Based on the traditional Chinese medicine(TCM) theory of "kidney-brain interaction", a two-sample Mendelian randomization(MR) analysis was conducted to investigate the causal effects of chronic kidney disease(CKD) on Alzheimer's disease(AD) and analyze the potential mechanisms of kidney-tonifying and essence-replenishing TCM to improve AD. From the perspective that CKD is closely related to the core pathogenesis of AD, namely "kidney deficiency, essence loss, and marrow reduction", genome-wide association study(GWAS) data was used, with the inverse variance weighting(IVW) method as the main approach to reveal the causal association between CKD and AD. Sensitivity analysis was conducted to evaluate the robustness of the results. To further investigate the causal effects of CKD on AD, two different AD datasets were used as outcomes, and the urinary albumin-to-creatinine ratio(UACR) data was used as the exposure for a supplementary analysis. On this basis, the modern scientific mechanism of the kidney-tonifying and essence-replenishing method for improving AD was further explored. The IVW analysis show that CKD(ieu-b-2: OR=1.084, 95%CI[1.011, 1.163], P=0.024; ieu-b-5067: OR=1.001, 95%CI[1.000, 1.001], P=0.002) and UACR(ieu-b-2: OR=1.247, 95%CI[1.021, 1.522], P=0.031; ieu-b-5067: OR=1.001, 95%CI[1.000, 1.003], P=0.015) both have significant causal effects on AD in different datasets, with CKD increasing the risk of AD. The sensitivity analysis further confirmed the reliability of the results. Genetic studies have shown that CKD has a significant causal effect on AD, suggesting that controlling CKD is an important intervention measure for preventing and treating AD. Therefore, further research on CKD's role in AD is crucial in clinical practice. The research enriches the theoretical implication of "kidney-brain interaction", deepens the understanding of AD' etiology, and provides further insights and directions for the prevention and treatment of AD with TCM, specifically from a kidney-based perspective.
Humans ; Alzheimer Disease/genetics* ; Renal Insufficiency, Chronic/genetics* ; Kidney/metabolism* ; Brain/physiopathology* ; Genome-Wide Association Study ; Medicine, Chinese Traditional ; Mendelian Randomization Analysis

This study explored the efficacy and mechanisms of Shenqi Buqi Granules in treating chronic heart failure(CHF) of Qi deficiency using proteomics and bioinformatics methods. A total of 18 healthy participants(health group) and 19 patients with Qi deficiency-type CHF(experimental group) were enrolled and treated with Shenqi Buqi Granules for 12 weeks. Clinical indicators, including Qi deficiency scores, complete blood count, biochemical parameters, lipid profiles, and cardiac function, were collected from pre-and post-experimental groups. Serum proteomics analysis was performed. Differential proteins were screened through differential analysis and K-means clustering. Further analyses, including subcellular localization, Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment, and protein-protein interaction(PPI) network construction, were conducted to identify pathways and proteins associated with Shenqi Buqi Granules treatment. Spearman correlation analysis focused on proteins most correlated with the core phenotype of CHF of Qi deficiency. The results show that Shenqi Buqi Granules treatment reduced Qi deficiency scores and brain natriuretic peptide levels of pre-experimental group. A total of 1 594 proteins were quantified in the proteomics analysis, with 98 proteins showing differential expression between healthy group and experimental group before and after treatment. Subcellular localization analysis revealed 6 protein sources, while KEGG pathway enrichment highlighted biological processes including angiogenesis, immune inflammation, calcium homeostasis, cytoskeletal regulation, protein synthesis, and energy metabolism. Core genes identified included CD34, CSF1, CALM1, CALML3, PPP1CA, PFN1, and 3 ribosomal large subunit proteins. Correlation analysis between core proteins and Qi deficiency scores revealed that CD34(r=-0.67, P<0.05) and PPP1CA(r=0.62, P<0.01) were most strongly associated with Qi deficiency scores. This study suggests that Shenqi Buqi Granules improves Qi deficiency scores and CHF symptoms by regulating angiogenesis, immune inflammation, calcium homeostasis, cytoskeletal regulation, protein synthesis, and energy metabolism. CD34 and PPP1CA are identified as core proteins involved in the therapeutic effects of Shenqi Buqi Granules on Qi deficiency.
Humans ; Drugs, Chinese Herbal/therapeutic use* ; Heart Failure/metabolism* ; Male ; Female ; Proteomics ; Middle Aged ; Qi ; Aged ; Protein Interaction Maps/drug effects* ; Adult ; Chronic Disease

