Difficulties In Treatment Research Articles

Challenges in Obstructive Sleep Apnea Management in Elderly Patients

With the aging of the population, obstructive sleep apnea (OSA) in elderly patients is now more commonly seen in clinical practice. In older people, sleepiness is less marked than in younger patients, but insomnia symptoms are more common. Comorbidities are numerous and related to cardiometabolic and cognitive conditions. Polygraphy can be used to establish the diagnosis in the vast majority of cases, but polysomnography is indicated in cases of comorbid sleep disorders. Continuous positive airway pressure (CPAP) remains the cornerstone of treatment, but compliance decreases with age, especially in those over 80, and when cognitive disorders are also present. In these patients, CPAP can be beneficial in terms of nighttime symptoms, sleepiness, mood, and cognition but can also prevent cardiovascular and cerebrovascular disorders, especially in severeOSA patients. For this reason, we should offer this treatment to elderly patients and devise strategies to support them with treatment difficulties (e.g., therapeutic education, adapted masks, and telemonitoring). In the future, we need prospective studies to help identify elderly patients who will gain the greatest long-term benefit from treatment. Dedicated sleep testing, OSA severity markers, and specific questionnaires need to be developed in this older, but large, OSA population.

Phage-liposome nanoconjugates for orthopedic biofilm eradication

Infection by multidrug-resistant (MDR) bacteria has become one of the biggest threats to public health worldwide. One reason for the difficulty in treatment is the lack of proper delivery strategies into MDR bacterial biofilms, where the thick extracellular polymeric substance (EPS) layer impedes the penetration of antibiotics and nanoparticles. Here, we propose a novel bioactive nanoconjugate of drug-loaded liposomes and bacteriophages for targeted eradication of the MDR biofilms in orthopedic infections. Phage Sb-1, which has the ability to degrade EPS, was conjugated with antibiotic-loaded liposomes. Upon encountering the biofilm, phage Sb-1 degrades the EPS structure, thereby increasing the sensitivity of bacteria to antibiotics and allowing the antibiotics to penetrate deeply into the biofilm. As a result, effective removal of MDR bacterial biofilm was achieved with low dose of antibiotics, which was proved in this study by both in vitro and in vivo investigations. Notably, in the rat prosthetic joint infection (PJI) model, we found that the liposome-phage nanoconjugates could effectively decrease the bacterial load in the infected area and significantly promote osteomyelitis recovery. It is therefore believed that the conjugation of bacteriophage and liposomes could open new possibilities for the treatment of orthopedic infections, possibly other infections in the deep tissues.

Trends on Novel Targets and Nanotechnology-Based Drug Delivery System in the Treatment of Parkinson's disease: Recent Advancement in Drug Development.

Parkinson's disease (PD) is a progressive neurodegenerative disorder that impacts a significant portion of the population. Despite extensive research, an effective cure for PD remains elusive, and conventional pharmacological treatments often face limitations in efficacy and management of symptoms. There has been a lot of discussion about using nanotechnology to increase the bioavailability of small- molecule drugs to target cells in recent years. It is possible that PD treatment might become far more effective and have fewer side effects if medication delivery mechanisms were to be improved. Potential alternatives to pharmacological therapy for molecular imaging and treatment of PD may lie in abnormal proteins such as parkin, α-synuclein, leucine-rich repeat serine and threonine protein kinase 2. Published research has demonstrated encouraging outcomes when nanomedicine-based approaches are used to address the challenges of PD therapy. So, to address the present difficulties of antiparkinsonian treatment, this review outlines the key issues and limitations of antiparkinsonian medications, new therapeutic strategies, and the breadth of delivery based on nanomedicine. This review covers a wide range of subjects, including drug distribution in the brain, the efficacy of drug-loaded nano-carriers in crossing the blood-brain barrier, and their release profiles. In PD, the nano-carriers are also used. Novel techniques of pharmaceutical delivery are currently made possible by vesicular carriers, which eliminate the requirement to cross the blood-brain barrier (BBB).

