搜索结果：Pakistan journal of pharmaceutical sciences

Astragalus membranaceus is a Traditional Chinese Medicine (TCM) often used to modulate intestinal flora. This study aims to analyze the effects of Astragalus membranaceus on intestinal flora and chemotherapy-related complications in patients undergoing chemotherapy for colon cancer through clinical research and to explore the possible mechanism. The study included 86 patients with colon cancer who were assigned to the Chemotherapy (Che) and Astragalus (Ast) groups. The Che group was treated with bevacizumab combined with oxaliplatin and capecitabine and the Ast group was treated with Astragalus granules on the basis of the Che group. The intestinal flora and the incidence of chemotherapy-related complications were compared between the two groups. Astragalus granules can reduce a variety of complications during chemotherapy in patients with colon cancer. At the same time, this study detected the feces of patients before and after chemotherapy and found that Astragalus can effectively increase the content of intestinal Bifidobacterium and Lactobacillus and reduce the content of Enterococcus and Escherichia coli in patients. In addition, by detecting the serum of patients in this study, it was found that Astragalus granules can increase the level of serum CD4+ T cells and reduce the level of CD8+ T cells in patients. At the same time, Astragalus granules can also relieve the inflammatory state of patients during chemotherapy. TCM formula based on astragalus can effectively regulate the intestinal flora of patients, reduce the complications of chemotherapy and relieve the inflammatory state of the body during the chemotherapy of patients with colon cancer. Astragalus membranaceus has significant advantages in effectively improving the imbalance of intestinal flora caused by chemotherapy, improving the immune function of patients and reducing the incidence of chemotherapy-related complications.

Piperacillin/tazobactam is commonly used for the treatment of severe infections in hospitalized patients. While its pharmacokinetics have been extensively studied in critically ill patients, data on non-critically ill hospitalized patients remain limited. This study aimed to characterize the population pharmacokinetics of piperacillin in non-critically ill Pakistani patients and to identify significant covariates influencing drug disposition. This prospective, single-center study was conducted at Ayub Teaching Hospital. Serial plasma samples were collected at multiple post-dose time points to quantify piperacillin concentrations using high-performance liquid chromatography. Demographic, clinical and laboratory data were systematically recorded. Population pharmacokinetic modeling was performed using Monolix 2024R1 and model selection was guided by standard diagnostic criteria, the Akaike Information Criterion and objective function values. Twenty-five non-critically ill patients (median age: 54 years) were enrolled. The pharmacokinetic profile of piperacillin was adequately described by a two-compartment model with first-order elimination. The estimated glomerular filtration rate by the CKD-EPI 2021 equation, significantly influenced clearance, which was estimated at 15.58 L/h. The central volume of distribution was 27.06 L, the peripheral volume of distribution was 4.48 L and the intercompartmental clearance rate was 4.16 L/h. Piperacillin pharmacokinetics in non-critically ill patients are primarily influenced by renal function, with the CKD-EPI 2021 equation providing the most reliable estimates of clearance. Despite the limited sample size, these findings provide a foundation for future individualized and model-informed precision dosing approaches, particularly in Pakistan.

Vonoprazan fumarate (VF) is indicated to treat drug-induced peptic and gastroduodenal ulcers. Various chromatographic, fluorometric and spectrophotometric methods have been reported for the quantification and identification of known and unknown impurities of VF in pharmaceutical formulations and biological samples. The study aimed to develop a robust and cost-effective HPLC validated method for the analysis of VF. The method is also capable of detecting all possible degradation products and is used to characterize the stability of the VF. An RP-HPLC method with UV detection (254 nm) using C8 column (4.6 X 150mm, 5µm) was developed and validated for the quantification of VF and used to detect all possible degradation products in fast-dispersible tablets. The method validation of fast dispersible VF tablets was performed by adopting various standard validation parameters (i.e. linearity, precision, accuracy, specificity, limit of detection, limit of quantitation and robustness). The forced degradation studies have been carried to investigate the stability of the VF as per ICH guidelines. The tR of VF was 2.6 min. The method showed reproducibility within ±2%. The forced degradation studies show that VF is highly prone to degradation under alkaline conditions, while exhibiting greater stability in acidic media. The oxidative stress, photo and thermal degradation of VF show comparatively lesser degradation or relatively greater stability of VF. A simple, robust and cost-effective chromatographically validated method has been established to analyze fast-dispersible VF tablets and has been successfully applied to the stability characterization of VF.

