Assessment of the approach to managing medical emergencies during dental procedures.

OBJECTIVE: This study aims to investigate the knowledge of dental interns and post-graduated doctors regarding dental emergencies and their occurrence in the clinic and examine the doctors' ability to intervene in these emergencies. METHODS: Note that, 150 dental interns and 101 post-graduated doctors were surveyed with sixteen questions regarding their knowledge and experience with syncope, orthostatic hypotension, myocardial infarction, angina pectoris, asthma, and anaphylactic shock. Also, post-graduate doctors answered nine additional questions about their emergency response capabilities. RESULTS: This study found that interns and doctors exhibited similar knowledge about emergencies. Nonetheless, the count of dental interns encountering emergencies is relatively limited. Syncope was the most frequently encountered condition (61.8%). Doctors' increase in years of experience correlated positively with a higher rate of intervention in epilepsy, orthostatic hypotension, and anaphylactic shock (p = 0.001, 0.024, and 0.02, respectively). The ability to check the carotid pulse and to perform intramuscular injections was high in post-graduated doctors (90.09% and 81.2%, respectively). DISCUSSION: Although interns believe their knowledge about emergencies to be sufficient, their intervention skills may need to be improved due to the low frequency of encounters. After graduation, their inability to intervene adequately during emergencies in the clinic can lead to fatal consequences. The lack of improvement in doctors' knowledge and intervention abilities with experience could be attributed to insufficient training after completing their formal education. To prevent such scenarios, regular training sessions should be provided to interns and doctors, focusing on the emergencies they may encounter.

Clinical research progress on ß-cell dysfunction in T2DM development in the Chinese population.

The prevalence of type-2 diabetes mellitus (T2DM) has increased over 10-fold in the past 40 years in China, which now has the largest T2DM population in the world. Insulin resistance and ß-cell dysfunction are the typical features of T2DM. Although both factors play a role, decreased ß-cell function and ß-cell mass are the predominant factors for progression to T2DM. Considering the differences between Chinese T2DM patients and those of other ethnicities, it is important to characterize ß-cell dysfunction in Chinese patients during T2DM progression. Herein, we reviewed the studies on the relationships between ß-cell function and T2DM progression in the Chinese population and discussed the differences among individuals of varying ethnicities. Meanwhile, we summarized the risk factors and current treatments of T2DM in Chinese individuals and discussed their impacts on ß-cell function with the hope of identifying a better T2DM therapy.

Evaluating Vacuum and Steam Heat to Eliminate Pinewood Nematodes in Naturally Infested Whole Pine Logs.

Pinewood nematodes threaten forest health and continue to interfere with international trade because they can be spread around the globe via nematode-infested wood. International Standards for Phytosanitary Measure (ISPM-15) requires that all pine wood be treated at 56°C for 30 min to ensure that all pests and pathogens are killed within sawn wood, whereas fumigation with methyl bromide is the currently approved practice and widely used in treating whole logs. A method of treatment that uses less energy and time or does not rely on environmentally damaging gases is urgently needed. Because vacuum with steam has shown promise in treating several different commodities, the purpose of this study was to use it to eradicate pinewood nematodes in whole logs. Three protocols were applied: 1) 48°C for 15 min., 2) 56°C for 30 min., and 3) 60°C for 60 min. The third protocol reduced the population to statistically zero; however, some samples contained at least 1 survivor. Unfortunately, these surviving nematodes increased in number one month after treatment, and one year later, they continued to reproduce in the wood. Therefore, this protocol needs to be further refined to remove pinewood nematodes completely. Explanation of the survival of individual nematodes within whole logs remains a matter for conjecture: 1) certain portions of the wood were somehow insulated from the heat and did not achieve the lethal temperature, and 2) survival stages may be able to survive temperatures that are deadly to the normal life stages.

Cognitive Decline in Ageing and Disease: Risk factors, Genetics and Treatments.

