Immunomodulatory Precision: A Narrative Review Exploring the Critical Role of Immune Checkpoint Inhibitors in Cancer Treatment.

An immune checkpoint is a signaling pathway that regulates the recognition of antigens by T-cell receptors (TCRs) during an immune response. These checkpoints play a pivotal role in suppressing excessive immune responses and maintaining immune homeostasis against viral or microbial infections. There are several FDA-approved immune checkpoint inhibitors (ICIs), including ipilimumab, pembrolizumab, and avelumab. These ICIs target cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1), and programmed death ligand 1 (PD-L1). Furthermore, ongoing efforts are focused on developing new ICIs with emerging potential. In comparison to conventional treatments, ICIs offer the advantages of reduced side effects and durable responses. There is growing interest in the potential of combining different ICIs with chemotherapy, radiation therapy, or targeted therapies. This article comprehensively reviews the classification, mechanism of action, application, and combination strategies of ICIs in various cancers and discusses their current limitations. Our objective is to contribute to the future development of more effective anticancer drugs targeting immune checkpoints.

Genomics-Microbiome Based Assessment of Bidirectional Causality Between Gut Microbiota and Psoriasis.

Background: Traditional observational studies have found a possible risk association of the gut microbiota for psoriasis. Meanwhile, psoriasis may also affect the changes in the gut microbiota. However, the available evidence does not demonstrate a reciprocal relationship between the gut microbiota and psoriasis. This limits our understanding on the role of the gut microbiota in the mechanisms of psoriasis. Methods: To address this question we used Mendelian randomization, a novel epidemiological approach, and acquired the largest current gut microbiota GWAS data from the MiBioGen consortium as well as psoriasis GWAS data from the FinnGen consortium, and performed two-sample bidirectional MR analyses using a multiple MR analysis approach. Finally, the robustness of the results was assessed by sensitivity analysis. Results: Our results indicate that five bacterial genera are causally related to psoriasis and psoriasis is causally related to four bacterial genera. Conclusion: These results suggest a bidirectional causal influence of psoriasis on the gut microbiota. Our results somewhat challenge the causal inferences of previous observational studies. We found that the specific bacterial genera with a risk effect on psoriasis were different from those found to characterize psoriasis in previous observational studies, and that these psoriasis-characterizing genera were inversely associated with psoriasis.

Automated classification of lay health articles using natural language processing: a case study on pregnancy health and postpartum depression.

Objective: Evidence suggests that high-quality health education and effective communication within the framework of social support hold significant potential in preventing postpartum depression. Yet, developing trustworthy and engaging health education and communication materials requires extensive expertise and substantial resources. In light of this, we propose an innovative approach that involves leveraging natural language processing (NLP) to classify publicly accessible lay articles based on their relevance and subject matter to pregnancy and mental health. Materials and methods: We manually reviewed online lay articles from credible and medically validated sources to create a gold standard corpus. This manual review process categorized the articles based on their pertinence to pregnancy and related subtopics. To streamline and expand the classification procedure for relevance and topics, we employed advanced NLP models such as Random Forest, Bidirectional Encoder Representations from Transformers (BERT), and Generative Pre-trained Transformer model (gpt-3.5-turbo). Results: The gold standard corpus included 392 pregnancy-related articles. Our manual review process categorized the reading materials according to lifestyle factors associated with postpartum depression: diet, exercise, mental health, and health literacy. A BERT-based model performed best (F1 = 0.974) in an end-to-end classification of relevance and topics. In a two-step approach, given articles already classified as pregnancy-related, gpt-3.5-turbo performed best (F1 = 0.972) in classifying the above topics. Discussion: Utilizing NLP, we can guide patients to high-quality lay reading materials as cost-effective, readily available health education and communication sources. This approach allows us to scale the information delivery specifically to individuals, enhancing the relevance and impact of the materials provided.

Effects of online support and social media communities on gestational diabetes: A systematic review.