Doxofylline (DFL) is a medication widely employed in the management of asthma and chronic obstructive pulmonary disease. Evodiamine (EVO), a bioactive alkaloid from traditional Chinese medicine (TCM), is commonly utilized for treating hypertension, gastropathy, and eczema. Cytochrome P450 enzymes primarily mediate the metabolism of both pharmaceuticals and TCMs in-vivo, which potentially lead to drug-drug interactions. This study aimed to investigate the effects of oral EVO on the pharmacokinetics (PK) of DFL and its metabolite, theophylline (TPL), in rats. Twelve rats were randomly assigned to control and experimental groups. The experimental group received 50 mg/kg EVO orally once daily for one week, while the control group received 0.5% sodium carboxymethyl cellulose. On day 7, DFL (80 mg/kg) was administered 2 h post-treatment. Venous blood specimens were collected from the retro-orbital venous plexus at 0.1667, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 and 48 h post-dose. Plasma concentrations of DFL and TPL were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Compared with the control group, the experimental group showed significant alterations in several PK parameters for both DFL and TPL. The administration of EVO markedly increased MRT(0-&#x221e;), MRT(0-t), VRT(0-&#x221e;), VRT(0-t), t1/2z, and Vz/F for DFL while also enhancing CLz/F and Vz/F for TPL. Conversely, EVO notably decreased AUC(0-&#x221e;), AUC(0-t), and MRT(0-t) values associated with TPL. Concomitant administration of EVO alongside DFL resulted in substantial modifications to key PK parameters concerning both DFL and its metabolite TPL in rats. Specifically, EVO prolonged the retention time and increased the volume of distribution of DFL, while simultaneously reducing the bioavailability and accelerating the clearance of TPL (P<0.05). Therefore, it is imperative to closely monitor the impact of TCM EVO on the PKs of DFL and TPL in experimental animals, necessitating further research and clinical observation.

Objectives and key results (OKRs), a popular management tool in enterprises, have rarely been explored in healthcare. This study assessed the impact of OKRs on an antimicrobial stewardship program (ASP) in a large tertiary hospital. A retrospective analysis was conducted before and after the implementation of OKRs in ASP (the pre-study period was from March to December 2018 and the post-study period was from March to December 2019) on the number of deaths directly caused by infections, the intensity of antimicrobial use and the incidence of bacterial resistance. A total of 259,143 hospitalized patients were included in the study (130,956 before and 128,187 after). The results showed that after the implementation of OKRs in ASP, the antibiotic use density (AUD) decreased by 4.24 DDDs/100 person-days, with a statistically significant difference (p<0.017), while there was no statistical difference in the number of deaths directly caused by infections and the incidence of bacterial resistance. Further analysis revealed that the rate of antimicrobial use among hospitalized patients decreased by 1.87%, the average length of hospital stay was shortened by 0.61 days and the per capita cost of antimicrobial drugs decreased by 48 yuan, all with statistical significance (P<0.01). OKRs, as a simple and practical management tool, have proven highly effective for ASP management and should be widely promoted in the medical field.

