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

OBJECTIVE: To analyze the phenotype and genotype of a neonate with Hypoparathyroidism-sensorineural deafness-renal dysplasia syndrome (HDR). METHODS: A female neonate with HDR syndrome and thyroid deficiency detected at the First Affiliated Hospital of Zhengzhou University on December 6,2023 was selected as the study subject, Low-coverage whole-genome sequencing (Lc WGS) and whole exome sequencing (WES) were carried out. Using "hypoparathyroidism""sensorineural deafness""renal dysplasia""HDR""Barakat" and"GATA3" as keywords, the CNKI, Wanfang Data Knowledge Service Platform and PubMed database were searched, and the retrieval time was set from the establishment to March 2025. RESULTS: A proband, a full-term female infant, had presented with feeding difficulty, micrognathia, and low-set ears. Serological test revealed hypocalcemia, hyperphosphatemia, hypoparathyroidism, low T3, low T4 and high TSH. Hearing test revealed bilateral sensorineural deafness. Ultrasonic test revealed absence of right kidney and thyroid. WES revealed that the she has harbored a deletion of approximately 6.67 Mb at 10p15.1p13, and Lc WGS confirmed the presence of a 6.70 Mb deletion in the same region, which was verified as a de novo variant. Literature review suggested that HDR was rarely diagnosed among neonates. Among the nine cases diagnosed in neonatal period, 66.6% (6/9) exhibited the typical triad, 77.7% (7/9) had hypoparathyroidism with hypocalcemic convulsion as the initial symptom, 22.2% (2/9) had sensorineural hearing loss or renal malformation, and 66.6% (6/9) had multiple malformations including facial dysmorphism and congenital heart disease. 55.5% (5/9) had a large deletion in the 10p15 region, whilst 33.3% (3/9) had a single gene variant. The range of the deletion had correlated with the diversity of clinical phenotypes in HDR syndrome, but the classic triad of symptoms may presented in any combination, independent of deletion size. Association of HDR with thyroid deficiency has been unreported previously. CONCLUSION For neonates presenting with one of the symptoms of HDR triad or in combination with other malformations, genetic testing should be carried out.
Humans ; Hypoparathyroidism/diagnosis* ; Female ; Infant, Newborn ; Hearing Loss, Sensorineural/diagnosis* ; GATA3 Transcription Factor/genetics* ; Nephrosis/genetics* ; Phenotype ; Exome Sequencing

Objective To evaluate the longitudinal imaging features of coronary artery plaques in elderly male patients with CHD and myocardial bridges and explore the longitudinal changing pat-terns.Methods A total of 117 elderly male CHD patients who underwent two examinations of coronary computed tomography angiography in our medical center from January 2018 to Septem-ber 2023 were enrolled in this study.Then 216 small plaques(0.1-50 mm3 in size)were subjec-ted,and classified into the proximal myocardial bridge group(98 plaques)and other heart part group(118 plaques)according to the site of the plaques.Plaque volume,plaque composition vol-ume,FAI,and CT-derived fraction flow reserve(CT-FFR)were calculated and recorded.Results In the 2 groups of plaques,there were no statistically differences in the plaque length,plaque nec-rotic core volume,and FAI derived from the second examination than the baseline one(P＞0.05).The plaque volume,intra-plaque fibers,and dense calcified volume of plaques in the second exami-nation were significantly greater than those at baseline,and CT-FFR was obviously smaller than the baseline level in both groups(P＜0.05,P＜0.01).In the proximal myocardial bridge group,the intra-plaque fibrofat volume in the second examination was significantly larger than that of baseline,while opposite phenomenon was observed in the plaques of the other heart part group(P＜0.05).The annual changing rates of intraplaque fibrofat volume and FAI were significantly higher in the proximal myocardial bridge group than the other heart part group[0.51％(-0.32％,0.51％)vs 0.02％(-0.46％,0.20％),P=0.046;0.55％(-2.44％,1.76％)vs 0.33％(-1.36％,2.63％),P=0.044].Conclusion In elderly male patients,the intraplaque fibrofat vol-ume,FAI and CT-FFR are more likely to change in the proximal plaques of the left anterior de-scending artery myocardial bridge than the plaques of other parts of heart,so the proximal plaques of the left anterior descending artery need more clinical attention and early intervention.