BACKGROUND: Gestational diabetes mellitus (GDM) is a common complication in pregnancy that can lead to negative maternal and fetal outcomes. Online support interventions have been suggested as a potential tool to improve the management of GDM. OBJECTIVE: This systematic review aimed to summarize the effectiveness of social media and online support interventions for the management of GDM. METHODS: We conducted a thorough systematic search across Web of Science, Scopus, and PubMed, following PRISMA guidelines, and supplemented it with a manual search. Our results included both qualitative and quantitative research. We rigorously assessed quantitative studies for bias using ROBINS-I and RoB 2 tools, ensuring the reliability of our findings. RESULTS: We incorporated a total of 22 studies, which were comprised of ten qualitative and twelve quantitative studies. Online support interventions were found to have a positive impact on promoting self-care and improving healthcare outcomes for women with GDM. Individualized diet and exercise interventions resulted in lower odds of weight gain and GDM diagnosis, while online prenatal education increased breastfeeding rates. In addition, telemedicine options reduced the need for in-person clinical visits and improved patient satisfaction. CONCLUSIONS: Online support interventions show potential to improve outcomes in patients with GDM in this small literature review. Future research is also necessary to determine the effectiveness of different types of online interventions and identify strategies to improve engagement and the quality of the information provided through online resources.

Efficacy and safety of laser-related therapy for melasma: A systematic review and network meta-analysis.

BACKGROUND: Melasma is a prevalent, persistent hyperpigmentation disorder that negatively affects the psychological health of patients. However, the treatment outcome remains unsatisfactory due to the complexity of pathogenesis, recurrence characteristics, and relatively high morbidity. OBJECTIVES: To compare the performance of laser-related therapies in improving the melasma area severity index (MASI) score of melasma and the occurrence of adverse effects by network meta-analysis (NMA). METHODS: From the inception to November 2022, eligible randomized controlled trials were identified. Two investigators independently searched relevant studies from PUBMED, EMBASE, and the Cochrane Library database. RESULTS: A total of 39 clinical studies with 1394 participants were eligible for enrollment. For efficacy, the NMA demonstrated that Q-switched Nd: YAG laser + topical medications (QSND+TM) was superior to Q-switched Nd:YAG laser (QSND) [MD = -4.21 (-6.80, -1.63)], Er: YAG laser + topical medications (ERYL+TM) [MD = -3.52 (-6.84, -0.19)], and picosecond laser + topical medications (PICO+TM) [MD = -4.80 (-9.33, -0.27)]. The microneedling + topical medications (MN+TM) was superior to picosecond laser (PICO) [MD = -5.26 (-10.44, -0.08)] and topical medications (TM) [MD = -5.22 (-9.20, -1.23)]. The top five of the surface under the cumulative ranking curve value (SUCRA) are Q-switched Nd:YAG laser + topical medications (QSND+TM 85.9%), oral tranexamic acid (oTA 80.1%), microneedling + topical medications (MN+TM 79.7%), Q-switched Nd:YAG laser + intense pulse light (QSND+IPL 78.9%), and fractional carbon dioxide laser + topical medications (FCDL+TM 70.5%). CONCLUSIONS: In conclusion, the Qs-Nd:YAG laser with topical medications is the first choice for treating melasma according to the SUCRA value. Among the three treatment modalities, namely MN + TM, PICO, and TM, our recommendation favors MN+TM as the superior choice for enhancing the curative efficacy in melasma. However, the actual clinical choice should also take into account the adverse effects, the skin type of the patient, the duration of the disease, and other relevant factors.

Artificial intelligence-assisted dermatology diagnosis: From unimodal to multimodal.