Ocular surface bacterial colonization is a key risk factor for postoperative infection after blepharoplasty, yet clinical evidence on the impact of levofloxacin eye drops remains limited. This study aims to evaluate the actual impact of perioperative levofloxacin eye drops on bacterial colonization density, changes in bacterial spectrum and postoperative infection rates in patients undergoing blepharoplasty. This single-center retrospective cohort study reviewed the electronic medical records of 215 patients who underwent blepharoplasty between January 2023 and January 2025. Based on the treatment they actually received, patients were categorized into two groups: the combination group (n=108), who received levofloxacin eye drops (4 times daily for 1 week) in addition to basic treatment and the control group (n=107), who received basic treatment only. The primary outcome was the incidence of postoperative infection. Secondary outcomes included the bacterial colonization positivity rate and density (days 3 and 7), changes in the bacterial spectrum, ocular surface irritation scores, wound-healing time, and adverse reactions. The postoperative infection rate in the combination group was 2.78% (3/108), which was significantly lower than that in the control group (11.21% (12/107), p = 0.013). Multivariate regression analysis showed that levofloxacin use was a protective factor for postoperative infection (OR = 0.23, 95% CI: 0.07-0.81), while a history of diabetes was an independent risk factor (OR = 3.47, 95% CI: 1.14-10.55). There was no significant difference in the time to wound healing between the two groups (7.5 &#xb1; 1.2 days vs 7.7 &#xb1; 1.4 days, p = 0.258). Perioperative levofloxacin eye drops may reduce ocular surface bacterial colonization and the risk of postoperative infection in blepharoplasty patients without delaying wound healing.

Diabetic neuropathic pain (DNP) is a prevalent and debilitating complication of diabetes mellitus, characterized by persistent pain and neuroinflammation. Current treatments often provide inadequate relief, highlighting the need for novel therapeutic strategies targeting its underlying mechanisms. This study aimed to investigate the therapeutic potential of tetrandrine (Tet) in alleviating DNP and to elucidate its effects on two key pathological processes: neuronal autophagy and microglial polarization. To establish the DNP model, rats received an intraperitoneal injection of streptozotocin. Pain behavior was assessed weekly using mechanical withdrawal threshold and thermal withdrawal latency tests. Relevant markers were analyzed via reverse-transcription quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay, immunofluorescence, or Western blot. To further investigate the underlying mechanisms, in-vitro experiments were conducted using high glucose-treated neuronal cells and lipopolysaccharide-stimulated BV2 microglia. Tet administration significantly alleviated pain hypersensitivity and neuroinflammation in DNP rats. Mechanistically, this effect might be achieved through a dual modulation of neuroimmune processes and intracellular clearance pathways. Tet shifted microglial polarization from the pro-inflammatory M1 phenotype toward the anti-inflammatory M2 state. Concurrently, it enhanced autophagic activity, as evidenced by an increased LC3-II level and LC3-II/LC3-I ratio, restored expression of the mitophagy-related proteins PINK1 and parkin and reduced p62 accumulation. In-vitro findings corroborated these mechanisms: Tet balanced the expression of M1 and M2 markers in activated microglia and similarly upregulated key autophagy-related proteins (LC3-II, PINK1, parkin) in neurons under high-glucose stress. Tet alleviates DNP, potentially through the concurrent modulation of microglial phenotypic transition and neuronal autophagy. These findings identify Tet as a promising multi-target agent for DNP and elucidate its potential mechanisms of action.

Cholestatic liver injury (CLI) is a rapidly progressive liver disorder characterized by the accumulation of bile acids (BA). The therapeutic effects of current medicines used to treat CLI are unsatisfactory. This study aimed to prepare galactosylated solid lipid nanoparticle (SLN) with swertiamarin (STM) by using a galactosylated lipid, N-hexadecyl lactobionamide (N-HLBA) and evaluate its anti-cholestasis effect in-vitro. The galactosyl-lipid N-HLBA was prepared via the lactone form intermediates of lactobionic acid and synthesized by anchoring galactose to hexadecylamine lipid. The STM-loaded galactosylated SLN (STM-GalSLN) was successfully prepared by a melt-emulsification-ultrasound method. The prescription was optimized by orthogonal test. The morphology was observed by transmission electron microscope. The particle size and zeta potential were determined by laser granularity equipment. The encapsulation efficiency (EE) and drug loading capacity (DL) were determined by ultrafiltration, centrifugation and HPLC method. The optimized prescription was as follows: 50 mg of STM, 20 mg of N-HLBA, 500 mg of glyceryl behenate, 400 mg of soybean lecithin, 200 mg of poloxamer188 and 500 mg of Tween 80. The STM-GalSLN was spherical in shape and its particle size, zeta potential, EE and DL were 164.40 &#xb1;4.68 nm, -14.53 &#xb1;3.20 mV, 82.41 &#xb1;2.88 % and 0.32 &#xb1;0.02 %, respectively, and the EE of STM-GalSLN did not change significantly over 30 days at 4&#xb0;C. Furthermore, STM-GalSLN alleviated cholestatic liver injury (CLI) in a concentration-dependent manner in-vitro. The findings from this study indicated that the melt-emulsification-ultrasound method was rational and reliable, which provided an experimental basis for developing a new nano preparation of STM for CLI.