This study adopted a three-dimensional "effect-dose-mechanism" evaluation system to screen the optimal regimen of Yuxuebi Tablets(YXB) combined with ibuprofen(IBU) for chronic musculoskeletal pain(CMP) intervention and elucidate its pharmacological mechanism, so as to provide a scientific basis for the clinical application of the regimen. The experiments were conducted using 8-week-old ICR mice, which were randomly divided into sham operation(sham) group, model(CFA) group, IBU group, YXB group, stasis paralysis tablets combined with ibuprofen low-dose group(IBU-L-YXB), stasis paralysis combined with ibuprofen high-dose group(IBU-H-YXB), stasis paralysis tablets combined with ibuprofen high-dose with ibuprofen discontinuation on the 10th day of administration(IBU-10-YXB), and stasis paralysis tablets combined with ibuprofen high-dose with ibuprofen halving on the 10th day of administration(IBU-1/2-YXB) group. An animal model was established using the CFA plantar injection method. On D0(the second day post-modeling), the success of model establishment was assessed, followed by continuous drug administration for 18 consecutive days from D1 to D18. During this period, mechanical pain threshold was measured by the Von Frey test; thermal hyperalgesia was detected by the hot plate test, and depression-like behavior was observed by the tail suspension test. After treatment, peripheral blood was collected from all groups for complete blood biochemical analysis, and the injected feet of the sham, CFA, IBU, YXB, IBU-YXB, and IBU-10-YXB groups were subjected to oxylipin metabolomics analysis. Immunofluorescence double staining was further performed to detect the co-expression of key oxylipin metabolic enzymes(COX2, LTA4H, and 5/12/15-LOX) and macrophage marker CD68 in the sham, CFA, IBU, and YXB-L/M/H groups. Subsequently, confirmatory analysis of positive indicators was conducted in the sham, CFA, IBU, YXB, IBU-YXB, and IBU-10-YXB groups. On D6(acute phase), mechanical pain sensitivity data showed that compared with the CFA group, only the three combination groups(IBU-YXB, IBU-10-YXB, and IBU-1/2-YXB) exhibited significantly increased paw withdrawal thresholds. On D17(chronic phase), only the IBU-10-YXB group showed a mechanical pain threshold significantly higher than all other monotherapy and combination groups. On D17, thermal pain data showed that compared with the CFA group, all groups except IBU-1/2-YXB had significantly prolonged paw withdrawal latency. On D18, tail suspension data showed that compared with the CFA group, the YXB, IBU-YXB, and IBU-10-YXB groups had significantly reduced immobility time. In summary, IBU-10-YXB stably improved the core symptoms of acute and chronic inflammatory pain. Complete blood count data showed that compared with the sham group, the CFA group had significantly increased mean platelet volume(MPV), while compared with the CFA group, the IBU-YXB and IBU-10-YXB groups had significantly reduced MPV. Moreover, the platelet distribution width(PDW) of the IBU-10-YXB group was further reduced compared with the CFA group. These data suggest that the IBU-10-YXB combination regimen has superior effects on inflammation and blood circulation improvement compared with other treatment groups. At the mechanistic level, each treatment group differentially regulated pro-inflammatory and pro-resolving oxylipin(SPM). Specifically, compared with the CFA group, the IBU and IBU-YXB groups significantly inhibited the synthesis of the prostaglandin family downstream of COX2, reducing pro-inflammatory oxylipins PGD2 and 6-keto-PGF1α but inhibiting PGE1 and PGE2, which played positive roles in peripheral circulation, vasodilation, and inflammation resolution. Compared with the CFA group, the YXB group tended to inhibit the pro-inflammatory oxylipin LTB4 downstream of LTA4H and increase SPMs such as LXA4. The IBU-10-YXB group bidirectionally regulated pro-inflammatory oxylipins and SPMs. Compared with IBU, IBU-10-YXB significantly inhibited the pro-inflammatory mediator 5-HETE. Meanwhile, IBU-10-YXB broadly upregulated SPMs, as evidenced by significant upregulation of LXA4 compared with the CFA group, significant upregulation of LXA5 compared with the IBU and IBU-YXB groups, significant upregulation of RvD1 compared with the CFA group and all other treatment groups, and significant upregulation of RvD5 compared with the sham group. Immunofluorescence double staining results were as follows: compared with the CFA group, the IBU group specifically inhibited the oxylipin metabolic enzyme COX2. In the YXB group, COX2, LTA4H, and 5/12-LOX were significantly inhibited. Within the optimal analgesic dose range, YXB's inhibitory effects on COX2 and LTA4H were dose-dependent, while its inhibitory effects on 5/12-LOX were inversely dose-dependent. The two combination groups(IBU-YXB and IBU-10-YXB) inhibited COX2 and LTA4H without significantly affecting 5-LOX, while IBU-10-YXB further significantly inhibited 12-LOX. These results suggest that the IBU-10-YXB combination regimen effectively maintains stable inhibition of COX2, LTA4H, and 12-LOX while enhancing 5-LOX expression. This combinatorial strategy effectively suppresses pro-inflammatory oxylipins and promotes SPM biosynthesis, overcoming IBU's analgesic ceiling effect and its blockade of pain resolution pathways while compensating for YXB's inability to effectively intervene in acute pain and inflammation. Therefore, it achieves more stable anti-inflammatory, analgesic, and antidepressant effects.
Animals ; Ibuprofen/administration & dosage* ; Mice ; Mice, Inbred ICR ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Musculoskeletal Pain/immunology* ; Tablets ; Humans ; Chronic Pain/metabolism* ; Drug Therapy, Combination ; Disease Models, Animal

