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

Purpose: Our previous study showed that circulating tumor cell (CTC) count combined with gene mutation detection might help differentiate benign and malignant pulmonary nodules (PNs). Herein, we aimed to expand the study cohort and conduct further sequencing analysis. Materials and Methods: Patients with PNs were included, and CTCs were identified before operation. Low-coverage whole-genome sequencing (LC-WGS) and lung cancer-related targeted gene sequencing were performed on CTCs. The diagnostic efficacy was evaluated by receiver operating characteristic (ROC) curve. The differences in CTC counts among subgroups classified by demographic–clinical characteristics were analyzed. LC-WGS–based copy number variation (CNV) analysis and targeted gene mutation analysis were conducted. Results: A total of 172 patients were included. CTC count of 2.5 was identified by the ROC curves as the optimal diagnostic cutoff. The sensitivity and specificity of CTC count for differentiating benign and malignant PNs were 54.2% and 78.6%, respectively. The diagnostic sensitivity and specificity of combined CTC count, radiological nodule type, and any malignant imaging features were 84.7% and 71.4%, respectively. The CTC counts were significantly greater in patients with aggressive tumors, later stage, and spread through air spaces. CTCs from malignant cases had more CNVs than those from benign cases. Conclusion CTC count can be used in identifying malignant PNs. The diagnostic efficacy can be improved if combined with computed tomography imaging characteristics. Further CNV analysis might help differential diagnosis. Greater CTC count might suggest more aggressive tumors. CTC detection can provide important information and guidance for subsequent management of PNs.

Inflammation plays a pivotal role in the etiology and progression of various diseases. In traditional Chinese medicine, the whole plants of Thesium chinense Turcz. and its preparations (e.g. Bairui Granules) have been employed to manage inflammatory conditions. While flavonoids were previously considered the primary anti-inflammatory components, other potentially active constituents have been largely overlooked and not thoroughly investigated. This study presents a novel finding that the total alkaloids of T. chinense (BC-Alk) are potent active substances underlying the traditional and clinical applications of T. chinense and Bairui Granules as anti-inflammatory agents. UPLC-MS/MS analysis identified the composition of BC-Alk as quinolizidine alkaloids. The anti-inflammatory efficacy of BC-Alk was evaluated using a lipopolysaccharide (LPS)-induced lung inflammation model in mice. Results demonstrated that BC-Alk significantly mitigated LPS-induced lung inflammation, attenuated the overproduction of IL-1β and the overproduction of inflammatory factors (TNF-α), and ameliorated lung tissue hyperplasia in mice in vivo. Mechanistic studies in vitro revealed that BC-Alk upregulated the expression of Nrf2 and its downstream proteins NQO1 and glutamate-cystine ligase and modifier subunit (GCLM), inhibited NF-κB phosphorylation, and suppressed NLRP3 activation. Collectively, these findings indicate that BC-Alk exerts potent inhibitory effects against lung inflammation by modulating Nrf2, NF-κB, and NLRP3 pathways. This study provides new insights into the anti-inflammatory constituents of T. chinense and Bairui Granules.
Animals ; Lipopolysaccharides/adverse effects* ; Alkaloids/pharmacology* ; NF-kappa B/metabolism* ; NF-E2-Related Factor 2/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Mice ; Signal Transduction/drug effects* ; Anti-Inflammatory Agents/pharmacology* ; Male ; Mice, Inbred C57BL ; Humans ; Drugs, Chinese Herbal/administration & dosage* ; Pneumonia/genetics*

Adolescents and young adults (AYAs) are one of the major populations susceptible to tuberculosis. However, little is known about the unique characteristics and diagnostic biomarkers of tuberculosis in this population. In this study, 81 AYAs were recruited, and the high-quality serum proteome of the AYAs with tuberculosis was profiled by quantitative proteomics. The data of serum proteomics indicated that the relative abundance of hemoglobin and apolipoprotein was significantly reduced in the patients with active tuberculosis (ATB). The pathway enrichment analysis showed that the downregulated proteins in the ATB group were mainly involved in the antioxidant and cell detoxification pathways, indicating extensive oxidative stress damage. Random forest (RF) and extreme gradient boosting (XGBoost) were employed to evaluate protein importance, which yielded a set of candidate proteins that can distinguish between ATB and non-ATB. The analysis with the support vector machine algorithm (recursive feature elimination) suggested that the combination of apolipoprotein A-I (APOA1), hemoglobin subunit beta (HBB), and hemoglobin subunit alpha-1 (HBA1) had the highest accuracy and sensitivity in diagnosing ATB. Meanwhile, the levels of hemoglobin (HGB) and albumin (ALB) can be used as blood biochemical indicators to evaluate changes in the protein levels of APOA1 and HBB. This study established the serum proteome landscape of AYAs with tuberculosis and identified new biomarkers for the diagnosis of tuberculosis in this population.
Humans ; Proteomics/methods* ; Biomarkers/blood* ; Adolescent ; Young Adult ; Apolipoprotein A-I/blood* ; Machine Learning ; Tuberculosis/blood* ; Proteome/analysis* ; Male ; Hemoglobins/analysis* ; Female ; Blood Proteins/analysis* ; Adult

