, we attempted to tackle this limitation by introducing a novel in vitro test based on optical coherence tomography (OCT) that allows an in-situ investigation of the sub-surface processes occurring during the drug release. Using a commercially available tablet based on osmotic-controlled release oral delivery systems (OROS), we demonstrated the performance of the presented prototype in terms of monitoring the membrane thickness and thickness variability, the surface roughness, the core swelling behavior, and the porosity of the core matrix throughout the in vitro drug release process from OROS. The superior spatial (micron scale) and temporal (less than 10 ms between the subsequent tomograms) resolution achieved in the proposed setup provides an improved understanding of the dynamics inside the microstructure at any given time during the dissolution procedure with the previously unattainable resolution, offering new opportunities for the design and testing of patient-centric dosage forms.

Geometry-Driven Fabrication of Mini-Tablets via 3D Printing: Correlating Release Kinetics with Polyhedral Shapes.

The aim of this study was to fabricate mini-tablets of polyhedrons containing theophylline using a fused deposition modeling (FDM) 3D printer, and to evaluate the correlation between release kinetics models and their geometric shapes. The filaments containing theophylline, hydroxypropyl cellulose (HPC), and EUDRAGIT RS PO (EU) could be obtained with a consistent thickness through pre-drying before hot melt extrusion (HME). Mini-tablets of polyhedrons ranging from tetrahedron to icosahedron were 3D-printed using the same formulation of the filament, ensuring equal volumes. The release kinetics models derived from dissolution tests of the polyhedrons, along with calculations for various physical parameters (edge, SA: surface area, SA/W: surface area/weight, SA/V: surface area/volume), revealed that the correlation between the Higuchi model and the SA/V was the highest (R2 = 0.995). It was confirmed that using 3D- printing for the development of personalized or pediatric drug products allows for the adjustment of drug dosage by modifying the size or shape of the drug while maintaining or controlling the same release profile.

Herb induced liver injury by Xianling Gubao Tablets: A case assessed for causality using updated RUCAM and integrated evidence chain.

Objective: A typical case of Xianling Gubao (XLGB) Tablets-induced liver injury was systematically studied in the clinic and the laboratory. Methods: A patient with herb-induced liver injury (HILI) and a history of taking XLGB Tablets before disease onset was engaged as the study subject, and the case was diagnosed according to the updated Roussel Uclaf Causality Assessment Method (RUCAM) and the integrated evidence chain (iEC) method recommended by the Guidelines for Diagnosis and Treatment of Herb-induced Liver Injury (HILI Guidelines). Results: Clinical history, biochemical indexes and imaging tests were used to exclude the influence of fundamental diseases and confusing liver diseases such as viral, alcoholic and autoimmune liver diseases on the diagnosis. Based on an investigation of the patient's medication history, she was suspected to have HILI caused by XLGB Tablets, as the patient was only taking an oral preparation of XLGB Tablets, and the influence of other drugs on the diagnosis was excluded. This patient with alanine aminotransferase (ALT) ≥ 3 × upper limit of normal (ULN) and a calculated R of 6 was diagnosed with possible acute drug-induced hepatocellular injury. The relationship was considered "highly probable" (score of 9) using the updated RUCAM of 2016. Moreover, the fingerprint similarity between the preparation taken by the patient and a commercially available preparation was 0.99, suggesting that the patient was consuming XLGB Tablets rather than another drug. LC-MS technology and the Agilent Fake TCM-Drugs database were used to investigate the drug, and no chemical additions were found. Examination of the drug for pesticide residues, heavy metals, aflatoxins and other exogenous substances indicated compliance with the content limits of the Chinese Pharmacopoeia. Conclusion: In summary, the final diagnosis of XLGB-induced liver injury reached the clinical diagnosis of HILI and was acute severe hepatocellular injury type by the updated RUCAM and iEC. Therefore, this study provides scientific evidence regarding the causality evaluation of compound preparations of traditional Chinese medicines-induced liver injury.

Apixaban and clopidogrel in a fixed-dose combination: Formulation and in vitro evaluation.