The efficacy mechanism of the alcoholic extract of Gnaphalium affine was investigated by observing its influence on oxidative stress and intestinal flora in rats modeled for chronic obstructive pulmonary disease(COPD). UPLC-MS was used to evaluate the quality of the alcoholic extract of G. affine, and 72 rats were randomly divided into six groups, with COPD models established in five groups by cigarette smoke combined with airway drip lipopolysaccharide, and the rats were given the positive drug of Danlong Oral Solution, as well as low-, medium-, and high-doses alcoholic extract of G. affine, respectively. After two weeks of continuous gastric gavage, the body weights and general morphology observations were performed; HE staining and Masson staining were used to verify the effects of the alcoholic extract of G. affine on alveolar inflammation and collagen deposition area in COPD rats; the oxidative stress indexes CAT and GSH in serum and SOD and MDA in lung tissue of the rats were measured, and the mRNA expression of HO-1, Nrf2, and NQO1 were determined by qRT-PCR. The protein expressions of HO-1, Nrf2, and NQO1 were determined by the Western blot method, and the mechanism by which the alcoholic extract of G. affine affected oxidative stress in COPD rats was explored. Finally, the influence of G. affine on the changes in intestinal flora caused by COPD was studied by 16S rRNA sequencing. The results showed that a total of 121 chemical components were identified by UPLC-MS, including 70 positive and 51 negative ion modes. In animal experiments, it was found that the alcoholic extracts of G. affine were able to reduce the percentage of collagen deposition, affect the oxidative stress indexes such as CAT, GSH, SOD, MDA, as well as the mRNA and protein expression of Nrf2, HO-1, and NQO1. The 16S rRNA sequencing results showed an increase in the level of Lactobacillales and a decrease in the level of Desulfovibrio and Desulfovibrionales, suggesting that the alcoholic extracts of G. affine could reverse the changes in intestinal flora caused by COPD. In conclusion, the alcoholic extracts of G. affine may exert anti-COPD effects by affecting the oxidative stress pathway and modulating the changes in intestinal flora.
Animals ; Oxidative Stress/drug effects* ; Pulmonary Disease, Chronic Obstructive/genetics* ; Rats ; Male ; Gastrointestinal Microbiome/drug effects* ; Rats, Sprague-Dawley ; Drugs, Chinese Herbal/administration & dosage* ; NF-E2-Related Factor 2/metabolism* ; Humans ; Lung/metabolism*

INTRODUCTION

Chronic Kidney Disease (CKD) is a leading cause of morbidity and mortality in the Philippines. Most Filipino CKD patients prefer hemodialysis due to barriers such as cost and availability of Kidney Transplant. End-stage kidney disease (ESKD) patients face high symptom burden and unmet palliative care needs. Even with advancement in dialysis technology, the annual mortality rate of dialysis patients remains between 20% and 25%. While Advance Care Planning (ACP) can help align care with patient preferences by facilitating discussions about values and future decisions, its utilization in dialysis population remains low due to barriers in implementation. There is limited research specifically addressing the preferences and influencing factors of Advance Care Planning among CKD patients on hemodialysis in the Philippines.

This study aimed to determine the ACP preferences of CKD patients undergoing hemodialysis and to identify the clinicodemographic factors associated with these preferences.

