Pemphigus vulgaris (PV) is the most common subtype of pemphigus. It predominantly affects adults, with pediatric cases being exceedingly rare. Despite advancements in clinical treatment, the mortality rate of pediatric PV (PPV) has historically been alarmingly high, ranging from 70% to 100% in the absence of proper diagnosis and treatment. Although recent improvements in therapeutic strategies have led to a gradual decline in mortality, early and appropriate intervention remains crucial, particularly for children with acute onset and rapid disease progression, to prevent severe complications. However, due to the rarity of PPV, no standardized diagnostic and treatment guidelines are currently available. This study retrospectively analyzed 104 PPV cases recorded in the PubMed and China National Knowledge Infrastructure (CNKI) databases between 1969 and 2024, with the aim of providing insights for the standardized diagnosis and management of PPV. PPV presents with flaccid blisters affecting both cutaneous and mucosal surfaces. Upon rupture, these blisters result in painful, sharply demarcated erythematous erosions, accounting for approximately 1.4%-3.7% of all reported PV cases. The age of onset ranges from 1.5 to 18 years, with an average of 12.4 years, and no significant gender differences have been observed. In pediatric patients, the oral mucosa is typically the earliest and most frequently affected site, with an involvement rate as high as 87.3%, and it most commonly affects the buccal mucosa (27.9%). Other mucosal sites are affected in 52.9% of cases, with genital (28.8%) and perianal (6.7%) involvement being more frequent than in adult patients. Skin lesions are present in 80.4% of pediatric cases, a significantly higher rate than 16.0%-68.4% observed in adults. If lesions are relatively localized, local glucocorticoid therapy can be attempted first, with 8.3% of children achieving complete remission through local treatment alone. Systemic glucocorticoid therapy is the preferred option for cases that respond poorly to local therapy. Among these cases, 75.3% of pediatric patients were treated with prednisone, with 85.1% starting at an oral dose of 0.5-1.5 mg/kg/day, while 14.9% received an initial dose of 2 mg/kg/day. Alternative treatments, such as immunosuppressants, biologics, or other adjuvant medications, may be considered for pediatric patients who exhibit an inadequate response to glucocorticoid therapy or experience severe adverse effects. The most commonly used agents include azathioprine (24.0%), dapsone (21.7%), and rituximab (12.5%). The follow-up period for pediatric patients ranged from 1 to 120 months, with an average duration of 38 months. Prognosis in pediatric patients was more favorable compared to adults, with 43.8% achieving complete remission (cessation of treatment), 37.5% achieving partial remission (low-dose maintenance therapy), 9.6% still undergoing treatment, and only 1.1% succumbing to pneumonia or sepsis. Compared to adults, prolonged corticosteroid use in children poses a greater risk to physiological and psychological well-being, making them more susceptible to adverse effects related to growth, metabolism, and ocular health. Severe adverse reactions occurred in 22.1% of pediatric patients receiving corticosteroids, with Cushingoid facies (73.9%) and weight gain (39.1%) being the most common. In addition, 30.4% experienced growth and skeletal abnormalities, including growth retardation (17.4%), osteoporosis (8.7%), and fractures (4.3%). While PPV shares certain etiological, clinical, and histopathological characteristics with adult PV (APV), early diagnosis and timely intervention remain critical for optimal outcomes. Multidisciplinary collaboration is often necessary to ensure comprehensive management, improve treatment adherence, and safeguard the physical and psychological health of pediatric patients.

Vascular aging (VA) is a common etiology of various chronic diseases and represents a major public health concern. Intermittent hypoxia (IH) associated with obstructive sleep apnea-hypopnea syndrome (OSAHS) is a primary pathological and physiological driver of OSAHS-induced systemic complications. A substantial proportion of OSAHS patients, estimated to be between 40% and 80%, have comorbidities such as hypertension, heart failure, coronary artery disease, pulmonary hypertension, atrial fibrillation, aneurysm, and stroke, all of which are closely associated with VA. This review examines the molecular and cellular features common to both OSAHS and VA, highlighting decreased melatonin secretion, impaired autophagy, increased apoptosis, increased inflammation and pyroptosis, increased oxidative stress, accelerated telomere shortening, accelerated stem cell depletion, metabolic disorders, imbalanced protein homeostasis, epigenetic alterations, and dysregulated neurohormonal signaling. The accumulation and combination of these features may underlie the pathophysiological link between OSAHS and VA, but the exact mechanisms by which OSAHS affects VA may require further investigation. Taken together, these findings suggest that OSAHS may serve as a novel risk factor for VA and related vascular disorders, and that targeting these features may offer therapeutic potential to mitigate the vascular risks associated with OSAHS.
Humans ; Sleep Apnea, Obstructive/pathology* ; Aging/physiology* ; Oxidative Stress/physiology* ; Animals