Hypertension frequently coexists with coronary heart disease (CHD) and integrated management is essential to reduce cardiovascular and renal complications. To evaluate the efficacy and safety of add-on sustained-release diltiazem capsules in patients with hypertension and CHD. This retrospective cohort analysis included 302 consecutive patients with CHD treated at the Affiliated Hospital of Jiangnan University between May 2021 and May 2024. Patients were divided into a control group (n=158) receiving standard guideline-directed therapy and a diltiazem group (n=144) receiving add-on diltiazem sustained-release capsules. Propensity scores were used to match and balance baseline covariates to reduce selection bias. Following matching, intergroup comparisons for baseline characteristics, occurrence of cardiorenal composite endpoints, blood pressure, heart rate (HR) control during follow-up and adverse drug reactions were conducted. Multivariate regression analysis was used to determine predictors of cardiorenal endpoint events. After matching, baseline covariates were well-balanced between groups. During a median follow-up of 18 months, the cumulative incidence of cardiorenal composite endpoint events was lower in the diltiazem group than in controls (16.39% vs. 32.79%, P=0.002). Multivariate Cox analysis showed that diltiazem therapy was independently associated with a lower risk of composite outcomes (hazard ratio = 0.465, 95% CI: 0.284-0.760, P = 0.002). Patients receiving diltiazem also had a lower mean HR and higher achievement rates for HR control and combined blood pressure/HR targets (all P<0.05). The reduction in composite outcomes was primarily driven by fewer heart failure rehospitalizations. Drug-related adverse events were comparable between groups. Adding sustained-release diltiazem capsules to standard therapy is associated with a lower cardiorenal composite endpoint risk in patients with hypertension and CHD. The observed benefit was mainly driven by fewer heart failure rehospitalizations, alongwith improved control of blood pressure and heart rate. The renal findings should be considered exploratory because the number of renal events was limited.

Renal interstitial fibrosis (RIF) is a critical pathological outcome of chronic kidney disease (CKD). Aconitine has been shown to induce RIF, with the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway potentially playing a key role in this process. Quercetin, a natural flavonoid compound, exhibits anti-fibrotic effects that may be associated with this pathway. However, there is no clear evidence yet regarding its role in aconitine-induced RIF. This study aimed to investigate the intervention effect of quercetin on aconitine-induced RIF and the role of PI3K/Akt pathway in its mechanism. A mouse model of RIF was established and the animals were randomly assigned to the following groups: normal control, aconitine model, low-dose quercetin, medium-dose quercetin, high-dose quercetin and high-dose quercetin combined with the PI3K inhibitor S27673-MA. The extent of fibrosis and the expression of key molecules in the PI3K/Akt pathway were evaluated using histopathology, qPCR and Western blot. Compared to the model group, the high-dose quercetin group exhibited an approximately 60% reduction in fibrotic area (P<0.01). Moreover, quercetin significantly suppressed the overexpression of phospho-PI3K (p-PI3K), phospho-AKT (p-AKT), neutrophil elastase (NE) and nuclear factor kappa B p65 (NF-&#x3ba;B p65) at both transcriptional and protein levels in renal tissues (P<0.05). The use of the PI3K inhibitor S27673-MA further enhanced the anti-fibrotic effect of quercetin and its inhibitory effect on the aforementioned molecules. Quercetin ameliorates aconitine-induced RIF by inhibiting the PI3K/Akt pathway and its downstream NE/NF-&#x3ba;B axis.

