OBJECTIVE: To analyze the phenotype and genotype of a neonate with Osteo-oto-hepato-enteric syndrome (O2HE) and review the literature. METHODS: A female neonate diagnosed with O2HE syndrome on December 13, 2024 at the First Affiliated Hospital of Zhengzhou University was selected as the study subject, and her clinical characteristics were analyzed, and pathogenic variants were explored by whole exome sequencing (WES). This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: 2025-KY-1038). RESULTS: The proband, a female infant, was delivered by Cesarean section at 36⁺¹ weeks of gestation. Five days after birth, she had developed severe diarrhea, mild cholestasis, sensorineural hearing loss, and growth retardation. WES revealed that she has harbored novel compound heterozygous variants c.512delA (p.Lys171Serfs*64) and c.698C>A (p.Thr233Asn) of the UNC45A gene, which were inherited from her mother and father, respectively. A total of 8 English papers were retrieved, which involved 16 patients from 14 families. Combined with our case, the 17 patients included 13 (76.5%) females and 4 (23.5%) males. Four patients (23.5%) had consanguineous parents. One case was excluded from further genetic analysis due to co-morbidity with other genetic variants. The primary clinical features included diarrhea (87.5%), cholestasis (81.3%), sensorineural hearing loss (31.3%), bone fragility (37.5%), and developmental delay (50.0%). Bi-allelic compound heterozygous mutations were identified in 12 patients (75.0%), and homozygous variants in 4 (25.0%). These included missense, nonsense, frameshift and deletional variants. The c.710T>C (p.Leu237Pro) variant was identified for 5 times, 3 of which were in homozygote forms. CONCLUSION O2HE syndrome should be suspected in cases with diarrhea, cholestasis, and hearing abnormalities during early postnatal period. Genetic testing facilitate early identification, genetic diagnosis and treatment.
Humans ; Female ; Infant, Newborn ; Male ; Mutation ; Hearing Loss, Sensorineural/genetics* ; Diarrhea, Infantile/genetics* ; Exome Sequencing ; Phenotype ; Fetal Growth Retardation ; Hair Diseases ; Facies

Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality, characterized by poor prognosis due to its high proliferative and invasive potential. Tumor metabolic reprogramming, particularly involving glucose metabolism, is essential for tumor survival. This study investigates the role of the Hippo pathway effector transcriptional co-activator with PDZ-binding motif (TAZ) in regulating gluconeogenesis and promoting tumorigenesis in HCC. Methods: TAZ expression in HCC was analyzed using The Cancer Genome Atlas data and validated in clinical samples and cell lines. TAZ was overexpressed or silenced in HCC cell lines to evaluate its effects on cell proliferation, apoptosis, migration, and invasion. The expression and prognostic relevance of the gluconeogenesis-related genes phosphoenolpyruvate carboxykinase 1 (PCK1) and glucose-6-phosphatase (G6PC) were examined, along with their correlation with TAZ expression. Tumor growth was assessed in nude mice. Interactions between TAZ and the glucocorticoid receptor (GR) were investigated using co-immunoprecipitation, immunofluorescence, and chromatin immunoprecipitation assays. Results: TAZ was significantly upregulated in HCC tissues and cell lines. TAZ overexpression enhanced proliferation, reduced apoptosis, and promoted migration and invasion. In contrast, PCK1 and G6PC were downregulated in HCC and showed a negative correlation with TAZ expression. Conclusion TAZ modulates gluconeogenesis and accelerates tumor growth, whereas its knockdown attenuates tumor progression. TAZ interacts with GR, suppressing its transcriptional activity on gluconeogenic gene promoters.