Natural antimicrobial peptides (AMPs) are promising candidates for the development of a new generation of antimicrobials to combat antibiotic-resistant pathogens. They have found extensive applications in the fields of medicine, food, and agriculture. However, efficiently screening AMPs from natural sources poses several challenges, including low efficiency and high antibiotic resistance. This review focuses on the action mechanisms of AMPs, both through membrane and non-membrane routes. We thoroughly examine various highly efficient AMP screening methods, including whole-bacterial adsorption binding, cell membrane chromatography (CMC), phospholipid membrane chromatography binding, membrane-mediated capillary electrophoresis (CE), colorimetric assays, thin layer chromatography (TLC), fluorescence-based screening, genetic sequencing-based analysis, computational mining of AMP databases, and virtual screening methods. Additionally, we discuss potential developmental applications for enhancing the efficiency of AMP discovery. This review provides a comprehensive framework for identifying AMPs within complex natural product systems.

Sustained inflammatory responses are closely related to various severe diseases, and inhibiting the excessive activation of inflammasomes and pyroptosis has significant implications for clinical treatment. Natural products have garnered considerable concern for the treatment of inflammation. Huanglian-Wumei decoction (HLWMD) is a classic prescription used for treating inflammatory diseases, but the necessity of their combination and the exact underlying anti-inflammatory mechanism have not yet been elucidated. Inspired by the supramolecular self-assembly strategy and natural drug compatibility theory, we successfully obtained berberine (BBR)-chlorogenic acid (CGA) supramolecular (BCS), which is an herbal pair from HLWMD. Using a series of characterization methods, we confirmed the self-assembly mechanism of BCS. BBR and CGA were self-assembled and stacked into amphiphilic spherical supramolecules in a 2:1 molar ratio, driven by electrostatic interactions, hydrophobic interactions, and π-π stacking; the hydrophilic fragments of CGA were outside, and the hydrophobic fragments of BBR were inside. This stacking pattern significantly improved the anti-inflammatory performance of BCS compared with that of single free molecules. Compared with free molecules, BCS significantly attenuated the release of multiple inflammatory mediators and lipopolysaccharide (LPS)-induced pyroptosis. Its anti-inflammatory mechanism is closely related to the inhibition of intracellular nuclear factor-kappaB (NF-κB) p65 phosphorylation and the noncanonical pyroptosis signalling pathway mediated by caspase-11.

Diabetic kidney disease (DKD) with increasing global prevalence lacks effective therapeutic targets to halt or reverse its progression. Therapeutic targets supported by causal genetic evidence are more likely to succeed in randomized clinical trials. In this study, we integrated large-scale plasma proteomics, genetic-driven causal inference, and experimental validation to identify prioritized targets for DKD using the UK Biobank (UKB) and FinnGen cohorts. Among 2844 diabetic patients (528 with DKD), we identified 37 targets significantly associated with incident DKD, supported by both observational and causal evidence. Of these, 22% (8/37) of the potential targets are currently under investigation for DKD or other diseases. Our prospective study confirmed that higher levels of three prioritized targets-insulin-like growth factor binding protein 4 (IGFBP4), family with sequence similarity 3 member C (FAM3C), and prostaglandin D2 synthase (PTGDS)-were associated with a 4.35, 3.51, and 3.57-fold increased likelihood of developing DKD, respectively. In addition, population-level protein-altering variants (PAVs) analysis and in vitro experiments cross-validated FAM3C and IGFBP4 as potential new target candidates for DKD, through the classic NLR family pyrin domain containing 3 (NLRP3)-caspase-1-gasdermin D (GSDMD) apoptotic axis. Our results demonstrate that integrating omics data mining with causal inference may be a promising strategy for prioritizing therapeutic targets.