In experimental models of central nervous system damage, thyrotropin-releasing hormone (TRH) has been shown to have neuromodulatory, antioxidant and anti-inflammatory effects. Its neuroprotective efficacy in embolic cerebral ischemia remains unknown. This study evaluated the effects of intrathecal TRH administration on cerebral infarct volume, oxidative stress and inflammatory markers in a rabbit model of embolic cerebral ischemia. Twenty adult female New Zealand white rabbits were randomly divided into two groups (n = 10 per group): a control group and a TRH-treated group. Injecting broken autologous blood clots into the right common carotid artery caused cerebral ischemia. Forty-five minutes after embolization, the treatment group received intrathecal TRH (0.20 mg/kg) via the cisterna magna. Serum interleukin-1&#x3b2; (IL-1&#x3b2;) concentrations and levels of lactate and malondialdehyde (MDA) in the cerebrospinal fluid (CSF) were assessed at baseline and 24 hours after embolization. Computerized histopathological image analysis was used to measure the volume of the cerebral infarct. The mean cerebral infarct volumes at 24 hours varied slightly between the TRH-treated group (122.84 &#xb1; 15.84 mm&#xb3;) and the control group (126.79 &#xb1; 14.04 mm&#xb3;) (p = 0.496). Serum levels of IL-1&#x3b2;, MDA and CSF lactate increased statistically significantly (p <.05) in both the TRH-treated and control groups. Following embolization, the TRH-treated group had decreased serum levels of CSF lactate, CSF MDA and IL-1&#x3b2;; nevertheless, none of the group comparisons were significant (p >.05). Although no statistically significant differences were observed, consistent directional reductions in infarct volume and biochemical markers suggest potential biological activity of TRH that may require optimization of dosing and study design. At the dosage and duration employed in this study, TRH showed limited efficacy under the experimental conditions.

With high incidence and mortality rates, lung cancer has brought a huge burden to patients' families and society. Sparganii Rhizoma, a famous anti-cancer herb, has demonstrated good effects on lung cancer. However, the underlying active ingredients and mechanism of Sparganii Rhizoma on lung cancer were not yet clear. This study integrated network pharmacology, molecular docking and molecular dynamics simulation to explore the active ingredients and mechanism of Sparganii Rhizoma on Lung Cancer. Three databases and several related studies were used to screen the ingredients and targets of Sparganii Rhizoma and lung cancer, respectively. The enrichment analyses were performed using the Matascape database, and the protein-protein interaction (PPI) and ingredient-target-pathway networks were constructed. Finally, molecular docking and molecular dynamics simulations were used to verify the key active ingredients and targets of Sparganii Rhizoma in lung cancer. A total of 129 ingredients and 1101 targets of Sparganii Rhizoma, and 150 targets of lung cancer, were obtained. Network pharmacology identified 57 active ingredients, 27 targets, and 86 signaling pathways for Sparganii Rhizoma in lung cancer. The results of molecular docking indicated that the key active ingredients included sparstolonin B, emodin, adenosine, 4-hydroxycinnamic acid, and so on, and the key targets were Cytochrome P450 1A2 (CYP1A2), Prostaglandin G/H synthase 2 (PTGS2), and Dual specificity mitogen-activated protein kinase kinase 1 (MAP2K1). In a molecular dynamics simulation, sparstolonin B bound to CYP1A2, PTGS2, and MAP2K1 with good affinity. Based on the integration of network pharmacology, molecular docking and molecular dynamics simulation, this study revealed the potential active ingredients and mechanisms of Sparganii Rhizoma on lung cancer.