Aging is the primary risk factor for cognitive decline, impacting multiple cognitive domains and significantly elevating the risk of conditions such as mild cognitive impairment and dementia. In addition to aging, several diseases contribute to cognitive decline. Alzheimer's disease, a progressive neurodegenerative disorder, leads to the loss of neurons and synapses in the brain, resulting in a profound decline in cognitive abilities and functional capacity. Several studies provide compelling evidence that modifiable lifestyle factors play a crucial role in influencing cognitive health. Adopting healthier behaviors has been shown to significantly reduce the risk of cognitive decline. Genetic factors also play a crucial role in cognitive decline, with several genes being identified that influence the risk of developing conditions like Alzheimer's disease and other dementias. Long-term use of opioids and cocaine is also associated with cognitive decline, affecting functions such as memory and executive processes. Understanding the factors contributing to cognitive decline in aging and disease is essential for developing strategies to mitigate its impact. The drugs available to treat patients with cognitive decline due to advanced aging and drug abuse are also summarize.

Temperature as an effective biosecurity tool against invasive snakes.

The application of thermal treatments could serve as a biosecurity tool to avert snake introduction, which often leads to irreversible ecological impacts. Here, we tested the applicability of conductive heating and thermal fumigation to prevent the spread of the California kingsnake (Lampropeltis californiae), a damaging species established on the island of Gran Canaria, likely to reach other vulnerable regions, and included among the most concerning invasive species of the European Union. We exposed 24 individuals to a thermal gradient to determine species selected temperatures, range of preferred temperatures and voluntary thermal maximum and used other 24 individuals to analyse their response to conductive heating, thermal fumigation and control (no heat) treatments. Lampropeltis californiae selected temperatures of 27.80 ± 1.05 °C (ranging 26.86 °C ± 1.21 °C to 28.68 °C ± 1.25 °C) and a voluntary thermal maximum of 32.50 ± 3.69 °C. Conductive heating and thermal fumigation performed equally well, inducing the exit of 83.33% and 91.67% of all individuals after 14.36 ± 9.25 min and 11.13 ± 8.60 min of exposition, and at a body temperature of 35.66 ± 3.53 °C and 35.57 ± 2.41 °C, respectively. Control treatments produced the exit of 29.17% of all individuals, which came out of the box in 24.80 ± 8.83 min and at a body temperature of 28.60 ± 1.38 °C. Thermal treatments could serve as an effective tool to prevent the inadvertent transportation of L. californiae and other invasive snakes threatening numerous regions around the globe.

[The future of diabetes treatment]. / L'avenir des traitements du diabète.

Numerous therapeutic advances in the management of diabetes have been made in recent years, leading to the 2023 update of the Société francophone du diabète's position paper. These new treatments, for both autoimmune type 1 and type 2 diabetes, will continue to develop, offering patients personalized care.

Ethnobotanical Study of Medicinal Plants in Tehuledere District, Northwest Ethiopia.

Medicinal plants have constituted a fundamental aspect of human health and wellness for millennia. The objective of this study was to document medicinal plants used to treat human and livestock ailments in the Tehuledere District. The data were collected using semistructured interviews, focus group discussions, and field observations with local informants. Preference ranking, direct matrix ranking, and informant consensus factor were used for data analysis. A total of 63 medicinal plant species belonging to 59 genera and 41 families were documented. The predominant families identified were Lamiaceae and Asteraceae, each containing 6 and 5 species, respectively. Of the recorded medicinal plants, 53 (80.95%) species were used for human ailments, whereas 12 (19.05%) species were used for animal health issues. Among the recorded medicinal plant species, shrubs constitute the highest number with 35% species. The most frequently used plant parts were leaves, accounting for 59% of remedies targeting human ailments. The administration of herbal treatments was primarily oral, aimed at addressing various diseases. The most significant threat to these medicinal plants was attributed to agricultural expansion, followed by the collection of firewood. The aim of documenting the use of medicinal plants in the treatment of diseases was to capture traditional practices, with species such as Eucalyptus globulus, Olea europaea subsp. cuspidata, and Lepidium sativum serving as the foundational basis for future pharmacological studies. It is imperative to prioritize the conservation of Laggera tomentosa and Urtica simensis to safeguard biodiversity and the cultural traditions associated with these endangered species. Engaging local communities in the management and conservation of plant resources, along with the preservation of their traditional knowledge, presents a cost-effective and sustainable solution.

Recent advances and applications of stimuli-responsive nanomaterials for water treatment: A comprehensive review.

