Objective:To investigate the association between small vulnerable newborn (SVN) phenotypes and the risk of neurodevelopmental delay at the age of 1 year.Methods:A prospective cohort study was conducted. A total of 25 860 singleton infants from "The Born in Guangzhou Cohort Study" who completed the Gesell developmental scale assessment at 1 year of age between January 2013 and June 2025 were included. Maternal sociodemographic characteristics, and other information were collected using a self-administered questionnaire, and maternal pregnancy-related information and neonatal birth data were extracted from medical records. Global developmental delay (GDD) was defined as a developmental quotient below 86 in ≥3 domains of the Gesell developmental scale, which assesses the adaptive, gross motor, fine motor, language, and personal-social domains. The random forest algorithm was employed for missing data imputation. Based on prematurity, small for gestational age (SGA), and low birth weight (LBW), newborns were categorized into 6 phenotypes: preterm-SGA-LBW, preterm-appropriate for gestational age (AGA)-LBW, preterm-AGA-nonLBW, term-SGA-LBW, term-LBW-only or term-SGA-only, and term-AGA-nonLBW phenotype. Among these, the first 5 were classified as SVN phenotypes, and the last one served as the reference group. Inter-group comparisons were performed using analysis of variance (ANOVA), χ2 tests, or Kruskal-Wallis test, as appropriate.?? Multivariable robust Poisson regression models were applied to analyze the association of different SVN phenotypes with the risks of GDD and developmental delays in specific domains, with stratified analyses by sex. Results:Among the 25 860 infants, 13 719 (53.1%) were male and 12 141 (46.9%) were female. The gestational age at birth was 39.4 (38.6, 40.0) weeks. The overall detection rate of GDD at 1 year of age was 3.7% (962/25 860). The rates of delay across developmental domains, in descending order, language in 8 134 cases (31.5%), gross motor in 4 488 cases (17.4%), personal-social in 1 271 cases (4.9%), adaptive in 1 262 cases (4.9%), and fine motor in 621 cases (2.4%). Compared with the reference group, preterm-AGA-LBW, preterm-SGA-LBW, preterm-AGA-noneLBW, and term-SGA-LBW phenotypes were all associated with an increased risk of GDD, with the adjusted RR (95% CI) of 6.07(5.01-7.35), 4.81(3.11-7.46), 2.10(1.54-2.88) and 1.89(1.29-2.76) respectively.The preterm-AGA-noneLBW phenotype was all associated with an increased risk of delay in gross motor, language and personal-social functional domains (all P<0.05). The term-SGA-LBW phenotype was associated with an increased risk of delay in gross motor, fine motor and personal-social functional domains (all P<0.01). Whereas the term-LBW-only or term-SGA-only phenotype showed no statistically association with developmental delay in any functional domain (all P≥0.05). Conclusion:The combined classification based on gestational age and birth weight helps identify infants at high risk for neurodevelopmental delay at 1 year of age, suggesting that it may offer a reference for the rational allocation of clinical resources.

Chronic eczema has a high prevalence in China， significantly impacting patients’ quality of life. Leveraging the unique advantages of pattern identification/syndrome differentiation and treatment， along with a holistic approach， traditional Chinese medicine （TCM）， which integrates internal and external therapies， has been widely applied in the management of chronic eczema. It has demonstrated significant efficacy and distinctive strengths in alleviating symptoms， reducing recurrence rates， maintaining disease stability， and enhancing patients’ quality of life. Oral administration of TCM（e.g. modified Longdan xiegan decoction） can improve patients’ clinical symptoms through systemic regulation. External use of TCM can directly act on the skin lesion with the help of steaming and washing， hydropathic compress， ointment and other forms. At the same time， it can effectively relieve the clinical symptoms of chronic eczema by combining with non-drug therapies such as acupuncture， moxibustion， acupoint catgut embedding， blood-letting puncture and cupping. In addition， characteristic therapies such as oral administration of TCM combined with external treatment， a combination of various external treatments and a combination of Chinese and Western medicine have also demonstrated certain advantages in regulating immune function， alleviating skin lesions， and relieving itching symptoms. These therapies cooperate with each other， creating a synergistic effect that treats both the symptoms and the root cause simultaneously. It is suggested that more high-quality， large-scale clinical research should be conducted in the future to systematically confirm the therapeutic advantages of TCM and further explore the specific molecular mechanism of action.

