Drug Design, Development and Therapy最新文献

Knee osteoarthritis (KOA), a prevalent degenerative joint disorder characterized by progressive cartilage degradation, synovial inflammation, and joint dysfunction, remains a major cause of disability worldwide with limited therapeutic options. Ginkgo biloba extract (EGb 761), a standardized multi-component natural product containing flavonoid glycosides and terpene lactones, has demonstrated anti-inflammatory, antioxidant, anti-apoptotic, and Chondroprotection. This narrative review synthesizes current experimental and clinical findings on the potential therapeutic role of EGb 761 in KOA. To provide a comprehensive overview, relevant literature published up to 2025 was identified through searches in PubMed, Scopus, and Web of Science, as well as by screening reference lists of key studies. Considering the complex pathogenesis of KOA and the multi-target pharmacological actions of EGb 761, this review aims to consolidate existing findings and clarify its potential role as an adjunctive therapy. Preclinical and clinical studies suggest that EGb 761 may reduce inflammation, oxidative stress, and chondrocyte apoptosis, leading to modest improvements in pain relief and joint function, while demonstrating a favorable safety profile. However, current evidence is limited by small sample sizes, methodological heterogeneity, short study durations, and risk of bias. While the available evidence is promising, it remains inconclusive that EGb 761 offers significant therapeutic benefits for individuals with KOA. Further high-quality randomized controlled trials are warranted.

Purpose: This study aims to compare the impact of ciprofol and propofol on post-induction hypotension in hypertensive patients undergoing gynecological surgery.

Patients and methods: A total of 96 patients undergoing gynecological day surgery were enrolled and randomly assigned to either the propofol group or the ciprofol group. The ciprofol group received 0.5 mg/kg for anesthesia induction, while the propofol group received 2 mg/kg. The primary outcomes included the incidence of hypotension during anesthesia induction and the area under the curve (AUC) of hypotension during the induction phase. The secondary outcomes included the change in mean arterial pressure (MAP), the cumulative dose of vasopressors during induction, the time to loss of consciousness, BIS values, recovery time, the incidence of injection pain, and the incidence of postoperative nausea and vomiting (PONV) in the PACU.

Results: The ciprofol group exhibited significantly better hemodynamic stability compared to the propofol group, with a lower incidence of hypotension (66.7% vs 89.6%, RR= 0.415, 95% CI= 0.189-0.915, P=0.007) and a smaller area under the curve during induction (-274.81±88.41mmHg·min vs -323.40±101.32mmHg·min, P=0.014). Secondary outcomes revealed that ciprofol administration resulted in less pronounced MAP fluctuations (37.27±12.83mmHg vs 44.94±13.06mmHg, P=0.005), reduced vasopressor requirements (6.0mg [0.0-6.0] vs 6.0mg [6.0-6.0], P=0.007), and lower incidence of injection pain (4.2% vs 72.9%, P=0.001). While no significant differences were observed in time to loss of consciousness and BIS values during induction (P>0.05), the ciprofol group demonstrated a slightly prolonged recovery time (7.0min [5.0-8.0] vs 5.0min [4.0-6.0], P=0.004). In the PACU, there was no difference in the incidence of PONV between the two groups (4.2% vs 2.1%, P = 1.000).

Conclusion: Compared with propofol, ciprofol demonstrates superior hemodynamic stability during anesthesia induction in hypertensive patients.

Background: Childhood IgA nephropathy (IgAN) and IgA Vasculitis-associated nephritis (IgAVN) are same in pathogenesis and still a challenge to pediatricians.

Purpose: To evaluate the efficacy and safety of Telitacicept in pediatric patients with IgAN or IgAVN.

Patients and methods: This was a retrospective single-centre study of pediatric IgAN or IgAVN with urine protein-to-creatinine ratio (UPCR) over 500 μg/mg who were treated with subcutaneous administration of Telitacicept and followed for at least 6 months. The effects on induction of remission and side effects were evaluated.

Results: 13 pediatric patients including 7 with IgAN and 6 with IgAVN were enrolled in the study. After 6-month treatment, 6 of 13 (46.15%) patients achieved remission, 4 (30.77%) patient achieved complete remission. The median percent reduction in UPCR was 90.74% (84.38%, 94.76%). The median percent reduction in urine red blood cells count was 96.21% (75.33%, 98.99%). Compared with baseline, serum albumin increased significantly [P < 0.001, 95% CI (-10.30, -4.04)], and estimated glomerular filtration rate (eGFR) remained stable and within the normal range. Significant reductions were observed in levels of IgA [P < 0.001; 95% CI (1.15, 2.49)], IgM [P = 0.002; 95% CI (0.53, 1.08)], as well as CD19+ lymphocytes [P = 0.012; 95% CI (6.63, 34.67)]. The average follow-up was 6.5 ± 0.8 months, 5 patients achieved glucocorticoid discontinuation. No severe adverse events were observed.

Conclusion: Telitacicept was safe in pediatric IgAN/IgAVN patients and could significantly induce renal remission through reducing proteinuria and hematuria.