Fixed-dose combination (FDC) products represent a novel, safe, and cost-effective formulation. Combined use of anticoagulant and antiplatelet medications is common among comorbid cardiovascular patients. This study aimed to formulate FDC tablets for Apixaban and Clopidogrel, as prophylaxis and treatment of thrombo-embolic events. FDC tablets were developed by combining small tablets of Immediate-Release Clopidogrel 75 mg and Extend-Release Apixaban 5 mg through direct compression and wet granulation. Particularly, Apixaban tablets were developed using design expert software, and various types and concentrations of polymers were entered. For Clopidogrel tablets, various diluents were used to develop the formulation. Then, the dissolution profile for each formula was studied. Finally, the optimized formulations were encapsulated within hard gelatin capsules. Apixaban formulation followed zero-order with super case Ⅱ transport mechanism as the dominant mechanism of drug release. The Apixaban drug release rate was affected by the type and concentration of the polymers in the formulation (P < 0.05). As the HPMC concentration was increased, Apixaban release was retarded. For, Clopidogrel, the formulated tablets with spray-dried lactose filler and sodium stearyl fumarate lubricant were found to be stable with good properties. In conclusion, the optimum formulation yielded Clopidogrel and extended-release Apixaban for 24 h with the desired in vitro drug dissolution.

Xue Ping Tablets treat abnormal uterine bleeding via VEGF-ERK1/2 pathway.

Objective: To investigate the protective effects against abnormal uterine bleeding (AUB) and possible mechanisms of Xue Ping tablets (XPT) using a rat model. Methods: A total of 58 unmated female and 25 male SPF SD rats aged 8-9 weeks were selected. Eight unmated female rats were selected as the blank control group according to the complete random method. The other 50 rats were mated in a female/male ratio of 2:1. In the morning after mating, vaginal smears were collected. Presence of vaginal plug or sperm was regarded as the first day of pregnancy. All pregnant rats were given 8.3 mg/kg of mifepristone by gavage at 8:00 a.m. and 100 µg/kg misoprostol by gavage at 6:00 p.m. on the seventh day of pregnancy to induce incomplete abortion, thereby establishing a rat model of AUB. Forty rats were randomly divided into model, low- (220 mg/kg), medium- (441 mg/kg), high-dose (882 mg/kg) XPT, and positive control groups. The positive group was given 130 mg/kg Gong Xue Ning (GXN). The model group and the blank group were given an equal amount of distilled water. Results: Compared with the model group, the volume of bleeding in the positive and middle- and high-dose XPT groups decreased (P < 0.05). Moreover, compared with the model group, the progesterone levels in the positive and XPT groups were significantly increased. Immunohistochemistry showed that XPT significantly decreased the expression levels of VEGF, p-ERK, NF-κB, SAA, MMP-2, MMP-9, TIMP-1, TIMP-2 and TIMP-3. WB results showed that XPT significantly decreased the expression levels of p-ERK, MMP-9, NF-κB, MMP-2 and VEGF. QRT-PCR results showed that XPT significantly decreased the expression levels of VEGF, NF-κB, SAA, MMP-2, TIMP-1, TIMP-2 and TIMP-3 (P < 0.05). Conclusions: XPT could reduce AUB by inhibiting the inflammatory factors involved in the VEGF-ERK1/2 pathway.

Network pharmacology and in vivo experiment-based strategy for investigating the mechanism of chronic prostatitis/chronic pelvic pain syndrome in QianLieJinDan tablets.

Background: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common urinary system disease that is prone to recurrence. It typically leads to varying degrees of pelvic pain and discomfort, as well as symptoms related to the urinary system in affected patients. QianLieJinDan tablets (QLJD), a traditional Chinese medicine, have shown promising therapeutic effects on CP/CPPS in clinical practice, but the underlying mechanisms of QLJD in treating CP/CPPS have not been determined. Objective: To reveal the phytochemical characterization and multitarget mechanism of QLJD on CP/CPPS. Methods: The concentrations of the components of QLJD were determined using UHPLC-Q Exactive Orbitrap-MS. Utilizing network pharmacology approaches, the potential components, targets, and pathways involved in the treatment of CP/CPPS caused by QLJD were screened. Molecular docking calculations were employed to assess the affinity between the components of the QLJD and potential targets, revealing the optimal molecular conformation and binding site. Finally, the therapeutic efficacy and potential underlying mechanisms of QLJD were investigated through pharmacological experiments. Results: In this study, a total of 35 components targeting 29 CP-related genes were identified, among which quercetin, baicalin, icariin, luteolin, and gallic acid were the major constituents. Enrichment analysis revealed that the potential targets were involved mainly in the regulation of cytokines, cell proliferation and apoptosis, and the oxidative stress response and were primarily associated with the cytokine‒cytokine receptor interaction pathway, the IL-17 signaling pathway, the Th17 cell differentiation pathway, and the JAK-STAT signaling pathway. In vivo experiments demonstrated that QLJD effectively attenuated the infiltration of CD3+ T cells and the expression of ROS in a CP/CPPS model rat prostate tissue. Furthermore, through the inhibition of IL-6 and STAT3 expression, QLJD reduced the differentiation of Th17 cells, thereby ameliorating pathological injury and prostatic index in prostate tissue. Conclusion: The potential of QLJD as an anti-CP/CPPS agent lies in its ability to interfere with the expression of IL-6 and STAT3, inhibit Th17 cell differentiation, reduce inflammatory cell infiltration in rat prostate tissue, and alleviate oxidative stress damage through its multi-component, multi-target, and multi-pathway effects.

