Polyketides from the mangrove-derived fungus Penicillium robsamsonii HNNU0006.

Seven polyketides, including an undescribed depsidone (1) and six previously reported 3,6,8-trihydroxy-1-methylxanthone (2), 7-hydroxy-2-(2-hydroxypropyl)-5-methylchromone (3), methyl3-chloro-6-hydroxy-2-(4-hy-droxy-2-methoxy-6-methylphenoxy)-4- methoxybenzoate (4), xylarianin A (5), 4,5-dihydroxy-6-(6'-methylsalicyloxy)-2-hydro-xymethyl-2-cyclohexen-1-one (6) and alternariol (7), have been isolated from cultures of the mangrove-derived fungus Penicillium robsamsonii HNNU0006. The structure of compound 1 was elucidated by extensive spectroscopic analysis and X-ray crystallography. Furthermore, all the compounds were evaluated their cytotoxic activities, and compounds 1 and 7 showed weak cytotoxicity against two cell lines Vero and A549 with IC50 values ranging from 95.6 and 296.5 µM, relative to the positive control Etoposide phosphate with IC50 values of 24.5 and 18.7 µM, respectively.

Potential role of molecular hydrogen therapy on oxidative stress and redox signaling in chronic kidney disease.

Oxidative stress plays a key role in chronic kidney disease (CKD) development and progression, inducing kidney cell damage, inflammation, and fibrosis. However, effective therapeutic interventions to slow down CKD advancement are currently lacking. The multifaceted pharmacological effects of molecular hydrogen (H2) have made it a promising therapeutic avenue. H2 is capable of capturing harmful •OH and ONOO- while maintaining the crucial reactive oxygen species (ROS) involved in cellular signaling. The NRF2-KEAP1 system, which manages cell redox balance, could be used to treat CKD. H2 activates this pathway, fortifying antioxidant defenses and scavenging ROS to counteract oxidative stress. H2 can improve NRF2 signaling by using the Wnt/ß-catenin pathway and indirectly activate NRF2-KEAP1 in mitochondria. Additionally, H2 modulates NF-κB activity by regulating cellular redox status, inhibiting MAPK pathways, and maintaining Trx levels. Treatment with H2 also attenuates HIF signaling by neutralizing ROS while indirectly bolstering HIF-1α function. Furthermore, H2 affects FOXO factors and enhances the activity of antioxidant enzymes. Despite the encouraging results of bench studies, clinical trials are still limited and require further investigation. The focus of this review is on hydrogen's role in treating renal diseases, with a specific focus on oxidative stress and redox signaling regulation, and it discusses its potential clinical applications.

Effect of spectacle correction on hyperopic children.

Background: Hyperopia is a significant refractive error in children, often leading to vision impairment. This study aimed to investigate whether partial or full spectacle correction is benefit for hyperopia in preschool-aged children. Methods: A retrospective study was conducted on hyperopic children visited to teaching medical center outpatient clinic between October 2011 and October 2018, and were categorized into three groups: full correction, overcorrection, and undercorrection. The study was approved by the institutional ethical committee of Tri-Service General Hospital. Results: Following a minimum of one-year follow-up period, no statistically significant differences were observed in best-corrected visual acuity (BCVA) among children receiving full, over, or under spectacle correction. Notably, the overcorrection group exhibited a significant reduction in spherical equivalent (SE) compared to both the full and under correction groups, indicating a better SE with spectacle overcorrection. Conclusions: Spectacle overcorrection may offer potential benefits for enhancing SE in preschool children with hyperopia. Nevertheless, further investigation through randomized controlled trials is warranted to establish the validity of this approach and its impact on visual outcomes in this hyperopic pediatric population.

The Association between Diabetic Retinopathy and Macular Degeneration: A Nationwide Population-Based Study.