Synthesis of novel enzyme inhibitors and antioxidants is active research in pharmaceuticals sciences. Novel compounds with potential therapeutic value can be synthesized to help the body combat oxidative-stress related diseases. This study comprised synthesis of 4-(3-bromophenyl)-[2,2'-bipyridine]-6-carboxylic acid, its complexation with Fe(II), Cu(II) and Ni(II), and the evaluation of these compounds as lipoxygenase inhibitors and antioxidant agents. The ligand and its complexes were characterized using NMR, IR, UV-Vis and mass spectroscopies. The synthesized compounds were also screened to evaluate their antioxidant and lipoxygenase properties. Two sample t-test and ANOVA were used to evaluate the significance of biological activity of the complexes. The ligand acted as a tridentate donor forming ML2 complexes. Cu(II) and Ni(II) complexes showed significant lipoxygenase inhibition with the respective IC50 values of 50.6 and 59.8 &#xb5;M, while antioxidant activity was largely attributed to the ligand itself with IC50 value of 56.4 &#xb5;M. The study demonstrated that Cu(II) and Ni(II) complexes of the synthesized ligand were promising candidates for lipoxygenase inhibition, while the free ligand exhibited significant antioxidant activity.

Jasmine oil massage has a thousand years of traditional history of curing and treating various ailments like hypertension, diabetes and muscle cramps without any sound pharmacological evidence. Traffic wardens have to stand throughout their duty hours, which can lead to muscle fatigue and compression and those suffering from stage 2 hypertension have to face worsened cardiovascular issues. To assess the therapeutic effectiveness of jasmine oil massage, administered manually and in combination with an electrical massager, on blood pressure and related cardiovascular parameters in traffic wardens with stage 2 hypertension and to investigate the potential molecular interactions of key jasmine oil phytoconstituents with human voltage-gated sodium channels. The randomized controlled trial study (IRCT20230103057033N2) was conducted from November 2022 to March 2023. A total of 300 patients were randomly divided into three groups. Group A was treated with jasmine oil and an electrical massager. Group B was treated with jasmine oil manually. Group C was treated with only an electrical massager. The treatment regimen was 3 weeks, distributed as 6 sessions/week, each session lasted for 40 minutes. Blood pressure, blood cholesterol, respiration rate, heart rate and oxygen saturation of all the patients with hypertension were measured before and after treatment. The major phytoconstituents, phytosterol, &#x3b1;-pinene, benzyl acetate and linalool were docked with human voltage-gated sodium channels (Na < sub > v < /sub > 1.9, Na < sub > v < /sub > 1.8 and Na < sub > v < /sub >1.7). Jasmine oil showed more significant results (p = 0.0001) in patients treated with jasmine oil and an electrical massager, significant results (p<0.005) in patients treated with jasmine oil and non-significant results in patients treated with an electrical massager only (p>0.005). Na < sub > v < /sub > 1.9 exhibited slightly better binding across most ligands compared to Na < sub > v < /sub > 1.7 and Na < sub > v < /sub > 1.8, suggesting that this isoform may offer a more favorable binding pocket for phytochemicals were tested. The results support better drug absorption and effects when jasmine oil was applied with an electrical massager and project a newer, non-invasive alternative, less expensive and safer treatment protocol for traffic wardens suffering from stage 2 hypertension.

Adolescent diabetic kidney disease (DKD) represents an early-onset microvascular complication characterized by prolonged metabolic exposure and accelerated renal decline. Elevated serum creatinine and blood urea nitrogen (BUN) are key biochemical indicators of impaired renal function. This scoping review aims to systematically map and evaluate pharmacological strategies for slowing the rise of creatinine and BUN in adolescents (aged 10-19 years) with DKD, with emphasis on renoprotective mechanisms, therapeutic sequencing and the potential applicability of these therapies to adolescent populations. A scoping review was conducted in accordance with PRISMA-ScR guidelines. A comprehensive literature search was performed using PubMed, Scopus and Google Scholar for studies published between 2020 and 2025. Eligible studies included clinical trials, observational studies, clinical guidelines and relevant reviews focusing on pharmacological interventions in adolescents (10-19 years) with diabetic kidney disease. Study selection was based on predefined inclusion and exclusion criteria. A total of 35 studies and guideline-based references were included in the final synthesis. Intensive glycemic control (insulin for type 1 diabetes; metformin &#xb1; insulin for type 2 diabetes) was associated with improved metabolic control and favorable renal outcomes. Renin-angiotensin system blockers consistently reduced albuminuria and induced an acute hemodynamic reduction but stabilized the long-term decline in estimated glomerular filtration rate (eGFR). Sodium-glucose cotransporter-2 (SGLT2) inhibitors demonstrated additional renoprotective effects in type 2 diabetes; risks (euglycemic DKA) limit use in type 1. In adult studies, finerenone attenuated inflammatory and fibrotic pathways; no adolescent data exist. Glucagon-like peptide-1 receptor agonists improved metabolic control and reduced obesity-associated renal stress. However, pediatric-specific evidence remains limited, and much of the available evidence is derived from adult studies. Adult data suggest potential benefits of early multi-target pharmacotherapy, but adolescent-specific evidence is needed to confirm a critical role in delaying renal deterioration. Whether integration of conventional and novel agents improves long-term renal outcomes in adolescents requires direct investigation. Further pediatric-focused research is required to establish safety, efficacy and optimal therapeutic strategies.