Amelioration of tableting properties and dissolution rate of naproxen co-grinded with nicotinamide: preparation and characterization of co-grinded mixture.

OBJECTIVE AND SIGNIFICANCE: Reducing the dimensions, when other additives are present, shows potential as a method to improve the dissolution and solubility of biopharmaceutical classification system class II drugs that have poor solubility. In this investigation, the process involved grinding naproxen with nicotinamide with the aim of improving solubility and the rate of dissolution. METHODS: Naproxen was subjected to co-milling with urea, dimethylurea, and nicotinamide using a planetary ball mill for a duration of 90 min, maintaining a 1:1 molar ratio for the excipients (screening studies). The co-milled combinations, naproxen in its pure milled form, and a physical mixture were subjected to analysis using X-ray powder diffraction (XRPD), scanning electron microscopy (SEM), and solubility assessment. The mixture displaying the highest solubility (naproxen-nicotinamide) was chosen for further investigation, involving testing for intrinsic dissolution rate (IDR) and Fourier-transform infrared spectroscopy (FTIR) after co-milling for both 90 and 480 min. RESULTS AND CONCLUSION: The co-milled combination, denoted as S-3b and consisting of the most substantial ratio of nicotinamide to naproxen at 1:3, subjected to 480 min of milling, exhibited a remarkable 45-fold increase in solubility and a 9-fold increase in IDR. XRPD analysis of the co-milled samples demonstrated no amorphization, while SEM images portrayed the aggregates of naproxen with nicotinamide. FTIR outcomes negate the presence of any chemical interactions between the components. The co-milled sample exhibiting the highest solubility and IDR was used to create a tablet, which was then subjected to comprehensive evaluation for standard attributes. The results revealed improved compressibility and dissolution properties.

[Mechanism of Chaijin Jieyu Anshen Tablets in regulating abnormal ACC-vHPC glutaminergic neural circuit to alleviate synaptic remodeling of ventral hippocampal neurons in depressed rats].

This study aims to reveal the molecular mechanism of Chaijin Jieyu Anshen Tablets(CJJYAS) in regulating the abnormal anterior cingulate cortex(ACC)-ventral hippocampus(vHPC) glutaminergic neural circuit to alleviate synaptic remodeling of ventral hippocampal neurons in depressed rats. Firstly, the study used chemogenetics to localize glutaminergic adeno-associated virus(AAV) into the ACC brain region of rats. The model of depressed rats was established by chronic unpredictable mild stress(CUMS) combined with independent feeding. The rats were randomly divided into control group, model group, AAV empty group, AAV group, AAV+ glucocorticoid receptors(GR) blocker group, AAV+chemokine receptor 1(CX3CR1) blocker group, and AAV+CJJYAS group. Depressive-like behaviors of rats were evaluated by open-field, forced-swimming, and Morris water maze tests, combined with an animal behavior analysis system. The morphological and structural changes of ACC and vHPC neurons in rats were observed by hematoxylin-eosin(HE) staining. Immunofluorescence and nuclear phosphoprotein(c-Fos) were used to detect glutaminergic neural circuit activation of ACC-vHPC in rats. The changes in dendrites, synaptic spines, and synaptic submicrostructure of vHPC neurons were observed by Golgi staining and transmission electron microscopy, respectively. The expressions of synaptic remodeling-related proteins N-methyl-D-asprtate receptor 2A(GRIN2A), N-methyl-D-asprtate receptor 2B(GRIN2B), Ca~(2+)/calmodulin-dependent protein kinase Ⅱ(CaMKⅡ), mitogen-activated protein kinase-activated protein kinase 2(MK2), and a ubiquitous actin-binding protein(cofilin) in vHPC glutaminergic neurons of rats were detected by immunofluorescence and Western blot, respectively. The results indicated that the activated glutaminergic AAV aggravated the depressive-like behaviors phenotype of rats in the model group and deteriorated the damage of morphology and structure of ACC and vHPC neurons and synaptic ultrastructure. However, both GR and CX3CR1 bloc-kers could reverse the abnormal changes to varying degrees, suggesting that the abnormal activation of ACC-vHPC glutaminergic neural circuit mediated by GR/CX3CR1 signals in gliocytes in the ACC brain region may be closely related to the occurrence and development of depression. Interestingly, CJJYAS significantly inhibited the activation of the ACC-vHPC glutaminergic neural circuit induced by AAV and the elevated Glu level. Furthermore, CJJYAS could also effectively reverse the aggravation of depressive-like behaviors and synaptic remodeling of vHPC neurons of rats in the model group induced by the activated AAV. Additionally, the findings suggested that the molecular mechanism of CJJYAS in improving synaptic damage of vHPC neurons might be related to the regulation of synaptic remodeling-related signals such as NR/CaMKⅡ and MK2/cofilin. In conclusion, this research confirms that CJJYAS effectively regulates the abnormal ACC-vHPC glutaminergic neural circuit and alleviates the synaptic remodeling of vHPC glutaminergic neurons in depressed rats, and the molecular mechanism might be associated with the regulation of synapse-related NR/CaMKⅡ and MK2/cofilin signaling pathways, which may be the crucial mechanism of its antidepressant effect.

