Cancer stem cells (CSCs) represent a distinct subpopulation of cells characterized by self-renewal capacity, differentiation potential, and critical roles in driving tumor progression, therapeutic resistance, recurrence, and maintenance of the tumor microenvironment. Targeting CSCs has emerged as a pivotal direction in cancer research, offering novel strategies to overcome drug resistance and prevent metastasis and relapse. Lysosomes, traditionally recognized as central organelles for intracellular degradation and recycling, are indispensable for cellular homeostasis. Dysregulation of lysosomal function is intimately linked to various diseases, including cancer. In tumors, aberrant lysosomal activity can promote malignant progression through mechanisms such as altering metabolic pathways, enhancing lysosomal exocytosis, modulating drug resistance, and interfering with autophagy-lysosomal pathways. Recent studies have underscored the involvement of lysosomes in regulating CSC properties. This review synthesizes findings on lysosomal regulation of CSCs through the following aspects. (1) Lysosomes exert complex and critical bidirectional control over CSC stemness maintenance through three degradation pathways that are dependent on their degradative function. (i) The lysophagy pathway. This pathway exhibits dual roles. Activation can sustain CSC functions; for instance, in glioblastoma, hypoxia upregulates Gal-8 via the STAT3/HIF1α signaling axis to induce autophagy, supporting stem cell survival. In head and neck squamous cell carcinoma, degradation of GSK3β activates the Wnt pathway, enhancing stemness. Conversely, this pathway can suppress stemness by degrading stemness-related proteins such as BMI-1 and OCT4A, thereby impairing CSC self-renewal capacity. (ii) Mitophagy pathway. In non-small cell lung cancer stem cells, mitophagy-related mechanisms, such as the accumulation of mitochondrial DNA (mtDNA) activating the TLR9-Notch1-AMPK signaling axis, have been shown to promote CSC proliferation. (iii) Autophagosome-dependent lysosomal degradation pathway. This pathway directly regulates stemness-related proteins in a bidirectional manner. Enhanced degradative function can promote CSC properties, exemplified by the degradation of NUMB to activate Notch signaling. Conversely, attenuated degradative function can also enhance stemness by stabilizing oncoproteins (e.g., protecting Frizzled-1 from degradation to sustain Wnt signaling) or preventing the degradation of tumor suppressors (e.g., inhibiting Notch degradation). (2) Constituent proteins of lysosomes, including membrane proteins and luminal acid hydrolases, participate in regulating CSC stemness. Regarding membrane proteins, LAMP2A facilitates chaperone-mediated autophagy to maintain stemness in glioblastoma and ovarian cancer. V-ATPase, by maintaining an acidic luminal environment, promotes proliferation and drug resistance in glioma stem cells. Among hydrolases, cathepsins B and L are highly expressed in pancreatic and ovarian cancers and correlate with poor prognosis. Furthermore, targeting lysosomes to induce lysosomal membrane permeabilization (LMP) triggers lysosome-mediated cell death, presenting a potential therapeutic strategy for eradicating CSCs.(3) The acidic luminal environment, single-membrane structure, and the presence of transmembrane transporters (e.g., ABCA3) enable lysosomes to passively trap or actively uptake and sequester chemotherapeutic drugs. Subsequent drug extrusion via exocytosis confers drug resistance. In CSCs, this lysosome-mediated drug sequestration, often cooperating with autophagy, establishes multimodal drug resistance. Therefore, targeting lysosomal function represents a potential strategy to overcome therapy resistance. The central role of lysosomes in regulating CSC stemness and resistance positions them as highly promising therapeutic targets. Strategies aimed at disrupting lysosomal function to selectively eliminate CSCs include: inhibiting the lysosome-autophagy system using agents like IITZ or lovastatin; inducing lysosomal membrane permeabilization (LMP) with compounds such as hexamethylene amiloride to compromise membrane stability; and disrupting the acidic luminal environment using drugs like siramesine or the K/H transport compound 2. In conclusion, lysosomes critically regulate CSC stemness maintenance and drug resistance through degradative pathways, membrane protein functions, luminal hydrolase activities, and drug sequestration mechanisms. This redefines the lysosome from a traditional “waste disposal unit” to a “signal integration center” in CSCs. The duality and context-dependency of lysosomal function in CSCs offer novel insights into the heterogeneity observed across different tumors. Targeting lysosomal vulnerabilities—such as inducing LMP, disrupting acidity, or blocking autophagic flux—provides a strategy to bypass canonical CSC resistance mechanisms and directly trigger cell death. This establishes the lysosome as a key target to overcome CSC-mediated therapy resistance, paving the way for developing diverse candidate drugs and innovative combination therapies in oncology.