A 51-year-old male presented with nasal obstruction, followed by progressive hearing loss and blurred vision. Imaging identified space-occupying lesions in the paranasal sinuses, orbits, and paraspinal regions, while laboratory tests confirmed positive anti-proteinase 3 anti-neutrophil cytoplasmic antibody(PR3- ANCA) immunoglobulin G (IgG)and markedly elevated serum IgG4. Despite treatment with corticosteroids, immunosuppressants, and radiotherapy, the patient exhibited steroid dependency with relentless disease progression. Following multidisciplinary consultation, a diagnosis of inflammatory myofibroblastic tumor (IMT) coexisting with ANCA- associated vasculitis (AAV) was favored, though IgG4-related disease remained a critical differential. Ultimately, profound immunosuppression precipitated a severe herpesvirus infection, leading to disseminated intravascular coagulation and multiple organ dysfunction syndrome. This case underscores the rarity and diagnostic complexity of concurrent IMT and AAV, highlights the therapeutic dilemma of balancing primary disease control against fatal opportunistic infections, and emphasizes the critical role of multidisciplinary collaboration in the diagnosis and treatment of complex diseases.

Objective:To investigate the association between small vulnerable newborn (SVN) phenotypes and the risk of neurodevelopmental delay at the age of 1 year.Methods:A prospective cohort study was conducted. A total of 25 860 singleton infants from "The Born in Guangzhou Cohort Study" who completed the Gesell developmental scale assessment at 1 year of age between January 2013 and June 2025 were included. Maternal sociodemographic characteristics, and other information were collected using a self-administered questionnaire, and maternal pregnancy-related information and neonatal birth data were extracted from medical records. Global developmental delay (GDD) was defined as a developmental quotient below 86 in ≥3 domains of the Gesell developmental scale, which assesses the adaptive, gross motor, fine motor, language, and personal-social domains. The random forest algorithm was employed for missing data imputation. Based on prematurity, small for gestational age (SGA), and low birth weight (LBW), newborns were categorized into 6 phenotypes: preterm-SGA-LBW, preterm-appropriate for gestational age (AGA)-LBW, preterm-AGA-nonLBW, term-SGA-LBW, term-LBW-only or term-SGA-only, and term-AGA-nonLBW phenotype. Among these, the first 5 were classified as SVN phenotypes, and the last one served as the reference group. Inter-group comparisons were performed using analysis of variance (ANOVA), χ2 tests, or Kruskal-Wallis test, as appropriate.?? Multivariable robust Poisson regression models were applied to analyze the association of different SVN phenotypes with the risks of GDD and developmental delays in specific domains, with stratified analyses by sex. Results:Among the 25 860 infants, 13 719 (53.1%) were male and 12 141 (46.9%) were female. The gestational age at birth was 39.4 (38.6, 40.0) weeks. The overall detection rate of GDD at 1 year of age was 3.7% (962/25 860). The rates of delay across developmental domains, in descending order, language in 8 134 cases (31.5%), gross motor in 4 488 cases (17.4%), personal-social in 1 271 cases (4.9%), adaptive in 1 262 cases (4.9%), and fine motor in 621 cases (2.4%). Compared with the reference group, preterm-AGA-LBW, preterm-SGA-LBW, preterm-AGA-noneLBW, and term-SGA-LBW phenotypes were all associated with an increased risk of GDD, with the adjusted RR (95% CI) of 6.07(5.01-7.35), 4.81(3.11-7.46), 2.10(1.54-2.88) and 1.89(1.29-2.76) respectively.The preterm-AGA-noneLBW phenotype was all associated with an increased risk of delay in gross motor, language and personal-social functional domains (all P<0.05). The term-SGA-LBW phenotype was associated with an increased risk of delay in gross motor, fine motor and personal-social functional domains (all P<0.01). Whereas the term-LBW-only or term-SGA-only phenotype showed no statistically association with developmental delay in any functional domain (all P≥0.05). Conclusion:The combined classification based on gestational age and birth weight helps identify infants at high risk for neurodevelopmental delay at 1 year of age, suggesting that it may offer a reference for the rational allocation of clinical resources.