Infective endocarditis in injection drug users: disease course, diagnostic and clinical aspects (clinical case analysis)

Aim. To present and clinically analyze a case of “injection drug users” infective endocarditis (IE) to increase awareness among general practitioners and cardiologists about this special variant of IE.Materials and methods. Clinical observation of a 39-year-old female patient with long-term heroin and methadone addiction, viral hepatitis C, who was diagnosed with acute primary IE caused by methicillin-sensitive Staphylococcus aureus localized on the tricuspid and mitral valves. Bilateral septic pulmonary embolism and respiratory failure, secondary anemia, thrombocytopenia, nephrotic syndrome due to secondary glomerulonephritis were observed. On the 21st day of treatment, the patient underwent tricuspid valve replacement surgery with a biological prosthesis and multicomponent reconstruction of the mitral valve, the postoperative period was complicated by the development of exudative pericarditis.Results. The clinical picture and the course of a complex case of “injection drug users” IE are discussed. The difficulties of early diagnostics of IE caused by the absence of pathognomonic clinical manifestations of the disease and the variability of the debuts of IE with the prevalence of extracardiac manifestations is highlighted. The principles of antibacterial therapy and indications for surgical treatment are reviewed.Conclusion. Clinical observation draws the attention to the high probability of diagnosing IE in cases of fever in intravenous drug users and demonstrates both the difficulties of treatment and the possibility of a favorable outcome of this serious disease with timely diagnosis, appropriate antibacterial therapy, and early cardiac surgery.

Diagnosis and treatment experience of Chlamydia psittaci pneumonia: A multicenter retrospective study in China

BackgroundIn recent years, clinical cases of Chlamydia psittaci pneumonia have gradually increased. Chlamydia psittaci pneumonia can quickly progress to severe pneumonia, leading to respiratory failure. Chlamydia psittaci cannot be detected by commonly used detection methods, leading to difficulties in clinical diagnosis and treatment, which may eventually develop into severe Chlamydia psittaci pneumonia. Therefore, we should improve our diagnostic and treatment capabilities for this disease.MethodsThis article retrospectively studied 61 cases of pneumonia from 12 different provinces in China, and classified them into severe pneumonia and non-severe pneumonia. Divided into two groups, with 23 cases of severe pneumonia and 38 cases of non-severe pneumonia. We compared the two groups in terms of imaging, laboratory testing, treatment, prognosis, etc., hoping to provide better explanations and help clinical physicians better diagnose the disease.ResultsThere is no difference in age, gender, contact history, smoking history, or basic disease between severe and non-severe Chlamydia psittaci pneumonia. The most prominent symptom is fever, with a median body temperature of 39.7 ℃, and other symptoms similar to common respiratory infections. White blood cells and neutrophils may not show significant elevation, but C-reactive protein (CRP) and procalcitonin (PCT) will both show significant elevation, often accompanied by a decrease in arterial oxygen pressure. Some patients may experience liver and kidney dysfunction, but there is no statistically significant difference between the two groups. Doxycycline remains the preferred drug for severe Chlamydia psittaci pneumonia. The imaging mainly shows consolidation and bronchial inflation sign, and may also present with pleural effusion.ConclusionsThe imaging of Chlamydia psittaci pneumonia usually shows consolidation with bronchial inflation sign, which can also be manifested as ground glass changes or solid masses. Atypical images are prone to misdiagnosis in the early stages. There are some differences in laboratory examination and imaging between severe pneumonia and non-severe pneumonia, which can help identify severe patients in the early stage. Metagenomic next-generation sequencing (mNGS) played an important role in the diagnosis of all cases in this article. Timely treatment has a good prognosis for the disease, and imaging lesions can be completely absorbed.

Comorbidities and Treatment Outcomes in Patients Diagnosed with Drug-Resistant Tuberculosis in Rural Eastern Cape Province, South Africa.

