Voltage-gated sodium channels (VGSCs) play pivotal roles in cancer progression and have emerged as promising therapeutic targets and biomarkers. VGSCs comprise multiple subtypes with distinct tissue distributions, influencing tumour characteristics in different ways. Among these, the tetrodotoxin-sensitive α-subunits and the β1 subunit, commonly found in breast cancer, have been implicated in metastasis and tumour aggressiveness. The NaV1.5 channel and its neonatal variant (nNaV1.5) are overexpressed in aggressive cancers such as breast, prostate, colorectal, and lung cancers, thereby enhancing their invasive capacity. nNaV1.5 is particularly significant due to its tumour-specific expression and strong association with poor prognosis, especially in breast cancer, where it regulates cell proliferation, invasion, and tumour microenvironment remodelling. This review highlights nNaV1.5 as a critical ion channel that drives metastasis through ion regulation, extracellular acidification, and cytoskeletal remodelling. We further evaluate current therapeutic strategies, including siRNA, monoclonal antibodies, and small-molecule inhibitors, while addressing translational challenges such as tumour heterogeneity, drug delivery limitations, and off-target cardiotoxicity due to its similarity with the adult isoform. In addition, we explore the potential of nNaV1.5 as a biomarker subject to epigenetic regulations by factors including RE1-silencing transcription factor (REST) and histone deacetylase 2 (HDAC2), which may facilitate patient stratification and treatment optimization. By integrating mechanistic insights, therapeutic opportunities, and translational challenges, this review goes beyond descriptive summaries to provide a framework for advancing nNaV1.5 research from preclinical studies toward clinical application in cancer therapy.

Introduction: Partial androgen insensitivity syndrome is a rare X-linked 46, XY disorder caused by androgen receptor dysfunction, producing variable genital ambiguity and complex diagnostic challenges in early infancy and childhood. Case: We report a term infant, currently aged 9 months, who was admitted to the Neonatal Intensive Care Unit at birth for glucose-6-phosphate dehydrogenase (G6PD) deficiency and noted to have ambiguous genitalia. The infant had no hypoglycemia, feeding intolerance, or electrolyte disturbances throughout admission. She is the second child of non-consanguineous parents, with no family history of disorders of sex development. Examination of the external genitalia revealed a prominent phallus without erectile tissue with mildly pigmented and rugated labioscrotal folds. There was no labioscrotal fusion. Bilateral gonads were palpable in both labioscrotal folds with one opening seen. Pelvic ultrasonography showed bilateral small testes within the labioscrotal folds, with absence of Müllerian structures. Karyotype analysis confirmed 46, XY genotype. Human chorionic gonadotropin stimulation (HCG) testing at day 7 of life demonstrated normal baseline testosterone 4.9 nmol/L, but minimal testosterone rise 5.4 nmol/L at day 4 post HCG. Normal testosterone to dihydrotestosterone ratio and testosterone to androstenedione ratio excluded defects in androgen synthesis, while normal adrenal steroid profile ruled out congenital adrenal hyperplasia. Gonadotropin-releasing hormone stimulation at 2 months old revealed a peak follicle-stimulating hormone of 8 IU/L and peak LH of 4 IU/L. Anti-Müllerian hormone level was markedly elevated >328 pmol/L (normal 5.5–103 pmol/L). Whole-exome sequencing identified a hemizygous androgen receptor gene variant, p.(Pro818Ala), classified as a variant of uncertain significance with deleterious in silico predictions, consistent with X-linked partial androgen insensitivity syndrome. Conclusion This case highlights the necessity of early, systematic endocrine evaluation integrated with genomic testing in 46, XY DSD to achieve a definitive diagnosis, optimize sex assignment, and guide longitudinal, multidisciplinary management.
Male ; Infant ; Androgen-Insensitivity Syndrome