OBJECTIVE: To investigate the antidepressant effects of Xiaoyao Pill (XYP) by exploring its interactions with gut microbiota and tryptophan metabolism. METHODS: Utilizing network pharmacology, the functional substance groups, key targets, and pathways of XYP in the treatment of depression were identified. The chronic unpredictable mild stress (CUMS) protocol was implemented in male Sprague-Dawley rats to establish depression model. Thirty rats were randomly divided into 3 groups according to their body weight (10 for each): control, CUMS and XYP groups (1.8 g/kg). After 28-day interventions, behavioral phenotyping including sucrose preference test (SPT) and open field test (OFT) were performed. Biochemical validation encompassed enzyme-linked immunosorbent assay for serum cortisol, hematoxylin-eosin histopathology, and immunohistochemistry. Liquid chromatography-mass spectrometry was utilized to profile serum metabolites, while fecal samples underwent metagenomic sequencing for gut microbiota characterization. RESULTS: Network pharmacology studies predicted that key components can protect the nervous system by regulating inflammatory pathways through the blood-brain barrier. SPT and OFT showed that XYP treatment significantly ameliorated depressive-like behaviors (all P<0.05). XYP treatment also restored hippocampal neuronal density, increased serum neurotransmitter levels of neurotransmitters such as 5-hydroxytryptamine and vasoactive intestinal peptide, and while suppressing inflammatory markers such as tumor necrosis factor-alpha, interleukin-1 beta (IL-1 β), and IL-6 (all P<0.05). Metagenomics revealed significant restructuring of gut microbiota, notably the regulation of Parabacteroides distasonis (P<0.05). Non-targeted metabolomics analysis showed that the level of metabolites in the tryptophan and kynurenine pathway significantly changed (variable importance in the projection >1, P<0.05), and the change of metabolic flux was significantly correlated with behavioral improvement (P<0.05). CONCLUSIONS XYP exerts antidepressant effects by increasing neurotransmitter levels, reducing inflammatory makers and modulating Parabacteroides distasonis. Through further exploration of metabolomics, we found that XYP may play a protective role in depression by regulating tryptophan metabolism.
Animals ; Tryptophan/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Gastrointestinal Microbiome/drug effects* ; Rats, Sprague-Dawley ; Depression/blood* ; Male ; Stress, Psychological/drug therapy* ; Behavior, Animal/drug effects* ; Rats ; Chronic Disease ; Hippocampus/drug effects*

Emerging evidences have indicated the role of ferroptosis in the progression of metabolic-associated fatty liver disease (MAFLD); thus, inhibiting ferroptosis is a promising strategy for the development of MAFLD therapeutics. Recent studies have demonstrated the antioxidative effect of the gut commensal bacterium Akkermansia muciniphila (A. muc); however, whether it can alleviate ferroptosis remains unclear. The current study indicates A. muc intervention efficiently reversed high-fat high-fructose diet (HFHFD)-induced lipid peroxidation and ferroptosis in the liver. These beneficial effects were mediated by activation of the hepatic AMPK/SIRT1/PGC-1α axis, as evidenced by the finding that AMPK deficiency abrogated the amelioration of lipid peroxidation in vitro and in vivo. Furthermore, the short-chain fatty acids (SCFAs) were enriched upon A. muc treatment, and acetate was identified as a key activator of hepatic AMPK signalling. Mechanistically, microbiota-derived acetate was transported to the liver and metabolized to adenosine monophosphate (AMP), which triggered AMPK activation. Furthermore, a colonization assay in germ-free mice confirmed that A. muc mediated antiferroptotic effects in the absence of other microbes. These data indicated that A. muc exerts antiferroptotic effects against MAFLD, at least partially by producing acetate, which activates the hepatic AMPK/SIRT1/PGC-1α axis to alleviate ferroptosis via the inhibition of polyunsaturated fatty acid (PUFA) synthesis.

OBJECTIVES: To explore the bioactive components in Jiawei Xiaoyao Pills (JWXYP) and their mechanisms for alleviating depression-like behaviors. METHODS: The active compounds, key targets, and pathways of JWXYP were identified using TCMSP and TCMIP databases. Thirty-six SD rats were randomized equally into 6 groups including a control group and 5 chronic unpredictable mild stress (CUMS)-induced depression groups. After modeling, the 5 model groups were treated with daily gavage of normal saline, 1.8 mg/kg fluoxetine hydrochloride (positive control drug), or JWXYP at 1.44, 2.88, and 4.32 g/kg. The depression-like behaviors of the rats were evaluated using behavioral tests, and pathological changes in the liver and hippocampus were examined with HE staining. The biochemical indicators in the serum and brain tissues were detected using ELISA. Serum metabolomics analysis was performed to identify the differential metabolites using OPLS-DA, and gut microbiota changes were analyzed using 16S rDNA sequencing. RESULTS: Network pharmacology revealed that menthone and paeonol in JWXYP were capable of penetrating the blood-brain barrier to regulate inflammatory pathways and protect the nervous system. In the rat models subjected to CUMS, treatment with JWXYP significantly improved body weight loss, sucrose preference and open field activities, reduced liver inflammation, alleviated structural changes in the hippocampal neurons, decreased serum levels of TNF‑α, IL-1β, IL-6 and LBP, and increased 5-HT and VIP concentrations in the serum and brain tissue, and these effects were the most pronounced in the high-dose group. Metabolomics analysis showed changes in such metabolites as indole-3-acetamide and acetyl-L-carnitine in JWXYP-treated rats, involving the pathways for bile acid biosynthesis and amino acid metabolism. 16S rDNA analysis demonstrated increased gut microbiota diversity and increased abundance of Lactobacillus species in JWXYP-treated rats. CONCLUSIONS JWXYP alleviates depression-like symptoms in rats by regulating the neurotransmitters, inhibiting inflammation and oxidation, and modulating gut microbiota.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Gastrointestinal Microbiome/drug effects* ; Rats, Sprague-Dawley ; Depression/drug therapy* ; Neurotransmitter Agents/metabolism* ; Rats ; Inflammation ; Male ; Hippocampus ; Behavior, Animal/drug effects*