[Mechanism of Fuzheng Huayu Tablets against hepatic fibrosis based on transcriptome and single-cell sequencing].

This study aimed to investigate the role of macrophage polarization in the treatment of liver fibrosis by Fuzheng Huayu Tablets(FZHY) through single-cell, transcriptome sequencing and in vitro and in vivo experiments. Liver fibrosis-related datasets, transcriptomic datasets, and single-cell sequencing datasets were obtained from the Gene Expression Omnibus(GEO) database to screen differential genes. Liver fibrosis-related genes were obtained from GeneCards, DisGeNET, NCBI, PharmgKB, TTD and OMIM databases. Macrophage polarization-related genes were obtained from the GeneCards database. The above three gene sets were intersected to construct a protein-protein interaction(PPI) network. Cytoscape software was used to screen core proteins, and the expression pattern of core proteins was visualized by single-cell sequencing. A mouse model of liver fibrosis was constructed using carbon tetrachloride(CCl_4). Hematoxylin-eosin(HE) staining and Masson staining were used to observe the pathological morphology of liver tissues. The expressions of α-smooth muscle actin(α-SMA) and transforming growth factor-ß1(TGF-ß1) were detected by immunohistochemistry. The levels of alanine aminotransferase(ALT) and aspartate aminotransferase(AST) were detected by colorimetry. The le-vels of inflammatory factors in serum were detected by the enzyme-linked immunosorbent assay(ELISA). Furthermore, the expressions of α-SMA, TGF-ß1, cluster of differentiation 86(CD86) and thrombospondin 1(THBS1) in liver tissues were detected by Western blot(WB). Lipopolysaccharide(LPS) was used to stimulate RAW264.7 cells to construct the M1 macrophage polarization model. The cell counting kit-8(CCK-8) method was used to detect cell viability. WB was used to detect the protein expressions of CD86 and THBS1 in cells, and the messenger ribonucleic acid(mRNA) expression levels of tumor necrosis factor-α(TNF-α) and interleukin(IL)-1ß by real-time fluorescent quantitative reverse transcription polymerase chain reaction(RT-qPCR). The results showed that a total of 26 potential genes related to the polarization of liver fibrosis macrophages were obtained, and 10 core proteins related to the polarization of liver fibrosis macrophages such as THBS1, lumican(LUM) and fibulin-5(FBLN5) were screened. Single-cell data analysis indicated that THBS1, ranking highest, may be expressed by M1 macrophages. Animal experiments demonstrated that FZHY reduced inflammatory cell infiltration and collagen deposition in CCl_4-induced mouse liver, relieved liver injury and inflammation levels, and inhibited the expressions of α-SMA, TGF-ß1, CD86, and THBS1 proteins. Cell experiments revealed that FZHY significantly reduced intracellular expression of CD86 and THBS1 proteins and mRNA levels of TNF-α and IL-1ß. In conclusion, FZHY may ameliorate liver fibrosis by inhibiting THBS1 protein expression, suppressing M1 macrophage polarization, and reducing inflammation.