Tuberculosis (TB) remains a significant global health challenge, with drug-resistant tuberculosis (DR-TB) posing a greater threat due to difficulty in treatment. This study aimed to investigate the relationship between comorbidities and treatment outcomes in patients diagnosed with DR-TB in rural Eastern Cape using logistic regression. Data on patient characteristics, comorbidities, and treatment outcomes were extracted from the medical records and analyzed using Python version 3.8. and R version 4.1.1 software. A logistic regression model was used to determine the effects of selected variables on treatment outcomes of DR-TB cases. Hearing loss and hypertension (HTN) were the most frequently observed comorbidities across various DR-TB cases, particularly rifampicin-resistant (RR), multidrug-resistant (MDR), and pre-extensively drug-resistant (pre-XDR-TB) cases. A hearing loss prevalence of 5.8% (26/445) was found among patients receiving treatment for TB, with the intensity of impairment ranging from mild to severe. Gender is significantly associated with the occurrence of HTN among these patients (p-value: 0.022). Comorbidities such as epilepsy, hearing loss, and HTN significantly impact treatment success, with higher risks of mortality and incomplete cure. Using logistic regression, obesity (OR = 3.0884; e = 1.1277; p = 0.0408) and HIV-positive status (OR = 0.4458; e = 0.8078; p = 0.0001) were highly likely and less likely associated with better treatment outcomes, respectively. The logistic regression model achieved an accuracy of 64.0%, a precision of 63.0%, and a recall of 95.0%, with an F-1 score of 76.0%. The findings underscore the importance of implementing integrated management strategies that address both DR-TB and its comorbidities, particularly in resource-limited settings where such patients are prevalent. Public health policies should incorporate strategies to provide nutritional assessments and interventions, particularly for individuals with low BMI. This could include food supplementation programs or partnerships with local food kitchens to ensure that patients have access to adequate nutrition during DR-TB treatment.

Pediatric eosinophilic esophagitis: a Belgian single-center retrospective analysis reveals real-life difficulties in diagnosis and treatment.

Eosinophilic esophagitis (EoE) is a chronic immune-mediated disorder characterized by eosinophilic infiltration of the esophageal mucosa. This study aimed to provide insights into the clinical characteristics, diagnostic evaluation, treatment modalities, and outcomes of EoE in a pediatric population through a retrospective analysis of 79 patients followed in a single tertiary referral center between 2014 and 2020. As expected, a higher male prevalence was observed. Median age at diagnosis was 8.9 years, aligning with the typical presentation in childhood, emphasizing the need for early recognition. Clinical presentation varied, with vomiting, dysphagia, and abdominal pain being the most frequently reported symptoms. IgE-sensitization, food allergy and atopy were highly prevalent, with cow's milk, wheat, egg, soy, and peanuts being the most common allergens. Endoscopy results mostly revealed macroscopic abnormalities with linear furrows and microabscesses/white plaques being the most common features although a significant proportion of initial endoscopies (14/79) showed no macroscopic abnormalities, highlighting the importance of esophageal biopsies. Proton pump inhibitors (PPIs) were commonly used as a first-line treatment, with most patients receiving PPI therapy. Other treatment modalities, such as oral budesonide and exclusion diets either single or in combination, were also used. Remission was achieved in 69/79 or 87% patients, with different treatment regimens contributing to successful outcomes but subject to relapse upon time. This study provides valuable insights into the clinical characteristics, diagnostic evaluation, treatment modalities, and outcomes of EoE in the pediatric population. It underscores the importance of early recognition, accurate diagnosis, and regular follow-up to effectively manage this chronic immune-mediated disorder but also demonstrates its complexity in real-life clinical setting.

Revisiting tuberculosis as a cause of gastric outlet obstruction: Insights from a case report.

Gastroduodenal tuberculosis (GD-TB) is exceptionally rare. The clinical manifestations of gastrointestinal TB are diverse and non-specific, which makes diagnosis difficult, leading to delayed diagnosis and high mortality. As a peer-reviewer of World Journal of Clinical Cases, I would like to share my opinion on the article published by this journal. The patient had no family history of TB or contact with people with TB. Primary GD-TB presenting as gastric outlet obstruction and normal findings of thoracic computed tomography increased the difficulty of diagnosis and treatment in this patient. The diagnosis and treatment scheme of this typical case have reference value for the clinical treatment of GD-TB.

NVESTIGAÇÃO CLÍNICA DE DOENÇA INFLAMATÓRIA INTESTINAL EM CÃES (DII): ESTUDO DE CASO

Inflammatory Bowel Disease (IBD) in dogs is a chronic condition that affects the gastrointestinal tract, manifesting through symptoms such as diarrhea, vomiting, and weight loss. This case study aims to analyze the occurrence of IBD in a dog, highlighting the difficulties in early diagnosis and appropriate treatment. The medical record of a dog with chronic gastrointestinal symptoms was reviewed, focusing on the tests performed and the treatment administered. The analysis revealed shortcomings in the diagnostic process, including the underutilization of complementary tests, such as endoscopy with biopsy, and the lack of early referral to a veterinary gastroenterology specialist. The study emphasizes the importance of a specific clinical protocol for differential diagnosis and appropriate treatment of IBD.

