2024年 · 第10卷第03期

Calcium-sensing receptor (CaSR), a family C G-protein-coupled receptor, plays a crucial role in regulating calcium homeostasis by sensing small concentration changes of extracellular Ca²⁺, Mg²⁺, amino acids (e.g., L-Trp and L-Phe), small peptides, anions (e.g., HCO₃^- and PO₄^3-), and pH. CaSR-mediated intracellular Ca²⁺ signaling regulates a diverse set of cellular processes including gene transcription, cell proliferation, differentiation, apoptosis, muscle contraction, and neuronal transmission. Dysfunction of CaSR with mutations results in diseases such as autosomal dominant hypocalcemia, familial hypocalciuric hypercalcemia, and neonatal severe hyperparathyroidism. CaSR also influences calciotropic disorders, such as osteoporosis, and noncalciotropic disorders, such as cancer, Alzheimer's disease, and pulmonary arterial hypertension. This study first reviews recent advances in biochemical and structural determination of the framework of CaSR and its interaction sites with natural ligands, as well as exogenous positive allosteric modulators and negative allosteric modulators. The establishment of the first CaSR protein-protein interactome network revealed 94 novel players involved in protein processing in endoplasmic reticulum, trafficking, cell surface expression, endocytosis, degradation, and signaling pathways. The roles of these proteins in Ca²⁺-dependent cellular physiological processes and in CaSR-dependent cellular signaling provide new insights into the molecular basis of diseases caused by CaSR mutations and dysregulated CaSR activity caused by its protein interactors and facilitate the design of therapeutic agents that target CaSR and other family C G-protein-coupled receptors.

One in two cardiac patients fear having another heart event or their heart condition getting worse. Research in other chronic illnesses demonstrates that screening for fear of progression and recurrence is vital for adequately addressing such concerns in clinical care. The current project aims to develop and validate a measure for fear of progression and recurrence in cardiac patients.

The Fear of Cardiac Recurrence and Progression Scale (FCRP) will be developed through a multistep process. An initial item pool will be generated through a review of the literature and existing measures and consultation with and feedback from key informants. The item pool will be tested in a sample of over 250 adults who have ever had an acute coronary event, undergone cardiac surgery, or a chronic cardiac condition. Exploratory factor analysis will be used to identify the underlying factors, and Rasch analysis will be used to reduce the number of items. A short form version of the FCRP will be developed for use as a brief screening tool, informed by clinical relevance and Rasch psychometric indices.

While many cardiac patients experience fears related to the progression or recurrence of their illness, there remains the need for a validated tool with which these concerns can be identified and measured. It is expected that the design and validation of the FCRP will aid identification of cardiac patients suffering from clinically significant levels of fear of progression and recurrence and facilitate the design of tailored psychological interventions to target these fears.

Despite the adverse effects of ambient fine particulate matter (PM_2.5) on type 2 diabetes and the beneficial role of physical activity (PA), the influence of PM_2.5 on the relationship between PA and type 2 diabetes remains unclear.

In this prospective study with 71,689 participants, PA was assessed by a questionnaire and was categorized into quartiles for volume and three groups for intensity. Long-term PM_2.5 exposure was calculated using 1-km resolution satellite-based PM_2.5 estimates. PM_2.5 exposure and PA's effect on type 2 diabetes were assessed by cohort-stratified Cox proportional hazards models, individually and in combination.

In 488,166 person-years of follow-up, 5487 incident type 2 diabetes cases were observed. The association between PA and type 2 diabetes was modified by PM_2.5. Compared with the lowest quartile of PA volume, the highest quartile was associated with reduced type 2 diabetes risk in low PM_2.5 stratification (≤65.02 μg/m³) other than in high PM_2.5 stratification (>65.02 μg/m³), with the hazard ratio (HR) of 0.75 (95% confidence interval [CI]: 0.66-0.85) and 1.10 (95% CI: 0.99-1.22), respectively. Similar results were observed for PA intensity. High PM_2.5 exposure combined with the highest PA levels increased the risk of type 2 diabetes the most (HR= 1.79, 95% CI: 1.59-2.01 for PA volume; HR = 1.82, 95% CI: 1.64-2.02 for PA intensity).

PA could reduce type 2 diabetes risk in low-pollution areas, but high PM_2.5 exposure may weaken or even reverse the protective effects of PA. Safety and health benefits of PA should be thoroughly assessed for long-term polluted residents.

Studies have found that the ratio of total cholesterol to high-density lipoprotein cholesterol (TC/HDL-C) was associated with the development of chronic kidney disease (CKD). However, the relationship in different genders was rarely discussed. The aim of this study was to explore this relationship and assess its predictive power for both males and females.

Based on a prospective cohort platform in northwest China, 32,351 participants without CKD were collected in the baseline and followed up for approximately 5 years. Cox proportional hazard model and restricted cubic spline regression analysis were performed to investigate the association between TC, HDL-C, TC/HDL-C and CKD in adult female and male. The clinical application value of the indicators in predicting CKD was evaluated by the receiver operator characteristic curve.