Objective:To investigate the age-specific distribution characteristics of plantar pressure parameters in healthy children aged 3-12 years.Methods:This cross-sectional study retrieved data from the hospital information system in January 2025 for 272 children aged 3-12 years who underwent physical examinations and voluntarily completed plantar pressure analysis at Beijing Children′s Hospital, Capital Medical University, from July 2022 to December 2024. Demographic and clinical data, including anthropometric measurements (height and weight), flatfoot diagnosis and plantar pressure parameters (maximum pressure, time to maximum force, and contact time percentage in bilateral forefoot, midfoot, and hindfoot) were recorded. Participants were categorized into 3 age groups (3-6 years, 7-9 years, and 10-12 years) and were grouped by gender as well. Intergroup comparisons used one-way ANOVA or least-significant difference test or χ2 tests. Spearman′s rank correlation assessed the relationship between flatfoot prevalence and age. Results:Among 272 children (143 boys, 129 girls), age groups comprised 3-6 years (118 children, 64 boys and 54 girls), 7-9 years (96 children, 49 boys and 47 girls), and 10-12 years (58 children, 30 boys and 28 girls). Flatfoot prevalence was higher in boys than in that of girls (41.3% (59/143) vs. 28.7% (37/129), χ2=4.70, P=0.030), and negatively correlated with age ( r=-0.21, P<0.001). There all had statistically differences in the maximum pressure values of the bilateral forefoot and hindfoot among the 3 age groups (all P<0.001), and after pairwise comparison, those of the group of aged 3-6 years were all the lowest, and those of the group of aged 10-12 years were all the highest (all P<0.05). The maximum pressure values of bilateral midfoot in the group of aged 10-12 years were all higher than those of the other two groups (all P<0.001). There had no statistically differences in the time maximum force value of the bilateral forefoot among the 3 age groups (all P>0.05). The time maximum force values of bilateral midfoot in the group of aged 3-6 years were all lower than those of the other two groups (all P<0.05). There all had statistically differences in the time maximum force value of the bilateral hindfoot among the 3 age groups (all P<0.001), and after pairwise comparison, those of the group of aged 3-6 years were all the lowest, and those of the group of aged 10-12 years were all the highest (all P<0.05). There all had statistically differences in the contact time percentage values of the bilateral forefoot among the 3 age groups (all P<0.001), and after pairwise comparison, those of the group of aged 3-6 years were all the lowest, and those of the group of aged 10-12 years were all the highest (all P<0.05). There had no statistically differences in the contact time percentage values of the bilateral midfoot among the 3 age groups (all P>0.05). There all had statistically differences in the contact time percentage values of the bilateral hindfoot among the 3 age groups (all P<0.001), and after pairwise comparison, those of the group of aged 3-6 years were all lower than those of the other two groups (all P<0.05). Conclusion:Plantar pressure parameters exhibit distinct age-related patterns, reflecting the development of gait patterns and foot arch formation, which will be useful for monitoring physical growth and sports rehabilitation.

Cancer-related sarcopenia is mainly characterized by protein degradation and muscle depletion caused by catabolism, leading to a decrease in the quality, strength, and function of skeletal muscles. Pancreatic cancer has the highest incidence of cancer-associated sarcopenia. More than 80% of pancreatic cancer patients have the Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations, which promote the progress of sarcopenia. The authors systematically elaborate the interaction mechanism between KRAS-mutant pancreatic cancer and sarcopenia, mainly in four aspects: (1) KRAS driven metabolic reprogramming leads to depletion of muscle energy reserves, affecting the redistribution of muscle fiber energy and resulting in unidirectional energy flow for cancer cell proliferation. (2) By altering the cytokine profile, activating the ubiquitin protease system and the autophagy lysosome pathway, the cancer cells promote myotube degradation, inhibit muscle regeneration, disrupt muscle homeostasis, and lead to unidirectional flow of nutrients to support tumor growth. (3) Oxidative stress caused by cancer cells damages skeletal muscles. (4) Cancer cells induce immune cell remodeling in skeletal muscle. Meanwhile, the authors review the treatment progress of KRAS-mutant pancreatic cancer-related sarcopenia. With the deepening research of KRAS-mutant pancreatic cancer-related sarcopenia, targeted therapy and personalized intervention are expected to become important means to improve the prognosis and quality of life of patients.