OBJECTIVE: Age-related macular degeneration (AMD), particularly its exudative form, is a primary cause of vision impairment in older adults. As diabetes becomes increasingly prevalent in aging, it is crucial to explore the potential relationship between diabetic retinopathy (DR) and AMD. This study aimed to assess the risk of developing overall, non-exudative, and exudative AMD in individuals with DR compared to those without retinopathy (non-DR) based on a nationwide population study in Taiwan. METHODS: A retrospective cohort study was conducted using the Taiwan National Health Insurance Database (NHIRD) (2000-2013). A total of 3413 patients were placed in the study group (DR) and 13,652 in the control group (non-DR) for analysis. Kaplan-Meier analysis and the Cox proportional hazards model were used to calculate the hazard ratios (HRs) and adjusted hazard ratios (aHRs) for the development of AMD, adjusting for confounding factors, such as age, sex, and comorbid conditions. RESULTS: Kaplan-Meier survival analysis indicated a significantly higher cumulative incidence of AMD in the DR group compared to the non-DR group (log-rank test, p < 0.001). Adjusted analyses revealed that individuals with DR faced a greater risk of overall AMD, with an aHR of 3.50 (95% CI = 3.10-3.95). For senile (unspecified) AMD, the aHR was 3.45 (95% CI = 3.04-3.92); for non-exudative senile AMD, it was 2.92 (95% CI = 2.08-4.09); and for exudative AMD, the aHR was 3.92 (95% CI = 2.51-6.14). CONCLUSION: DR is a significant risk factor for both overall, senile, exudative, and non-exudative AMD, even after adjusting for demographic and comorbid conditions. DR patients tend to have a higher prevalence of vascular comorbidities; however, our findings indicate that the ocular pathologies inherent to DR might have a more significant impact on the progression to AMD. Early detection and appropriate treatment of AMD is critically important among DR patients.

Alkaloid-metabolites from the mangrove-derived fungus Penicillium robsamsonii HNNU0006.

Nine metabolites, including three undescribed alkaloids pyripyropenes VW (1-2), penicioxa A (4), two previously reported pyripyropene A (3), oxaline (5), three grisephenone-type xanthone derivatives (6-8), and a diphenyl ether derivative 4-chloro-7,4'-dihydroxy-5,2'-dimethoxy-2-methylformate-6'-methybenzophone (9), were isolated from cultures of the mangrove-derived fungus Penicillium robsamsonii HNNU0006. Their structures were determined by spectroscopic analysis, ECD calculations, together with DP4+ probability analysis. Furthermore, all the isolated compounds were tested for cytotoxicity and anti-phytopathogenic fungal activities. Compounds 6-8 showed moderate cytotoxicity against tumor cell lines A549, with IC50 values ranging from 5.68 ± 0.21 to 9.71 ± 0.34 µg/mL, respectively.

Polystyrene microplastic-induced extracellular vesicles cause kidney-related effects in the crosstalk between tubular cells and fibroblasts.

Plastic waste accumulation and its degradation into microplastics (MPs) and nanoplastics (NPs) pose environmental concerns. Previous studies have indicated that polystyrene (PS)-MPs harm living animals. Extracellular vesicles (EVs) are associated with metabolic reprogramming and mitochondrial dysfunction in various kidney diseases. In this article, we evaluated how PS-MPs affected tubular cells and fibroblasts. The results demonstrated that PS-MPs increased EV production in human tubular cells and caused endoplasmic reticulum (ER) stress-related proteins without inducing inflammation-related proteins in human tubular cells. The uptake of PS-MPs and incubation with the conditioned medium of PS-MPs induced reactive oxygen species (ROS) production and ER stress-related proteins in fibroblast cells. The fibroblast cells treated with the conditioned medium of PS-MPs also increased the expression of fibrosis-related proteins. Our findings suggested that the expression of EV-related markers increased in tubular cells via Beclin 1 after PS-MP treatment. In addition, PS-MPs induced ROS production in vitro and in vivo. We found that PS-MPs also altered the expression of EV markers in urine, and CD63 expression was also increased in vitro and in vivo after PS-MP treatment. In conclusion, PS-MP-induced EVs lead to ER stress-related proteins, ROS production and fibrosis-related proteins in tubular cells and fibroblasts.