Purpose: To investigate the association between perioperative ketamine exposure and postoperative atrial fibrillation/flutter (POAF) risk following video-assisted thoracoscopic surgery (VATS).

Patients and methods: A retrospective cohort study utilizing the TriNetX Research Network database analyzed adult patients aged ≥18 years who underwent elective VATS between January 2010 and April 2025. After excluding patients with pre-existing arrhythmias, critical illness, and emergency procedures, propensity score matching created 7,972 matched pairs comparing patients receiving perioperative ketamine/esketamine versus standard non-opioid analgesics (ketorolac/celecoxib). Primary outcome was 30-day POAF incidence. Secondary outcomes included other cardiac arrhythmias, pneumonia, mortality, and opioid use assessed at 30 days and 30-90 day intervals.

Results: Ketamine exposure was significantly associated with an increased 30-day POAF risk (2.9% vs 2.2%; hazard ratio [HR] 1.33, 95% confidence interval [CI] 1.10-1.62, p=0.004) and other cardiac arrhythmias (2.0% vs 1.3%; HR 1.60, 95% CI 1.25-2.06, p<0.001). Sensitivity analyses confirmed these findings, with POAF risk elevated in the medical center (HR 1.37, 95% CI 1.10-1.71), contemporary (HR 1.32, 95% CI 1.07-1.62), and non-malignant cohorts (HR 1.49, 95% CI 1.12-1.98). No significant interaction effects were observed in the subgroup analyses. Delayed mortality between 30-90 days was higher with ketamine (HR 1.54, 95% CI 1.07-2.20, p=0.018). Multivariable analysis confirmed ketamine as an independent predictor of POAF (HR 1.25, 95% CI 1.07-1.47, p=0.006).

Conclusion: Our findings suggest a potential association between perioperative ketamine exposure and POAF; however, given the retrospective design and substantial unmeasured confounding, prospective studies with detailed anesthetic and opioid dosing information are required to clarify this relationship.

Liver cancer progression is a multifactorial, multistage, and complex malignancy. Dihydroartemisinin (DHA) is widely recognized for its antimalarial, antifibrotic, and anticancer activities. This review highlights that DHA in the hepatitis-to-hepatocellular carcinoma (HCC) cascade and explores its underlying mechanisms. DHA has remarkable effectiveness in suppressing inflammatory cytokines and promoting tissue recovery, primarily targeting the phosphoinositide 3-Kinase (PI3K)/protein kinase B (Akt) and interleukin signaling pathways. During hepatic fibrosis, DHA inhibits hepatic stellate cell activation through mechanisms including α-smooth muscle actin (α-SMA) and nuclear factor kappa B (NF-kB) pathways. It further modulates inflammatory responses, suppresses hematopoietic stem cell proliferation, induces ferroptosis, and regulates lipid droplet metabolism. Moreover, DHA inhibits the PI3K/Akt/mammalian target of rapamycin (mTOR) pathway and yes-associated protein 1 (YAP1) signaling, thereby suppressing the proliferation, invasion, and metastatic potential of HCC cells, while simultaneously activating apoptotic and autophagic pathways. Additionally, it counteracts drug resistance and improves responsiveness to chemotherapy. Notably, lipid metabolism is identified as a promising therapeutic target in this cascade, and some nanoparticle drug delivery systems have been demonstrated to optimize DHA's therapeutic efficacy. DHA demonstrates broad therapeutic efficacy by targeting multiple molecular pathways, supporting its potential clinical application in hepatocellular carcinoma prevention and treatment.

Background: Autoimmune encephalitis (AE) is a severe neurological disorder, but limited evidence comparing the efficacy of double filtration plasmapheresis (DFPP) and intravenous methylprednisolone (IVMP) as first-line treatments in the acute phase. This study aimed to evaluate the clinical outcomes of DFPP versus IVMP in antibody-positive patients with AE.

Methods: A prospective observational cohort study was conducted at Renji Hospital from July 2018 to May 2024. Thirty-eight patients with antibody-confirmed AE in the acute phase who received either DFPP (n=22) or IVMP (n=16) as first-line therapy were included. The primary outcome was improvement in the Modified Rankin Scale (mRS), and the secondary outcome was improvement in the Clinical Assessment Scale for Autoimmune Encephalitis (CASE). Adverse events were recorded for safety assessment. Univariate and multivariate logistic regression analyses were performed.

Results: The DFPP group demonstrated significantly higher rates of functional improvement, with 68.2% (15/22) achieving mRS reduction compared to 31.3% (5/16) in the IVMP group (p=0.047). Similarly, symptomatic improvement (CASE score reduction) was observed in 72.7% (17/22) of DFPP patients versus 43.8% (7/16) with IVMP (p=0.099). Multivariate analysis identified DFPP as the sole independent predictor of better outcomes (OR: 5.234, 95% CI: 1.179-23.235, p=0.030). Adverse events were limited to the DFPP group (3/22), including manageable deep venous thrombosis and hepatic impairment.

Conclusion: DFPP demonstrated superior short-term efficacy compared to IVMP in improving functional and symptomatic outcomes in acute-phase AE, suggesting its potential as a preferred first-line therapy. Further large-scale randomized trials are warranted to validate these findings.