Artificial Intelligence (AI) is progressively permeating medicine, notably in the realm of assisted diagnosis. However, the traditional unimodal AI models, reliant on large volumes of accurately labeled data and single data type usage, prove insufficient to assist dermatological diagnosis. Augmenting these models with text data from patient narratives, laboratory reports, and image data from skin lesions, dermoscopy, and pathologies could significantly enhance their diagnostic capacity. Large-scale pre-training multimodal models offer a promising solution, exploiting the burgeoning reservoir of clinical data and amalgamating various data types. This paper delves into unimodal models' methodologies, applications, and shortcomings while exploring how multimodal models can enhance accuracy and reliability. Furthermore, integrating cutting-edge technologies like federated learning and multi-party privacy computing with AI can substantially mitigate patient privacy concerns in dermatological datasets and further fosters a move towards high-precision self-diagnosis. Diagnostic systems underpinned by large-scale pre-training multimodal models can facilitate dermatology physicians in formulating effective diagnostic and treatment strategies and herald a transformative era in healthcare.

Successful Treatment of Psoriasis Combined with Bullous Pemphigoid with Dupilumab: A Case Report.

Psoriasis is an immune-mediated chronic inflammatory disease that can be combined with complications such as diabetes, cardiovascular disease, obesity, and kidney disease. The comorbidity of psoriasis with autoimmune bullous diseases (AIBD) has been reported previously in several cases, the most frequent of which is bullous pemphigoid (BP). The underlying mechanisms of psoriasis with BP are not clear and there are no uniform treatment criteria. Based on previous case reports, the coexistence of psoriasis and BP may be related to inflammatory activity, medications, phototherapy, and infection. We report a case of a psoriasis patient who developed BP after taking Chinese herbal compounds and was successfully treated with dupilumab, which is the first reported case of applying dupilumab to treat psoriasis with BP comorbidities.

Fibroblast growth factor 21 prolongs lifespan and improves stress tolerance in the silkworm, Bombyx mori.

BACKGROUND: Fibroblast growth factor 21 (FGF21), an FGF family member, is an atypical hormone and pro-longevity factor. METHODS: To better understand of the effects of exogenous administration of FGF21 on lifespan and stress tolerance, and the underlying molecular basis, we used the silkworm, Bombyx mori, as an experimental animal model to evaluate FGF21's pharmaceutical effects. RESULTS: Lifespan was significantly prolonged in female silkworms with FGF21 replenishment, whereas no effect was observed in the male silkworms. FGF21 replenishment also significantly improved the activity of antioxidant systems such as glutathione-S-transferase (GST) and superoxide dismutase (SOD) and significantly decreased malondialdehyde (MDA) content. Moreover, FGF21 was found to play a critical role in enhancing stress resistance, including ultraviolet (UV) irradiation tolerance and thermotolerance. Furthermore, AMPK, FoxO, and sirtuins were activated by FGF21 and may be responsible for the prolonged lifespan and enhanced antioxidant activity observed in silkworms. CONCLUSIONS: Collectively, the results suggest the molecular pathways underlying of FGF21-induced longevity and stress tolerance, and support the use of silkworms as a promising experimental animal model for evaluating the pharmaceutical effects of small molecules.

Metformin prolongs lifespan through remodeling the energy distribution strategy in silkworm, Bombyx mori.

Metformin is a hypoglycemic agent used clinically in the treatment of type 2 diabetics. In addition, metformin is being investigated as a potential geroprotector. Here, we investigated the effects of metformin silkworm lifespan and the underlying molecular pathways involved. We found that metformin prolonged the lifespan of the male silkworm without reducing body weight, which suggests metformin can increase lifespan through remodeling of the animal's energy distribution strategy. Consistent with that idea, metformin reduced silk production and thus the energy devoted to that process. Metformin also increased fasting tolerance and levels of the antioxidant glutathione, and also activated an adenosine monophosphate-activated protein kinase-p53-forkhead box class O signaling pathway in silkworm. These results suggest that activity in this pathway may contribute to metformin-induced lifespan extension in silkworm by increasing stress resistance and antioxidative capacity while reducing energy output for silk product. The results also show that the silkworm is a potential useful animal model for evaluating the effects of small molecules with potential clinical utility.