The influence of uremic toxins on low bone turnover disease in chronic kidney disease.

Uremic toxins play a crucial role in the development of low bone turnover disease in chronic kidney disease (CKD) through the induction of oxidative stress. This oxidative stress disrupts the delicate balance between bone formation and resorption, resulting in a decline in both bone quantity and quality. Reactive oxygen species (ROS) activate nuclear factor kappa-B and mitogen-activated protein kinase signaling pathways, promoting osteoclastogenesis. Conversely, ROS hinder osteoblast differentiation by facilitating the binding of Forkhead box O proteins (FoxOs) to ß-catenin, triggering apoptosis through FoxOs-activating kinase phosphorylation. This results in increased osteoblastic receptor activator of nuclear factor kappa-B ligand (RANKL) expression and decreased nuclear factor erythroid 2-related factor 2 levels, compromising antioxidant defenses against oxidative damage. As CKD progresses, the accumulation of protein-bound uremic toxins such as indoxyl sulfate (IS) and p-cresyl sulfate (PCS) intensifies oxidative stress, primarily affecting osteoblasts. IS and PCS directly inhibit osteoblast viability, induce apoptosis, decrease alkaline phosphatase activity, and impair collagen 1 and osteonectin, impeding bone formation. They also reduce cyclic adenosine 3',5'-monophosphate (cAMP) production and lower parathyroid hormone (PTH) receptor expression in osteoblasts, resulting in PTH hyporesponsiveness. In summary, excessive production of ROS by uremic toxins not only reduces the number and function of osteoblasts but also induces PTH hyporesponsiveness, contributing to the initiation and progression of low bone turnover disease in CKD.

Sleep Duration and Kidney Function - Does Weekend Sleep Matter?

Objective: Weekend sleep duration is linked to health issues, including mortality. However, how weekend sleep duration can impact chronic kidney disease (CKD) still needs to be understood. Therefore, we aimed to analyze how weekend sleep duration is associated with kidney function. Methods: This is a cross-sectional study. Data were obtained from the 2017-2018 National Health and Nutrition Examination Survey. We included 5362 study participants and categorized them into nine subgroups by sleep duration (short: ≤6 hours, normal: 6-9 hours, and long: ≥9 hours) on weekdays and weekends and analyzed for the respective association with renal function using stratified multivariable linear regression. Results: Weekend sleep duration for 9 hours or more was associated with decreasing estimated glomerular filtration rate (eGFR) levels by 2.8 to 6.4 mL/min/1.73 m2 among people with long to short weekday sleep duration compared with short weekday and weekend sleep durations (control group) after adjusting for demographic characteristics, body measurement, sleep quality, smoking, and comorbidities. The study population with short weekday sleep duration (sWK) and long weekend sleep duration (lWD) had the most significant decline in eGFR. For the study population with sWK, eGFR level significantly decreased by 1.1 mL/min/1.73 m2 as sleep duration on weekends increased by one hour. Conclusion: The underlying mediators of lWD and CKD could be the dysregulation of human behaviors, metabolism, or biological functions. Longer weekend sleep duration was linked to a decrease in eGFR levels. It warrants further study to clarify the mediators.

Drimane-type sesquiterpenoids and their anti-inflammatory evaluation from Pyrrhoderma noxium HNNU0524.

Chemical investigation of a culture broth from the marine-derived fungus Pyrrhoderma noxium HNNU0524 yielded two new compounds including a drimane-type sesquiterpenoid named pyrrnoxin A (1) and a benzoic acid derivative, pyrrnoxin B (5), together with three related known analogues (2-4). The chemical structures of 1 and 5 were determined by detailed analysis of spectroscopic data, single-crystal X-ray crystallography, quantum mechanics-based DP4+ and ECD calculations. Compounds 2 and 3 moderately inhibited NO production of lipopolysaccharide-induced microglia cells BV2 with IC50 values of 26.6 and 60.5 µM, respectively.