Introduction: Severe thyrotoxicosis is particularly difficult to manage when antithyroid drugs are contraindicated. Therapeutic plasma exchange (TPE) is an adjunctive option in complicated hyperthyroidism, including thyroid storm and refractory thyrotoxicosis, through the rapid removal of circulating thyroid hormones, hormone-binding proteins, cytokines, and thyroid autoantibodies. However, its precise role and indications remain incompletely defined. We report two patients with Graves’ disease complicated by carbimazole-induced agranulocytosis in whom TPE was used as bridging therapy before total thyroidectomy. Cases: The first patient was a 32-year-old female who developed carbimazole-induced agranulocytosis 1 month after the diagnosis of hyperthyroidism. Biochemical control remained unsatisfactory despite second-line therapy with high-dose lithium, cholestyramine, propranolol, corticosteroids, and 5 days of Lugol’s iodine. Over 8 days, free thyroxine (fT4) increased by 13%, necessitating TPE for preoperative stabilization. Following three cycles over 4 days, fT4 decreased by 20%, from 52 to 41 pmol/L, enabling successful total thyroidectomy. The second patient was a 26-year-old female who presented with neutropenic sepsis and severe agranulocytosis 2 months after being diagnosed with Graves’ disease. She received second-line therapy, and neutrophil recovery occurred only after 7 days of granulocyte colony-stimulating factor. TPE, together with Lugol’s iodine, was then initiated as bridging therapy before surgery. After 5 days of Lugol’s iodine and three TPE cycles, fT4 decreased by 43%, from 58 to 33 pmol/L, permitting total thyroidectomy. Conclusion These cases highlight TPE as a useful bridging strategy in Graves’ thyrotoxicosis when antithyroid drugs are precluded by agranulocytosis, and conventional secondline therapy fails to achieve adequate biochemical control. TPE may facilitate timely stabilization and safe progression to definitive surgical treatment.
Plasma Exchange ; Agranulocytosis ; Graves Disease

This study was conducted to bridge the gap between modern dietary guidelines and revelation-based dietary principles through the development of a faith-based dietary model grounded in Quranic teachings. The main objective was to identify food items mentioned in the Quran, analyse their frequency, and integrate these findings with contemporary nutrition knowledge to develop the Islamic Quranic Pie Chart (iQ-Carta PAI™). A two-phase approach was applied, where selected Quranic verses were analysed using classical tafsir and digital corpus tools, resulting in the identification of 188 food references across 53 surahs. These food items were grouped into key nutritional categories, including fruits, protein sources, cereals, water, and healthy fats, and further classified according to plant or animal origin. The frequency of food mentions was used to inform the proportional visual weighting of each category in the Pie Chart, serving both descriptive and structural purposes in the model design. The developed model highlights key Islamic dietary principles such as halalan tayyiban (lawful and wholesome food), moderation (wasatiyyah), and avoidance of excess and waste. When compared with the Malaysian Dietary Guidelines (2020), the findings showed clear alignment, particularly in the emphasis on plant-based foods, balanced intake, and moderation. Overall, iQ-Carta PAI™ provides a simple and spiritually relevant dietary guideline model that integrates Quranic values with modern nutrition principles and may support nutrition education, public health programmes, and faith-based health promotion among Muslim communities

Severe hyponatraemia is defined as a sodium level of less than 120 mEq/L, and it is frequently accompanied by neurological symptoms like coma, convulsions, respiratory arrest, and death. Clinical cardiac toxicity from hyponatremia, such as bradyarrhythmia, is extremely rare. In this article, we present a case of acute severe hyponatraemia that induced unstable bradyarrhythmia and led to refractory bradycardia, which did not improve despite receiving treatment in accordance with the standard Advanced Cardiovascular Life Support protocol. The patient’s bradyarrhythmia has completely resolved with the administration of 3% hypertonic saline, which restored her sodium levels. Due to the possibility that severe hyponatremia may contribute to the aetiology of cardiac malfunction, this case raises awareness about the significance of closely monitoring electrocardiograms and telemetry in patients with severe hyponatremia.

Mullerian agenesis or Mayer-Rokitansky-Kuster-Hauser Syndrome (MRKH) Type-II is a congenital defect in the Mullerian duct that results in the absence of a uterus in women. The aetiology of this syndrome is unknown and has been considered a sporadic genetic disease. MRKH, together with anorectal anomaly, is an extremely rare condition and has only been reported in a few cases without any information on genetic analysis. This study investigated the mutational profile of a girl diagnosed with MRKH and anorectal anomalies with rectovaginal fistula. The whole exome sequencing (WES) trio-genetic analysis of a 5-year-old Malaysian girl diagnosed with MRKH (having anorectal anomaly with rectovaginal fistula) was performed together with her normal parents, using the Ion AmpliSeq Exome RDY kit (ThermoFisher Scientific, USA). Data were analysed using Torrent Suite v.5.0.4 and annotated using ANNOVAR. Single nucleotide polymorphisms (SNPs) with an allele frequency >0.01 were excluded, and the remaining variants were filtered based on de novo mutations, autosomal recessive, and autosomal recessive genetic traits. Related genes were analysed by biological pathway analysis (g:Profiler) and protein-protein interaction (HIPPIE v.2.3, STRING v.11.5, dan GeneMANIA). A total of 36 mutations were identified, and two of them, the LHX5 (p.P358Q), inherited from the father, and CFTR (p.R1158X), inherited from the mother. There were 28 de-novo mutations from 28 genes. All genes were involved in 27 biological processes that connected with 23 interactions, and are likely to cause MRKH syndrome in this patient.