WD repeat domain 1(WDR1)is a highly conserved cytoskeleton-associated protein that plays a crucial role in physiological processes such as actin cytoskeleton remodeling,dynamic regulation of intercellular junctions,cell division,and migration.WDR1 exhibits abnormal high ex-pression in various malignant tumors,including breast cancer,ovarian cancer,and thyroid cancer,and has been demonstrated to significantly promote the invasive and migratory capabilities of tumor cells,suggesting its important role in the malignant progression of tumors.Moreover,the expression level of WDR1 is closely related to the clinical prognosis of patients with multiple malignant tumors.Especially in patients with esophageal cancer and osteosarcoma,its high expression often indicates a poor overall survival rate.WDR1 can promote tumor initiation and progression by regulating the Wnt/β-Catenin signaling pathway and the Hippo-YAP signaling pathway.Meanwhile,its expression is also subject to multi-level regulation by transcription activation factors and long non-coding RNAs(lncR-NAs),thereby influencing the proliferation,migration,and other biological behaviors of tumor cells.Additionally,WDR1 can further drive the invasive growth and metastatic potential of tumors by regu-lating the epithelial-mesenchymal transition(EMT)process.This article aimed to systematically re-view the research progress in recent years regarding the biological functions and molecular mechanisms of WDR1 in tumor initiation and development,with a view to providing new theoretical foundations and research directions for the early diagnosis,prognosis assessment,and individualized treatment of clinical tumors.

Objective To investigate the effects of light-at-night exposure on anxiety and depression behaviors in mice and to explore the underlying neural mechanisms.Methods Six-week-old male C57BL/6J mice were randomly assigned to a control(Ctrl)group and a light-at-night exposure(LAN)group.Mice in the LAN group were exposed to 460 nm blue light for 1 h daily during the zeitgeber time(ZT)13-14 while the Ctrl group mice were maintained under a 12-h light/12-h dark cycle.Behavioral tests were conducted at different time points following LAN exposure to evaluate anxiety and depression behaviors in the mice.Immunofluorescence staining was used to observe the effect of LAN on c-fos expressions in the medial prefrontal cortex(mPFC),basal ateral amygdala(BLA),paraventricular nucleus(PVN)and paraventricular thalamus(PVT).ELISA was performed to measure changes in serum corticosterone,adrenocorticotropic hormone(ACTH)and corticotropin-releasing hormone(CRH)levels.Golgi staining was applied to measurethe dendritic spine density and morphology from mPFC and CA1.Western blotting analysis was conducted to detect expression levels of brain-derived neurotrophic factors(BDNFs),phosphorylated tropomyosin receptor kinase B(p-TrkB)/TrkB,postsynaptic density protein 95(PSD95)and synaptophysin(SYP)in the mPFC.Results Mice exhibited anxiety-like behaviors after 14 days of LAN exposure,with depression-like behaviors emerging after 28 days.LAN exposure of 28 days led to a significant increase in the number of c-fos-positive neurons in the mPFC,BLA,PVN and PVT(P＜0.05),resulted in elevated serum corticosterone levels(P＜0.01)and reduced protein expression levels of BDNF and SYP(P＜0.05).Furthermore,there was a marked decrease in synapse numbers and synaptic density in the mPFC(P＜0.01).Conclusion Prolonged exposure to blue light at night enhances neuronal activity in the mPFC and BLA and suppresses the BDNF/TrkB signaling pathway by activating the hypothalamic-pituitary-adrenal axis(HPA),thus leading to synaptic structural and functional damage and inducing anxiety and depression behaviors in mice.

[Objective]To summarize Professor LI Xinmin's clinical experience in treating functional constipation in children based on the theory of spleen movement.[Methods]Through learning from the teacher,reading ancient medical books and sorting out clinical medical cases,this paper expounds the theoretical origin of the spleen-transportation theory,analyzes Professor LI's exploration of the etiology and pathogenesis of functional constipation in children from the perspective of"spleen transportation",as well as the clinical experience in treating children's functional constipation with the spleen-transportation theory,and attaches a verified case for evidence.[Results]Professor LI holds that the main etiology of functional constipation in children is the damage to the spleen and stomach caused by dietary stagnation.The key pathogenesis is characterized by"dry fecal accumulation being the secondary aspect with dysfunction of large intestine conduction,and spleen-stomach deficiency being the primary aspect with disharmony of Qi movement in internal organs",among which the disorder of ascending-descending mechanisms in the spleen-stomach and liver-lung axis is particularly prominent.Guided by the"spleen-transportation"theory and the principle of"three-adaptation therapy",clinical treatment employs the strategies of"strengthening the spleen for root cultivation with tonification in transportation,regulating pivotal mechanisms through combined therapies",forming the spleen-transporting pivot-regulation method featured by"dredging-transportation and pivot-regulation".The self-formulated Yunpi Decoction is used to invigorate spleen-earth,focusing on ascending spleen-Yang,regulating middle-Jiao,and regulating Qi movement.In clinical practice,therapies like digestion-promoting,heat-clearing,purging and Qi-supplementing are flexibly integrated based on concomitant syndromes.The harmony method is adeptly applied to reconcile cold-heat and deficiency-excess,emphasizing that medications should be mild to avoid excessive purgation from damaging vital Qi.The pathogenesis of the attached case belonged to spleen deficiency and lack of health,with poor pivot function and internal food stagnation.The treatment adopted the methods of invigorating the spleen and stomach,regulating Qi and promoting smoothness,guiding stagnation and relieving constipation,and administered with the self-designed modified Yunpi Decoction.[Conclusion]Based on the"spleen-transportation theory",Professor LI applies the spleen-transportation and pivot-regulation method featuring dredging-transportation and pivot-regulation.With its unique theory,this approach provides new ideas and methods for clinical practice,making it worthy of promotion and learning.