An analytic cross-sectional study was conducted involving 96 chronic kidney disease (CKD) patients undergoing hemodialysis at Baguio General Hospital and Medical Center (BGHMC) from October to November 2024. Data were collected using validated questionnaires administered either through face-to-face interviews or self-administration, depending on patients’ preferences and capabilities. Descriptive and inferential statistical methods were employed for data analysis.

The study revealed limited awareness of ACP among participants (86.5%), underscoring the need for education. Family-centered decision-making was prominent, with most participants preferring family members as surrogate decision-makers and confidants. Quality of life was prioritized over life extension, and preferences for “Do Not Resuscitate” (DNR) orders were notable. Educational attainment and ethnicity significantly influenced preferences, with higher education linked to greater awareness; and Ethnicity shaping preferences for decision-makers, confidants, timing of discussions, and resuscitation choices. Additionally, duration of dialysis was linked to care setting preferences, while social support systems influenced the preferred place for discussions.

The findings highlight critical associations between clinicodemographic factors and ACP preferences among hemodialysis patients. Addressing these associations through targeted education and culturally sensitive approach can promote high-quality end-of-life care, aligned with diverse patient needs, values, and preferences.

BACKGROUND

Chronic Kidney Disease (CKD) patients often face critical treatment decisions that significantly affect their quality of life, making Shared Decision-Making (SDM), a collaborative approach between patients and healthcare providers, an essential component of patient-centered care.

This study aimed to investigate the impact of SDM on decisional readiness and patient satisfaction among CKD patients undergoing hemodialysis (HD) at Southern Isabela Medical Center (SIMC).

An analytical cross-sectional design was utilized. The Tagalog Version of SDM Q-9 questionnaire, Decision survey and CSAT survey tool were given to HD patients of SIMC from September – October 2024. Descriptive statistics, Pearson product-moment correlation and chi square test were used to report and analyze data.

One hundred eight (108) CKD patients on HD were included in the study. Shared decision-making score was high and overall satisfaction on health services was outstanding. Higher decisional readiness was associated with greater odds of reporting outstanding satisfaction (OR = 3.47, 95% CI: 2.563–4.688, p = 0.009). There was no significant association between patient satisfaction and SDM (r= 0.111, p =0.253.). Shared decision-making had a significant but weak positive correlation with decisional readiness (r =0.2043, p 0.035).

This study showed that fostering SDM positively enhances patients’ preparedness to make healthcare decisions. Decisional readiness is strongly associated with patient satisfaction, as confident patients are more likely to be satisfied with their care. The findings underscore the need for improved patient education to boost decisional readiness and support ongoing SDM practices. Integrating SDM into clinical workflows is essential to advancing patient-centered care and improving health outcomes for CKD patients undergoing hemodialysis.

Peripheral nerve block (PNB) has been successfully used as the sole anesthetic for Peritoneal dialysis (PD) catheter insertion, and has been shown to provide satisfactory anesthesia and analgesia perioperatively, especially among critically – ill patients.

This report describes the anesthetic management of an 18 – year old underweight patient with End-stage renal disease (ESRD) and decompensated heart failure who was scheduled for PD catheter insertion. He was given a left lateral Transversus abdominis plane (TAP) block and a right Rectus sheath (RS) block as the main anesthetic. Fifteen mL of Isobaric Bupivacaine 0.375% with Epinephrine 1:400,000 dilution was injected for the TAP block, and 10mL for the RS block, for a total volume of 25mL (93.7mg). Sedation was given via a Remifentanil infusion at 0.1mcg/kg/min. Intraoperatively, the patient was awake, conversant, and comfortable, no pressors were used, and no conversion to general anesthesia was done. Post-operatively, he had good pain control, with a pain score of 1/10, and successfully underwent dialysis via the PD catheter on the 2ndhospital day.

This pediatric patient who is critically ill is not a good candidate for general or neuraxial anesthesia due to the risk of hemodynamic instability and perioperative decompensation. PNB was done to provide anesthesia, and ensure good pain control post-operatively, and a right TAP and left RS were done instead of a bilateral TAP to lower the LA volume and decrease the risk of LA toxicity.

Unilateral TAP with contralateral RS is a safe anesthetic technique among critically-ill pediatric patients who will undergo PD catheter insertion without the risk of hemodynamic instability with general or neuraxial anesthesia.