The development of stimuli-responsive nanomaterials holds immense promise for enhancing the efficiency and effectiveness of water treatment processes. These smart materials exhibit a remarkable ability to respond to specific external stimuli, such as light, pH, or magnetic fields, and trigger the controlled release of encapsulated pollutants. By precisely regulating the release kinetics, these nanomaterials can effectively target and eliminate contaminants without compromising the integrity of the water system. This review article provides a comprehensive overview of the advancements in light-activated and pH-sensitive nanomaterials for controlled pollutant release in water treatment. It delves into the fundamental principles underlying these materials' stimuli-responsive behaviour, exploring the design strategies and applications in various water treatment scenarios. In particular, the article indicates how integrating stimuli-responsive nanomaterials into existing water treatment technologies can significantly enhance their performance, leading to more sustainable and cost-effective solutions. The synergy between these advanced materials and traditional treatment methods could pave the way for innovative approaches to water purification, offering enhanced selectivity and efficiency. Furthermore, the review highlights the critical challenges and future directions in this rapidly evolving field, emphasizing the need for further research and development to fully realize the potential of these materials in addressing the pressing challenges of water purification.

Tape Stripping Method in Dermatological and Pharmacological Research: Evaluating Fresh and Frozen-Thawed Porcine Skin.

Background The stratum corneum (SC) plays a crucial role in protecting the skin and regulating water loss. Tape stripping is a well-established method for studying skin barrier function and evaluating topical treatments. However, the behavior of fresh versus frozen-thawed skin during tape stripping has not been extensively compared. Objective This study aims to compare the removal of the stratum corneum from fresh and frozen-thawed porcine skin using tape stripping. It also aims to assess the reliability of tape weighing versus histological methods in quantifying SC removal. Methods Fresh and frozen-thawed porcine ears were obtained, cleaned, and subjected to tape stripping at varying numbers of strips from zero to 40. Tape weight and histological measurements were used to quantify SC removal. Statistical analyses were conducted to compare SC thickness and tape weight between the two types of skin. Results The study found that frozen-thawed skin exhibited a non-linear rate (r = 0.65) of SC removal per tape strip in the first five strips compared to a linear removal for fresh skin (r = 0.96). By the fifth tape strip, frozen-thawed samples had lost 80.6% of their SC, while fresh samples had only lost 33.5% (P < 0.03). Tape weighing and histological measurements showed strong correlations (r = 0.93 for fresh skin and r = 0.95 for frozen-thawed skin), indicating that tape weighing is a reliable alternative to histology for assessing SC removal on both sample types. Conclusions Fresh and frozen-thawed porcine skin respond differently to tape stripping, with frozen-thawed skin showing accelerated SC removal in the first five strips. The strong correlation between tape weighing and histological analysis supports the use of tape weighing as a practical tool for evaluating SC removal. These findings have implications for specimen selection and methodological standardization in dermatological and pharmacological research. Future research should explore alternative preservation and SC thickness measurement methods and their impact on tape stripping outcomes.

Safety and efficacy of electro-thumbtack needle for acute mountain sickness patients: a protocol of a randomized, single-blinded, and placebo-controlled study.

BACKGROUND: Acute mountain sickness (AMS) is considered the most common altitude sickness. It can be detrimental to the health of tourists who rapidly ascend high mountains, and can also impair the performance of individuals who move to the plateau for work or education. Acupuncture has been shown to improve AMS as a simple, safe, and effective nonpharmacological method, in case electro-thumbtack needle (ETN) is a more convenient form of acupuncture for both doctor and patient. There are no studies validating the effectiveness of electro-thumbtack needle in improving symptoms in participants with AMS. In this study, we will conduct a randomized controlled trial to evaluate the clinical efficacy and safety of electro-thumbtack needle in participants with AMS. Our hypothesis is that electro-thumbtack needle is safe and effective in treating participants with AMS. METHODS: This study is a single-center, randomized, single-blinded, and placebo-controlled study involving at least 114 participants who were diagnosed with AMS. The participants randomly assigned in a 1:1 ratio to the electro-thumbtack needle group and the sham acupuncture group. The treatment protocol involved stimulation of seven predefined acupuncture points, including Zhong Wan (RN12), bilateral Nei Guan (PC6), bilateral He Gu (LI4), and bilateral Tai Yang (EX-HN5), for approximately one minute each, with continuous application over 48 h. The primary outcome was improvement in 2018 Lake Louise score (LLS) after 48 h of treatment. Secondary outcome indicators included the incidence of participants with moderate-to-severe AMS (AMS > 5)and AMS, the LLS, visual analogue scale of headache, clinical functioning scores, the Groningen Sleep Quality Survey, the Stanford Somnolence Scale, blood pressure, oxygen saturation, and heart rate, in addition to treatment-related adverse events were also captured. DISCUSSION: This trial aims to ascertain the therapeutic benefits of ETN in mitigating AMS symptoms, thereby contributing to the evidence base for traditional medical practices, particularly acupuncture, in high-altitude medicine. TRIAL REGISTRATION: Chinese Clinical Trials Registry: ChiCTR2300073882. Registered on 24 July 2023.

