BACKGROUND

Observational studies have increasingly reported transthyretin amyloid cardiomyopathy (ATTR-CM) as an under-recognized cause of heart failure. We report the first ATTR-CM diagnosed via multi-modality imaging in the Philippines signifying an important milestone in recognition and management of this formerly believed rare disease, locally. Utilization of non-invasive imaging such as echocardiography, cardiac MRI and technetium-99m pyrophosphate scintigraphy (PYP) demonstrates the potential for accurate diagnosis as well as timely and appropriate treatment strategies.

An 81/M Filipino with a history of carpal tunnel surgery, post-percutaneous coronary intervention (PCI), had three months’ history of refractory heart failure symptoms despite optimized medical treatment. His 2D-echo showed an ejection fraction (EF): 45%-50%, increased left ventricular (LV) posterior wall thickness with mild basal inferior wall hypokinesia and ECG: atrial fibrillation with low voltage. Speckle tracking imaging showed average global longitudinal strain: - 6.5% with cherry-on-top pattern on polar strain map. Cardiac MRI demonstrated diffuse late gadolinium enhancement from endocardial to transmural layers of biventricular and biatrial walls, highly suggestive of cardiac amyloidosis (CA). Light-chain amyloidosis was excluded by negative serum/urine protein electrophoresis/immunofixation. Tc-99m PYP scan revealed greater myocardial-than-bone uptake with a Perugini score 3 and calculated heart-to-contralateral ratio of 1.7. Congestion was controlled with intravenous loop diuretics and he was discharged stable with metoprolol succinate, dapagliflozin and apixaban. At the time of paper submission, he is currently being evaluated for tafamidis treatment.

The case highlighted the advantage of multi-modality imaging for noninvasive yet accurate identification of the disease. A tailored approach is required in slowing the disease progression and improving outcomes.

The aim of this study was to investigate the contribution of lung zinc ions to pathogenesis of lung ischemia/reperfusion (I/R) injury in rats. Male Sprague Dawley (SD) rats were randomly divided into control group, lung I/R group (I/R group), lung I/R + low-dose zinc chloride group (LZnCl₂+I/R group), lung I/R + high-dose ZnCl₂ group (HZnCl₂+I/R group), lung I/R + medium-dose ZnCl₂ group (MZnCl₂+I/R group) and TPEN+MZnCl₂+I/R group (n = 8 in each group). Inductively coupled plasma mass spectrometry (ICP-MS) was used to measure the concentration of zinc ions in lung tissue. The degree of lung tissue injury was analyzed by observing HE staining, alveolar damage index, lung wet/dry weight ratio and lung tissue gross changes. TUNEL staining was used to detect cellular apoptosis in lung tissue. Western blot and RT-qPCR were used to determine the protein expression levels of caspase-3 and ZIP8, as well as the mRNA expression levels of zinc transporters (ZIP, ZNT) in lung tissue. The mitochondrial membrane potential (MMP) of lung tissue was detected by JC-1 MMP detection kit. The results showed that, compared with the control group, the lung tissue damage, lung wet/dry weight ratio and alveolar damage index were significantly increased in the I/R group. And in the lung tissue, the concentration of Zn²⁺ was markedly decreased, while the cleaved caspase-3/caspase-3 ratio and apoptotic levels were significantly increased. The expression levels of ZIP8 mRNA and protein were down-regulated significantly, while the mRNA expression of other zinc transporters remained unchanged. There was also a significant decrease in MMP. Compared with the I/R group, both MZnCl₂+I/R group and HZnCl₂+I/R group exhibited significantly reduced lung tissue injury, lung wet/dry weight ratio and alveolar damage index, increased Zn²⁺ concentration, decreased ratio of cleaved caspase-3/caspase-3 and apoptosis, and up-regulated expression levels of ZIP8 mRNA and protein. In addition, the MMP was significantly increased in the lung tissue. Zn²⁺ chelating agent TPEN reversed the above-mentioned protective effects of medium-dose ZnCl₂ on the lung tissue in the I/R group. The aforementioned results suggest that exogenous administration of ZnCl₂ can improve lung I/R injury in rats.
Animals ; Reperfusion Injury/pathology* ; Male ; Rats, Sprague-Dawley ; Rats ; Chlorides/administration & dosage* ; Lung/pathology* ; Zinc Compounds/administration & dosage* ; Apoptosis/drug effects* ; Caspase 3/metabolism* ; Cation Transport Proteins/metabolism*

