OBJECTIVE: To summarize the clinical features and management of two brothers affected with X-linked inhibitor of apoptosis protein (XIAP) deficiency. METHODS: This study retrospectively analyzed the clinical presentations, treatment, and follow-up of two brothers with XIAP deficiency diagnosed at Shanghai Children's Hospital in 2020, and summarized similar cases recorded in databases such as PubMed, Wanfang, Chinese Medical Association Journals, and WIP from January 2006 to November 2024. This study was approved by the Medical Ethics Committee of our hospital (Ethics No.: 2025R128-E01). RESULTS: Patient 1 was the younger brother, who presented at 8 years of age with growth retardation, folliculitis, erythema nodosum, and perineal abscess. Sequencing revealed that he has carried a hemizygous c.566T>C (p.Leu189Pro) variant of the XIAP gene, which was inherited from his mother. He was allergic to infliximab treatment and underwent allogeneic stem cell transplantation (HSCT) in January 2021. During a follow-up of 3 years and 10 months post-transplantation, he showed no gastrointestinal symptoms and had a good outcome. Patient 2 was the elder brother, who presented at 10 years and 6 months of age with growth retardation, rash, and anal fistula. Genetic testing revealed the same variant. He was treated with oral azathioprine but did not have regular follow-ups. At 14-years-and-6-months of age, he had developed severe gastrointestinal infection and hemophagocytic lymphohistiocytosis, which was alleviated after treatment with antibiotics, glucocorticoids, immunoglobulin, and rituximab. He is currently being prepared for HSCT. A total of 13 publications were retrieved, which involved 64 patients from 23 families, with 23 different variants identified. The main clinical manifestations included splenomegaly (34 cases, 53.1%), hemophagocytic lymphohistiocytosis (27 cases, 42.2%), and inflammatory bowel disease or colitis (20 cases, 31.8%). There were significant phenotypic differences among patients from the same family. Thirteen patients (20.3%) underwent HSCT, with a survival rate of 61.5%. CONCLUSION For male children with early onset, poor treatment response, especially those with unexplained splenomegaly and IBD-like symptoms, early genetic testing is recommended. HSCT is a safe and effective treatment for XIAP deficiency. For patients with developmental delay, early onset, and severe IBD phenotype, early transplantation is recommended.
Humans ; Male ; X-Linked Inhibitor of Apoptosis Protein/deficiency* ; Child ; Genetic Diseases, X-Linked/therapy* ; Phenotype ; Siblings ; Retrospective Studies ; Hematopoietic Stem Cell Transplantation

OBJECTIVES

This study aimed to identify problems and highlight opportunities for pharmaceutical sciences research in the Philippine pharmaceutical industry's regulatory and clinical research sectors that might have been previously overlooked or underrepresented. It identified current issues that can be addressed by research covering four areas of pharmaceutical sciences: drug design and discovery, pharmacokinetic/pharmacodynamic studies, formulation design and pharmaceutical technology, and regulatory science.

METHODS

A descriptive qualitative approach was used in this study. Data collection was facilitated by key informant interviews (KII) using a standardized interview guide with open-ended questions to identify the pharmaceutical science research needs of the specific sectors. A purposive sampling method was employed, with five key informants (KIs), including the company vice president, director, and top-level managers from different local and multinational pharmaceutical companies. ATLAS.ti software was utilized to facilitate thematic synthesis for qualitative data analysis.

RESULTS

Thirteen common themes were identified from the KIs, such as (1) incomplete development of therapeutic compounds, (2) sustainability of raw materials supply, (3) regulation of herbal medicines versus food supplements, (4) mapping disease priorities through the Philippine pharmaceutical roadmap, (5) government incentives and policies to support research, (6) technical personnel, (7) suboptimal regulatory process, approvals, and implementation, (8) gap in utilization of acquired knowledge on regulations, (9) regulatory governance, (10) passive regulatory action on counterfeit drugs, (11) PIC/S GMP version 14 adaption, (12) formulation optimization, and (13) active pharmaceutical ingredient (API) sourcing and regulation. Based on insights from the International Pharmaceutical Federation regarding anticipated hurdles in pharmaceutical sciences over the next 5-10 years, priority research needs were identified through KIs' input. Relevant action plans were developed, including the creation of research proposals to isolate, purify, and determine chemical structures of natural products, as well as analyzing recent Philippine Health Statistics to help assess the appropriateness of new drug releases for patient needs. Other action plans include forecasting future disease burdens in the country, performing toxicology studies (Health-Based Evaluation Levels/No Observed Adverse Effect Level or HBEL/NOAEL) for common generic drugs, and ensuring that research efforts are directed toward addressing the Philippine pharmaceutical regulatory and clinical research sector's most pressing needs practically and feasibly.