OBJECTIVES: To analyze the differentially expressed exosomal miRNAs in patients with chronic heart failure (CHF) complicated by hyperuricemia (HUA) and explore their potential as novel diagnostic molecular markers and their target genes. METHODS: This study was conducted among 30 CHF patients with HUA (observation group) and 30 healthy volunteers (control group) enrolled between September, 2020 and September, 2023. Peripheral blood samples were collected from 6 CHF patients with HUA for analyzing exosomal miRNAs by high-throughput sequencing, and the results were validated in the remaining 24 patients using qRT-PCR. GO and KEGG enrichment analyses were performed to predict the the target genes of the identified differential miRNAs. We also validated the differentially expressed miRNAs by animal experiment. RESULTS: A total of 42 differentially expressed exosomal miRNAs were detected in observation group by high-throughput sequencing; among them, miR-27a-5p was significantly upregulated (P=0.000179), and miR-139-3p was significantly downregulated (P=0.000058). In the 24 patients with both CHF and PUA, qRT-PCR validated significant upregulation of miR-27a-5p (P=0.004) and downregulation of miR-139-3p (P=0.005) in serum exosomes. When combined, miR-27a-5p and miR-139-3p had a maximum area under the curve (AUC) of 0.899 (95% CI: 0812-0.987) for predicting CHF complicated by HUA. GO and KEGG enrichment analyses suggested that the differential expressions of miR-27a-5p and miR-139-3p was associated with the activation of the AMPK-mTOR signaling pathway to activate the autophagic response. We obtained the same conclusion from animal experiment. CONCLUSIONS Upregulated exosomal miR-27a-5p combined with downregulated exosomal miR-139-3p expression can serve as a novel molecular marker for diagnosis of CHF complicated by HUA, and their differential expression may promote autophagy in cardiomyocytes by activating the AMPK-mTOR signaling pathway.
Humans ; Hyperuricemia/diagnosis* ; Heart Failure/genetics* ; MicroRNAs/metabolism* ; Exosomes/metabolism* ; Chronic Disease ; Male ; Female ; Middle Aged ; Animals

OBJECTIVES: To identify the key genes and immunological pathways shared by type 2 diabetes mellitus (T2DM) and chronic obstructive pulmonary disease (COPD) and explore the potential therapeutic targets of T2DM complicated by COPD. METHODS: GEO database was used for analyzing the gene expression profiles in T2DM and COPD to identify the common differentially expressed genes (DEGs) in the two diseases. A protein-protein interaction network was constructed to identify the candidate hub genes, which were validated in datasets and disease sets to obtain the target genes. The diagnostic accuracy of these target genes was assessed with ROC analysis, and their expression levels and association with pulmonary functions were investigated using clinical data and blood samples of patients with T2DM and COPD. The abundance of 22 immune cells was analyzed with CIBERSORT algorithm, and their relationship with the target genes was examined using correlation analysis. DGIdb database was used for analyzing the drug-gene interactions and the druggable genes followed by gene set enrichment analysis. RESULTS: We identified a total of 175 common DEGs in T2DM and COPD, mainly enriched in immune- and inflammation-related pathways. Among these genes, CXCL12 was identified as the final target gene, whose expression was elevated in both T2DM and COPD (P<0.05) and showed good diagnostic efficacy. Immune cell infiltration correlation analysis showed significant correlations of CXCL12 with various immune cells (P<0.01). GESA analysis showed that high CXCL12 expression was significantly correlated with "cytokine-cytokine receptor interaction". Drug-gene analysis showed that most of CXCL12-related drugs were not targeted drugs with significant cytotoxicity. CONCLUSIONS CXCL12 is a potential common key pathogenic gene of COPD and T2DM, and small-molecule targeted drugs against CXCL12 can provide a new strategy for treatment T2DM complicated by COPD.
Humans ; Pulmonary Disease, Chronic Obstructive/complications* ; Diabetes Mellitus, Type 2/genetics* ; Chemokine CXCL12/metabolism* ; Protein Interaction Maps ; Gene Expression Profiling

INTRODUCTION

It is anticipated that Chronic Obstructive Pulmonary Disease (COPD) has greater risk in acquiring COVID-19 infection and poorer outcome. However, current worldwide data are conflicting.

This study primarily aims to compare the outcomes of COVID-19 patients with COPD and those without COPD in terms of length of hospital stay (LOS), recovery or mortality, treatment received, and predictors of mortality.

This is a retrospective cohort chart review of 1,017 admitted adult COVID-19 patients from July to December 2020. Age, gender, smoking status, current control and medications for COPD, COVID-19 severity, symptoms, treatment, and outcomes of the two study groups were compared.

Prevalence rate of COPD was 3.8%. COVID-19 patients with COPD were older (median age of 69 vs 54, pCONCLUSION

COPD increases the risk for severe COVID-19 and lengthens LOS.