ObjectiveTo investigate the potential mechanism of Danggui Buxuetang （DBT） in the treatment of vascular dementia （VAD）. MethodsSixty male SD rats were randomly assigned to the sham-operated group， model group， DBT low-， medium-， and high-dose groups， and the donepezil group. Except for the sham-operated group， rats in all other groups underwent bilateral common carotid artery ligation. After successful modeling， DBT was administered at doses of 9.2， 18.4， 36.8 g·kg^-1 for the low-， medium-， and high-dose groups， respectively， while the donepezil group received 3 mg·kg^-1 donepezil solution by gavage once daily. After 4 consecutive weeks of drug treatment， rats underwent the Morris water maze test， novel object recognition test， Nissl staining to observe hippocampal neurons， and immunofluorescence staining to detect the expression of neuronal nuclear protein （NeuN） in the hippocampus. Western blot was used to assess the expression of PTEN-induced kinase 1 （PINK1）， Parkin， microtubule-associated protein 1 light chain 3Ⅱ （LC3Ⅱ）， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax）. Transmission electron microscopy was used to observe hippocampal neuronal ultrastructure. Real-time PCR was used to detect the expression of NADPH oxidase subunits p22^phox and p47^phox in hippocampal tissues. The levels of malondialdehyde （MDA）， glutathione （GSH）， superoxide dismutase （SOD）， and total antioxidant capacity were measured to evaluate oxidative stress levels. ResultsIn the Morris water maze test， escape latency changed significantly over time in all groups except the model group. Compared with the sham-operated group， the model group showed significantly prolonged escape latency （P<0.01）. Compared with the model group， rats in the DBT groups and the donepezil group exhibited significantly shorter escape latency （P<0.05， P<0.01）. The number of crossings over the original platform was significantly reduced in the model group compared with the sham-operated group （P<0.01）， whereas rats in the DBT and donepezil groups showed significantly increased platform crossings compared with the model group （P<0.05， P<0.01）. Compared with the sham-operated group， exploration time of new objects was significantly reduced in the model group （P<0.01）. Compared with the model group， exploration time of new objects increased significantly in the medium- and high-dose DBT groups and the donepezil group （P<0.05， P<0.01）， while no significant change was observed in the low-dose DBT group. Compared with the high-dose DBT group， rats in the donepezil group had significantly prolonged escape latency and reduced platform crossings and new-object exploration time （P<0.05）. Nissl staining showed decreased density of healthy neurons in the CA1 and CA3 regions of the hippocampus in the model group， with loss of Nissl bodies and nuclear atrophy or disappearance. In the high-dose DBT group， neuronal density in CA1 and CA3 increased， with neurons arranged closely and displaying normal morphology. Immunofluorescence showed that compared with the sham-operated group， the hippocampal NeuN⁺ cell count in the VAD model group was significantly decreased（P<0.01）， compared with the VAD model group， the hippocampal NeuN⁺ cell count in the high-dose DBT group was significantly increased（P<0.01）. Compared with the sham-operated group， the expression of PINK1， Parkin， LC3Ⅱ， and Bax proteins was significantly increased（P<0.01）， while the expression of Bcl-2 was significantly decreased in the VAD model group（P<0.01）. Compared with the VAD model group， the high-dose DBT group showed significantly decreased expression of PINK1， Parkin， LC3Ⅱ， and Bax proteins（P<0.01）and significantly upregulated Bcl-2 expression（P<0.01）. The medium-dose DBT group exhibited significantly reduced expression of Parkin， LC3Ⅱ， and Bax proteins（P<0.05，P<0.01） and significantly increased Bcl-2 expression（P<0.01）， while no statistically significant differences were observed in the low-dose DBT group. Transmission electron microscopy showed mitochondrial pyknosis， thickened cristae， increased electron density， and the presence of mitochondrial autophagy in the model group. In contrast， hippocampal neurons in the high-dose DBT group contained abundant mitochondria with intact morphology， clear cristae， and uniform matrix. Compared with the sham-operated group， total antioxidant capacity， SOD activity， and GSH levels were significantly decreased， while MDA levels were significantly increased in the model group （P<0.01）. Compared with the model group， total antioxidant capacity and antioxidant levels （SOD， GSH） increased significantly， and MDA decreased significantly in the medium- and high-dose DBT groups （P<0.01）， while no significant changes were observed in the low-dose DBT group. Compared with the sham-operated group， mRNA expression of p22^phox and p47^phox was significantly increased in the model group （P<0.01）. Compared with the model group， expression of p22^phox and p47^phox was significantly decreased in the DBT groups （P<0.05， P<0.01）. ConclusionDBT may exert neuroprotective effects by regulating PINK1/Parkin-mediated mitochondrial autophagy， thereby improving learning and memory abilities and treating VAD.

