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.

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 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 explore the application value of CMR myocardial strain technique in eld-erly males with HCM.Methods A retrospective analysis was conducted on 50 elderly male pa-tients who underwent CMR examination at the Second Medical Center of Chinese PLA General Hospital from April 2020 to December 2024.According to being diagnosed with HCM or not,they were divided into a HCM group(24 cases)and a control group(26 cases).Post-processing soft-ware CVI42 was used to obtain two sets of basic functional and strain parameters of the left ven-tricle(LV)and left atrium(LA).The parameters of LV included LV mass,LV mass index(LV massi),global longitudinal strain(GLS),and so on,while the parameters of LA included minimum LA volume(LAV),minimum LA volume index(LA VI),LA passive strain(εe),LA peak early negative strain rate(SRe)and LA peak late negative strain rate(SRa),etc.The two sets of LV and LA parameters of basic functional and strain were compared between the two groups.Results The HCM group had significant higher LV mass and LV massi and minimum LAV and LAVI,but lower GLS,εe,SRe and SRa in 2D and 3D speckle-tracking echocardiography than the control group(P＜0.05,P＜0.01).The AUC value of 2D GLS,SRa,and logistic regres-sion model in predicting HCM was 0.887(95％CI:0.766-0.959),0.740(95％CI:0.597-0.854),and 0.929(95％CI:0.820-0.983),respectively,with a sensitivity of 76.92％,57.69％,and 84.62％,and a specificity of 70.83％,83.33％,and 91.67％,respectively.The logistic regression model demonstrated higher AUC value,sensitivity,and specificity than 2D GLS and SRa.Conclusion CMR myocardial strain technology is of significant diagnostic value for elderly male patients with HCM.

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*

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.