Enhanced Brain Tumor Detection and Privacy Preserving Using Federated Learning

Brain cancers pose significant difficulties for both diagnosis and treatment, underscoring the necessity for precise and private-protecting detection techniques. Federated learning is used to solve this, allowing several healthcare facilities to work together to train detection models without jeopardizing patient privacy. This paper presents an approach called federated learning that may be used to improve brain tumor identification while protecting patient privacy. Brain tumors are dangerous medical disorders that need to be accurately diagnosed in order to be effectively treated. However, sharing private patient information is a common practice in traditional medical data analysis methodologies, which raises privacy issues. Federated learning helps with this by enabling cooperative training of a common model amongst several hospitals or institutions without requiring the exchange of raw data. This method protects patient privacy by having each institution train the model using its own local data and only sharing model updates. We show through trials that our method is efficient in reliably identifying brain tumors while upholding privacy norms, presenting a viable option for improving medical diagnosis without jeopardizing patient privacy.

Clinical and etiological characteristics and cytokine profile in school-age children with community-acquired pneumonia

The urgent task of modern pediatrics is the study of the etiology and pathophysiology of community-acquired pneumonia in school-aged children due to difficulties in diagnosis and treatment, as well as the high risk of life-threatening complications and death.Purpose. To investigate the activity of pro-inflammatory and anti-inflammatory responses as measured by cytokine levels in the peripheral blood of children with community-acquired pneumococcal and non-pneumococcal pneumonia.Material and methods. The etiology of community-acquired pneumonia was confirmed by comparing the results of rapid testing of pneumococcus in urine and data from traditional bacteriological methods. The study included 118 children (57 boys and 61 girls) aged 7 to 16 years with various morphological variants of community-acquired pneumonia, which were divided into 2 groups. The first group included 28 children with pneumococcal etiology of community-acquired pneumonia, and the second group included 90 patients with non-pneumococcal community-acquired pneumonia. Levels of interleukins IL-1, IL-4, IL-8 and TNF-α were determined in all children by enzyme immunoassays.Results. In the etiology of community-acquired pneumonia in school-age children, atypical pathogens are responsible for more than 50% of cases. The clinical effectiveness of rapid testing of pneumococcal antigens in urine has been shown, and their use in routine pediatric practice has made it possible to timely identify a group of severe community-acquired pneumonia and reasonably prescribe antibacterial medications. It has been demonstrated that pneumococcal-induced pneumonia is characterized by higher levels of proinflammatory cytokines. These levels, along with the clinical course of the disease, confirm the high level of systemic inflammation. Relatively lower levels of proinflammatory cytokines corresponded to a more mild clinical picture of community-acquired pneumonia of non-pneumococcal etiology, which on the one hand may reflect a relatively «balanced» inflammatory response, and on the other hand determine the protracted and polyclinic course of the infectious process.Conclusion. The etiology of community-acquired pneumonia in school-age children is dominated by atypical pathogens. Community-acquired pneumonia of pneumococcal etiology has more severe clinical courses, and their early identification will allow for the appropriate prescription of initial antibacterial treatment.

EXTH-28. DEVELOPING A NOVEL INJECTABLE IMMUNOTHERAPEUTIC GEL FOR ENCAPSULATION OF NATURAL KILLER CELLS FOR POST-SURGICAL GLIOBLASTOMA TREATMENT

Abstract Malignant brain tumors are one of the leading causes of death among all cancers. Approximately 40,000 people are diagnosed with malignant brain tumors every year. Among these patients, 15,000 cases are glioblastoma (GBM) with a very poor prognosis; even after aggressive surgical resection and adjuvant chemo/radiotherapy, the median survival is only 14.6 months. The major reason for poor prognosis is the blood-brain barrier, which prevents therapeutic agents from reaching the target area. Therefore, there are only a few choices of drugs available for brain tumor treatment. To date, temozolomide (TMZ) and the Gliadel wafer have been clinically used as standard chemotherapy agents after brain tumor resection. However, drug resistance to TMZ and the poor drug diffusion rate of the Gliadel wafer still result in ineffective suppression of residual cancer cells. To overcome the above-mentioned difficulties in clinical brain tumor treatment, in situ self-crosslinking multifunctional hydrogels was developed to carry natural killer cells (NK cells) and radiosensitizers as a novel brain tumor treatment system. Unlike traditional hydrogels catalyzed by pH value or temperature, this new system is stable and consistent as an immune cell carrier. We used fibrinogen, thrombin, and alginic acid as the backbone of the in situ self-crosslinking hydrogel, tested the properties of the synthesized hydrogel, and analyzed the gel-formation time and swelling rate. The release rate of NK cells was also examined. In a brain tumor animal model, the use of hydrogel-NK cells significantly inhibited tumor proliferation and prolonged animal survival time. In conclusion, this therapeutic hydrogel carrying NK cells can serve as a novel post-operation adjuvant therapeutic tool for malignant brain tumors.