Objective:To investigate factors influencing frequent episodes (≥ 4 episodes within 1 year) in children with moderate-to-severe atopic dermatitis (AD) in China.Methods:A national multicenter cross-sectional study was conducted. Patients under the age of 18 years diagnosed with moderate-to-severe AD were enrolled at dermatology clinics in 18 medical institutions across 12 provinces and municipalities in China between June 12 and August 8, 2023. At the time of the visit, their guardians completed a structured questionnaire covering demographic characteristics, clinical features of AD, personal and family history, factors associated with frequent episodes of moderate-to-severe AD, compliance with treatment, and disease awareness. Statistical analyses included t tests, one-way analysis of variance, rank-sum tests, and chi-square tests, with multiple-response analysis applied for multiple-choice questions. Results:A total of 965 valid questionnaires were collected, and 965 children with moderate-to-severe AD were included. Among them, there were 531 males and 434 females, 678 (70.3%) were aged 2 - < 12 years, 837 (86.7%) were from urban areas, the age at onset was 2.47 ± 3.03 years, and the median frequency of AD episodes in the past year was 4 times. These children were divided into 2 groups based on the median episode frequency: < 4-episode group (439 cases, 45.5%) and ≥ 4-episode group (526 cases, 54.5%). Compared with the < 4-episode group, children in the ≥ 4-episode group showed younger ages at onset (2.22 ± 2.98 years vs. 2.76 ± 3.06 years, P = 0.006) and higher proportions of patients with comorbid allergic diseases in both the children themselves (82.9% [436/526] vs. 69.7% [306/439], χ2 = 23.42, P < 0.001) and their relatives (66.0% [347/526] vs. 57.4% [252/439], χ2 = 7.46, P = 0.006). Children in the ≥ 4- episode group also had higher monthly usage of moisturizers (150 [30, 300] g vs. 60 [6, 200] g) and daily frequency of moisturizer use, greater disease awareness, but more severe fear of medication use (all P < 0.05). The region and the human development index level were both significantly associated with the episode frequency (both P < 0.001), with the highest proportion of children from South China in the ≥ 4- episode group (36.3%, 191/526). Children in the ≥ 4-episode group also had a longer duration of topical glucocorticoid use than those in the < 4-episode group ( Z = -2.21, P = 0.027). External triggers associated with AD episodes mainly included heat exposure (50.36%, 486/965), hot water bathing (40.73%, 393/965), seafood (23.52%, 227/965), and dust mites (33.37%, 322/965) . Conclusion:In children with moderate-to-severe AD in China, factors influencing frequent episodes may include residence in southern or economically developed regions, earlier age at onset, having a personal or family history of allergic diseases, and fear of medication use.