Methods: Patients with severe kyphoscoliosis having coronal Cobb angle >90° were applied with modified halo-pelvic Ilizarov distraction assembly preoperatively. The modified assembly consisted of a pelvic component and halo ring, and distraction was given at the rate of 2–3 mm/day for 6–12 weeks. Complete clinical assessments along with pulmonary function tests were performed, and scoliosis series X-ray images were assessed for coronal and sagittal Cobb angle and other spinopelvic parameters before applying the assembly and during 2 years of follow-up. Results: Thirty-four patients (age, 9–27 years; male/female ratio of 18:16) were included. The coronal and sagittal Cobb angles were 116°±16.2° and 84°±28.3°, respectively. Correction rates obtained through modified halo-pelvic assembly were nearly 52% (p=0.001) in coronal and 40% (p=0.001) in sagittal Cobb angles, with improvement in height (p=0.001). Apical vertebral translation and coronal balance were also improved significantly (p=0.001). Further improvements in all the parameters were obtained after definitive surgery, with improvements in the forced expiratory volume in 1 second (p =0.002) and forced vital capacity (p=0.001). Conclusions Our modified halo-pelvic Ilizarov distraction assembly can achieve good correction in severe spinal deformities without significant risk to neurology, has fewer complications, and promotes good patient compliance.

Langerhans cell histiocytosis (LCH) is a rare condition in adults, especially when it is limited to a single area of the skull, known as solitary calvarial involvement. In this case report, we present a unique instance of LCH affecting the parietal bone with a pus-draining fistula. This is a rare and unusual presentation at this location, which has been scarcely reported in medical literature. A 30-year-old woman with no prior comorbidity presented with complaints of headache that persisted for a year. She also had swelling on her scalp and a yellowish discharge for 3 weeks, but no neurological problems were observed. Radiology revealed thinning of the calvaria, with ragged margins along the inner table, multiple focal erosions, and involvement of overlying soft tissue and bony sequestrum. The patient underwent biparietal craniotomy and excision of the lesion. The histopathology report showed LCH. After 8 months of follow-up, there was no recurrence. The management of solitary calvarial involvement by LCH with masquerading presentation as a scalp infection can be achieved through complete excision of the lesions, resulting in a favorable outcome.

A plethora of paraneoplastic syndromes have been reported as remote effects of colorectal carcinoma (CRC). However, there is a dearth of data pertaining to the association of this cancer with demyelinating neuropathies. Herein, we describe the case of a young woman diagnosed with chronic inflammatory demyelinating polyneuropathy (CIDP). Treatment with intravenous immunoglobulins and prednisone did not improve her condition, and her neurological symptoms worsened. Subsequently, she was readmitted with exertional dyspnea, lightheadedness, malaise, and black stools. Colonoscopy revealed a necrotic mass in the ascending colon, which directly invaded the second part of the duodenum. Pathologic results confirmed the diagnosis of locally advanced CRC. Upon surgical resection of the cancer, her CIDP showed dramatic resolution without any additional therapy. Patients with CRC may develop CIDP as a type of paraneoplastic syndrome. Clinicians should remain cognizant of this potential association, as it is of paramount importance for the necessary holistic clinical management.

Introduction: Aquilaria malaccensis, also known as “Pokok Karas” in Malaysia, is widely used in Southeast Asian countries for the treatment of joint pain, diarrhoea and inflammatory diseases, and has shown beneficial effects as an anticancer agent. The aim of this study was to investigate the effect of ethanol leaf extracts of A. malaccensis on MCF-7 cells. Methods: MTT-based cytotoxic and antiproliferative assay was used to determine the outcome of ethanolic extract toward MCF-7 cells. The mode of cell death was determined by the AO/PI double staining assay and the depolarisation of the mitochondria membrane potential. Results: IC50 value of the extract against MCF-7 cells treated for 72 hours was 4.1 ± 2.08 µg/mL, while the IC50 value for doxorubicin was 2.92 ± 0.12 µg/mL. The extract showed a lower cytotoxic effect against the NIH/3T3 cells and inhibited the growth of MCF-7 cells in a dose dependent manner. AO/PI double stain showed that the ethanolic extract of A. malaccensis leaves induced MCF-7 cells into apoptotic cell death. The present study showed that the ethanolic extract of A. malaccensis induced apoptosis through mitochondrial pathway as indicated by its ability to take up JC-1. Conclusion: The study found that ethanolic extract obtained from A. malaccensis leaves is cytotoxic on MCF-7 cells, resulting to apoptotic cell death of the cells.