Alternatives to surveillance for persistent human papillomavirus after a positive cervical screen: A systematic review and meta-analysis.

OBJECTIVES: In 2021, the World Health Organisation (WHO) updated its guidelines for cervical screening from cytology testing to primary high-risk human papillomavirus (HR-HPV) testing. This change in testing has effectively led to a 'new disease' as women are now aware of having a virus that induces changes that can cause cancer, which they would have been unaware of previously. While current management involves a 'watch and wait' approach and no active treatment, the anxiety associated with having HR-HPV may prompt some women to seek 'treatments' outside the screening programme. ● to identify potential treatment options available for women with persistent HR-HPV and/or low-grade cervical intraepithelial neoplasia (CIN), i.e. ≤CIN 1. ● to determine the clinical effectiveness of these treatments, namely by: ◦ HR-HPV clearance rate, and/or: ◦ CIN regression. METHODS: We searched MEDLINE, PubMed, EMBASE, Web of Science and the Cochrane Library. We included cohort studies and randomised controlled trials (RCTs) only. Records (n = 2135) were screened in Rayyan by two independent reviewers. Quality assessment was conducted using the ROBINS-I tool and the ROB-2 tool. RESULTS: 12 studies (four cohort studies and eight RCTs) were included: six oral medications, two topical medications, one vaccination, and three non-surgical device treatments. Meta-analysis revealed that some therapeutic interventions, including vaginal gels, photodynamic therapy, and some oral medications, may lead to earlier resolution of persistent HR-HPV and regression of low-grade CIN when compared with natural clearance. CONCLUSION: This review can better inform discussions with HR-HPV+ women and answer their questions about alternatives to surveillance.

Clinical question: Can virtual reality be an effective adjunctive to conventional treatment in patients with chronic lower back pain?

Background: Chronic low back pain is the most prevalent chronic pain condition worldwide, accounting for 15-20% of physician visits and costing billions of dollars. Without adequate treatment, it can lead to substance use disorder and increased risk of suicide. Current treatments include non-steroidal anti-inflammatory drugs (NSAIDs), opioids, surgery, and non-pharmacological adjuncts. Evidence suggests cognitive behavioral therapy (CBT) as adjunctive therapy can improve patient commitment to treatment but not pain intensity. However, CBT is limited due to availability, location and shortage of trained personnel. Virtual reality (VR) has been growing in interest in providing affordable, digital, home-based, and self-directed CBT to address the psychosocial aspect of pain. Methods: We searched the literature for meta-analysis, randomized control trials (RCT), and systemic reviews using the PubMed database with the terms virtual reality and chronic low back pain. Results: The review identified 31 studies. Six were chosen that were applicable to our clinical questions, one systematic review, two meta-analysis and three RCTs. The RCTs showed that virtual reality can improve pain in patients with chronic lower back pain as an effective adjunctive to pharmacological and surgical intervention. The systemic review and meta-analysis also concluded that VR is beneficial in pain management however, due to inconsistent results and the multifactorial aspect of chronic pain. Conclusions: Thus further research is required. The number of randomized trials, evidence on long-term application, and the efficacy of self-directed versus guided VR treatment limit our understanding of this topic.