Sevoflurane, an ether-derived inhalational anesthetic widely used for general anesthesia, requires comprehensive safety evaluation. This study aimed to identify sevoflurane-associated adverse events and detect unexpected safety signals using data from the FDA Adverse Event Reporting System (FAERS). We analyzed FAERS data from the first quarter of 2004 through the first quarter of 2024, applying four disproportionality analysis algorithms (ROR, PRR, BCPNN, MGPS) to reports designating sevoflurane as the "primary suspect" drug. Among 1,649 reports, we identified 27 significant preferred terms affecting four major organ systems. Notable unexpected safety signals included cardiac arrest, anesthesia awareness, delayed recovery, pulmonary alveolar hemorrhage, anaphylactic shock and seizures. These findings provide critical insights into sevoflurane's real-world safety profile, particularly revealing severe yet underrecognized risks that can inform enhanced clinical monitoring and safer anesthetic practice. However, it should be acknowledged that disproportionality analysis is a hypothesis-generating or refinement approach, and further confirmatory studies are warranted to establish causal relationships.

The Traditional Chinese Medicine (TCM) Inheritance Computing Platform (V3.0) provides advanced data-mining capabilities for analyzing large-scale clinical data, enabling systematic extraction of prescription patterns and therapeutic principles. This systematic review applied the TCM Inheritance Computing Platform to summarize clinical practice patterns in rUTIs, focusing on the clinical experience of Professor Qu Wei and evidence from clinical trials conducted between 2022 and 2025. Clinical trials were systematically retrieved from international registries (ClinicalTrials.gov, WHO ICTRP, ChiCTR, PubMed). Variables, including demographics, syndrome classification, interventions and outcomes, were standardized and encoded for analysis. Frequency analysis, association rule mining and hierarchical clustering were conducted to identify high-frequency symptoms, core prescriptions, herb compatibility patterns and therapeutic clusters. Thirty-eight clinical trials (3,462 patients) were analyzed, predominantly female (72.4%), aged 28-57 years, with 3-6 recurrent episodes annually. Damp-heat in the lower jiao (62.1%) was the most frequent TCM syndrome, followed by spleen-kidney qi deficiency (38.6%) and yin deficiency with heat (21.3%). Key herbs included Huang Bai (71%), Fu Ling (69%), Che Qian Zi (65%) and Bai Zhu (58%). Association rule mining highlighted core herb pairs such as Huang Bai-Fu Ling (support 61%, confidence 0.82). Cluster analysis revealed three therapeutic groups: (A) damp-heat clearing formulas, (B) damp-heat with qi stagnation and (C) kidney-tonifying prescriptions. Interventions reduced recurrence by 30-45%, improved symptoms, quality of life and showed immunomodulatory and microbiota-regulating effects. The TCM Inheritance Computing Platform effectively summarized rUTI practice patterns, validating damp-heat clearing and kidney-tonifying as core strategies. Herb pair associations strengthen evidence-based integration of TCM, offering a replicable, data-driven model for recurrent infection management.