Purpose: To investigate the incidence of Infusion-Related Reactions (IRRs) among cancer patients receiving Immune Checkpoint Inhibitors (ICIs) and immune-based combinations.

Patients and methods: The ARON-MOUSEION-013 was registered in PROSPERO (CRD420251018433). Observational, randomized and quasi-experimental studies were included in the present review, and rates in IRR among cancer adults (≥18 years) receiving ICIs were recorded and then analyzed.

Results: A total of 4 records were considered for analyses, with a total of 55 observations and 35 events. The overall prevalence of IRR, considering Any Grade, was 67.4% [95% CI: 3.9%; 99.1%]. Considering Grade ≥ 3, a total of 55 observations and 8 events were registered. The overall prevalence of irAEs in IRRs was 6% [95% CI: 0.2%; 74.7%].

Conclusion: Mild-to-moderate IRRs are not rare events in patients receiving ICIs. IRRs may be avoided to manage these infusions slowly; however, severe reactions require emergency handling.

Purpose: 18β-Glycyrrhetinic acid liposomes (18β-GA-Lips) were developed to enhance lung-specific drug delivery and optimize the therapeutic management of pulmonary arterial hypertension (PAH).

Methods: 18β-GA-Lips of varying particle sizes were formulated using the film-dispersion method and the thin-film dispersion-probe ultrasonic technique. Their characteristics, pharmacokinetics, and tissue distribution were thoroughly investigated, followed by an inhalation subacute toxicological analysis. Anti-PAH effects were assessed through hemodynamic measurements, right ventricular hypertrophy evaluation, echocardiography, histomorphometric, and morphological analyses.

Results: The 18β-GA-Lips, with varying particle sizes, exhibited a uniform spherical morphology, achieved entrapment efficiencies exceeding 80%, and had average particle sizes ranging from 150 to 1183 nanometers. These were categorized into four distinct size groups. The drug release profile demonstrated favorable sustained-release characteristics in vitro, and the formulation remained stable for up to 15 days when stored at 4°C. Pharmacokinetic analyses revealed that, compared with the 18β-GA-solution group, the AUC_(0→48), MRT_(0→48), t_1/2, t_max, and clearance rate of 18β-GA-Lips in each group were 4.42, 3.27, 4.28, 5.07, 2.10, 3.41, 1.73, 1.46, 1.53, 1.32, 1.79, 1.67, 0.61, 2.11, 0.71, 1.71, 1.15, 0.62, 0.96, and 0.90 times higher, respectively. Tissue distribution studies revealed that B-18β-GA-Lips exhibited the highest lung-targeting efficiency, with a Te value of 54.13%. No apparent signs of toxicity were observed. In vivo data demonstrate that rats treated with 18β-GA in different formulations (solution and liposomal) and with NO exhibited significantly lower mPAP and RVSP compared to the SuHx group, with no statistically significant differences observed among the treatment groups. Notably, 18β-GA-Lips exhibited a more pronounced reduction in RVHI compared to oral solutions and significantly attenuated pulmonary vascular remodeling. Furthermore, pharmacodynamic evaluations indicated that 18β-GA-Lips exhibited superior inhibitory effects on PAH in rats compared to both atomized and intragastric 18β-GA solutions.

Conclusion: These findings confirm that 18β-GA-Lips exhibit outstanding lung-targeting capabilities and lack inhalation toxicity, thereby significantly enhancing the therapeutic efficacy of treatments for PAH.

Thyroid nodules represent one of the most prevalent endocrine disorders, affecting up to 60% of adults worldwide, with diverse biological behaviors ranging from benign hyperplastic nodules to malignant thyroid carcinoma. Heat shock proteins (HSPs), especially HSP70 and HSP90, act as key molecular chaperones involved in cellular proliferation, stress tolerance, and survival, thereby contributing to both benign nodule persistence and malignant transformation. In parallel, phytochemicals such as curcumin, epigallocatechin gallate (EGCG), resveratrol, and quercetin have emerged as bioactive modulators capable of influencing HSP expression and activity. This review decodes the molecular crosstalk between HSPs and phytochemicals, elucidating how these natural compounds regulate signaling cascades including NF-κB, MAPK, and PI3K/Akt to mediate apoptosis, autophagy, and oxidative stress balance. Particular emphasis is placed on differentiating their therapeutic implications for benign nodule regression versus thyroid cancer inhibition. Preclinical evidence demonstrates that phytochemicals can downregulate HSPs, enhance apoptotic signaling, and sensitize tumor cells to therapy; however, clinical translation remains limited due to low bioavailability, off-target effects, and dosage optimization challenges. Addressing these pharmacokinetic and delivery barriers-through nanotechnology and precision-medicine-based approaches-may unlock new integrative strategies for thyroid disease management. Collectively, this review provides a mechanistic and translational framework highlighting HSP-phytochemical interactions as potential molecular targets for improving therapeutic outcomes in both benign and malignant thyroid pathologies.

[This retracts the article DOI: 10.2147/DDDT.S420135.].