Treatments for Onychomycosis: A Bibliometric Analysis.

Introduction: Oral antifungals were the earliest treatments to receive approval for the management of onychomycosis and have a long-standing record to support their efficacy. Topical antifungals and device-based treatments have been explored and some implemented in more recent years as alternatives to traditional oral antifungals. The present bibliometric analysis summarizes trends in publication frequency for onychomycosis treatment modalities over time and characterizes their body of literature in terms of types of studies available and relative level of evidence. Methods: A comprehensive literature search was performed using Web of Science and SCOPUS databases. Results: Covering all publications from 1970 to present day, our search identified oral therapeutics n = 295 articles (n = 63 randomized control trials [RCTs]), topical therapeutics n = 358 articles (n = 72 RCTs), and device-based treatments n = 158 articles (n = 37 RCTs). Spikes in research activity surround FDA approval of therapeutics for each treatment modality. Research activity within the last decade has focused on topical and device-based treatments. Evidence for efficacy of device-based treatments is lacking from relatively few high-quality RCTs. Conclusion: With growing concern for non-dermatophyte mold onychomycosis and terbinafine resistance, researchers should validate the efficacy and safety of device-based treatments with high-quality studies.

Improvement in health-related quality of life questionnaires with biologic treatment in severe asthma and comorbid chronic rhinosinusitis with or without nasal polyposis: a real-life experience.

BACKGROUND: Patients with severe asthma frequently have comorbid chronic rhinosinusitis (CRS) with or without nasal polyps, that can increase the symptom burden and complicate treatment. Real-life clinical data on the impact of biologic treatments on CRS-specific quality-of-life questionnaires are still lacking. MATERIALS AND METHODS: In this retrospective real-life study, we collected data from patients with severe asthma with comorbid CRS with/without nasal polyposis at baseline, and after 3, 6 and 12 months of treatment with omalizumab, mepolizumab, benralizumab or dupilumab. In particular, we evaluated improvements in HRQoL as measured by SinoNasal Outcome Test-22 (SNOT-22, 0 - 110), Visual Analog Scale symptom scores (VAS, 0-10), and Asthma Control Test (ACT, 5-25) and the proportion of patients meeting the minimal clinically important difference (MCID). RESULTS: Disease-specific HRQoL, as measured by SNOT 22 and VAS score improved in all patients at 3, 6, and 12 months of treatment compared with baseline (SNOT-22: 14, IQR: 0-52 vs 10, IQR:0-30 vs 0, IQR:0-15 vs 0, IQR:0-12, p < 0.001, VAS score: 1, IQR: 0-5 vs 0, IQR:0-3 vs 0, IQR:0-2 vs 0, IQR 0-1, p < 0.001). After 3 months of treatment >80% of patients reached the MCID for ACT, while only patients on dupilumab showed to reach a MCID in 100% of cases. The effect size depended upon the symptom burden at baseline. CONCLUSIONS: The study confirms the efficacy of omalizumab, mepolizumab, benralizumab, and dupilumab in a real-life setting, with a rapid improvement in CRS-specific HRQoL and general health status. These data highlight the importance of targeting type 2 inflammation in asthmatic patients with co-existing upper and lower airways disease.The Authors disclose that preliminary data and analysis of the present study have been presented in abstract form during the "X International Workshop on Lung Health - Respiratory Disease and Immune Response", held in Nice on 19-21 January 2023.

Antisense oligonucleotides and their applications in rare neurological diseases.

Rare diseases affect almost 500 million people globally, predominantly impacting children and often leading to significantly impaired quality of life and high treatment costs. While significant contributions have been made to develop effective treatments for those with rare diseases, more rapid drug discovery strategies are needed. Therapeutic antisense oligonucleotides can modulate target gene expression with high specificity through various mechanisms determined by base sequences and chemical modifications; and have shown efficacy in clinical trials for a few rare neurological conditions. Therefore, this review will focus on the applications of antisense oligonucleotides, in particular splice-switching antisense oligomers as promising therapeutics for rare neurological diseases, with key examples of Duchenne muscular dystrophy and spinal muscular atrophy. Challenges and future perspectives in developing antisense therapeutics for rare conditions including target discovery, antisense chemical modifications, animal models for therapeutic validations, and clinical trial designs will also be briefly discussed.

