Pakistan Journal of Pharmaceutical Sciences

Abstract: Background: Postoperative inflammation after arthroplasty contributes to pain, delayed mobilization and prolonged hospitalization. Recent randomized trials have evaluated pharmacological anti-inflammatory strategies within contemporary enhanced recovery pathways, but evidence after hip and shoulder arthroplasty remains scattered across different drug classes and perioperative regimens. Objectives: To synthesize recent randomized controlled trial (RCT) evidence on perioperative anti-inflammatory agents after hip and shoulder arthroplasty. Methods: PubMed, Embase, Cochrane Library and Web of Science were searched for English-language RCTs published from January 2020 to March 2026. The 2020-2026 window was selected to update evidence generated under modern arthroplasty, anesthesia, multimodal analgesia and enhanced recovery after surgery (ERAS) pathways. Eligible trials included adults undergoing hip or shoulder arthroplasty and compared corticosteroids, cyclooxygenase-2 (COX-2) inhibitors, nonsteroidal anti-inflammatory drug (NSAID)-based/local anti-inflammatory regimens, or related anti-inflammatory interventions with placebo, saline, no treatment, or the same regimen without the target component. Weighted mean differences (WMDs) were pooled using random-effects models. Results: Nine RCTs involving 800 patients were included. Anti-inflammatory interventions significantly reduced postoperative C-reactive protein (CRP) [WMD=-32.18, 95% confidence interval (CI) (-41.16, -23.21), P<0.001], interleukin-6 (IL-6) [WMD=-31.25, 95% CI (-41.79, -20.77), P<0.001], rest pain [WMD=-0.41, 95% CI (-0.58, -0.23), P<0.001], activity pain [WMD=-0.56, 95% CI (-0.83, -0.29), P<0.001] and hospital stay [WMD=-0.54, 95% CI (-0.92, -0.15), P=0.006]. Conclusion: Recent RCT evidence suggests that perioperative anti-inflammatory interventions can attenuate early inflammatory responses and improve short-term pain and recovery after hip and shoulder arthroplasty. Because data were limited and clinically heterogeneous, the findings should not be interpreted as evidence favoring a specific drug class, dose, route, or timing.

Abstract: Background: Gastric cancer (GC) remains a leading cause of cancer-related mortality worldwide and effective therapeutic targets remain limited. Objectives: This study aimed to investigate the expression and functional role of miR-326 in gastric cancer, identify its direct target gene and elucidate the underlying molecular mechanisms involving the PI3K/Akt signaling pathway and the regulation of inflammatory cytokines. Methods: miR-326 expression was detected by qRT-PCR in 56 paired GC tissues and adjacent normal tissues, as well as in GC cell lines (SGC-7901, MKN-45, AGS) and normal GES-1 cells. CCK-8 assays, flow cytometry, Transwell migration/invasion assays and ELISA were performed to assess cell proliferation, apoptosis, migration/invasion and cytokine secretion. Dual-luciferase reporter assay and Western blotting were used to validate the target gene and pathway activation. Results: miR-326 was significantly upregulated in GC tissues and cell lines. ETS1 was identified as a direct target of miR-326. Overexpression of miR-326 reduced ETS1 expression, activated the PI3K/Akt pathway (increased p-PI3K and p-AKT), promoted cell proliferation, migration and invasion, inhibited apoptosis and induced an imbalance of inflammatory cytokines (increased IL-6 and TNF-α; decreased IL-10 and IL-17). Co-overexpression of ETS1 or treatment with the PI3K inhibitor LY294002 reversed these effects. Conclusions: miR-326 promotes malignant phenotypes in gastric cancer cells by targeting ETS1, activating the PI3K/Akt signaling pathway, and inducing dysregulation of inflammatory cytokines. The miR-326/ETS1/PI3K/Akt axis may serve as a potential diagnostic biomarker and therapeutic target for gastric cancer.

Abstract: Background: Cardiac arrest (CA) is associated with high mortality and severe neurological sequelae. Artemisinin (ARS), a natural product from Artemisia annua, has potential neuroprotective effects, but its role in brain injury after CA resuscitation remains unclear. Objectives: This study investigated the effects of ARS on hippocampal neuronal apoptosis and cognitive dysfunction in rats after CA resuscitation and explored whether these effects are associated with the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway. Methods: Sixty male rats were randomly assigned to six groups: sham, model, artemisinin (40 mg/kg), dimethyl sulfoxide ((DMSO, 100 mg/kg), LY294002 (a phosphatidylinositol 3-kinase inhibitor, 25 mg/kg) and artemisinin plus LY294002. Cardiac arrest was induced by transcutaneous electrical stimulation. Outcome assessors were blinded. Neurological function was evaluated using the Neurological Deficit Scale. Hippocampal damage and apoptosis were assessed by hematoxylin and eosin staining and terminal deoxynucleotidyl transferase dUTP nick end labeling staining. Learning and memory were tested using novel object recognition and the Morris water maze. Protein expression was measured by Western blot. Results: Artemisinin significantly improved Neurological Deficit Scale scores, reduced terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells and alleviated hippocampal damage. Artemisinin also prolonged novel object exploration time, shortened escape latency, increased target quadrant time and upregulated phosphatidylinositol 3-kinase expression and the ratio of phosphorylated protein kinase B to protein kinase B. Co-administration of LY294002 partially reversed these effects. Conclusion: Artemisinin alleviates hippocampal neuronal apoptosis and improves neurological deficits and cognitive dysfunction in rats after cardiac arrest resuscitation, suggesting a possible association with activation of the phosphatidylinositol 3-kinase/protein kinase B pathway. Limitations include use of a single pharmacological inhibitor and lack of genetic validation.