Diabetic kidney disease(DKD)with increasing global prevalence lacks effective therapeutic targets to halt or reverse its progression.Therapeutic targets supported by causal genetic evidence are more likely to succeed in randomized clinical trials.In this study,we integrated large-scale plasma proteomics,genetic-driven causal inference,and experimental validation to identify prioritized targets for DKD using the UK Biobank(UKB)and FinnGen cohorts.Among 2844 diabetic patients(528 with DKD),we identified 37 targets significantly associated with incident DKD,supported by both observational and causal evi-dence.Of these,22％(8/37)of the potential targets are currently under investigation for DKD or other diseases.Our prospective study confirmed that higher levels of three prioritized targets-insulin-like growth factor binding protein 4(IGFBP4),family with sequence similarity 3 member C(FAM3C),and prostaglandin D2 synthase(PTGDS)—were associated with a 4.35,3.51,and 3.57-fold increased likeli-hood of developing DKD,respectively.In addition,population-level protein-altering variants(PAVs)analysis and in vitro experiments cross-validated FAM3C and IGFBP4 as potential new target candidates for DKD,through the classic NLR family pyrin domain containing 3(NLRP3)-caspase-1-gasdermin D(GSDMD)apoptotic axis.Our results demonstrate that integrating omics data mining with causal inference may be a promising strategy for prioritizing therapeutic targets.

Natural antimicrobial peptides(AMPs)are promising candidates for the development of a new gener-ation of antimicrobials to combat antibiotic-resistant pathogens.They have found extensive applications in the fields of medicine,food,and agriculture.However,efficiently screening AMPs from natural sources poses several challenges,including low efficiency and high antibiotic resistance.This review focuses on the action mechanisms of AMPs,both through membrane and non-membrane routes.We thoroughly examine various highly efficient AMP screening methods,including whole-bacterial adsorption binding,cell membrane chromatography(CMC),phospholipid membrane chromatography binding,membrane-mediated capillary electrophoresis(CE),colorimetric assays,thin layer chromatography(TLC),fluorescence-based screening,genetic sequencing-based analysis,computational mining of AMP data-bases,and virtual screening methods.Additionally,we discuss potential developmental applications for enhancing the efficiency of AMP discovery.This review provides a comprehensive framework for identifying AMPs within complex natural product systems.

Sustained inflammatory responses are closely related to various severe diseases,and inhibiting the excessive activation of inflammasomes and pyroptosis has significant implications for clinical treatment.Natural products have garnered considerable concern for the treatment of inflammation.Huanglian-Wumei decoction(HLWMD)is a classic prescription used for treating inflammatory diseases,but the necessity of their combination and the exact underlying anti-inflammatory mechanism have not yet been elucidated.Inspired by the supramolecular self-assembly strategy and natural drug compatibility theory,we successfully obtained berberine(BBR)-chlorogenic acid(CGA)supramolecular(BCS),which is an herbal pair from HLWMD.Using a series of characterization methods,we confirmed the self-assembly mechanism of BCS.BBR and CGA were self-assembled and stacked into amphiphilic spherical supra-molecules in a 2:1 molar ratio,driven by electrostatic interactions,hydrophobic interactions,and π-πstacking;the hydrophilic fragments of CGA were outside,and the hydrophobic fragments of BBR were inside.This stacking pattern significantly improved the anti-inflammatory performance of BCS compared with that of single free molecules.Compared with free molecules,BCS significantly attenuated the release of multiple inflammatory mediators and lipopolysaccharide(LPS)-induced pyroptosis.Its anti-inflammatory mechanism is closely related to the inhibition of intracellular nuclear factor-kappaB(NF-κB)p65 phosphorylation and the noncanonical pyroptosis signalling pathway mediated by caspase-11.