Comprehensive endometriosis care: a modern multimodal approach for the treatment of pelvic pain and endometriosis.

Endometriosis is a prevalent gynecological disease, leading to chronic pain and inflammation, affecting 1 in 10 individuals presumed female at birth. The diagnostic journey is often arduous, marked by neglect of the right diagnosis and prolonged wait times, significantly compromising the quality of life among those affected. This review provides a nuanced exploration of endometriosis-associated pain management, encompassing medical, surgical, and holistic approaches, all guided by accurate and refined diagnostics. Our paramount goal is to empower physicians as key figures in confronting this intricate challenge with a patient-centric approach, ultimately aiming to improve treatment and quality of life. Acknowledging each patient's unique needs, we emphasize the importance of tailoring a spectrum of options informed by current literature and insights gleaned from our experience in a high-volume tertiary endometriosis center. It is imperative to recognize endometriosis as a complex and chronic disease, often occurring with co-morbid conditions and nuanced complexities, necessitating a long-term personalized multimodal approach for each case. In addition, incorporating principles such as patient autonomy, profound respect for diverse experiences, and practical education on treatment choices is pivotal in enhancing treatment outcomes and overall patient satisfaction.

Navigating the landscape of endometriosis: a comprehensive approach to pain management and patient-centered care Endometriosis is a common gynecological condition characterized by persistent pelvic pain and inflammation, impacting approximately one in ten individuals assigned female at birth. Diagnosis often entails a challenging journey, with many experiencing delays in obtaining the correct diagnosis and treatment due to various factors, significantly affecting their quality of life. This review delves into the intricate landscape of managing pain associated with endometriosis, encompassing medical interventions, surgical procedures, and holistic therapies. Our primary aim is to equip healthcare providers with the tools and knowledge necessary to effectively address this complex issue, prioritizing patient-centered care to minimize delays in diagnosis and treatment initiation. Recognizing the individuality of each patient's needs, we advocate for a tailored approach informed by current evidence and clinical experience from specialized endometriosis centers. Furthermore, we underscore the importance of patient autonomy, respecting diverse perspectives, and providing comprehensive education on treatment options to optimize treatment outcomes and patient satisfaction.

An integrated framework for the study of exercise across the postdiagnosis cancer continuum.

Exercise plays many important roles across the entire cancer continuum that have been described in previous frameworks. These frameworks, however, have generally provided a simplified description of the roles of exercise postdiagnosis. The modern cancer treatment landscape has become complex and often consists of multiple lines of multimodal treatments combined concurrently and/or sequentially and delivered over many months or years. This complexity requires a more multifaceted and targeted approach to the study of exercise after a cancer diagnosis. Here, we propose a new integrated framework-Exercise Across the Postdiagnosis Cancer Continuum (EPiCC)-that highlights the distinct roles of exercise for disease treatment and supportive care from diagnosis until death. We also propose new terminology to clarify the distinct roles of exercise that emerge in the context of the modern cancer treatment landscape. The EPiCC Framework is structured around multiple sequential cancer treatments that highlight six distinct cancer treatment-related time periods for exercise-before treatments, during treatments, between treatments, immediately after successful treatments, during longer term survivorship after successful treatments, and during end of life after unsuccessful treatments. The EPiCC Framework proposes that the specific roles of exercise as a disease treatment and supportive care intervention will vary depending on its positioning within different cancer treatment combinations. As a cancer treatment, exercise may serve as a "priming therapy", primary therapy, neoadjuvant therapy, induction therapy, "bridging therapy", adjuvant therapy, consolidation therapy, maintenance therapy, and/or salvage therapy. As a supportive care intervention, exercise may serve as prehabilitation, intrahabilitation, interhabilitation, rehabilitation, "perihabilitation", health promotion/disease prevention, and/or palliation. To date, exercise has been studied during all of the cancer treatment-related time periods but only in relation to some cancer treatments and combinations. Moreover, fewer studies have examined exercise across multiple cancer treatment-related time periods within any cancer treatment combination. Future research is needed to study exercise as a disease treatment and supportive care intervention within and across the distinct cancer treatment-related time periods contained within different cancer treatment combinations. The aim of the EPiCC Framework is to stimulate a more targeted, integrated, and clinically-informed approach to the study of exercise after a cancer diagnosis.

