Vietnam is experiencing a significant change in its economic conditions, such a change has been accompanied by significant changes in the pattern of morbidity and mortality. The country’s Gross Domestic Product (GDP) is increasing at a fast pace: from US$31 176 000 000 in 2000 to US$241 272 000 000 in 2018; and the country has experienced remarkable gains in combatting poverty and hunger. Gross National Income per capita has increased from US$110 in 2000 to US$2400 in 2018.1 At the moment the country is ranked in the low middle income countries by the world population review. Parallel with the economic growth, the country has experienced a fast and wide process of urbanisation. Over the past 20 years, more and more Vietnamese have moved from the rural areas to large urban areas with a projected urbanisation rate of 40% by early 2020. The rapid urbanisation has been accompanied by environment deterioration, increased air pollution, deterioration of lifestyle habits (including physical inactivity and diet changes) and a big strain in healthcare services.2–4 This remarkable financial success has been accompanied by a significant reduction in communicable diseases that have been substituted in the ranking of major causes of mortality and morbidity by non-communicable diseases (NCDs), as shown in figure 1. The burden of communicable diseases in Vietnam has significantly diminished from representing 38% and 33% of the morbidity and mortality burden in 1996 to a projected 18% and 6%, respectively, in 2026. The projected mortality burden of 6% for communicable diseases is significantly lower than the projected average burden for other countries in South East Asia (SEA). The successful efforts in combatting communicable diseases has been the main reason for the observed increase in life expectancy. The average life expectancy in Vietnam in 2017 was 79.2 years for women and 70 years for men, with an increase of (6.5 years in women and 5 years in men between 1990 and 2017). Vietnam is one of SEA countries with the highest number of elderly individuals (60+)5 (11 million people, representing 11.95% of the population in 2017). Two million out of these 11 million people are over 80 years old. It is estimated that in 2038 the elderly will represent approximately 20% of the population. This rapid and significant shift in the age distribution of the population will create a significant increase in the demand of healthcare services for elders.

The novel findings of this study are type III sodium-phosphate cotransporters PiT-1 and -2-dependent depolarization by high Pi, leading to Ca²⁺ entry via voltage-gated Ca²⁺ channels in vascular smooth muscle cells. Cytosolic Ca²⁺ increase and subsequent oxidative stress are indispensable for osteogenic differentiation and calcification. In addition, plasmalemmal abundance of PiT-1/2 relies on Ca²⁺ overload and oxidative stress, establishing a positive feedback loop. Identification of mechanistic components of a vicious cycle could provide novel therapeutic strategies against vascular calcification in hyperphosphatemic patients.

Inorganic phosphate (Pi) is essential for maintaining cellular function but excess of Pi leads to serious complications, including vascular calcification. Accumulating evidence suggests that oxidative stress contributes to the pathogenic progression of calcific changes. However, the molecular mechanism underlying Pi-induced reactive oxygen species (ROS) generation and its detrimental consequences remain unclear. Type III Na⁺-dependent Pi cotransporter, PiT-1/-2, play a significant role in Pi uptake of vascular smooth muscle cells. Pi influx via PiT-1/-2 increases the abundance of PiT-1/-2 and depolarization-activated Ca²⁺ entry due to its electrogenic properties, which may lead to Ca²⁺ and Pi overload and oxidative stress. At least four mitochondrial Pi transporters are suggested, among which the phosphate carrier (PiC) is known to be mainly involved in mitochondrial Pi uptake. Pi transport via PiC may induce hyperpolarization and superoxide generation, which may lead to mitochondrial dysfunction and endoplasmic reticulum stress, together with generation of cytosolic ROS. Increase in net influx of Ca²⁺ and Pi and their accumulation in the cytosol and mitochondrial matrix synergistically increases oxidative stress and osteogenic differentiation, which could be prevented by suppressing either Ca²⁺ or Pi overload. Therapeutic strategies targeting plasmalemmal and mitochondrial Pi transports can protect against Pi-induced oxidative stress and vascular calcification.

Vascular calcification is a serious complication of hyperphosphatemia that causes cardiovascular morbidity and mortality. Previous studies have reported that plasmalemmal phosphate (Pi) transporters, such as PiT-1/2, mediate depolarization, Ca²⁺ influx, oxidative stress, and calcific changes in vascular smooth muscle cells (VSMCs). However, the pathogenic mechanism of mitochondrial Pi uptake in vascular calcification associated with hyperphosphatemia has not been elucidated. We demonstrated that the phosphate carrier (PiC) is the dominant mitochondrial Pi transporter responsible for high Pi-induced superoxide generation, osteogenic gene upregulation, and calcific changes in primary VSMCs isolated from rat aortas. Notably, acute incubation with high Pi markedly increased the protein abundance of PiC via ERK1/2- and mTOR-dependent translational upregulation. Genetic suppression of PiC prevented Pi-induced ERK1/2 activation, superoxide production, osteogenic differentiation, and vascular calcification of VSMCs in vitro and aortic rings ex vivo. Pharmacological inhibition of mitochondrial Pi transport using butyl malonate (BMA) or mersalyl abolished all pathologic changes involved in high Pi-induced vascular calcification. BMA or mersalyl also effectively prevented osteogenic gene upregulation and calcification of aortas from 5/6 subtotal nephrectomized mice fed a high-Pi diet. Our results suggest that mitochondrial Pi uptake via PiC is a critical molecular mechanism mediating mitochondrial superoxide generation and pathogenic calcific changes, which could be a novel therapeutic target for treating vascular calcification associated with hyperphosphatemia.

Many parts of the world have adopted a competency-based education (CBE) framework in developing medical education programs. This framework emphasizes individual progression toward defined milestones, acknowledging that learners advance at different rates. It requires frequent formative feedback and robust assessment through a Clinical Competency Committee. Because time is no longer the fixed variable in training, learners can progress at different rates, creating opportunities for more individualized training with documented competence and progression. This approach promotes learner ownership, continuous monitoring, and self-regulated learning. This core tenet of residency training in the United States has been adopted by the VinUniversity Internal Medicine Residency under the supervision of Penn’s Graduate Medical Education Curriculum Working Group through the Penn–Vingroup Alliance. In this paper, we share the experience of the Internal Medicine Residency Program at VinUniversity, where CBE is emerging. We describe how we align milestone assessments with outcomes and use feedback within individualized learning plans (ILPs) to help residents maximize learning opportunities and prepare for independent practice through explicit, evidence-based decisions. The significance of this work lies in demonstrating a feasible, context-adapted pathway for operationalizing CBE and embedding ILPs in a training program in Vietnam. It integrates milestones, programmatic assessment, and individualized learning plans into a continuous improvement cycle that is defensible for trainees, accountable to patients, and scalable to other programs in low- and middle-income settings.