Abstract Background: Dengue fever continues to spread worldwide, particularly in tropical regions. Some patients with dengue fever may progress to severe dengue, which is associated with significantly higher morbidity and mortality. Despite this, no definitive treatment has been found to prevent its progression. Montelukast, a leukotriene receptor antagonist, has shown potential in reducing plasma leakage, a key factor in the pathophysiology of severe dengue. Therefore, this study aimed to evaluate the effectiveness of montelukast in reducing the risk of severe dengue. Methods: A systematic literature search was conducted on April 16, 2025, using keywords related to montelukast and dengue across four databases, which included PubMed, Taylor and Francis, Cochrane Library, and ScienceDirect. A critical appraisal was performed using the Oxford Centre for Evidence-Based Medicine framework, evaluating the validity, importance, and applicability of each study. The primary outcomes were the incidence of dengue shock syndrome and dengue with warning signs. The secondary outcomes included mortality rate and hospitalization duration. Results: This study included three studies involving a total of 1057 patients. Montelukast is associated with a reduced incidence of dengue shock syndrome and shorter duration of hospitalization. However, the effect of montelukast on dengue with warning signs and mortality rate was inconclusive. Conclusion: Montelukast shows potential as an adjuvant therapy in preventing the progression of dengue fever to severe dengue. However, further research is required before montelukast can be widely recommended for dengue fever patients in daily clinical practice and possibly integrated into dengue fever clinical guidelines.
evidence-based case report ; severe dengue ; dengue fever ; leukotriene receptor antagonist ; montelukast

Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) improve glycemic control, promote weight loss, reduce insulin requirements, and confer cardiometabolic benefits in type 2 diabetes mellitus (T2DM). This audit evaluated glycemic and metabolic outcomes of GLP-1 RAs in T2DM patients at a single-centre diabetes clinic. Methodology: This audit included T2DM patients who initiated GLP1 RAs between January 2022 and March 2025 at Hospital Sultan Abdul Halim. Primary outcomes were changes in hemoglobin A1c (HbA1c), body weight, and body mass index (BMI) at 3 and 12 months. Secondary outcomes included percentage weight loss, changes in systolic blood pressure (SBP), insulin total daily dose (TDD), low-density lipoprotein (LDL) cholesterol, gastrointestinal adverse effects, and treatment discontinuation. Results: Sixteen patients were included; median age was 58.5 years (interquartile range [IQR] 47.5–65), and 56.3% were female. Median diabetes duration was 15 years (IQR 11.5–20.3). Median HbA1c decreased from 9.7% (IQR 8.6–10.4) at baseline to 8.8% (IQR 7.7–9.1) at 3 months and 7.8% (IQR 7.0–8.5) at 12 months. Body weight decreased from 88.1 kg (IQR 79.5–122.1) at baseline to 85.0 kg (IQR 75.9–113.7) at 3 months and 82.0 kg (IQR 74.8–117.3) at 12 months. BMI decreased from 37.8 kg/m² (IQR 31.7–47.1) to 37.3 kg/m² (IQR 30.7–45.5) at 3 months and 36.0 kg/m² (IQR 30.1–45.6) at 12 months. At 12 months, weight loss was 5.8% (IQR 3.0–8.0), with 56.5% achieving >5% weight reduction. In all, 93.8% achieved >1% HbA1c reduction. Mean SBP decreased by 10 ± 20 mmHg, LDL cholesterol 0.29 mmol/L (IQR -0.77 to 0.07), and insulin TDD 8 units/day (IQR -13 to 10). No gastrointestinal adverse effects reported. Three patients (18.8%) discontinued treatment due to excessive weight loss, treatment plateau, and limited drug availability. Conclusion From our single-centre experience, the observed improvements in glycemic and metabolic outcomes support the benefits of GLP-1 RAs in managing T2DM.