ObjectiveObesity, a global chronic metabolic disease, is closely associated with disruptions in lipid metabolism and gut microbiota. Current intervention strategies still have limitations in terms of safety and microecological regulation, necessitating the exploration of novel natural regulatory approaches. Based on the early pathological characteristics of obesity, this study innovatively employs a rectal delivery method alongside a high-fat diet (HFD)-induced obesity model to systematically evaluate the inhibitory effects, safety, and gut microbiota regulation mechanisms of leek-derived and konjac-derived extracellular vesicles on obesity development. By simulating early clinical intervention scenarios, this study aims to explore the preventive potential of plant-derived extracellular vesicles during the initial stages of obesity onset. MethodsExtracellular vesicles from leek and konjac were isolated using ultracentrifugation combined with density gradient centrifugation. Their nanoscale properties were characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM), and nanoparticle tracking analysis (NTA). Male C57BL/6J mice were randomly divided into four groups: normal control (NC), high-fat diet (HFD), leek-derived extracellular vesicles (LEVs), and konjac-derived extracellular vesicles (KEVs). Beginning simultaneously with HFD feeding, mice in the intervention groups received 20 g/L vesicles rectally every 3 d for 4 weeks. Body mass and body composition were monitored throughout. At endpoint, mouse serum, adipose tissue, and colonic contents were collected. Serum biochemical indices (lipid profile, liver and kidney function, cardiac markers) were assessed to evaluate safety and metabolic efficacy, while 16S rRNA sequencing was employed to analyze gut microbial structure and diversity. ResultsDLS, NTA, and TEM confirmed that both LEVs and KEVs exhibited typical cup-shaped nanostructures with average particle sizes of approximately 284 nm and 223 nm, respectively. LEVs and KEVs treatment significantly suppressed HFD-induced weight gain and elevation of body-fat percentage (P<0.05), and reduced accumulation of abdominal white and epididymal adipose tissue. Serological analyses showed that both vesicles lowered total cholesterol, triglycerides and LDL-cholesterol, and ameliorated liver enzyme profiles (ALT, AST), demonstrating lipid-metabolic regulation and hepatoprotective effects. No hepatic, renal or cardiac dysfunction was observed, indicating favorable safety. Gut microbiota analyses revealed that vesicle intervention partially restored HFD-depleted microbial diversity and reshaped community structure. Notably, LEVs markedly increased the relative abundance of the beneficial taxon Lachnospiraceae at the family level, which is known for producing short-chain fatty acids and enhancing intestinal barrier function. Furthermore, Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) functional prediction suggested that LEVs and KEVs modulated gut microbial functions through distinct mechanisms: LEVs downregulated pathways related to ribosomes and DNA replication while enhancing xenobiotic degradation, whereas KEVs tended to upregulate energy metabolism and protein synthesis toward healthy levels. ConclusionRectally administered LEVs and KEVs exhibit excellent safety and pronounced metabolic benefits during the early phase of obesity, suppressing weight gain, correcting lipid dysregulation, and exerting effects via modulation of gut microbial composition and function. This study provides systematic experimental evidence supporting plant-derived exosome-like vesicles as an early intervention strategy against obesity.