A modified Kushner-Moore approach to characterising small-scale blender performance impact on tablet compaction.

Continuous Direct Compaction (CDC) has emerged as a promising route towards producing solid dosage forms while reducing material, development time and energy consumption. Understanding the response of powder processing unit operations, especially blenders, is crucial. There is a substantial body of work around how lubrication via batch blender operation affects tablet critical quality attributes such as hardness and tensile strength. But, aside from being batch operations, the design of these blenders is such that they operate with low-shear, low-intensity mixing at Froude number values significantly below 0.4 (Froude number Fr being the dimensionless ratio of inertial to gravitational forces). The present work explores the performance of a mini-blender which has a fundamentally different mode of operation (static vessel with rotating blades around a mixing shaft as opposed to rotating vessel with no mixing shaft). This difference allows a substantially wider operating range in terms of speed and shear (and Fr values). The present work evaluates how its performance compares to other blenders studied in the literature. Tablet compaction data from blends produced at various intensities and regimes of mixing in the mini-blender follow a common trajectory. Model equations from literature are suitably modified by inclusion of the Froude number Fr, but only for situations where the Froude number was sufficiently high (1 < Fr). The results suggest that although a similar lubrication extent plateau is eventually reached it is the intensity of mixing (i.e. captured using the Froude number as a surrogate) which is important for the lubrication dynamics in the mini-blender, next to the number of revolutions. The degree of fill or headspace, on the other hand, is only crucial to the performance of common batch blenders. Testing using alternative formulations shows the same common trend across mixing intensities, suggesting the validity of the approach to capture lubrication dynamics for this system.

Utility of native emission quenching of erythrosine B for the determination of diltiazem in different dosage forms.

This study introduces a practical and cost-effective method for tracking diltiazem (DLZ) analytically. It utilizes a fluorimetric approach that relies on the modulation of fluorescence intensity of a dye called erythrosine B. Through a one-pot experiment performed in an acidic environment, a complex is rapidly formed between DLZ and erythrosine B. By observing the decrease in erythrosine B emission, a linear calibration plot is established, enabling the detection and quantification of DLZ concentrations ranging from 40 to 850 ng/ml. The estimated limits of detection and quantitation were 10.5 and 32.1 ng/ml, respectively. The variables affecting the DLZ-dye complex system were carefully adjusted. The validity of the approach was confirmed through a thorough evaluation based on the criteria set by ICH guidelines. The accuracy and precision of the methodology were evaluated, and the standard deviation and relative standard deviation were below 2. The strategy was successfully employed to analyze DLZ in tablets and capsules, and no significant variation between the proposed and reported methods as the values of the estimated t-test and F-test at five determinations were below 2.306 and 6.338, respectively. Notably, the method adheres to the principle of green chemistry by utilizing distilled water as the dispersing medium.

Effects of Combined Live Bifidobacterium, Lactobacillus, Enterococcus, and Bacillus Cereus Tablets on the Structure and Function of the Intestinal Flora in Rabbits Undergoing Hepatic Artery Infusion Chemotherapy.

Few studies have explored the biological mechanism by which probiotics alleviate adverse reactions to chemotherapy drugs after local hepatic chemotherapy perfusion by regulating the intestinal flora. This study investigates the effects of Combined Live Bifidobacterium, Lactobacillus, Enterococcus, and Bacillus Cereus Tablets on the intestinal microbial structure and intestinal barrier function, as well as the potential mechanism in rabbits after local hepatic chemotherapy infusion. Eighteen New Zealand White rabbits were randomly divided into a control group, a hepatic local chemotherapy perfusion group, and a hepatic local chemotherapy perfusion + Combined Live Bifidobacterium, Lactobacillus, Enterococcus, and Bacillus Cereus Tablets group to assess the effects of Combined Live Bifidobacterium, Lactobacillus, Enterococcus, and Bacillus Cereus Tablets on the adverse reactions. The administration of Combined Live Bifidobacterium, Lactobacillus, Enterococcus, and Bacillus Cereus Tablets alleviated the intestinal flora disorder caused by local hepatic perfusion chemotherapy, promoted the growth of beneficial bacteria, and inhibited the growth of harmful bacteria. The Combined Live Bifidobacterium, Lactobacillus, Enterococcus, and Bacillus Cereus Tablets also reduced the levels of serum pro-inflammatory cytokines and liver injury factors induced by local hepatic perfusion chemotherapy. Our findings indicate that Combined Live Bifidobacterium, Lactobacillus, Enterococcus, and Bacillus Cereus Tablets can ameliorate the toxicity and side effects of chemotherapy by regulating intestinal flora, blocking pro-inflammatory cytokines, reducing liver injury factors, and repairing the intestinal barrier. Probiotics may be used as a potential alternative therapeutic strategy to prevent the adverse reactions caused by chemotherapy with local hepatic perfusion.