Diabetes Mellitus, Type 2 ; Glucagon-Like Peptide-1 Receptor Agonists ; Clinical Audit

Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) induce clinically meaningful weight reduction in patients with type 2 diabetes mellitus (T2DM), but real-world data in Southeast Asian populations are limited. This study evaluated the effectiveness of GLP-1 RAs in achieving clinically significant weight loss in Malaysian patients with obesity and T2DM. Methodology: A retrospective cohort study was conducted among adults with T2DM and obesity attending the Endocrinology Clinic at Hospital Sultan Abdul Aziz Shah between January 2023 and December 2024. Patients receiving GLP-1 RAs (semaglutide or liraglutide) were compared with those on standard care. Anthropometric outcomes were assessed over 6–12 months, with weight loss thresholds of ≥3, ≥5, and ≥10%. Between-group comparisons used Fisher’s exact test, and odds ratios (OR) were calculated. Results: Eighty-five patients were included (GLP-1, n = 47; control, n = 38). The GLP-1 group achieved significantly higher rates of any weight loss (70.0% vs 41.2%; OR = 3.33, p = 0.019) and ≥3% weight loss (42.5% vs 14.7%; OR = 4.29, p = 0.011). Number needed to treat was 3–4 patients. Proportions achieving ≥5 and ≥10% weight loss were higher in the GLP-1 group but did not reach statistical significance. Conclusion GLP-1 RA therapy significantly improves the likelihood of clinically meaningful weight loss in Malaysian patients with obesity and T2DM. These findings support the integration of GLP-1 RAs into routine obesity management strategies in Southeast Asia.
Humans ; Diabetes Mellitus, Type 2 ; Glucagon-Like Peptide-1 Receptor Agonists ; Weight Loss

Introduction: While Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are effective for weight reduction in type 2 diabetes mellitus (T2DM), interindividual variability exists. Lifestyle factors, particularly baseline physical activity, may modify weight loss outcomes. This study examined whether baseline activity influences GLP-1 RA efficacy in Malaysian patients. Methodology: A retrospective cohort of adults with obesity and T2DM receiving GLP-1 RAs (semaglutide or liraglutide) from January 2023 to December 2024 was analyzed. Baseline physical activity was classified as active or inactive. Primary outcomes were achievement of ≥3 and ≥5% weight loss over 6–12 months. Associations were assessed using Fisher’s exact test and logistic regression. Results: Among GLP-1-treated patients, those reporting baseline physical activity were more likely to achieve ≥3% weight loss and demonstrated trends toward higher, ≥5%, weight loss. Logistic regression suggested baseline activity increased the odds of clinically meaningful weight reduction, though statistical significance was limited by sample size. Conclusion Baseline physical activity may enhance GLP-1 receptor agonist-mediated weight loss in obese patients with T2DM. Integrating lifestyle interventions with pharmacotherapy may optimize treatment outcomes. Larger prospective studies are warranted to confirm these findings.
Humans ; Glucagon-Like Peptide-1 Receptor Agonists ; Exercise ; Weight Loss ; Obesity ; Diabetes Mellitus, Type 2

OBJECTIVE: To investigate the expression and possible regulatory mechanism of miR-34a in the lung tissue of neonatal rat model of bronchopulmonary dysplasia (BPD) induced by hyperoxia. METHODS: In the study, 80 newborn SD rats were randomly divided into hyperoxia group (FiO₂=60%) and air group (FiO₂=21%) within 2 hours after birth, 40 rats per group. Lung tissue samples of the SD rats in each group were extracted on the 1st, 7th, 14th and 21st days after birth, and the pathological changes of lung tissue were observed under light microscope after HE staining. The number of radial alveolar counts (RAC) and the mean alveolar diameter (MAD) and the thickness of alveolar septal thickness (AST) were measured to evaluate the development of alveoli. Real-time fluorescence quantitative PCR was used