Objective To investigate the value of serum lipoprotein-associated phospholipase A2(Lp-PLA2)for predicting high-risk coronary plaques in elderly males.Methods A retrospective study was conducted on 46 elderly males aged ≥60 years undergoing health check-ups and coro-nary computed tomography angiography in our hospital between May and July 2024.Their general clinical data were collected.Artificial intelligence software was used to analyze coronary calcium scores and plaque characteristics.The participants were divided into a high-risk plaque group(n=15)and a non-high-risk plaque group(n=31).The differences were compared between the two groups.Multivariate logistic regression analysis was used to identify the influencing factors for high-risk coronary plaques.ROC curve was plotted to determine the predictive value of serum Lp-PLA2 for high-risk plaques,and its AUC value was calculated.Results The high-risk plaque group had significantly larger proportions of smoking history and hyperlipidemia,and higher level of homocysteine and Lp-PLA2 than the non-high-risk plaque group(P＜0.05,P＜0.01).Multiva-riate logistic regression analysis indicated that Lp-PLA2 was an independent risk factor for high-risk coronary plaques(HR=1.030,95％CI:1.008-1.053,P＜0.05).ROC curve analysis revealed that the AUC value of Lp-PLA2 in predicting high-risk coronary plaques was 0.833(95％CI:0.694-0.927,P＜0.01),with a sensitivity of 93.3％,a specificity of 71.0％,a positive predictive value of 62.5％,and a negative predictive value of 100％.Conclusion Serum Lp-PLA2 is of signif-icant value in predicting high-risk coronary plaques in elderly men.

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 discuss the regulatory mechanism of nucleotide-binding oligomerzation domain 2(NOD2)/receptor interacting protein 2(RIP2)signaling pathway on inflammatory activation of macrophages in intestinal mucosa and provide experimental evidence for intestinal mucosal inflammation caused by bacterial products.Methods Using the THP-1 monocyte cell line,macrophages were stimulated with muramyl dipeptide(MDP)at varying concentrations and durations.mRNA and protein expression levels of NOD2 and RIP2 were detected.The secretion levels of tumor necrosis factor(TNF)-α and interleukin(IL)-1β in the cell culture supernatant were measured.The most effective siRNA targeting RIP2 and optimal transfection concentration were screened,and the impact of RIP2 gene silencing on MDP-induced inflammatory activation of macrophages was observed.Results After silencing the RIP2 gene,MDP induced a significant decrease in TNF-α and IL-1βsecretion in macrophages,but the changes in cell phenotype were not significantly affected.Conclusion This study revealed the important role of NOD2/RIP2 signaling pathway in inflammatory activation of macrophages,and it is possible to effectively inhibit inflammatory activation of macrophages by interfering with this signaling pathway.

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.