Efficacy and safety of the first-line systemic treatments in patients with advanced-stage urothelial carcinoma: a systematic review and network meta-analysis.

Introduction: In recent years, some clinical studies of first-line treatment for advanced-stage urothelial carcinoma (aUC) have reached the main endpoint, showing inconsistent clinical efficacy. We hope to explore the efficacy and safety of first-line treatment for aUC. Methods: The relevant literature from January 2000 to February 2024 was searched, and the R language (version 4.3.1) was used to perform a network meta-analysis based on the JAGS package and GEMTC package under the Bayesian framework. The main indicators included OS, PFS, ORR and adverse events of grade 3 or higher. This study has been registered in PROSPERO (CRD42024525372). Results: A total of 8 RCTs involving 5539 patients and 12 treatments were included. Pembrolizumab plus Enfortumab Vedotin (PEM+EV) was significantly better than other groups in OS, PFS and ORR. In terms of OS, PEM+EV was significantly better than nivolumab plus platinum-based chemotherapy (NIVO+platinumCT) (HR=0.60; 95% CI: 0.45-0.81), PEM+platinumCT (HR=0.55; 95%CI: 0.42-0.72), atezolizumab (ATE) + platinumCT (HR=0.57; 95%CI: 0.43-0.75) and platinumCT (HR=0.47; 95%CI: 0.38-0.58). In terms of PFS, PEM+EV was also significantly better than NIVO+platinumCT (HR=0.62; 95%CI: 0.48-0.82), PEM+platinumCT (HR=0.58; 95%CI: 0.45-0.74), ATE+platinumCT (HR=0.55; 95%CI: 0.43-0.69) and platinumCT (HR=0.45; 95%CI: 0.38-0.54). In terms of ORR, PEM+EV had a significant be nefit compared with other treatment measures, which was 2.63 times that of platinumCT (OR=2.63; 95%CI: 2.00-3.45). The adverse events of grade 3 or higher in immunotherapy (ATE, PEM, durvalumab) was significantly lower than other treatment measures. Conclusions: PEM+EV can significantly prolong OS and PFS compared with other treatments, and has a higher ORR. The adverse events of grade 3 or higher of ATE was the lowest. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024525372, identifier CRD42024525372.

Gut microbiota metabolites: potential therapeutic targets for Alzheimer's disease?

Background: Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive decline in cognitive function, which significantly increases pain and social burden. However, few therapeutic interventions are effective in preventing or mitigating the progression of AD. An increasing number of recent studies support the hypothesis that the gut microbiome and its metabolites may be associated with upstream regulators of AD pathology. Methods: In this review, we comprehensively explore the potential mechanisms and currently available interventions targeting the microbiome for the improvement of AD. Our discussion is structured around modern research advancements in AD, the bidirectional communication between the gut and brain, the multi-target regulatory effects of microbial metabolites on AD, and therapeutic strategies aimed at modulating gut microbiota to manage AD. Results: The gut microbiota plays a crucial role in the pathogenesis of AD through continuous bidirectional communication via the microbiota-gut-brain axis. Among these, microbial metabolites such as lipids, amino acids, bile acids and neurotransmitters, especially sphingolipids and phospholipids, may serve as central components of the gut-brain axis, regulating AD-related pathogenic mechanisms including ß-amyloid metabolism, Tau protein phosphorylation, and neuroinflammation. Additionally, interventions such as probiotic administration, fecal microbiota transplantation, and antibiotic use have also provided evidence supporting the association between gut microbiota and AD. At the same time, we propose an innovative strategy for treating AD: a healthy lifestyle combined with targeted probiotics and other potential therapeutic interventions, aiming to restore intestinal ecology and microbiota balance. Conclusion: Despite previous efforts, the molecular mechanisms by which gut microbes act on AD have yet to be fully described. However, intestinal microorganisms may become an essential target for connecting the gut-brain axis and improving the symptoms of AD. At the same time, it requires joint exploration by multiple centers and multiple disciplines.