Objective To establish and verify a mature and stable glioblastoma(GBM)organoid model,so as to provide an accurate and personalized preclinical model for the research and treatment of GBM.Methods Fresh GBM tissues obtained through surgical procedures were initially processed,and then GBM stem cells(GSCs)were isolated using stem cell culture medium and were identified.Subsequently,GSCs were cultured in organoid culture medium for 3D cultivation,and GBM organoids were successfully obtained.The histological morphology of GBM organoids was observed by hematoxylin-eosin(H-E)staining;the stemness and similarity to the parental tumor were identified by immunofluorescence staining;and the in vivo tumorigenic ability of GBM organoids was identified by orthotopic tumorigenesis experiments in nude mice.Results A total of 7 GBM organoids were constructed from 9 human GBM samples,with a morphology resembling"neurosphere",and the average duration for organoid formation was 1 week.H-E staining results showed that the histological morphology of GBM organoids under high-power microscope was very similar to that of GBM tumor tissues;immunofluorescence staining results indicated that the GBM organoids possessed stemness characteristics and histological cellular similarity;and GBM organoids had a stronger tumorigenic ability compared to ordinary GBM cells in nude mice.Conclusion This study presents a stable and reliable method for constructing GBM organoids retaining the histological characteristics of the original GBM tissue,which providing new insights for future GBM research and clinical practice.

Objective:To investigate the clinical efficacy and major complications (postoperative hemorrhage and cerebral edema) of 3 surgical methods in spontaneous supratentorial intracerebral hemorrhage (SSICH).Methods:A retrospective analysis was performed; 294 patients with SSICH admitted to Department of Neurosurgery, Renmin Hospital of Wuhan University from December 2018 to October 2021 were selected. According to different surgical methods, these patients were divided into neuroendoscopic hematoma removal group ( n=126), stereotactic drilling and drainage group ( n=98), and craniotomy hematoma removal group ( n=70). The surgical efficacy and complications in the 3 groups were analyzed, and the postoperative residual hematoma and edema volumes were quantitatively calculated based on 3D Slicer software. Results:The hematoma evacuation rate in the neuroendoscopic hematoma removal group, stereotactic drilling and drainage group, and craniotomy hematoma removal group was 86.25%±2.27%, 44.45%±3.61%, and 75.45%±2.89%, respectively; Glasgow coma Scale scores at discharge were 13.51±1.28, 11.24±2.17 and 10.25±2.56, respectively; postoperative hemorrhage incidence was 16.1%, 26.0% and 22.9%, respectively; postoperative residual hematoma volume was (18.90±12.33) mL, (25.75±11.43) mL and (22.91±7.93) mL, and postoperative peak edema volume was (37.43±11.07) mL, (39.54±9.43) mL, and (42.26±10.94) mL, respectively; percentage of patients with peak edema on 3-5 days after surgery was 31.0%, 65.3% and 68.6%; the diameter of edema zone was (20.04±2.98) mm, (24.12±5.85) mm and (23.59±3.81) mm, respectively, on 7 days after surgery; percentage of patients with edema resolution was 45.2%, 24.5%, 42.9% and 76.2%, 57.1%, 62.9%, respectively, on 9-11 days and 12-14 days after surgery; these indexes in the neuroendoscopic hematoma removal group were significantly different compared with those in the other two groups ( P<0.05). Conclusion:Compared with stereotactic drilling and drainage or craniotomy hematoma removal, neuroendoscopic surgery can effectively remove the hematoma and reduce the occurrences of postoperative hemorrhage and brain edema.