to detect the expression of miR-34a, angiopoietin-1 (Ang-1) and tyrosine kinase receptor-2 (Tie-2) in lung tissue of rats in hyperoxia group and air group at different time points. Enzyme-linked immunosorbent assay (ELISA) was used to detect the proteins expression of Ang-1 and Tie-2 in the lung tissues of the two groups at different time points. RESULTS: The weight of rats in the hyperoxia group on the 7th, 14th and 21st days after birth was significantly lower than that in the air group (P all < 0.05). With the prolongation of oxygen exposure, the number of alveoli decreased, the volume increased, the structure simplified, the alveolar cavity enlarged obviously and the alveolar septum thickened in the hyperoxia group. On the 7th, 14th and 21st days after birth, the RAC in the hyperoxia group was significantly lower than that in the air group (P all < 0.05). Compared with the air group, MAD and AST increased significantly on the 7th, 14th and 21st days after birth in the hyperoxia group, and the difference was statistically significant (P all < 0.05). The expression level of miR-34a in lung tissue of hyperoxia group was significantly higher than that of air group on the 7th, 14th and 21st days after birth, and the difference was statistically significant (P all < 0.05). Compared with the air group at the same time point, the expression levels of Ang-1 and Tie-2 mRNA and protein in the hyperoxia group were lower than those in the air group on the 14th and 21st days after birth (P all < 0.05). CONCLUSION The new BPD model of newborn SD rats can be successfully established by continuous exposure to 60% hyperoxia. The expression of miR-34a was up-regulated in the lung tissue of the new BPD model of neonatal rats. MiR-34a may play an important role in the occurrence and development of BPD by regulating Ang-1/Tie-2 signal pathway.
Animals ; MicroRNAs/metabolism* ; Bronchopulmonary Dysplasia/genetics* ; Hyperoxia/metabolism* ; Rats, Sprague-Dawley ; Animals, Newborn ; Rats ; Angiopoietin-1/genetics* ; Disease Models, Animal ; Receptor, TIE-2/genetics* ; Lung/pathology* ; Male

OBJECTIVE: To investigate the biological activity and antitumor effect of pegylated recombinant human interleukin 2 (PEG-rhIL-2) obtained by site-specific conjugation of polyethylene glycol (PEG) with non-natural amino acids, and to explore its antitumor mechanism. METHODS: The binding activities of PEG-rhIL-2 at three different sites (T41, Y45, and V91) to human interleukin 2 receptors α (IL-2R_α) and β (IL-2R_β) and were detected by surface plasmon resonance (SPR) technology. Western blot was used to detect the levels of the Janus kinase-signal transducer and activator of transcription 5 (JAK-STAT5) signaling pathway activated by different doses of rhIL-2 and PEG-rhIL-2 in CTTL-2 and YT cells. Blood was collected after a single administration in mice to detect the drug concentration at different time points and evaluate the pharmacokinetic parameters of Y45-PEG-rhIL-2. Mouse hepatoma cell line Hepa1-6, pancreatic cancer cell line Pan-02, and colon cancer cell line MC-38 were selected. Tumor models were constructed in C57BL/6 mice. Different doses of Y45-PEG-rhIL-2 and excipient control were administrated respectively to evaluate the tumor suppression effect of the drug. In the MC-38 colon cancer model, the tumor suppression effect of Y45-PEG-rhIL-2 combined with anti-programmed death-1 (PD-1) monoclonal antibody was evaluated. Hepa1-6 mouse tumor models were constructed and rhIL-2, Y45-rhIL-2 and Y45-PEG-rhIL-2 were administrated respectively. The proportion of tumor-infiltrating lymphocytes was analyzed by flow cytometry. RESULTS: The SPR detection results showed that the binding activities of PEG-rhIL-2 to IL-2R_α/IL-2R_β were both reduced. The affinity of Y45-PEG-rhIL-2 to IL-2R_α was reduced to approximately 1/250, and its affinity to IL-2R_β was reduced to 1/3. Western blot results showed that the activity of Y45-PEG-rhIL-2 in stimulating JAK-STAT5 signaling in CTLL-2 