Objective:To analyze the phenotype and genotype of a neonate with Hypoparathyroidism-sensorineural deafness-renal dysplasia syndrome (HDR).Methods:A female neonate with HDR syndrome and thyroid deficiency detected at the First Affiliated Hospital of Zhengzhou University in on December 6, 2023 was selected as the study subject, Low-coverage whole-genome sequencing (Lc WGS) and whole exome sequencing (WES) were carried out. Using " hypoparathyroidism" " sensorineural deafness" " renal dysplasia" " HDR" " Barakat" and" GATA3" as keywords, the CNKI, Wanfang Data Knowledge Service Platform and PubMed database were searched, and the retrieval time was set from the establishment to March 2025. Results:A proband, a full-term female infant, had presented with feeding difficulty, micrognathia, and low-set ears. Serological test revealed hypocalcemia, hyperphosphatemia, hypoparathyroidism, low T3, low T4 and high TSH. Hearing test revealed bilateral sensorineural deafness. Ultrasonic test revealed absence of right kidney and thyroid. WES revealed that the she has harbored a deletion of approximately 6.67 Mb at 10p15.1p13, and Lc WGS confirmed the presence of a 6.70 Mb deletion in the same region, which was verified as a de novo variant. Literature review suggested that HDR was rarely diagnosed among neonates. Among the nine cases diagnosed in neonatal period, 66.6% (6/9) exhibited the typical triad, 77.7% (7/9) had hypoparathyroidism with hypocalcemic convulsion as the initial symptom, 22.2% (2/9) had sensorineural hearing loss or renal malformation, and 66.6% (6/9) had multiple malformations including facial dysmorphism and congenital heart disease. 55.5% (5/9) had a large deletion in the 10p15 region, whilst 33.3% (3/9) had a single gene variant. The range of the deletion had correlated with the diversity of clinical phenotypes in HDR syndrome, but the classic triad of symptoms may presented in any combination, independent of deletion size. Association of HDR with thyroid deficiency has been unreported previously.Conclusion:For neonates presenting with one of the symptoms of HDR triad or in combination with other malformations, genetic testing should be carried out.

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 construct a targeted drug delivery system, Ang-BEVs@Dox, based on Angiopep-2 peptide-modified bacterial extracellular vesicles （BEVs） loaded with doxorubicin （Dox）, overcome the challenges of blood-brain barrier （BBB） penetration and systemic toxicity in chemotherapy for glioblastoma （GBM）, enhance drug targeting to brain tumors and reduce its toxic side effects. Methods BEVs derived from Escherichia coli were isolated using ultracentrifugation. The targeting ligand Angiopep-2, specific for the LRP-1 receptor, was conjugated onto the surface of BEVs to construct the targeted carrier （Ang-BEVs）. Dox was loaded into Ang-BEVs using low-frequency sonication to form Ang-BEVs@Dox. The physicochemical properties （morphology and size） of the carriers were characterized by transmission electron microscopy （TEM） and dynamic light scattering （DLS）. The BBB-penetrating capability, in vitro/in vivo anti-tumor efficacy, and biosafety of the system were evaluated using cellular uptake assays, 3D tumor spheroid models, and orthotopic tumor-bearing mouse models. Results ① Carrier characterization and in vitro efficacy: Ang-BEVs@Dox exhibited a particle size of approximately 100 nm and maintained structural stability after Dox loading. It significantly enhanced cellular uptake efficiency in U87MG cells and achieved deep penetration within 3D tumor spheroids. Cytotoxicity assays demonstrated synergistic anti-tumor effects between the BEVs and Dox in the Ang-BEVs@Dox system. ② In vivo targeting and anti-tumor efficacy: In orthotopic tumor-bearing mouse models, Ang-BEVs@Dox effectively penetrated the BBB and significantly inhibited tumor growth, extending the median survival time of tumor-bearing mice to 33.5 days （compared to 23.5 days in the blank control group, P<0.001）. Immunohistochemical analysis revealed significant suppression of the tumor cell proliferation marker Ki-67 and enhancement of the apoptosis marker TUNEL staining signals. ③ Biosafety: Major organs from mice in the Ang-BEVs@Dox treatment group showed no observable pathological damage, indicating good biosafety. Conclusion This study successfully constructed an Angiopep-2 peptide-modified engineered BEVs delivery system （Ang-BEVs@Dox）. Through Angiopep-2-mediated BBB penetration and tumor targeting, it significantly enhanced the accumulation and therapeutic efficacy of BEVs at the GBM site. This method combined efficient delivery, low systemic toxicity, and clinical translation potential, which provided an innovative solution to overcome the therapeutic bottleneck in GBM treatment.