Retreatment and aesthetic restoration of maxillary incisor with calcified root canal using a dynamic navigation system: a case report

BackgroundPulp canal occlusion (PCO) increases the difficulty of root canal treatment as well as tooth preservation and restoration. This is the first case report of successful localization of a calcified root canal under the guidance of a dynamic navigation system (DNS) for complete root canal retreatment and aesthetic restoration after a failed attempt to locate the calcified root canal with a traditional dental operating microscope (DOM).Case presentationThe patient was scheduled for root canal treatment for a labially inclined maxillary central incisor and post-core crown restoration with resin veneers in another hospital, but the calcified root canal could not be located with a microscope, so the patient was referred to our department. Root canal retreatment was planned for tooth #8, and the calcified root canal of tooth #9 was planned to be located and dredged under the guidance of a DNS. We used a DNS for successful positioning and to complete the root canal retreatment operation in the following 4 steps: preoperative CBCT imaging, preoperative plan design, calibration and registration, and real-time dynamic navigation. Three months later, teeth #8 and #9 presented no clinical symptoms, after which the fiber post-cores and zirconia all-ceramic crown restorations were completed. At the 12-month follow-up visit, the patient continued to be symptom­free, and satisfied with the final aesthetic restoration.ConclusionsThis case report suggests that DNS may be a promising technique with high accuracy and effectiveness to reduce the risk of iatrogenic errors and provide maximal preservation of dentin, when the traditional treatment of calcified root canals approaches failure (lateral perforation).

Multiple system atrophy

Multiple systemic atrophy (MSA) is a rapidly progressive neurodegenerative disease characterized by the presence of autonomic dysfunction and movement disorders. It occurs in adults in most cases and is manifested by various clinical syndromes with varying degrees of severity, such as parkinsonism, cerebellar dysfunction, autonomic insufficiency, and urogenital and corticospinal dysfunction. Difficulties in diagnosis and treatment are largely due to incomplete understanding of pathogenesis. This review summarizes current literature on etiological, including genetic, risk factors, pathogenesis, clinical presentation, diagnosis, differential diagnosis, and treatment options for MSA.

Features of endodontic treatment of teeth with curved root canals according to a survey of dentists

Purpose: to identify difficulties of endodontic treatment of teeth with curved root canals according to a survey of dentists. Materials and methods: 90 dentists (26 men, 64 women) participated in the survey. 68 people had a therapeutic certificate, 19 people had an orthopedic certificate, 10 people had a surgical certificate, 6 people had a certificate in pediatric dentistry, and 43 people had a certificate in general dentistry (some respondents indicated that they had several certificates). The average age of respondents is 32 years (23–60). The interviewed dentists conduct practical work in public medical institutions, private dental clinics, and rented offices. The questionnaire included 20 questions (6 questions were aimed at collecting demographic data, 14 questions were aimed at obtaining information about the treatment of teeth with curved root canals). The questionnaire was submitted electronically to Google Forms. Statistical analysis of conjugacy tables using the Pearson chi-square test was performed using the program StatTech (Russia). Results: this survey reliably showed that dentists often experience difficulties in treating teeth with curved root canals. Dentists working in state institutions are significantly more likely to note that the rubberdam latex interferes (p= 0.049) and the clamp bow (p= 0.029) compared to doctors working in other institutions. Dentists working in a rented office are significantly more likely to report that a rubberdam latex interferes (p= 0.024) compared to doctors working in other institutions. Dentists who report difficult access when working with the mesial buccal canal of the lower molars are significantly more likely to note that a rubberdam latex interferes (p= 0.036). Dentists who use the approach «first negotiation to the working length – then coronal flaring» significantly more often experience difficulties when working with the mesial buccal first canal of the upper molars. Conclusions: the results of the survey demonstrated a number of differences in the performance of endodontic treatment of teeth with curved root canals. Based on the survey, statistically significant relationships were identified between some work features and difficulties encountered by doctors at the stages of treatment.