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 compare the effectiveness of video laryngoscopy and traditional direct laryngoscopy in neonatal endotracheal intubation teaching.Methods:A total of 52 undergraduate clinical interns in the Department of Neonatology at the First Clinical School of Medicine of Zhengzhou University in June 2024 were selected.The participants were randomly divided into a video laryngoscopy group and a traditional direct laryngoscopy group.After the training，skill assessments were conducted.And a questionnaire was used to evaluate whether there were differences in terms of teaching arrangement, teaching methods, classroom interaction, and teachers' attitudes.Results:The skill assessment score of the video laryngoscope group was (72.85 ± 3.36) points, significantly higher than that of the direct laryngoscope group[(65.81 ± 2.80) points], with a statistically significant difference ( P<0.05). The glottis recognition rate in the video laryngoscope group (88.46%) was higher than that in the direct laryngoscope group (61.54%) ( P<0.05).The intubation success rate in the video laryngoscope group (69.23%) was also higher than that in the direct laryngoscope group (38.7%) ( P<0.05). The results of the teaching satisfaction survey questionnaire showed that the satisfaction ratio for teaching methods in the video laryngoscope group was higher than that in the direct laryngoscope group ( P<0.05), while there were no statistically significant differences between the two groups in terms of teaching arrangements, classroom interaction, assessment and evaluation methods, and teacher attitudes ( P>0.05). Conclusion:Using video laryngoscopy for teaching helps interns better master neonatal tracheal intubation skills and is worth promoting.

Objective:To compare the effectiveness of video laryngoscopy and traditional direct laryngoscopy in neonatal endotracheal intubation teaching.Methods:A total of 52 undergraduate clinical interns in the Department of Neonatology at the First Clinical School of Medicine of Zhengzhou University in June 2024 were selected.The participants were randomly divided into a video laryngoscopy group and a traditional direct laryngoscopy group.After the training，skill assessments were conducted.And a questionnaire was used to evaluate whether there were differences in terms of teaching arrangement, teaching methods, classroom interaction, and teachers' attitudes.Results:The skill assessment score of the video laryngoscope group was (72.85 ± 3.36) points, significantly higher than that of the direct laryngoscope group[(65.81 ± 2.80) points], with a statistically significant difference ( P<0.05). The glottis recognition rate in the video laryngoscope group (88.46%) was higher than that in the direct laryngoscope group (61.54%) ( P<0.05).The intubation success rate in the video laryngoscope group (69.23%) was also higher than that in the direct laryngoscope group (38.7%) ( P<0.05). The results of the teaching satisfaction survey questionnaire showed that the satisfaction ratio for teaching methods in the video laryngoscope group was higher than that in the direct laryngoscope group ( P<0.05), while there were no statistically significant differences between the two groups in terms of teaching arrangements, classroom interaction, assessment and evaluation methods, and teacher attitudes ( P>0.05). Conclusion:Using video laryngoscopy for teaching helps interns better master neonatal tracheal intubation skills and is worth promoting.

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 establish a reference interval for the pepsinogen(PG)Ⅰ,PGⅡ and PGⅠ/PGⅡ in healthy adult subjects in Zhejiang Province.Methods The data of 45 504 healthy adult subjects were collected,and the levels of serum PGⅠ and PG Ⅱ were detected by chemiluminescence microparticle immunoassay.The reference range of PGs were determined according to the CLSI-C28-A3 file.Results The median serum PGⅠ concentration in male was 132.62μg/L,PGⅡ concentration was 8.10μg/L,and PGⅠ/PGⅡ was 15.9.For females,they were 107.44μg/L,6.96μg/L and 15.0,respectively.PGI,PGⅡ concentration and PGⅠ/PGⅡ ratio were significantly higher in males than in females(P<0.001).The levels of PGⅠ and PGⅡ increased with age(P<0.001).Serum PGⅠ reference interval for male:59.79-234.97μg/L for 19-39 years old,63.33-294.62μg/L for 40-59 years old,64.25-333.61μg/L for≥60 years old,PGⅡ reference interval:3.33-22.60μg/L for 19-39 years of age,3.79-33.89μg/L for 40-59 years of age,4.15-42.08μg/L for≥60 years of age,PGⅠ/PGⅡ reference interval:those aged 19-39 years ranged from 7.3 to 31.4,those aged 40-59 years ranged from 5.8 to 30.9,and those aged≥60 years ranged from 3.9 to 30.7.The reference intervals of female PGⅠ were 48.79-215.68μg/L,52.10-276.01μg/L,and 64.34-317.20μg/L,respectively.The reference intervals of female PgⅡwere:2.87-23.93μg/L,3.41-33.31μg/L and 3.88-39.16μg/L,respectively.The reference intervals of of female PGⅠ/PGⅡ are 6.6-28.1,5.2-27.9 and 3.6-26.2.Conclusion This study determined the reference range of serum PGs deficiency in healthy subjects of different sex and age in Zhejiang Province.

Objective To investigate the longitudinal association between alcohol abstinence and accelerated biological aging among middle-aged and older adults and to explore the potential effect modifiers influencing the association.Methods Utilizing the clinico-biochemical and anthropometric data from the baseline and first repeat survey of the UK Biobank(UKB),we employed the Klemera and Doubal method(KDM)to construct the biological age(BA)and calculate BA acceleration.Change analysis based on multivariate linear regression models was employed to explore the association between changes in alcohol abstinence and changes in BA acceleration.Age,sex,smoking status,tea and coffee consumption,and body mass index were considered as the stratification factors for conducting stratified analysis.Results A total of 5 412 participants were included.Short-term alcohol abstinence(β=1.00,95%confidence interval[CI]:0.15-1.86)was found to accelerate biological aging when compared to consistent never drinking,while long-term abstinence(β=-0.20,95%CI:-1.12-0.71)did not result in a significant acceleration of biological aging.Body mass index may be a potential effect modifier.Conclusion Short-term alcohol abstinence was associated with accelerated biological aging,but the effect gradually diminishes over extended periods of abstinence.