CONCLUSION

This study offers valuable insights into pharmaceutical sciences research and development initiatives within the regulatory and clinical research sectors in the Philippine pharmaceutical industry. These findings have the potential to catalyze transformative advancements in healthcare delivery and outcomes, positioning the Philippines for global excellence and competitiveness.

Occupational Groups ; No-observed-adverse-effect Level ; Social Control, Formal ; Patients ; Pharmaceutical Preparations

Against the backdrop of the Russia-Ukraine Conflict in 2022, this article reviews the characteristics of traumatic hemorrhage in modern warfare spanning the past century. It investigates several types of tourniquets used by the Russian and Ukrainian armed forces, including limb tourniquets and junctional tourniquets recommended by the Committee on Tactical Combat Casualty Care, tourniquets employed by the Armed Forces of the Russian Federation, and those used by the Armed Forces of Ukraine in the Russia-Ukraine Conflict. The analysis is conducted from perspectives, including the structure, usage methods, and limitations of different tourniquets. Additionally, the article synthesizes the research progress on tourniquets from 3 angles: battlefield adaptability, the impact of tourniquet application methods on patient outcomes, and training in tourniquet usage, offering insights from our team's perspective.
Tourniquets ; Humans ; Russia ; Hemorrhage/therapy* ; Ukraine ; Military Medicine/methods* ; Warfare ; Armed Conflicts

OBJECTIVE: Observational studies have shown inconsistent associations of loneliness or social isolation (SI) with ischemic heart disease (IHD), with unknown mediators. METHODS: Using data from genome-wide association studies of predominantly European ancestry, we performed a bidirectional two-sample Mendelian Randomization (MR) study to estimate causal effects of loneliness ( N = 487,647) and SI traits on IHD ( N = 184,305). SI traits included whether individuals lived alone, participated in various types of social activities, and how often they had contact with friends or family ( N = 459,830 to 461,369). A network MR study was conducted to evaluate the mediating roles of 20 candidate mediators, including metabolic, behavioral and psychological factors. RESULTS: Loneliness increased IHD risk ( OR= 2.129; 95% confidence interval [ CI]: 1.380 to 3.285), mediated by body fat percentage, waist-hip ratio, total cholesterol, and low-density lipoprotein cholesterol. For SI traits, only fewer social activities increased IHD risk ( OR= 1.815; 95% CI: 1.189 to 2.772), mediated by hypertension, high-density lipoprotein cholesterol, triglycerides, fasting insulin, and smoking cessation. No reverse causality of IHD with loneliness and SI was found. CONCLUSION These findings suggested more attention should be paid to individuals who feel lonely and have fewer social activities to prevent IHD, with several mediators as prioritized targets for intervention.
Loneliness/psychology* ; Humans ; Mendelian Randomization Analysis ; Social Isolation ; Myocardial Ischemia/etiology* ; Male ; Female ; Middle Aged ; Genome-Wide Association Study ; Risk Factors ; Aged

Advance medical directives allow patients to plan in advance their medical decisions in the event of incurable diseases or at the end of their lives when they have the capacity to make such decisions.This institutional design not only breaks through the traditional medical decision-making model and enables patients to make autonomous decisions across time and space,but also demonstrates the law's respect for and protection of patients' right to make autonomous decisions and their dignity of life.The Hong Kong Special Administrative Region submitted the bill related to advance medical directives to the Legislative Council for review at the end of 2023.On November 20,2024,the Advance Decision on Life-Sustaining Treatment Bill was passed,a move that is of great significance to regulating the legal issues in medical decision-making.This paper will delve into the basic principles,main contents,and related considerations of advance medical directives in Hong Kong,aiming to provide insights and references for the future improvement of relevant laws in the Chinese mainland.
Hong Kong ; Advance Directives/legislation & jurisprudence* ; Humans ; Decision Making