To optimize the traditional refining process of Hydrargyrum Chloratum Compositum(HCC) and explore the change law of substances before and after refining, this study applied the hierarchical analysis method(AHP)-entropy weight method, using appearance, yield, and mercuric chloride content as evaluation indexes. The temperature and time of mild and strong fire were examined as single factors, and an L_9(3~4) orthogonal experiment was used to optimize the refining process. An infrared thermal imaging platform was set up to record the temperature changes on the surface of the tank, aiming to establish a standardized operating procedure for the refining process. Elemental changes, physical phase changes, and thermal property changes of the materials before and after refining were analyzed using atomic absorption spectrophotometry(AAS), X-ray diffraction(XRD) and differential scanning calorimetry(DSC). The results showed that the average overall score of the finished product obtained from the optimized HCC refining process(with mild fire temperature of 102 ℃, mild fire refining time of 30 min, strong fire temperature of 178 ℃, and strong fire refining time of 68 min) was 91.59, with an RSD of 0.076%, indicating that the process is stable and feasible. Combined with thermal imaging data and related research results, it was found that, at the strong fire temperature, mercury ions and nitrate ions generated mercuric chloride under the catalysis of other ions. The mercury content of mercurous chloride, mercuric chloride synthesized from nitric acid, HCC, and the pre-refined sample was 84.535%, 72.376%, 70.838%, and 41.334%, respectively. The highest intensity of the(120) diffraction peak for HCC appeared around 20.36°, but the residual fit value was larger. The synthesis of mercuric chloride from HCC and nitric acid showed an exothermic peak at 190-204 ℃, with the peak shape exhibiting a rightward trend. This study optimized the traditional refining process of HCC and analyzed the elemental changes, physical phase changes, and thermal property changes before and after refining. The findings provide experimental data for exploring the changing patterns in the refining process of HCC and its pharmacological value, as well as for standardizing the traditional refining process in clinical practice.
Drugs, Chinese Herbal/chemistry* ; X-Ray Diffraction ; Temperature ; Calorimetry, Differential Scanning ; Mercuric Chloride/chemistry*

Although salt-related behaviors may influence urinary salt excretion in early childhood, this relationship remains unclear. This study aimed to examine salt-related behaviors using data from a salt check sheet and urinary salt excretion parameters using spot urine samples from 4-year-old children. This cross-sectional study included all 4-year-old children who underwent health checkups in Ohnan Town, Shimane Prefecture. The study sample consisted of 109 children (49 boys). Measures from spot urine samples included estimated salt excretion (g/day) and the sodium-potassium (Na/K) ratio. Salt-related behaviors were assessed using a salt check sheet that was completed by the parents or guardians. The associations between salt-related behaviors and urinary salt excretion parameters were analyzed using a generalized linear model. The median (M) and interquartile range (IQR) for urinary measures in 4-year-old children were as follows: estimated salt excretion (M = 4.4, IQR: 3.3-6.2) and Na/K ratio (M = 2.3, IQR: 1.4-3.3). The low frequency of consumption of high-salt foods ("such as pickles, pickled plums, etc." and "noodles such as udon and ramen") was associated with low salt excretion and low Na/K ratio. However, in the case of "consumption of udon, ramen, or other soups", the Na/K ratio was higher for "About half a bowl" and "Some" than for "An entire bowl." Additionally, for "eating out or having convenience-store-bought bento (lunch plate) for lunch", the Na/K ratio was higher for "No" than for "Almost every day." In conclusion, the frequency of high-sodium food intake was associated with both urinary sodium excretion and the Na/K ratio in 4-year-old children. Longitudinal investigations using the 24-hour urine collection method are needed to confirm these salt-related behaviors.
Humans ; Child, Preschool ; Male ; Cross-Sectional Studies ; Female ; Sodium Chloride, Dietary/urine* ; Parents ; Sodium/urine* ; Japan ; Potassium/urine*

The nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome plays a crucial role in the prognosis of subarachnoid hemorrhage (SAH). WNK1 kinase negatively regulates NLRP3 in various inflammatory conditions, but its role in early brain injury (EBI) after SAH remains unclear. In this study, we used an in vivo SAH model in rats/mice and AAV-WNK1 intraventricular injection to investigate its neuroprotective mechanisms. WNK1 expression was significantly reduced in SAH patient blood and SAH model brain tissue, correlating negatively with microglial activation. AAV-WNK1 alleviated brain edema, neuronal necrosis, behavioral deficits, and inflammation by inhibiting NLRP3 inflammasome activation. In hemin-stimulated BV-2 cells, WNK1 overexpression reduced NLRP3 activation and inflammatory cytokines. Chloride counteracted WNK1's inhibitory effects, and WNK1 suppressed P2X7R-induced NLRP3 activation. Mechanistically, WNK1 functioned via the OXSR1/STK39 pathway. These findings highlight WNK1 as a key regulator of intracellular chloride balance and neuroinflammation, presenting a potential therapeutic target for SAH treatment.
Animals ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Subarachnoid Hemorrhage/complications* ; Inflammasomes/metabolism* ; Rats ; Mice ; Neuroinflammatory Diseases/metabolism* ; WNK Lysine-Deficient Protein Kinase 1/genetics* ; Male ; Humans ; Chlorides/metabolism* ; Mice, Inbred C57BL ; Rats, Sprague-Dawley ; Brain Injuries/metabolism* ; Microglia/metabolism* ; Protein Serine-Threonine Kinases

OBJECTIVE: To explore the relationship between serum chloride levels and prognosis in patients with hepatic coma in the intensive care unit (ICU). METHODS: We analyzed 545 patients with hepatic coma in the ICU from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Associations between serum chloride levels and 28-day and 1-year mortality rates were assessed using restricted cubic splines (RCSs), Kaplan-Meier (KM) curves, and Cox regression. Subgroup analyses, external validation, and mechanistic studies were also performed. RESULTS: A total of 545 patients were included in the study. RCS analysis revealed a U-shaped association between serum chloride levels and mortality in patients with hepatic coma. The KM curves indicated lower survival rates among patients with low chloride levels (< 103 mmol/L). Low chloride levels were independently linked to increased 28-day and 1-year all-cause mortality rates. In the multivariate models, the hazard ratio ( HR) for 28-day mortality in the low-chloride group was 1.424 (95% confidence interval [ CI]: 1.041-1.949), while the adjusted hazard ratio for 1-year mortality was 1.313 (95% CI: 1.026-1.679). Subgroup analyses and external validation supported these findings. Cytological experiments suggested that low chloride levels may activate the phosphorylation of the NF-κB signaling pathway, promote the expression of pro-inflammatory cytokines, and reduce neuronal cell viability. CONCLUSION Low serum chloride levels are independently associated with increased mortality in patients with hepatic coma.
Humans ; Male ; Female ; Middle Aged ; Intensive Care Units ; Prognosis ; Chlorides/blood* ; Aged ; Coma/blood* ; Adult

Sodium ; Wastewater ; Potassium ; Diet ; Blood Pressure ; China ; Sodium, Dietary ; Sodium Chloride, Dietary

The aim of this study was to conduct in vivo experiments using laser speckle contrast imaging (LSCI) technology to investigate the effects of high salt diet on renal vascular reactivity in mice. LSCI is a technology for monitoring blood flow based on the laser speckle principle. It has been widely used to detect microcirculatory functions in tissues such as the skin and brain. The kidneys are located behind the peritoneum, and their position is easily affected by the movement of abdominal organs. Measuring renal microcirculation in a living individual is difficult. The present study used a self-made kidney cup to isolate the kidney and fix its position relatively, and then applied LSCI technology to explore the effect of high salt diet (8% Na⁺) on renal vascular reactivity in male and female mice in vivo. The results showed that a short-term high salt diet (1 week) did not affect the systolic blood pressure of the tail artery, while significantly increased glomerular filtration rate (GFR) and renal blood flow (RBF). Compared with the normal salt diet group, the high salt diet group showed a significant decrease in the ratio of post-occlusive reactive hyperemia (PORH) in male mice, while there was no significant change in the PORH ratio in female mice. These results suggest that, although a short-term high salt diet does not cause changes in blood pressure, it has already affected renal vascular reactivity and has gender differences in its effects. Furthermore, the present study provides a basis for renal microcirculation assessment using LSCI in vivo.
Animals ; Mice ; Male ; Female ; Kidney/blood supply* ; Renal Circulation/physiology* ; Laser Speckle Contrast Imaging ; Sodium Chloride, Dietary/adverse effects* ; Microcirculation/physiology* ; Mice, Inbred C57BL