DFS differs markedly among breast cancer subtypes with varied chemotherapy and targeted therapy regimens, making optimal regimen selection critical. To investigate the impact of diverse regimens on DFS across breast cancer molecular subtypes and identify the optimal therapeutic strategies. 106 breast cancer patients were stratified by subtype and treatment regimen and followed up for 3 years. These are preliminary findings from a 3-year follow-up: the overall 3-year DFS rate was 78.30%. In HER2-positive individuals, the 3-year DFS rate of the AC-TH&#xb1;P regimen (85.71%) was higher than that of the TH regimen (66.67%) with statistical significance (p=0.032), though the sample sizes in the partial HER2-positive subgroups were small and the results need to be verified with larger samples. In hormone receptor-positive individuals, the DFS rate of the AC-taxane regimen (83.33%) was higher than that of the TC regimen (72.73%) (p=0.045), dose-dense regimens outperformed conventional ones (86.84% vs 66.67%, p=0.033) and abemaciclib addition improved DFS in high relapse risk cases (90.91% vs 63.64%, p=0.024). In TNBC, dose-dense regimens showed higher DFS (72.73% vs 53.85%, p=0.040); capecitabine for high relapse risk and olaparib for BRCA1/2 mutations both significantly improved DFS (p<0.05). Multivariate analysis confirmed TNBC, positive lymph node metastasis and non-optimized regimens as independent DFS risk factors (all p<0.05). This preliminary 3-year follow-up study demonstrated that precision individualized treatment is necessary for each subtype of breast cancer: for HER2-positive breast cancer, the AC-TH&#xb1;P regimen is preferred; for HR-positive breast cancer, a dose-dense AC-taxane regimen is recommended, with abemaciclib added for high recurrence risk; for TNBC, dose-dense chemotherapy, with capecitabine added for high recurrence risk and olaparib added for BRCA1/2 mutations, can significantly prolong DFS.All conclusions are preliminary due to the short 3-year follow-up period and require validation with longer-term follow-up and larger sample sizes.

Pitavastatin (PVN), a BCS class-II drug, exhibits poor aqueous solubility leading to limited oral bioavailability and therapeutic efficacy. This study aimed to enhance the solubility and anti-hyperlipidemic efficacy of Pitavastatin (PVN) by encapsulating it in chitosan-based polymeric nanoparticles. Pitavastatin-loaded chitosan nanoparticles (NPs) were prepared using the ionic gelation method. Formulations were characterized by particle size, zeta potential, drug loading, In-vitro drug release and surface morphology. Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), thermal analysis (TGA and DSC), ex-vivo intestinal permeability and in-vivo pharmacodynamic analysis were also performed. The size of PVN-loaded NP ranged from 219.9&#xb1;1.11 to 292.7&#xb1;2.29 nm with PDI 0.2-0.4, surface charge of +28.4 &#xb1; 0.43 to 32.5 &#xb1; 1.02 mV and entrapment efficiency 65&#xb1;1.12-93&#xb1;1.23%. Solubility in different media (PBS (pH 6.8), 0.1N HCl (pH 1.2) and distilled water showed a 56-102-fold increase compared to PVN. SEM analysis revealed a smooth surface and spherical geometry of the NP. FTIR analysis confirmed that there was no physicochemical interaction between PVN and chitosan in NP formulations (NP1-NP5). XRD and thermal analysis indicated the amorphous nature of PVN-loaded NP. In-vitro drug release from NP formulations (NPI-NP5) ranged from 80.97&#xb1;4.80 to 81&#xb1;3.90% indicating sustained release, while ex-vivo intestinal permeability was 1.5-fold higher than PVN. The optimized formulation (NP1) followed Higuchi release model, indicating Fickian diffusion. Pharmacodynamic analysis of lipid profiles in hyperlipidemic albino rats suggested that NP1 reduced low-density lipoprotein (LDL) by 33&#xb1;1.24 %, total cholesterol by 29&#xb1;2.13% and triglycerides by 23&#xb1;1.21%, showing better results than PVN. Chitosan-based Pitavastatin nanoparticles successfully enhanced drug solubility and provided sustained release, leading to improved ex-vivo permeability and greater in-vivo anti-hyperlipidemic activity in albino rats. This approach represents a promising strategy for enhancing therapeutic potential of Pitavastatin.