Nursing leadership and scholarship in the Philippines have evolved alongside the country's shifting socio-political and educational landscape. This feature article presents a first-person narrative of a nurse leader's journey from humble beginnings in Santiago, Isabela, to national and global leadership roles in education, regulation, and advocacy. This article aimed to illustrate how personal vocation, grounded in service and faith, can transform into professional leadership and scholarship that shape institutions, influence policy, and nurture future generations of Filipino nurses. Using autobiographical lens, I recounted formative experiences across clinical practice, education, administration, and regulation. These reflections are interwoven with leadership theories and scholarly evidence from global nursing literature that demonstrate how enduring principles such as servant leadership, integrity, resilience, compassion, and mentorship can guide professional practice. This narrative highlighted milestones such as pioneering collegiate nursing education at UERMMC, spearheading faculty and curricular reforms as Dean, championing ethical practice during the nursing licensure examination scandal, and advancing professional regulation through initiatives like the Career Progression and Specialization Program. It also underscored the role of resilience in overcoming personal affliction, the importance of mentorship in sustaining legacy, and the impact of integrity in safeguarding nursing's credibility. From the parable of the mustard seed to the reality of nation-building through nursing, this life story affirmed that leadership and scholarship are not individual achievements but collective legacies. By embracing lifelong learning, ethical practice and a commitment to national service, Filipino nurses can continue to grow as competent practitioners, compassionate caregivers, and visionary leaders who contribute to equitable and sustainable health systems. In telling this story, I also sought to situate my journey within the broader context of nursing leadership in the Philippines, where enduring challenges and emerging opportunities continue to call for vision, resilience, and integrity.

Human ; Scholarship ; Fellowships And Scholarships ; Resilience ; Resilience, Psychological ; Regulation ; Social Control, Formal ; Mentorships ; Mentors ; Education, Nursing ; Philippines

Case 1 was a 7-year-old girl; Case 2 was her 3-year-old younger brother. Both children developed pink urine shortly after birth and exhibited blistering on photo-exposed areas (face and hands), followed by ulceration, crusting, scarring, and joint contractures leading to impaired mobility. Genetic testing in both patients identified a homozygous variant in the UROS gene, c.776T>C (p.Leu259Pro), confirming autosomal recessive congenital erythropoietic porphyria due to UROS mutations. This case report highlights that congenital erythropoietic porphyria should be considered in infants and young children with unexplained hemolytic anemia, pink urine, and severe photosensitive dermatitis. Early genetic testing is recommended to facilitate timely intervention and improve outcomes.
Humans ; Porphyria, Erythropoietic/genetics* ; Female ; Child ; Child, Preschool ; Male ; Siblings ; Mutation ; Uroporphyrinogen III Synthetase/genetics*

BACKGROUND: Studies have shown that married couples often share similar lifestyles, as well as lifestyle-associated conditions such as diabetes, hypertension, and hyperlipidemia. This study aims to prospectively investigate the association between an individual's development of a non-communicable disease and the subsequent development of the same condition in their spouse. METHODS: This population-based cohort study utilized 12 waves of annual prospective surveys from 2005 onwards in Japan, with a discrete-time design. A total of 9,417 middle-aged couples (18,834 participants; discrete-time observations = 118,876) were included. Each participant whose spouse had developed one of six conditions was propensity score-matched with five controls whose spouses had not been diagnosed with the condition: diabetes [n = 1374 vs n = 6870], hypertension [n = 2657 vs n = 13285], hypercholesterolemia [n = 3321 vs n = 16605], stroke [n = 567 vs n = 2835], coronary heart disease (CHD) [n = 1093 vs n = 5465] or cancer [n = 923 vs n = 4615]. Using conditional logistic regression, we assessed participants' development of the same condition within three years following their spouse's diagnosis. RESULTS: Participants whose spouses had developed diabetes, hypertension, hypercholesterolemia, or CHD were more likely to develop the same condition within three years. The odds ratios (ORs) and 95% confidence intervals (CIs) were: 1.96 (1.53-2.50), 1.20 (1.06-1.36), 1.63 (1.47-1.81) and 1.43 (1.05-1.95), respectively. No significant associations were observed in stroke [1.69 (0.80-3.58)] or cancer [1.08 (0.75-1.54)]. CONCLUSION Spouses of individuals recently diagnosed with certain metabolic conditions are at a higher risk of developing those conditions themselves. These findings may provide valuable guidance for targeting and personalizing chronic disease screening and prevention efforts.
Humans ; Spouses/statistics & numerical data* ; Male ; Female ; Middle Aged ; Aged ; Japan/epidemiology* ; Longitudinal Studies ; Noncommunicable Diseases/epidemiology* ; Prospective Studies ; Neoplasms/epidemiology* ; Diabetes Mellitus/epidemiology* ; Risk Factors ; Aged, 80 and over ; Adult ; Hypertension/epidemiology*