Effects of different storage and transportation devices on the temperatures of “internet plus drug delivery”in hospital under high-temperature conditions in summer / 中国药房

OBJECTIVE To explore suitable storage and transportation conditions for “internet plus drug delivery” under high- temperature conditions. METHODS A survey on high-temperature conditions in summer in Beijing was conducted； a retrospective analysis was conducted on “internet plus drug delivery” orders in our hospital from July 2021 to June 2022， summarizing the proportion and delivery range of drugs under different storage and transportation conditions. Additionally， simulation and validation experiments were performed to investigate optimal drug storage and transportation devices for “internet plus drug delivery” in Beijing under high-temperature conditions in summer. RESULTS The monthly average temperature in Beijing from June to August consistently exceeded 25.0 ℃ between 1991 and 2022. From July 2021 to June 2022， a total of 104 drugs were required to be stored below 25.0 ℃， accounting for 31.23% of the 333 drugs listed in our hospital’s “internet plus drug delivery” catalog in Beijing. These drugs were delivered 1 058 times， accounting for 19.63% of the total deliveries. Simulation and validation experiments demonstrated that the average maximum temperature during the next-day delivery process of “carton + foam box + composite aluminum film pearl cotton + 500 g ice bag×2 + gas column bag” was 9.6 ℃， the average minimum temperature was 2.7 ℃， and all the temperatures remained below 15.0 ℃， which could effectively ensure the quality of drugs. CONCLUSIONS Under the high-temperature conditions in summer in Beijing， the storage and transportation device of “carton + foam box + composite aluminum film pearl cotton + 500 g ice bag×2 + gas column bag” can meet the temperature requirements specified in the drug storage instructions for Beijing intra-city drug delivery.

Targeting Diverse Wounds and Scars: Recent Innovative Bio-design of Microneedle Patch for Comprehensive Management.

Wounds and the subsequent formation of scars constitute a unified and complex phased process. Effective treatment is crucial; however, the diverse therapeutic approaches for different wounds and scars, as well as varying treatment needs at different stages, present significant challenges in selecting appropriate interventions. Microneedle patch (MNP), as a novel minimally invasive transdermal drug delivery system, has the potential for integrated and programmed treatment of various diseases and has shown promising applications in different types of wounds and scars. In this comprehensive review, the latest applications and biotechnological innovations of MNPs in these fields are thoroughly explored, summarizing their powerful abilities to accelerate healing, inhibit scar formation, and manage related symptoms. Moreover, potential applications in various scenarios are discussed. Additionally, the side effects, manufacturing processes, and material selection to explore the clinical translational potential are investigated. This groundwork can provide a theoretical basis and serve as a catalyst for future innovations in the pursuit of favorable therapeutic options for skin tissue regeneration.

Influenza vaccination is associated with lower risk of renal cell carcinoma among chronic kidney disease patients: a population-based cohort study.

Background: Chronic kidney disease (CKD) patients possess a higher risk for renal cell carcinoma (RCC) possibly because of related underlying inflammation and immune dysregulation. In the current population-based cohort study, we evaluate the effects of influenza vaccination on RCC among CKD patients. Methods: We analysed the vaccinated and unvaccinated CKD patients (≥55 years of age) identified from the Taiwan National Health Insurance Database. Propensity score matching was used to reduce the selection bias. Subgroup analyses based on comorbid conditions, dialysis status and vaccinated dosages were also conducted. Results: The incidence of RCC decreased significantly in the vaccinated compared with unvaccinated group {unadjusted hazard ratio [HR] 0.50 [95% confidence interval (CI) 0.31-0.81], P < .01; adjusted HR 0.46 [95% CI 0.28-0.75], P < .01}. Such protective effects of influenza vaccination were noted significantly among those ≥75 years of age [unadjusted HR 0.29 (95% CI 0.12-0.74), P < .01; adjusted HR 0.22 (95% CI 0.08-0.58), P < .01]. A reverse association was noted between the total number of vaccinations and RCC events in both unadjusted and adjusted models. The Kaplan-Meier estimates of the RCC events showed significantly higher free survival rates in the vaccinated as compared with the unvaccinated patients (logrank P = .005). Conclusion: This population-based cohort study found a significant inverse relationship between influenza vaccination and the risk of RCC in CKD patients and the protective effects were more prominent in patients >75 years of age. A possible relation exists between the total number of vaccinations and RCC events. Future randomized clinical and basic studies will be needed to prove these findings and underlying pathophysiological mechanisms.