During a mean follow-up of 2.2 years, 484 males and 164 females developed CKD. After adjusted for relevant confounders, for every one standard deviation increase in TC, HDL-C and TC/HDL-C, the hazard ratios (HRs) and 95% confidence intervals (95% CIs) for CKD were 1.17 (1.05-1.31), 0.84 (0.71-0.99), and 1.15 (1.06-1.25) for males, 0.94 (0.78-1.13), 0.58 (0.35-0.95), and 1.19 (1.01-1.40) for females, respectively. The results also showed that TC, HDL-C, and TC/HDL-C were associated with CKD in a linear dose-response relationship. The TC/HDL-C had the largest area under the curve (AUC) compared to TC and HDL-C, and the AUC among the females was larger than that among males.

The TC/HDL-C was significantly associated with CKD in adult males and females and has better clinical value in predicting CKD than TC and HDL-C, especially in females.

Increased knowledge of the concept of adherence is needed for development patient-centered care, nursing interventions, and guidelines for patients with coronary heart disease (CHD). The aim of this study was to test and extend the Theory of Adherence to Treatment regarding informational support in patients with CHD.

The study utilized an explanatory and descriptive survey. The study was conducted in 2013 and involved 416 patients in five hospitals in Finland. The Adherence of Patients with Chronic Disease instrument and the Social Support for People with CHD instrument were used. The model was tested using structural equation modeling (SEM).

SEM confirmed direct associations between motivation (β = 0.49, p < 0.001) and results of care (β = 0.29, p < 0.01), and indirect associations between sense of normality, fear of complications, support from nurses and next of kin, and informational support to adherence to a healthy lifestyle and medication. Informational support included information and advice on CHD risk factors, physical exercise, chest pain, medication, continuum of care, and rehabilitation. Indirect standardized path coefficients varied between 0.14 and 0.45. The model explained 45% of adherence to a healthy lifestyle and medication.

The results of this study showed that informational support is a justified extension to the original Theory of Adherence to Treatment in Patients with CHD. Informational support seems to offer a new perspective that can be used to develop patient-centered nursing interventions and thus support adherence to treatment by patients with a lifelong disease such as CHD.

Noncommunicable diseases (NCDs) are the main reasons of mortality worldwide. One of every two person is dying due to NCDs in Afghanistan. International policy actors, mainly the World Health Organization (WHO), published several reports and declarations on controlling and preventing NCDs. This study aimed to provide a situation for governance of NCDs in Afghanistan and proper solutions for identified challenges.

We conducted qualitative research utilizing interpretive phenomenology. A self-developed questionnaire was developed to conduct the semi-structured interviews with 39 experts from Afghanistan. The results were analyzed using a deductive framework analysis. Six building block framework of health system developed by the WHO was used as predefined framework for this study.

The governance building block of health system consists of five subthemes including policy making, planning, organizing, stewardship, and control. We identified main strengths, weaknesses, opportunities, and challenges for these subthemes. The experts also provided key recommendations to address the challenges.

Management of NCDs is a neglected part of the health system in Afghanistan. Strengthening evidence-based policy making with technical and indigenous planning, establishing responsive units with adequate financial and human resources within different ministries to address "health in all policies" concept, passing and implementing national laws and regulations to support national strategies for prevention and control of NCDs, and establishing decentralized monitoring systems to control the implementation of these strategies are the main recommendations of this study. Local government and international policy actors should invest and support the development of a multisectoral coordination system at national level for Afghanistan.

Cardiovascular diseases (CVDs) account for 17.9 million deaths annually. Behavioral risk factors increase the risk of dying from CVD. Air pollution is not included in this risk calculation since the appreciation of air pollution as a modifiable risk factor is still limited. The purpose of this study was to analyze CVD mortality attributed to air pollution in all World Health Organization WHO member states and demonstrate the association of CVD mortality with air pollution depending on countries' income level.

The CVD death rate was calculated by dividing the number of deaths by the total population. The proportion of the population with primary reliance on clean fuels and technologies for cooking was calculated as an indicator of household air pollution. The annual mean concentration of fine particulate matter ≤2.5 µg/m³ and ≤10.0 µg/m³ to which the population is exposed was used as an indicator of ambient air pollution.

There is a gradual increase in CVD mortality attributed to air pollution from high-income countries (HICs) to low-income countries (LICs). Household air pollution is the major cause of CVD mortality in LICs. Ischemic heart disease mortality attributed to ambient air pollution in all countries is higher than stroke mortality attributed to ambient air pollution. In LIC, mortality from stroke is attributed to household air pollution of 39.27 ± 14.47, which is more than twice the stroke mortality attributed to ambient air pollution at 18.60 ± 5.64, t= 7.17, p < 0.01.

Air pollution control should be an essential component of the CVD preventive strategy, along with lifestyle modifications and effective disease management.