Presurgery and postsurgery: advancements in artificial intelligence and machine learning models for enhancing patient management in infective endocarditis.

Infective endocarditis (IE) is a severe infection of the inner lining of the heart, known as the endocardium. It is characterized by a range of symptoms and has a complicated pattern of occurrence, leading to a significant number of deaths. IE poses significant diagnostic and treatment difficulties. This evaluation examines the utilization of artificial intelligence (AI) and machine learning (ML) models in addressing IE management. It focuses on the most recent advancements and possible applications. Through this paper, the authors observe that AI/ML can significantly enhance and outperform traditional diagnostic methods leading to more accurate risk stratification, personalized therapies, as well and real-time monitoring facilities. For example, early postsurgical mortality prediction models like SYSUPMIE achieved 'very good' area under the curve (AUROC) values exceeding 0.81. Additionally, AI/ML has improved diagnostic accuracy for prosthetic valve endocarditis, with PET-ML models increasing sensitivity from 59 to 72% when integrated into ESC criteria and reaching a high specificity of 83%. Furthermore, inflammatory biomarkers such as IL-15 and CCL4 have been identified as predictive markers, showing 91% accuracy in forecasting mortality, and identifying high-risk patients with specific CRP, IL-15, and CCL4 levels. Even simpler ML models, like Naïve Bayes, demonstrated an excellent accuracy of 92.30% in death rate prediction following valvular surgery for IE patients. Furthermore, this review provides a vital assessment of the advantages and disadvantages of such AI/ML models, such as better-quality decision support approaches like adaptive response systems on one hand, and data privacy threats or ethical concerns on the other hand. In conclusion, Al and ML must continue, through multicentric and validated research, to advance cardiovascular medicine, and overcome implementation challenges to boost patient outcomes and healthcare delivery.

Evaluation of Fuel Consumption and Exhaust Emissions in a Single Cylinder Four-Stroke Diesel Engine Using Biodiesel Derived from Chicken Waste with Additives

Biodiesel is a renewable, locally generated fuel made from vegetable oils, trans fats, or recycled restaurant grease for use in diesel automobiles and other diesel-powered equipment. The physical qualities of biodiesel are comparable to those of petroleum diesel. Biodiesel is used in compression-ignition engines in the same way as petroleum diesel. Biofuel can be made from biomass, but according to the Indian National Policy on Biofuels, biofuel extraction from edible oils is not permitted because it would result in a massive increase in consumer goods prices and perhaps lead to product scarcity. Hence, there is a need to search for alternative biofuel so that it does not affect our nation's national policy. Recently there has been a drastic increase in the consumption of chicken grown in farms. There is a huge problem in disposing of their waste. One major difficulty in waste treatment is poultry manure, often known as slaughter waste. This waste is sometimes dumped on wastelands, roadsides, and the banks of rivers, lakes, and ponds. This creates more sanitary problems for society. According to polls, poultry feces begin to decompose in around three hours. The odor of butcher's waste causes a lot of pollution in the air, as well as an increase in the density of bacteria in the atmosphere. Measures have been taken by the government for the safe disposal of these wastes. One of the major ways of disposal is to recycle this chicken slaughter waste in a useful manner so that it can serve society in a positive way. This could be done by converting this waste into fuel through various processes such as rendering, hydrolysis, extraction, acid esterification, alkaline transesterification, and finally by the extraction process. This produced fuel could be blended with existing diesel in varying concentrations and used in diesel engine-powered vehicles. In this work, the fuel is extracted from the chicken waste and blended with pure diesel and an Al2O3 additive in various proportions. These combinations are then tested on a single-cylinder diesel engine for fuel consumption and emission analysis. The results exhibited an overall better performance when compared to pure diesel.

Targeting Wnt Pathways with Small Molecules as New Approach in Cardiovascular Disease.