Abstract: Background: Elderly patients with cervical radiculopathy present therapeutic challenges owing to comorbidities and medication-related risks. Long-term pharmacotherapy and surgical interventions are often suboptimal, necessitating evaluation of optimized pulsed radiofrequency strategies under image guidance. Objectives: This superiority trial compared the efficacy and safety of ultrasound-guided cervical nerve root high-voltage pulsed radiofrequency (HVP-PRF) versus conventional pulsed radiofrequency (C-PRF) for pain management in elderly patients with cervical radiculopathy. Methods: This single-center, parallel-group, assessor-blinded randomized controlled trial enrolled patients aged 60–85 years with cervical radiculopathy, randomly assigned (1:1) to HVP-PRF (70 V) or C-PRF (45 V). Procedures were performed under ultrasound guidance with sensory/motor stimulation confirmation and temperature ≤42°C. The primary outcome was change in upper-limb radiating pain on the Numeric Rating Scale (ΔNRS) from baseline to 3 months. Secondary outcomes included Neck Disability Index (NDI), neck pain NRS, Patient Global Impression of Change, responder rates, rescue analgesia use, and adverse events. Follow-up occurred at 1 week, 1, and 3 months. Results: A total of 104 patients were randomized and 101 received treatment. At 3 months, HVP-PRF demonstrated significantly greater radiating pain improvement versus C-PRF (adjusted mean difference 1.24, 95% CI 0.46–2.02, P=0.002). Functional improvement (NDI) was superior in the HVP-PRF group at 3 months (AMD 6.47, 95% CI 2.11–10.83, P=0.004). Responder rates (≥50% pain reduction) were higher with HVP-PRF at 3 months (68.75% vs. 42.22%, OR 3.01, P=0.011) and 6 months (65.22% vs. 43.18%, OR 2.52, P=0.035). Rescue analgesic use was lower in the HVP-PRF group during 1–3 months intervals (both P<0.05). Adverse event rates were comparable (27.45% vs. 32.00%). Conclusion: Under ultrasound visualization and electrical stimulation-based target confirmation with temperature control ≤42°C, HVP-PRF provided greater and more durable relief of upper limb radiating pain compared with C-PRF in elderly patients with cervical radiculopathy, with a comparable safety profile.

Abstract: Background: Ulcerative colitis (UC) is a chronic inflammatory bowel disease impacting quality of life. Combination oral and topical mesalazine is guideline-recommended for left-sided UC, but real-world data remain limited. Objectives: This retrospective study evaluated the efficacy and safety of mesalazine enteric-coated tablets plus a retention enema in patients with mild-to-moderate E2-type (left-sided) active UC. Methods: Patients with mild to moderate E2-type active UC treated at a single center from January 2021 to December 2022 were retrospectively screened. After applying inclusion and exclusion criteria, 88 patients were included and assigned to either the study group (mesalazine enteric-coated tablets 1.0 g four times daily plus mesalazine retention enema 4.0 g once daily) or the control group (oral mesalazine enteric-coated tablets 1.0 g four times daily alone) based on clinical availability and patient preference. Treatment duration was 30 days. Outcomes included clinical efficacy (using modified local criteria and Mayo score components), symptom relief and time to improvement, endoscopic findings (Mayo Endoscopic Subscore), and adverse events. Results: The “effective” rate was significantly higher in the study group (77.27% vs. 34.09%; OR=6.58, P<0.001). Symptom relief rate was 97.73% vs. 72.73% (OR=13.44, P=0.002). Symptom improvement times were shorter in the study group (all P<0.05). Post-treatment Mayo Endoscopic Subscore was lower in the study group (1.14±0.41 vs. 2.05±0.65; mean difference -0.91, P<0.001). Ulcer and congestion/edema incidences were lower in the study group (6.82% and 18.18% vs. 25.00% and 47.73%). Adverse events were mild and comparable between groups (13.64% vs. 11.36%, P=0.746). Conclusion: Mesalazine enteric-coated tablets combined with retention enema demonstrated superior efficacy compared to oral monotherapy for short-term symptom relief and mucosal healing in patients with mild to moderate E2-type active UC, with a favorable safety profile. Larger prospective studies with longer follow-up are needed to confirm these findings and evaluate long-term outcomes.