ObjectiveObesity, a global chronic metabolic disease, is closely associated with disruptions in lipid metabolism and gut microbiota. Current intervention strategies still have limitations in terms of safety and microecological regulation, necessitating the exploration of novel natural regulatory approaches. Based on the early pathological characteristics of obesity, this study innovatively employs a rectal delivery method alongside a high-fat diet (HFD)-induced obesity model to systematically evaluate the inhibitory effects, safety, and gut microbiota regulation mechanisms of leek-derived and konjac-derived extracellular vesicles on obesity development. By simulating early clinical intervention scenarios, this study aims to explore the preventive potential of plant-derived extracellular vesicles during the initial stages of obesity onset. MethodsExtracellular vesicles from leek and konjac were isolated using ultracentrifugation combined with density gradient centrifugation. Their nanoscale properties were characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM), and nanoparticle tracking analysis (NTA). Male C57BL/6J mice were randomly divided into four groups: normal control (NC), high-fat diet (HFD), leek-derived extracellular vesicles (LEVs), and konjac-derived extracellular vesicles (KEVs). Beginning simultaneously with HFD feeding, mice in the intervention groups received 20 g/L vesicles rectally every 3 d for 4 weeks. Body mass and body composition were monitored throughout. At endpoint, mouse serum, adipose tissue, and colonic contents were collected. Serum biochemical indices (lipid profile, liver and kidney function, cardiac markers) were assessed to evaluate safety and metabolic efficacy, while 16S rRNA sequencing was employed to analyze gut microbial structure and diversity. ResultsDLS, NTA, and TEM confirmed that both LEVs and KEVs exhibited typical cup-shaped nanostructures with average particle sizes of approximately 284 nm and 223 nm, respectively. LEVs and KEVs treatment significantly suppressed HFD-induced weight gain and elevation of body-fat percentage (P<0.05), and reduced accumulation of abdominal white and epididymal adipose tissue. Serological analyses showed that both vesicles lowered total cholesterol, triglycerides and LDL-cholesterol, and ameliorated liver enzyme profiles (ALT, AST), demonstrating lipid-metabolic regulation and hepatoprotective effects. No hepatic, renal or cardiac dysfunction was observed, indicating favorable safety. Gut microbiota analyses revealed that vesicle intervention partially restored HFD-depleted microbial diversity and reshaped community structure. Notably, LEVs markedly increased the relative abundance of the beneficial taxon Lachnospiraceae at the family level, which is known for producing short-chain fatty acids and enhancing intestinal barrier function. Furthermore, Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) functional prediction suggested that LEVs and KEVs modulated gut microbial functions through distinct mechanisms: LEVs downregulated pathways related to ribosomes and DNA replication while enhancing xenobiotic degradation, whereas KEVs tended to upregulate energy metabolism and protein synthesis toward healthy levels. ConclusionRectally administered LEVs and KEVs exhibit excellent safety and pronounced metabolic benefits during the early phase of obesity, suppressing weight gain, correcting lipid dysregulation, and exerting effects via modulation of gut microbial composition and function. This study provides systematic experimental evidence supporting plant-derived exosome-like vesicles as an early intervention strategy against obesity.

Introductions: Patients with primary podocytopathies such as minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) with nephrotic syndrome are at risk for adverse outcomes. This study reports on the long -term outcomes, specifically kidney failure and death among patients treated for primary podocytopathies in a tertiary centre in Singapore. Materials and Methods: This was a single -centre, retrospective cohort study of all adults aged ≥21 years old diagnosed between 2016 and 2020 with MCD and FSGS with nephrotic -range proteinuria. We excluded patients with membranous nephropathy and secondary glomerulonephritides (lupus nephritis, ANCA - associated vasculitis, membranoproliferative glomerulonephritis, and diabetic nephropathy). Sociodemographic, comorbidity, laboratory and pharmacotherapy data were retrieved from the electronic medical records. The outcomes assessed were incidence of death or kidney failure (estimated glomerular filtration function [eGFR]<15 ml/min/1.73 m2 or required kidney replacement therapy). Results: Sixty patients (Chinese 80%, Malay 6%, Indian 3% and other races 3%) with MCD (37 patients) and FSGS (23 patients) were included. The morphological lesions in FSGS included cellular (n=2), tip (n=2), perihilar (n=7), collapsing (n=3) and not otherwise specified (n=17). At a median follow -up of 26.3 (8.9, 50.3) months, 12 (20%) outcomes were recorded, 11 (47.8%; death 6 and kidney failure 5) in the FSGS group and 1 (2.7%; died) in the MCD group. The causes of death were attributed to kidney failure (n=1), cardiovascular disease (n=1), infection (n=3); and unknown (n=2). The Kaplan -Meier survival curve showed that patients with MCD had better patient and kidney outcomes than those with FSGS (log rank p<0.001). Cox regression analysis (adjusted for age) found that FSGS was significantly associated with death or kidney failure (adjusted hazard ratio 18.17, 95% confidence interval 2.28 -145.07, p=0.006), compared with MCD. Conclusion: Adults with severe primary podocytopathy due to FSGS had worse patient and kidney outcomes than MCD