Currently Used Methods to Evaluate the Efficacy of Therapeutic Drugs and Kidney Safety.

Kidney diseases with kidney failure or damage, such as chronic kidney disease (CKD) and acute kidney injury (AKI), are common clinical problems worldwide and have rapidly increased in prevalence, affecting millions of people in recent decades. A series of novel diagnostic or predictive biomarkers have been discovered over the past decade, enhancing the investigation of renal dysfunction in preclinical studies and clinical risk assessment for humans. Since multiple causes lead to renal failure, animal studies have been extensively used to identify specific disease biomarkers for understanding the potential targets and nephropathy events in therapeutic insights into disease progression. Mice are the most commonly used model to investigate the mechanism of human nephropathy, and the current alternative methods, including in vitro and in silico models, can offer quicker, cheaper, and more effective methods to avoid or reduce the unethical procedures of animal usage. This review provides modern approaches, including animal and nonanimal assays, that can be applied to study chronic nonclinical safety. These specific situations could be utilized in nonclinical or clinical drug development to provide information on kidney disease.

[Direct and Indirect Effects of Land Use on Dissolved Organic Matter in a Typical Karst River].

Land use can directly affect the abundance of riverine dissolved organic matter (DOM) by transporting terrestrial organic matter to rivers and can also indirectly enhance local production of DOM by increasing riverine nutrient loading. This study investigated the characteristics and spatial distribution of DOM components in the Furong River during the rainy season (July) using ultraviolet-visible light absorption spectroscopy (UV-VIS) and three-dimensional excitation emission matrix fluorescence spectroscopy-parallel factor analysis (EEM-PARAFAC) techniques. Furthermore, correlation analysis and the partial least squares path model (PLS-PM) were used to identify and quantify the direct and indirect impacts of land use on DOM at multiple scales. The results revealed that:① the direct effects of land use on DOM were generally stronger than the indirect effects. ② The responses of different DOM components to riverine nutrient status and land use varied, with dissolved organic carbon (DOC) and colored dissolved organic matter (CDOM) components being more susceptible to riverine nutrient status and fluorescent dissolved organic matter (FDOM) being more sensitive to land use. ③ The direct impact intensity of land use on DOC and CDOM fluctuated slightly with the spatial scale, but the total impact intensity had no visible spatial scale difference, and the direct impact intensity on the FDOM component decreased with the increase in spatial scale. ④ Dryland, urban and other construction land, patch density (PD), edge density (ED), and Shannon's diversity index (SHDI) were typical land use metrics that exacerbated DOM abundance, whereas paddy field, shrubland, largest patch index (LPI), and aggregation index (AI) were typical land use metrics that effectively mitigated DOM abundance. Total nitrogen (TN), nitrate nitrogen (NO3--N), and dissolved total phosphorus (DTP) were water quality parameters that were significantly affected by land use and were closely related to DOM components, that is, nitrogen and phosphorus played an important "intermediary" role in "land use-riverine DOM." FDOM could be used as indicators to measure the strength of terrestrial organic matter directly input to rivers by land use.

Effect of Annual Influenza Vaccination on the Risk of Lung Cancer Among Patients With Hypertension: A Population-Based Cohort Study in Taiwan.