BACKGROUND: Cancer is a major public health concern, particularly among middle-aged and elderly populations, who are disproportionately affected by rising cancer incidence. Environmental pollution has been identified as a significant risk factor for cancer development. China's Carbon Emission Trading Policy (CETP), implemented in pilot regions since 2013, aims to reduce carbon emissions and improve air quality. This study evaluates the impact of CETP on pan-cancer incidence, with a focus on its effects on specific cancer types and vulnerable populations. METHODS: This quasi-natural experiment utilized data from the China Health and Retirement Longitudinal Study (CHARLS) and environmental data from the China National Environmental Monitoring Center (2011-2018). A staggered difference-in-differences (DID) model was employed to estimate the impact of CETP on cancer incidence. Robustness tests, including parallel trend tests, placebo analysis, and entropy balancing, validated the findings. Subgroup analyses were performed to assess the policy's heterogeneous effects based on gender, Body Mass Index (BMI), and smoking status. RESULTS: CETP implementation significantly reduced the incidence of six cancer types: endometrial, cervical, gastric, esophageal, breast, and lung cancers. Overall, pan-cancer incidence significantly declined post-policy implementation (CETP × POST: -47.200, 95% CI: [-61.103, -33.296], p < 0.001). The policy demonstrated stronger effects in highly polluted areas and among individuals with poorer mental health. Subgroup analysis revealed that females, individuals with lower BMI, and non-smokers experienced more substantial benefits. CONCLUSIONS CETP significantly reduces cancer incidence by improving environmental quality and influencing mental health, with particularly strong effects observed among high-risk populations. This study highlights the important role of environmental economic policies in mitigating cancer burden and promoting public health. Future research should further explore the long-term impacts of this policy and its applicability across different national and regional contexts.
Humans ; Incidence ; Neoplasms/epidemiology* ; China/epidemiology* ; Middle Aged ; Female ; Male ; Aged ; Air Pollution/legislation & jurisprudence* ; Carbon/analysis* ; Longitudinal Studies ; Air Pollutants/analysis* ; Environmental Exposure

BACKGROUND: Growing up with a sibling with a chronic health problem or a disability requiring assistance can affect the lives of the family members in various ways. Previous studies documented health problems among siblings of children with a chronic health problem or a disability. However, these studies are limited in that they tend to rely on small convenience samples of children with specific illnesses/disabilities. This study aims to investigate mental health and self-rated health status of siblings of such children using data from a population study in Japan. METHODS: We used data from the 2016 wave of Japan's Comprehensive Survey of Living Conditions. The analytic sample included 16,510 adolescents aged 15-19 years who were living with a sibling with or without care needs. The outcomes were psychological distress as defined by K6 score of 13 or higher and poor self-rated health. We examined these health outcomes of adolescents who have a sibling with care needs to relative to adolescents with a sibling without such needs via logistic regression. RESULTS: Adolescents who live with a sibling with care needs were more likely to have psychological distress (Odds Ratio (OR) 2.47; 95% Confidence Interval (CI), 1.46-4.17) and poor self-rated health (OR 2.21; 95% CI, 1.30-3.75). These associations were more pronounced in post-high school age (18-19 years old) group than in high school age (15-18 years old) group. CONCLUSION The presence of a child with care needs in the household was associated with spillover psychological distress and poorer subjective health among siblings. Providing support for children/adolescents with care needs may have additional benefits in terms of well-being of their siblings.
Humans ; Adolescent ; Male ; Female ; Siblings/psychology* ; Young Adult ; Psychological Distress ; Japan/epidemiology* ; Health Status