cells expressing heterotrimeric IL-2 receptor complex IL-2R_αβγwas reduced to approximately 1/300, while its activity in YT cells expressing heterodimeric IL-2 receptor complex IL-2R_βγwas reduced to approximately 1/3. The pharmacokinetic evaluation after a single dose in the mice showed that the elimination half-life of Y45-PEG-rhIL-2 was 17.7 h. Y45-PEG-rhIL-2 has pharmacokinetic characteristics superior to those of rhIL-2. Y45-PEG-rhIL-2 showed dose-dependent tumor suppression activity, and the combination of Y45-PEG-rhIL-2 and anti-PD-1 antibody had a better tumor-inhibiting effect than the single use of Y45-PEG-rhIL-2 or anti-PD-1 antibody. Flow cytometry analysis demonstrated that 72 h after the administration of Y45-PEG-rhIL-2, the proportion of tumor-infiltrating cytotoxic T lymphocytes (CD8⁺T cells) increased by 86.84%. At 120 h after administration, the ratio of CD8⁺T cells to regulatory T cells (Treg) increased by 75.10%. CONCLUSION Y45-PEG-rhIL-2 obtained by site-specific conjugation via non-natural amino acids changed its receptor binding activity and inhibited tumor growth in dose-dependent manner in multiple tumor models by regulating CD8⁺T cells.
Interleukin-2/pharmacokinetics* ; Animals ; Mice ; Humans ; Recombinant Proteins/pharmacology* ; Polyethylene Glycols/chemistry* ; Cell Line, Tumor ; Antineoplastic Agents/pharmacokinetics* ; Signal Transduction/drug effects* ; STAT5 Transcription Factor/metabolism* ; Interleukin-2 Receptor alpha Subunit/metabolism* ; Interleukin-2 Receptor beta Subunit/metabolism*

OBJECTIVE: To explore the effect of concurrent administration of goserelin for ovarian function protection on the pathological complete response (pCR) rate and objective response rate (ORR) of neoadjuvant chemotherapy (NAC) in young breast cancer patients. METHODS: The study enrolled breast cancer patients aged 18-45 with clinical stages ⅡA~ⅢC from January 2016 to May 2020. According to patients' willingness, they were divided into two groups: Those who chose to receive goserelin to protect ovarian function during NAC (goserelin group) and those who did not (chemotherapy group). The pCR rate and ORR were compared between the two groups, and subgroup analysis was conducted for patients with different molecular subtypes. RESULTS: A total of 93 patients were included in this study (31 in the goserelin group and 62 in the chemotherapy group). After propensity score weighting (PSW) adjustment, baseline data such as age, preoperative clinical stage, postoperative pathological stage, pa-thological type, hormone receptor status, human epidermal growth factor receptor 2 (HER2) and Ki-67 expression, molecular subtypes, and chemotherapy regimens were well-matched between the two groups. There was no significant difference in the pCR rate between the goserelin group and the chemotherapy group, with rates of 29.0% and 25.8%, respectively (P=0.741). Similarly, there was no significant difference in ORR between the two groups (90.3% vs. 87.1%, P=0.746). Subgroup analysis revealed that among the patients with hormone receptor-positive tumors, there were no significant differences in pCR rate (6.3% vs. 7.7%, P=0.852) or ORR (87.5% vs. 82.1%, P=0.839) between the goserelin and chemotherapy groups. Among the patients with hormone receptor-negative tumors, there were also no significant differences in pCR rate (53.3% vs. 56.5%, P=0.847) or ORR (93.3% vs. 95.7%, P=0.975) between the two groups. One year after the completion of chemotherapy, the incidence of chemotherapy-induced amenorrhea (CIA) was significantly lower in the goserelin group compared with the chemotherapy group (9.5% vs. 33.3%, P=0.036). CONCLUSION For young breast cancer patients with clinical stages of ⅡA~ⅢC, there was no statistical difference in pCR rate and ORR whether or not using goserelin during NAC. However, it is still necessary to expand the sample size and carry out a longer follow-up to evaluate the effect of goserelin on the long-term survival of young patients.