[Objective]This study aims to investigate the effects of methionine sulfoxide reductase A(MSRA)on the proliferation,apoptosis,invasion,and metastasis of clear cell renal cell carcinoma(ccRCC)through cellular and animal experiments to elucidate its potential biological mechanisms,providing new molecular targets and strategies for the treatment of ccRCC.[Methods]MSRA-overexpressing cell lines were constructed with transfection.The effects of MSRA on the proliferation,apoptosis,invasion,and migration of ccRCC cells were assessed through proliferation assays,colony formation assays,apoptosis assays,wound healing assays,and invasion assays.Further,the mechanisms and related signaling pathways were explored via ROS detection,RT-qPCR,and Western blot.Subsequently,a subcutaneous xenograft mouse model was employed to verify the effect of MSRA on ccRCC tumor growth and metastasis at the animal level to explore its potential molecular mechanisms.[Results]The mRNA and protein expressions of MSRA in OS-RC-2 and 786-O cell lines were low(RT-qPCR:0.57±0.09,0.56±0.04;WB:0.26±0.13,0.24±0.09).RT-qPCR and Western blot experiments confirmed the successful construction of OS-RC-2-pLVSO2-MSRA(RT-qPCR:108.04±1.80;WB:117.01±20.19)and 786-O-pLVSO2-MSRA(973.45±51.37;WB:190.34±30.13)overexpressed cell lines,with statistically significant differences(P＜0.001).Proliferation assays showed reduced proliferation in OS-RC-2-pLVSO2-MSRA(72 h:1.246±0.003)and 786-O-pLVSO2-MSRA(72 h:1.468±0.001),with significant differences(P＜0.001).Colony formation assays revealed a decrease in colony numbers in OS-RC-2-pLVSO2-MSRA(0.090±0.002)and 786-O-pLVSO2-MSRA(0.080±0.002),with significant differences(P＜0.001).Apoptosis assays demonstrated increased apoptosis rates in OS-RC-2-pLVSO2-MSRA(2.013±0.116)and 786-O-pLVSO2-MSRA(4.767±0.199),with significant differences(P＜0.001).Wound healing assays indicated less migration distance in OS-RC-2-pLVSO2-MSRA(0.643±0.028)and 786-O-pLVSO2-MSRA(0.603±0.034),with significant differences(P＜0.001).Transwell assays showed a reduction in the numbers of penetrative cells in OS-RC-2-pLVSO2-MSRA(16.80±2.28)and 786-O-pLVSO2-MSRA(21.40±4.78),with significant differences(P＜0.001).Fluorescence assays indicated a decreased ROS levels in OS-RC-2-pLVSO2-MSRA(50.59±6.24)and 786-O-pLVSO2-MSRA(62.87±5.35),with significant differences(P＜0.001).Western blot analysis showed a decrease in the expression of N-cadherin and Vimentin,and an increase in the expression of E-cadherin in OS-RC-2-pLVSO2-MSRA and 786-O-pLVSO2-MSRA(P＜0.001).Western blot analysis revealed a significant decrease in the expression levels of p-ERK1/2 and p-SMAD3 in OS-RC-2-pLVSO2-MSRA and 786-O-pLVSO2-MSRA(P＜0.001).Animal experiments showed reduced tumor volumes in OS-RC-2-pLVSO2-MSRA(155.00±50.46),with significant differences(P＜0.001).Western blot analysis of tumor tissues from animals confirmed the decreased expression of N-cadherin and Vimentin,and the increased expression of E-cadherin,with significant differences(P＜0.001).IHC experiments of OS-RC-2-pLVSO2-MSRA tumors revealed a decrease in the expression of Ki-67,N-cadherin,and Vimentin,and an increase in the expression of E-cadherin,with significant differences(P＜0.001).[Conclusion]MSRA overexpression inhibits ROS expression in ccRCC,suppresses the EMT process,and consequently inhibits the proliferation,invasion,and metastasis of ccRCC.

Severe open tibiofibular fractures account for approximately 28.1% of all open fractures. Among them, Gustilo-Anderson type IIIB/C fractures present significant clinical challenges due to associated bone and soft tissue defects, high infection rates, and risk of amputation. Inadequate preoperative assessment may lead to suboptimal emergency surgical planning or intraoperative complications. Historically, external fixation was often preferred, but this approach has been associated with limitations such as restricted joint mobility, delayed bone union, joint stiffness, and disuse osteoporosis, resulting in poor functional recovery. With advancements of debridement techniques, standardization of antibiotic use, and popularization of early soft tissue coverage, early internal fixation has gained broader acceptance. Nevertheless, controversies persist regarding the choice of fixation method, timing of definitive fixation, use of reamed versus unreamed intramedullary nailing, and necessity of fibular fixation. To standardize the diagnosis and early management of severe open tibiofibular fractures, reduce complication rates, and improve functional recovery, the Society of Microsurgery of the Chinese Medical Association organized a panel of domestic experts to develop the Evidence-based guideline for the diagnosis and early fixation of severe open tibiofibular fractures ( version 2025), using evidence-based methodology. The guidelines provided 12 recommendations covering diagnostic and early fixation strategies of severe open tibiofibular fractures, aiming to provide clinicians with scientifically grounded and standardized guidance.