Introductions: Patients with primary podocytopathies such as minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) with nephrotic syndrome are at risk for adverse outcomes. This study reports on the long -term outcomes, specifically kidney failure and death among patients treated for primary podocytopathies in a tertiary centre in Singapore. Materials and Methods: This was a single -centre, retrospective cohort study of all adults aged ≥21 years old diagnosed between 2016 and 2020 with MCD and FSGS with nephrotic -range proteinuria. We excluded patients with membranous nephropathy and secondary glomerulonephritides (lupus nephritis, ANCA - associated vasculitis, membranoproliferative glomerulonephritis, and diabetic nephropathy). Sociodemographic, comorbidity, laboratory and pharmacotherapy data were retrieved from the electronic medical records. The outcomes assessed were incidence of death or kidney failure (estimated glomerular filtration function [eGFR]<15 ml/min/1.73 m2 or required kidney replacement therapy). Results: Sixty patients (Chinese 80%, Malay 6%, Indian 3% and other races 3%) with MCD (37 patients) and FSGS (23 patients) were included. The morphological lesions in FSGS included cellular (n=2), tip (n=2), perihilar (n=7), collapsing (n=3) and not otherwise specified (n=17). At a median follow -up of 26.3 (8.9, 50.3) months, 12 (20%) outcomes were recorded, 11 (47.8%; death 6 and kidney failure 5) in the FSGS group and 1 (2.7%; died) in the MCD group. The causes of death were attributed to kidney failure (n=1), cardiovascular disease (n=1), infection (n=3); and unknown (n=2). The Kaplan -Meier survival curve showed that patients with MCD had better patient and kidney outcomes than those with FSGS (log rank p<0.001). Cox regression analysis (adjusted for age) found that FSGS was significantly associated with death or kidney failure (adjusted hazard ratio 18.17, 95% confidence interval 2.28 -145.07, p=0.006), compared with MCD. Conclusion: Adults with severe primary podocytopathy due to FSGS had worse patient and kidney outcomes than MCD

ObjectiveTo investigate the urate-lowering effect of Shenling Qushi prescription in the mouse model of hyperuricaemia. MethodsSixty-three C57BL/6N mice were randomly assigned to the following groups （n=9）： Control， model， low-dose （6 g·kg^-1） Shenling Qushi prescription， medium-dose （12 g·kg^-1） Shenling Qushi prescription， high-dose （24 g·kg^-1） Shenling Qushi prescription， medium-dose Shenling Qushi prescription plus febuxostat （12+0.003 g·kg^-1）， and febuxostat （3 mg·kg^-1）. A mouse model of persistent hyperuricaemia was established via intraperitoneal injection of potassium oxazolamide （250 mg·kg^-1） combined with oral administration of allopurinol （300 mg·kg^-1） over a 28-day period. Concurrently， the prescription was administered orally at the specified doses once daily for 21 consecutive days. Throughout the experiment， mouse body weight， food intake， water consumption， and urine output were measured and recorded. Kidney and liver indices were calculated. Renal histopathological changes were observed by haematoxylin and eosin staining. Serum uric acid （SUA） and urinary uric acid （UUA） levels， along with xanthine oxidase （XOD） and adenosine deaminase （ADA）， alanine aminotransferase （ALT） and aspartate aminotransferase （AST） activities， were determined. Real-time PCR was employed to assess the mRNA levels of urate anion transporter 1 （URAT1） and glucose transporter 9 （GLUT9） in the renal tissue， alongside those of XOD and ADA in the liver tissue. The protein levels of URAT1 and GLUT9 in the renal tissue were determined by Western blot. ResultsCompared with the normal group， model mice exhibited reduced food intake and body weight （P<0.01）， decreased water consumption yet increased urine output， no significant change in the liver index but increased kidney index （P<0.01）. Pathological findings revealed renal tissue damage including glomerular atrophy， epithelial cell detachment， and inflammatory cell infiltration. Furthermore， the model group exhibited elevated UUA and SUA levels （P<0.01）， enhanced activities of ALT， AST， XOD， and ADA in the liver tissue （P<0.05， P<0.01）， upregulated mRNA and protein levels of URAT1 and GLUT9 in the renal tissue （P<0.05）， alongside markedly elevated mRNA levels of XOD and ADA in the liver （P<0.01）. Compared with the model group， the Shenling Qushi prescription groups showed no significant changes in body weight or food intake， with water consumption and urine output remaining within normal ranges， alleviated glomerular atrophy， with reduced pathological damage such as inflammatory infiltration， declined UUA and SUA levels （P<0.01）， and increased activities of ALT， AST， XOD， and ADA in the serum （P<0.01）. Real-time PCR results demonstrated that Shenling Qushi prescription downregulated the mRNA levels of URAT1 and GLUT9 in the renal tissue （P<0.05， P<0.01） and XOD and ADA in the hepatic tissue （P<0.05， P<0.01）. Western blot results demonstrated Shenling Qushi prescription reduced the protein levels of URAT1 and GLUT9 （P<0.05， P<0.01）. ConclusionShenling Qushi prescription modulates fluid balance and reduces uric acid levels， thereby alleviating renal injury in hyperuricaemic mice. This effect is highly likely mediated through inhibition of uric acid synthesis and reabsorption.