Humans ; Goserelin/administration & dosage* ; Female ; Breast Neoplasms/pathology* ; Neoadjuvant Therapy/methods* ; Adult ; Middle Aged ; Young Adult ; Adolescent ; Chemotherapy, Adjuvant ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Antineoplastic Agents, Hormonal/therapeutic use* ; Treatment Outcome ; Receptor, ErbB-2

OBJECTIVE: To investigate the effect of aquaporin 5 (AQP5) on Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor κB (NF-κB) signaling pathway in Sjögren syndrome (SS) rats. METHODS: The SS gene expression data sets GSE406611 and GSE84844 were extracted from the Gene Expression Omnibus (GEO), and the AQP5 mRNA expression was analyzed by R software. The rat SS model was constructed. The successfully modeled rats were divided into SS group, SS+NC group, and SS+pc group, 10 rats in each group; and 10 rats were set as Normal group. The rats in the SS+NC group were injected with 10 μg of rno-pcDNA3.1-AQP5-NC at the submandibular gland, subcutaneously every day for 28 days. The rats in the SS+pc group were injected with 10 μg of rno-pcDNA3.1-AQP5 at the submandibular gland, subcutaneously every day for 28 days. The enzyme-linked immunosorbent assay (ELISA) kit was used to detect the content of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in the serum. High-throughput sequencing was used to identify the target genes. Quantitative real-time PCR (qPCR) and Western blot were used to detect the mRNA and protein expressions of AQP5, TLR4, MyD88, and NF-κB in the rat submandibular gland tissue. RESULTS: In the SS dataset GSE406611 and GSE84844, the mRNA expression of AQP5 in SS was significantly reduced. Compared with the Normal group, the content of TNF-α and IL-1β in the serum, the mRNA and protein expressions of TLR4, MyD88, and NF-κB in the SS group were significantly increased, the mRNA and protein expressions of AQP5 were significantly decreased. After overexpression of AQP5, the content of TNF-α and IL-1β in the serum, the mRNA and protein expressions of TLR4, MyD88, and NF-κB in the SS+pc group were significantly decreased, the mRNA and protein expressions of AQP5 were significantly increased. The differences were statistically significant (all P < 0.05). CONCLUSION The expression of AQP5 is involved in the progression of SS. Increasing the expression of AQP5 can significantly inhibit inflammatory stress and reduce the pathological damage of submandibular gland tissue. This may be related to the inhibition of TLR4/MyD88/NF-κB conduction.
Animals ; Toll-Like Receptor 4/genetics* ; Myeloid Differentiation Factor 88/genetics* ; Aquaporin 5/metabolism* ; Sjogren's Syndrome/genetics* ; Signal Transduction ; NF-kappa B/metabolism* ; Rats ; Rats, Sprague-Dawley ; Interleukin-1beta/metabolism* ; Female

OBJECTIVE: To elucidate the effect of Huanglian-Renshen-Decoction (HRD) on ameliorating type 2 diabetes mellitus by maintaining islet β -cell identity through regulating paracrine and endocrine glucagon-like peptide-1 (GLP-1)/GLP-1 receptor (GLP-1R) in both islet and intestine. METHODS: The db/db mice were divided into the model (distilled water), low-dose HRD (LHRD, 3 g/kg), high-dose HRD (HHRD, 6 g/kg), and liraglutide (400 µ g/kg) groups using a random number table, 8 mice in each group. The db/m mice were used as the control group (n=8, distilled water). The entire treatment of mice lasted for 6 weeks. Blood insulin, glucose, and GLP-1 levels were quantified using enzyme-linked immunosorbent assay kits. The proliferation and apoptosis factors of islet cells were determined by immunohistochemistry (IHC) and immunofluorescence (IF) staining. Then, GLP-1, GLP-1R, prohormone convertase 1/3 (PC1/3), PC2, v-maf musculoaponeurotic fibrosarcoma oncogene homologue A (MafA), and pancreatic and duodenal homeobox 1 (PDX1) were detected by Western blot, IHC, IF, and real-time quantitative polymerase chain reaction, respectively. RESULTS: HRD reduced the weight and blood glucose of the db/db mice, and improved insulin sensitivity at the same time (P<0.05 or P<0.01). HRD also promoted mice to secrete more insulin and less glucagon (P<0.05 or P<0.01). Moreover, it also increased the number of islet β cell and decreased islet α cell mass (P<0.01). After HRD treatment, the levels of GLP-1, GLP-1R, PC1/3, PC2, MafA, and PDX1 in the pancreas and intestine significantly increased (P<0.05 or P<0.01). CONCLUSION HRD can maintain the normal function and identity of islet β cell, and the underlying mechanism is related to promoting the paracrine and endocrine activation of GLP-1 in pancreas and intestine.