The increasing incidences of morbidity and mortality associated with cardiovascular diseases represent significant difficulties for clinical treatment and have a major impact on patient health. Wnt signaling pathways are highly conserved and are well known for their regulatory roles in embryonic development, tissue regeneration, and adult tissue homeostasis. Wnt signaling is classified into two distinct pathways: canonical Wnt/β-catenin signaling and noncanonical pathways, including planar cell polarity and Wnt/Ca2+ pathways. A growing body of experimental evidence suggests the involvement of both canonical and non-canonical Wnt signaling pathways in the development of cardiovascular diseases, including myocardial hypertrophy, arrhythmias, diabetic cardiomyopathy, arrhythmogenic cardiomyopathy, and myocardial infarction. Thus, to enhance patient quality of life, diagnosing and treating cardiac illnesses may require a thorough understanding of the molecular functions played by the Wnt pathway in these disorders. Many small-molecule inhibitors specifically target various components within the Wnt signaling pathways, such as Frizzled, Disheveled, Porcupine, and Tankyrase. This study aims to present an overview of the latest findings regarding the functions of Wnt signaling in human cardiac disorders and possible inhibitors of Wnt, which could lead to novel approaches for treating cardiac ailments.

The Survival and Medical Dilemma of Rare Disease Patients in the Greater Bay Area

The population of rare disease patients in China faces many difficulties in disease diagnosis and treatment, medical security, economic burden, quality of life, social assistance, employment opportunities, mental health, and other aspects. It is of great significance to identify the common problems faced by this group and try to propose possible solutions, calling on all sectors of society to pay attention to the rare disease minority group, help them solve their survival and security difficulties, and enable more patients to return to society. This paper investigates and addresses the survival and security challenges faced by rare disease minority patients in the Guangdong-Hong Kong-Macao Greater Bay Area (GBA) of China. Through a survey of 223 rare disease patients in the Greater Bay Area, the study reveals that these patients face many challenges in diagnosis, treatment, drug access, and economic support. The conclusion emphasizes the necessity of improving diagnostic efficiency, accelerating drug development, and improving the medical insurance system. Thus, it further puts forward practical suggestions.

Comprehensive Analysis of Prognostic Alternative Splicing Signatures in Tumor Immune Infiltration in Bladder Cancer.

Bladder cancer exhibits substantial heterogeneity encompassing genetic expressions and histological features. This heterogeneity is predominantly attributed to alternative splicing (AS) and AS-regulated splicing factors (SFs), which, in turn, influence bladder cancer development, progression, and response to treatment. This study aimed to explore the immune landscape of aberrant AS in bladder cancer and establish the prognostic signatures for survival prediction. Bladder cancer-related RNA-Seq, transcriptome, and corresponding clinical information were downloaded from The Cancer Genome Atlas (TCGA). Gene set enrichment analysis (GSEA) was used to identify significantly enriched pathways of cancer-related AS events. The underlying interactions among differentially expressed genes (DEGs) and cancer-related AS events were assessed by a protein-protein interaction network. Univariate and multivariate Cox regression analyses were performed to identify crucial prognostic DEGs that co-occurred with cancer-related AS events (DEGAS) for overall survival. The area under the curve (AUC) of receiver operating characteristic (ROC) curves was used to assess the efficiency of the prognostic signatures. The CIBERSORT algorithm was used to explore the abundance of immune infiltrating cells. A total of 3755 cancer-related AS events and 3110 DEGs in bladder cancer were identified. Among them, 379 DEGs co-occurred with cancer-related AS events (DEGAS), of which 102 DEGAS were associated with 14 dysregulated SFs. GSEA and KEGG analysis showed that cancer-related AS events were predominantly enriched in pathways related to immunity, tumorigenesis, and treatment difficulties of bladder cancer. Multivariate Cox regression analysis identified 8 DEGAS (CABP1, KCNN2, TNFRSF13B, PCDH7, SNRPA1, APOLD1, CX3CL1, and DENND5A) significantly associated with OS, and they were further integrated into the prediction model with good AUCs at 3-year, 5-year and 7-year ROC curves (all>0.7). Immune infiltration analysis revealed the significant enrichment of three immune cell types (B cells naïve, dendritic cells resting, and dendritic cell activated) in high-risk bladder cancer patients. This study not only unveiled comprehensive prognostic signatures of AS events in bladder cancer but also established a robust prognostic model based on survival-related DEGAS. These aberrant AS events, dysregulated SFs, and the identified 8 DEGAS may have significant clinical potential as therapeutic targets for bladder cancer.