Objectives: Lung cancer is a main contributor to all newly diagnosed cancers worldwide. The chemoprotective effect of the influenza vaccine among patients with hypertension remains unclear. Methods: A total of 37,022 patients with hypertension were retrospectively enrolled from the Taiwan National Health Insurance Research Database. These patients were further divided into a vaccinated group (n = 15,697) and an unvaccinated group (n = 21,325). Results: After adjusting for sex, age, comorbidities, medications, level of urbanization and monthly income, vaccinated patients had a significantly lower risk of lung cancer occurrence than unvaccinated patients (adjusted hazard ratio [aHR]: 0.56, 95% confidence interval [CI]: 0.47-0.67). A potential protective effect was observed for both sexes and in the elderly age group. With a greater total number of vaccinations, a potentially greater protective effect was observed (aHR: 0.75, 95% CI 0.60-0.95; aHR: 0.66, 95% CI: 0.53-0.82; aHR: 0.26, 95% CI: 0.19-0.36, after receiving 1, 2-3 and ≥4 vaccinations, respectively). Conclusion: Influenza vaccination was associated with a lower risk of lung cancer among patients with hypertension. The potentially chemoprotective effect appeared to be dose dependent.

Indoxyl sulfate induced frailty in patients with end-stage renal disease by disrupting the PGC-1α-FNDC5 axis.

OBJECTIVE: Sarcopenia or frailty is common among patients with chronic kidney disease (CKD). The protein-bound uremic toxin indoxyl sulfate (IS) is associated with frailty. IS induces apoptosis and disruption of mitochondrial activity in skeletal muscle. However, the association of IS with anabolic myokines such as irisin in patients with CKD or end-stage renal disease (ESRD) is unclear. This study aims to elucidate whether IS induces frailty by dysregulating irisin in patients with CKD. MATERIALS AND METHODS: The handgrip strength of 53 patients, including 28 patients with ESRD, was examined. Serum concentrations of IS and irisin were analyzed. CKD was established in BALB/c mice through 5/6 nephrectomy. Pathologic analysis of skeletal muscle was assessed through haematoxylin and eosin and Masson's trichrome staining. Expression of peroxisome proliferator-activated receptor-gamma coactivator PGC-1α and irisin were analyzed using real-time polymerase chain reaction and Western blotting. RESULTS: Handgrip strength was lower among patients with ESRD than among those without ESRD. In total, 64.3% and 24% of the patients in the ESRD and control groups had low handgrip strength, respectively (p < 0.05). Serum concentrations of IS were significantly higher in the ESRD group than in the control group (222.81 ± 90.67 µM and 23.19 ± 33.28 µM, respectively, p < 0.05). Concentrations of irisin were lower in the ESRD group than in the control group (64.62 ± 32.64 pg/mL vs. 99.77 ± 93.29 pg/mL, respectively, p < 0.05). ROC curves for low handgrip strength by irisin and IS were 0.298 (95% confidence interval (CI): 0.139-0.457, p < 0.05) and 0.733 (95% CI: 0.575-0.890, p < 0.05), respectively. The percentage of collagen was significantly higher in mice with 5/6 nephrectomy than in the control group. After resveratrol (RSV) treatment, the percentage of collagen significantly decreased. RSV modulates TGF-ß signaling. In vitro analysis revealed that IS treatment suppressed expression of PGC-1α and FNDC5 in a dose-dependent manner, whereas RSV treatment attenuated IS-induced phenomena in C2C12 cells. CONCLUSION: IS was positively correlated with frailty in patients with ESRD through the modulation of the PGC-1α-FNDC5 axis. RSV may be a potential drug for reversing IS-induced suppression of the PGC-1α-FNDC5 axis in skeletal muscle.

Systematic Appraisal of Guidelines for the Diagnosis and Treatment of Choledocholithiasis.