Animals ; Glucagon-Like Peptide 1/metabolism* ; Diabetes Mellitus, Type 2/metabolism* ; Glucagon-Like Peptide-1 Receptor/metabolism* ; Insulin-Secreting Cells/pathology* ; Drugs, Chinese Herbal/pharmacology* ; Male ; Blood Glucose/metabolism* ; Insulin/blood* ; Mice ; Intestinal Mucosa/pathology* ; Apoptosis/drug effects* ; Cell Proliferation/drug effects* ; Islets of Langerhans/pathology*

OBJECTIVES: Injury to human cardiac microvascular endothelial cells (HCMECs) compromises myocardial microcirculation and may contribute to major cardiovascular events such as coronary heart disease, posing a serious health threat. Understanding the mechanisms of hypoxia-induced HCMEC damage is thus of great clinical relevance. This study aims to investigate the protective effects and underlying mechanisms of Li Qi Huo Xue Di Wan against hypoxia-induced HCMEC injury. METHODS: HCMECs were cultured under hypoxic conditions for 24 hours to establish a cellular model of hypoxic injury. Cells were divided into six groups: normal control, hypoxia, hypoxia + low-dose Li Qi Huo Xue Di Wan, hypoxia + medium-dose, hypoxia + high-dose, and hypoxia + salvianolic acid B (positive control). Cell viability was assessed using the MTS assay. Lactate dehydrogenase (LDH) release and malondialdehyde (MDA) content were measured to evaluate cytotoxicity and oxidative stress. Activities of superoxide dismutase (SOD), catalase (CAT), caspase-3, and caspase-8 were determined with corresponding assay kits. Apoptosis was analyzed by flow cytometry, and expression of necroptosis-related proteins, receptor-interacting protein kinase 1 (RIPK1) and its phosphorylated form (p-RIPK1), receptor-interacting protein kinase 3 (RIPK3) and its phosphorylated form (p-RIPK3), mixed lineage kinase domain-like protein (MLKL) and its phosphorylated form (p-MLKL), was examined via Western blotting. RESULTS: Compared with the control group, hypoxia significantly decreased cell viability (P<0.01), increased MDA levels (P<0.05), and reduced CAT and SOD activity (P<0.05), accompanied by elevated apoptosis (P<0.01) and increased levels of p-RIPK1, p-RIPK3, and p-MLKL (P<0.05). High-dose Li Qi Huo Xue Di Wan significantly improved cell viability (P<0.01), reduced MDA content (P<0.05), increased CAT activity (P<0.05), and suppressed necroptosis-related protein expression (P<0.05) compared with the hypoxia group. CONCLUSIONS Li Qi Huo Xue Di Wan exerts a protective effect against hypoxia-induced injury in HCMECs. This effect is mediated by attenuation of oxidative stress, thereby reducing both apoptosis and necroptosis.
Humans ; Apoptosis/drug effects* ; Necroptosis/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Cell Hypoxia/drug effects* ; Endothelial Cells/pathology* ; Oxidative Stress/drug effects* ; Cells, Cultured ; Cell Survival/drug effects* ; Receptor-Interacting Protein Serine-Threonine Kinases/metabolism*