Acceptability of an Orange-Flavoured Zinc Sulphate Dispersible Tablet in the Management of Acute Diarrhoea in Under-five Children in Lagos, Nigeria.

BACKGROUND: Acute diarrhoea is a significant cause of morbidity and mortality in children under five, especially in subSaharan Africa. The WHO recommends using oral rehydration solution (ORS) and zinc therapy for its management, but the metallic taste of zinc often hinders adherence. METHOD: This prospective open-label intervention study took place at three health facilities in Lagos, Southwest Nigeria, involving children aged 3 to 59 months with acute diarrhoea. Sociodemographic and diarrhoea-related data were obtained. Palatability was assessed using a 5-point hedonic scale, and adherence was determined by the proportion of prescribed zinc sulfate tablets consumed. Caregivers received a 10-day supply of the study drug and ORS sachets for each child, along with participant diaries for tracking drug intake, palatability scores, and adverse events. Follow-up was conducted on Days 3 and 7, and diaries were collected between Days 10 and 14. RESULTS: Out of the 294 participants, most caregivers were mothers (86.0%), had at least a secondary education (88.1%), and were employed (70.7%). The majority of children were male (54.2%), and under 18 months old (52.2%). The average palatability score was 2.65 (±0.78), with no significant differences based on age or gender. Mean adherence was 93.03%, with 89.3% achieving ≥80% adherence, and adherence did not significantly differ by age or gender. The only reported adverse event, vomiting, decreased from 18.8% on Day 1 to 0.5% on Day 10. CONCLUSION: The study indicates that the orange-flavored dispersible zinc sulfate tablet is well-accepted by children aged 3 to 59 months with acute diarrhoea in Lagos, Nigeria.

CONTEXTE: La diarrhée aiguë est une cause significative de morbidité et de mortalité chez les enfants de moins de cinq ans, en particulier en Afrique subsaharienne. L'OMS recommande l'utilisation de la solution de réhydratation orale (SRO) et de la thérapie au zinc pour sa prise en charge, mais le goût métallique du zinc entrave souvent l'observance. MÉTHODE: L'étude d'intervention prospective à ciel ouvert a eu lieu dans trois établissements de santé à Lagos, dans le sud-ouest du Nigeria, impliquant des enfants de 3 à 59 mois souffrant de diarrhée aiguë. Des données sociodémographiques et liées à la diarrhée ont été obtenues. La palatabilité a été évaluée à l'aide d'une échelle hédonique à 5 points, et l'observance a été déterminée par la proportion de comprimés de sulfate de zinc prescrits consommés. Les aidants ont reçu une provision de 10 jours du médicament de l'étude et des sachets de SRO pour chaque enfant, ainsi que des journaux de suivi pour noter la prise du médicament, les scores de palatabilité et les événements indésirables. Un suivi a été effectué aux jours 3 et 7, et les journaux ont été collectés entre les jours 10 et 14. RÉSULTATS: Sur les 294 participants, la plupart des aidants étaient des mères (86,0%), avaient au moins une éducation secondaire (88,1%), et étaient employées (70,7%). La majorité des enfants étaient de sexe masculin (54,2%) et avaient moins de 18 mois (52,2%). La note moyenne de palatabilité était de 2,65 (±0,78), sans différences significatives en fonction de l'âge ou du sexe. L'observance moyenne était de 93,03%, avec 89,3% atteignant une observance ≥ 80%, et l'observance ne différait pas de manière significative en fonction de l'âge ou du sexe. Le seul événement indésirable signalé, les vomissements, est passé de 18,8% le jour 1 à 0,5% le jour 10. CONCLUSION: L'étude indique que le comprimé de sulfate de zinc dispersible à l'arôme d'orange est bien accepté par les enfants de 3 à 59 mois souffrant de diarrhée aiguë à Lagos, au Nigeria. MOTS-CLÉS: Diarrhée, moins de cinq ans, Enfants, Arôme d'orange, Comprimés de zinc, Palatabilité, Acceptabilité, Échelle hédonique, Lagos, Nigeria.