BACKGROUND: To systematically evaluate the methodological quality of the current up-to-date guidelines pertaining to choledocholithiasis, we conducted a comprehensive analysis of key recommendations and corresponding evidence, focusing on the heterogeneity among these guidelines. METHOD: Systematic searches across various databases were performed to identify the latest guidelines. The identified guidelines, which met the inclusion criteria, underwent evaluation using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool. The key recommendations and evidence from the included guidelines were extracted and reclassified using the Oxford Centre for Evidence-Based Medicine (OCEBM) grading system, and the obtained results were analyzed. RESULTS: Nine guidelines related to choledocholithiasis were included in this study, out of which 4 achieved an overall standardized score of more than 60%, indicating their suitability for recommendation. Upon closer examination of the main recommendations within these guidelines, we discovered significant discrepancies concerning the utilization of similar treatment techniques for different diseases or different treatment methods under comparable conditions, and discrepancies in the recommended treatment duration. High-quality research evidence was lacking, and some recommendations either failed to provide supporting evidence or cited inappropriate and low-level evidence. CONCLUSION: The quality of guidelines pertaining to choledocholithiasis is uneven. Recommendations for the treatment of choledocholithiasis demonstrate considerable disparities among the guidelines, particularly regarding the utilization of endoscopic retrograde cholangiopancreatography as a treatment method and the management approaches for difficult stone cases. Improvements by guideline developers for these factors contributing to the heterogeneity would be a reasonable approach to further update the guidelines for cholangiolithiasis.

Transitions of dialysis status and outcomes after the unplanned first dialysis: a nationwide population-based cohort study.

In Taiwan, most first-time dialysis was started without the creation of an arteriovenous shunt. Here, we aimed to elucidate the transitions of dialysis status in the unplanned first dialysis patients and determine factors associated with their outcomes. A total of 50,315 unplanned first dialysis patients aged more than 18 years were identified from the National Health Insurance Dataset in Taiwan between 2001 and 2012. All patients were followed for 5 years for the transitions in dialysis status, including robust (dialysis-free), sporadic dialysis, continued dialysis, and death. Furthermore, factors associated with the development of continued dialysis and death were examined by the Cox proportional hazard models. After 5 years after the first dialysis occurrence, there were 5.39% with robust status, 1.67% with sporadic dialysis, 8.45% with continued dialysis, and 84.48% with death. Notably, we have identified common risk factors for developing maintenance dialysis and deaths, including male gender, older age, diabetes, coronary heart disease, stroke, heart failure, sepsis, and surgery. There was an extremely high mortality rate among the first unplanned dialysis patients in Taiwan. Less than 10% of these patients underwent continued dialysis during the 5-year follow-up period. This study highlighted the urgent need for interventions to improve patient outcomes.

Drug repurposing screens to identify potential drugs for chronic kidney disease by targeting prostaglandin E2 receptor.

Renal inflammation and fibrosis are significantly correlated with the deterioration of kidney function and result in chronic kidney disease (CKD). However, current therapies only delay disease progression and have limited treatment effects. Hence, the development of innovative therapeutic approaches to mitigate the progression of CKD has become an attractive issue. To date, the incidence of CKD is still increasing, and the biomarkers of the pathophysiologic processes of CKD are not clear. Therefore, the identification of novel therapeutic targets associated with the progression of CKD is an attractive issue. It is a critical necessity to discover new therapeutics as nephroprotective strategies to stop CKD progression. In this research, we focus on targeting a prostaglandin E2 receptor (EP2) as a nephroprotective strategy for the development of additional anti-inflammatory or antifibrotic strategies for CKD. The in silico study identified that ritodrine, dofetilide, dobutamine, and citalopram are highly related to EP2 from the results of chemical database virtual screening. Furthermore, we found that the above four candidate drugs increased the activation of autophagy in human kidney cells, which also reduced the expression level of fibrosis and NLRP3 inflammasome activation. It is hoped that these findings of the four candidates with anti-NLRP3 inflammasome activation and antifibrotic effects will lead to the development of novel therapies for patients with CKD in the future.

The importance of temperature monitoring in predicting wound healing.

CONCLUSION: Upon wound formation, the wound temperature rises in the first 3-4 days until reaching its peak. It then falls at about one week after wound formation. In the second week after wound formation, the wound temperature decreases steadily to the baseline indicating a good wound condition and progression towards healing. While a continuous high temperature is often a sign of excessive inflammation or infection, which indicates urgent need of intervention and treatment.