OBJECTIVES: To explore the risk factors for malnutrition in patients with ulcerative colitis complicated with pyoderma gangrenosum and establish a nutritional risk prediction model for these patients. METHODS: A total of 277 patients with ulcerative colitis complicated with pyoderma gangrenosum treated from 2019 to 2024 were divided into malnutrition group (n=185) and normal nutrition group (n=92) according to whether malnutrition occurred. The data of 25 potential related factors pertaining to general demography, living and eating habits, and disease-related data were compared between the two groups. Lasso regression was used to screen the risk factors, and a nomogram model was established based on the screened factors and its prediction performance was assessed. RESULTS: The patients in the malnutrition group and normal nutrition group showed significant differences in 21 factors including gender, age, education level, BMI, place of residence, course of disease, and SAS language score (P<0.05). Lasso regression analysis identified 6 factors associated with malnutrition in these patients, namely the duration of ulcerative colitis, activity of ulcerative colitis, duration of pyoderma gangrenosum, number of chronic diseases, SAS score, and sleep quality. The nomogram prediction model established based on these 6 factors had an AUC of 0.992 (95% CI: 0.984-1.000) for predicting malnutrition in these patients, and its application in 14 clinical cases achieved an accuracy rate of 100%. CONCLUSIONS The duration of ulcerative colitis, activity of colitis, duration of pyoderma gangrenosum, number of chronic diseases, anxiety, and sleep quality are closely related with malnutrition in patients with ulcerative colitis complicated by pyoderma gangrenosum, and the nomogram prediction model based on these factors can provide assistance for predicting malnutrition in these patients.
Humans ; Colitis, Ulcerative/complications* ; Malnutrition/etiology* ; Risk Factors ; Pyoderma Gangrenosum/complications* ; Female ; Male ; Adult ; Nomograms ; Middle Aged ; Nutritional Status ; Regression Analysis

Radiochemotherapy-induced oral mucositis (OM) is a common oral complication in patients with tumors following head and neck radiotherapy or chemotherapy. Erosion and ulcers are the main features of OM that seriously affect the quality of life of patients and even the progress of tumor treatment. To date, differences in clinical prevention and treatment plans for OM have been noted among doctors of various specialties, which has increased the uncertainty of treatment effects. On the basis of current research evidence, this expert consensus outlines risk factors, clinical manifestations, clinical grading, ancillary examinations, diagnostic basis, prevention and treatment strategies and efficacy indicators for OM. In addition to strategies such as basic oral care, anti-inflammatory and analgesic agents, anti-infective agents, pro-healing agents, and photobiotherapy recommended in previous guidelines, we also emphasize the role of traditional Chinese medicine in OM prevention and treatment. This expert consensus aims to provide references and guidance for dental physicians and oncologists in formulating strategies for OM prevention, diagnosis, and treatment, standardizing clinical practice, reducing OM occurrence, promoting healing, and improving the quality of life of patients.
Humans ; Chemoradiotherapy/adverse effects* ; Consensus ; Risk Factors ; Stomatitis/etiology*

Ursodeoxycholic acid (UDCA) is a naturally occurring, low-toxicity, and hydrophilic bile acid (BA) in the human body that is converted by intestinal flora using primary BA. Solute carrier family 7 member 11 (SLC7A11) functions to uptake extracellular cystine in exchange for glutamate, and is highly expressed in a variety of human cancers. Retroperitoneal liposarcoma (RLPS) refers to liposarcoma originating from the retroperitoneal area. Lipidomics analysis revealed that UDCA was one of the most significantly downregulated metabolites in sera of RLPS patients compared with healthy subjects. The augmentation of UDCA concentration (≥25 μg/mL) demonstrated a suppressive effect on the proliferation of liposarcoma cells. [¹⁵N₂]-cystine and [¹³C₅]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione (GSH) synthesis. Mechanistically, UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis, leading to reactive oxygen species (ROS) accumulation and mitochondrial oxidative damage. Furthermore, UDCA can promote the anti-cancer effects of ferroptosis inducers (Erastin, RSL3), the murine double minute 2 (MDM2) inhibitors (Nutlin 3a, RG7112), cyclin dependent kinase 4 (CDK4) inhibitor (Abemaciclib), and glutaminase inhibitor (CB839). Together, UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity, and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA. More importantly, in combination with other antitumor chemotherapy or physiotherapy treatments, UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.