Excessive sodium/salt intake is the leading dietary risk factor for the loss of healthy life in the Chinese population. The "Healthy China 2030" Action Plan set the goal of reducing salt intake by 20% by 2030. However, salt intake in China is still at a very high level in the world, with adults reaching 11 g/d, more than twice the recommended limit of 5 g/d. The current policies and action plans of China have targeted catering workers, children, adolescents, and home chefs in salt, oil, and sugar reduction actions. However, there are still obvious deficiencies in the coordinated promotion and implementation. This study, therefore, proposed a set of comprehensive strategies (named CHRPS that is composed of communication and education, salt reduction in home cooking, salt reduction in restaurants, reducing salt content in pre-packaged food, and surveillance and evaluation) and key implementation points for further deepening the salt reduction action in China. These strategies were developed based on the main sources of dietary sodium for Chinese residents, the status of "knowledge, attitude and practice" in salt reduction, evidence of effective intervention measures, existing policies and requirements, and the salt reduction strategies of the World Health Organization and experience from some other countries. As a scientific reference, the CHRPS strategies will help the government and relevant organizations quickly implement salt reduction work and facilitate the earlier realization of China's salt reduction goal.
Adult ; Child ; Adolescent ; Humans ; Sodium Chloride, Dietary ; Sodium, Dietary ; Diet ; Food ; China

This study aims to investigate the therapeutic effects and potential mechanisms of resveratrol(Res) on poor ovarian response(POR) in mice. The common target genes shared by Res and POR were predicted by network pharmacology, used for Gene Ontology(GO) annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment, and then validated by animal experiments. The mice with regular estrous cycle after screening were randomized into normal, POR, and low-and high-dose(20 and 40 mg·kg~(-1), respectively) Res groups. The normal group was administrated with an equal volume of 0.9% sodium chloride solution by gavage, and the mice in other groups with tripterygium glycosides suspension(50 mg·kg~(-1)) by gavage for 2 weeks. After the modeling, the mice in low-and high-dose Res groups were treated with Res by gavage for 2 weeks, and the mice in normal and POR groups with an equal volume of 0.9% sodium chloride solution by gavage. Ovulation induction and sample collection were carried out on the day following the end of treatment. Vaginal smears were collected for observation of the changes in the estrous cycle, the counting of retrieved oocytes, and the measurement of ovarian wet weight and ovarian index. The enzyme-linked immunosorbent assay(ELISA) was employed to measure the levels of anti-mullerian hormone(AMH), follicle-stimulating hormone(FSH), estradiol(E_2), and luteinizing hormone(LH) in the serum. The ovarian tissue morphology and granulosa cell apoptosis were observed by hematoxylin-eosin(HE) staining and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL), respectively. Western blot was employed to determine the protein levels of phosphatidylinositol 3-kinase(PI3K), protein kinase B(AKT), forkhead box O(FOXO) 3a, hypoxia-inducible factor(HIF)-1α, B-cell lymphoma-2(Bcl-2), and Bcl-2-associated X protein(Bax). A total of 222 common targets shared by Res and POR were collected. GO annotation indicated that these targets were mainly involved in oxidative stress response. KEGG enrichment analysis revealed that Res can intervene in POR via PI3K/AKT, HIF-1, and FOXO signaling pathways. Animal experiments showed that the model group had higher rate of estrous cycle disorders, lower number and poorer morphology of normally developed follicles at all levels, more atretic follicles, higher apoptosis of ovarian granulosa cells, lower number of retrieved oocytes, lower ovarian wet weight and ovarian index, higher serum levels of FSH and LH, lower levels of AMH and E_2, higher expression levels of HIF-1α, FOXO3a and Bax, and lower expression levels of PI3K, AKT, and Bcl-2 in the ovarian tissue than the normal group. Compared with the POR group, low-and high-dose Res decreased the rate of estrous cycle disorders, improved the follicle number and morphology, reduced atretic follicles, promoted the apoptosis of ovarian granulosa cells, increased retrieved oocytes, ovarian wet weight and ovarian index, and lowered serum FSH and LH levels. Moreover, Res down-regulated the expression levels of HIF-1α, FOXO3a and Bax, and up-regulated the expression levels of PI3K, AKT and Bcl-2 in the ovarian tissue. In summary, Res can inhibit apoptosis and mitigate poor ovarian response in mice by regulating the PI3K/AKT/FOXO3a and HIF-1α pathways.
Female ; Mice ; Animals ; Proto-Oncogene Proteins c-akt/metabolism* ; Resveratrol/pharmacology* ; bcl-2-Associated X Protein ; Phosphatidylinositol 3-Kinases/metabolism* ; Sodium Chloride ; Follicle Stimulating Hormone ; Proto-Oncogene Proteins c-bcl-2