Objectives: This study aimed to achieve expert consensus on menopause management in the Asia-Pacific region, taking into account patient diversity, the latest evidence, and current treatment options. Methods: A focused literature search was performed to identify clinical practice statements on menopause management. Menopause experts were nominated by members of the Asia-Pacific Menopause Federation (APMF) society. A modified Delphi methodology, involving iterative rounds of anonymous surveys, was employed until consensus was reached for each statement. Consensus was defined as ≥ 70% of experts voting ‘agree’ or ‘strongly agree’ for a given clinical practice statement. Results: A total of 39 participants from 14 different APMF member societies were involved. Eighty-five clinical practice statements reached a consensus. Based on the clinical practice statements, an algorithm was created as a tool to guide clinicians on menopause management. APMF experts agreed that, in addition to vasomotor symptoms, Asian women experiencing somatic or psychological symptoms may also benefit from treatment with menopausal hormone therapy (MHT). MHT should also be considered for the prevention of osteoporosis in asymptomatic peri- and postmenopausal women. Conclusions This APMF consensus statement supersedes the previous one published in 2008. It provides guidance to gynecologists, endocrinologists, family physicians, and other healthcare professionals in delivering optimal care to menopausal women in the ethnically and culturally diverse Asia-Pacific region.

Objectives: This study aimed to achieve expert consensus on menopause management in the Asia-Pacific region, taking into account patient diversity, the latest evidence, and current treatment options. Methods: A focused literature search was performed to identify clinical practice statements on menopause management. Menopause experts were nominated by members of the Asia-Pacific Menopause Federation (APMF) society. A modified Delphi methodology, involving iterative rounds of anonymous surveys, was employed until consensus was reached for each statement. Consensus was defined as ≥ 70% of experts voting ‘agree’ or ‘strongly agree’ for a given clinical practice statement. Results: A total of 39 participants from 14 different APMF member societies were involved. Eighty-five clinical practice statements reached a consensus. Based on the clinical practice statements, an algorithm was created as a tool to guide clinicians on menopause management. APMF experts agreed that, in addition to vasomotor symptoms, Asian women experiencing somatic or psychological symptoms may also benefit from treatment with menopausal hormone therapy (MHT). MHT should also be considered for the prevention of osteoporosis in asymptomatic peri- and postmenopausal women. Conclusions This APMF consensus statement supersedes the previous one published in 2008. It provides guidance to gynecologists, endocrinologists, family physicians, and other healthcare professionals in delivering optimal care to menopausal women in the ethnically and culturally diverse Asia-Pacific region.

A 19-year-old male patient with a history of congenital left oval window defect has had recurrent admissions to a children’s hospital for bacterial meningitis since the age of 7. Investigations revealed a left-sided type 1 incomplete partition deformity of the left ear with a congenital oval window defect, leading to communication between the cranium and the middle ear. The patient underwent a left canal wall down mastoidectomy and oval window defect repair, remaining well for 3 years. He experienced two more episodes of bacterial meningitis as he got older, prompting repeated exploratory tympanotomy and repair of the cerebrospinal fluid (CSF) leak after each episode. Recently, he was referred again for recurrent meningitis. Investigations showed a recurrent oval window defect. After undergoing left external ear canal transection, mastoid and middle ear obliteration, and left Eustachian tube obliteration, he remained well without further leaks or meningitis. Congenital oval window defect is rare and may present with recurrent bacterial meningitis secondary to spontaneous CSF leak via the oval window. Radiology plays a crucial role in identifying the source of the CSF leak, facilitating more precise preoperative counseling and surgical intervention.