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:Increasing evidence supports the association between different exercise intensities and the risk of osteoarthritis,but this may be affected by confounding and reverse causality,and the conclusions have not been unified. OBJECTIVE:To explore the causal association between different exercise intensities and osteoarthritis using Mendelian randomization method. METHODS:Data from genome-wide association studies associated with different exercise intensities were selected,and instrumental variables were screened with a threshold of P＜5×10-8.Causal associations between exposure and risk of outcome were assessed using five analysis methods of Mendelian randomization with inverse variance weighting as the primary analysis method.Selected instrumental variables were used to assess causal associations between different exercise intensities and osteoarthritis,and sensitivity analyses with inverse Mendelian randomization were performed. RESULTS AND CONCLUSION:In the analysis results of the inverse variance weighting method,low-intensity exercise showed a significant protective effect on knee osteoarthritis[odds ratio(OR)=0.14,95%confidence interval(CI):0.06-0.32,P＜0.001],while sedentary behavior without exercise intensity,such as watching TV,was confirmed to be a risk factor for knee osteoarthritis and hip osteoarthritis(OR=2.24,95%CI:1.74-2.88,P＜0.001;OR=1.34,95%CI:1.01-1.78,P=0.04).Through the reverse Mendelian randomization analysis of osteoarthritis to different exercise intensities,it was found that osteoarthritis was negatively correlated with low-intensity exercise and positively correlated with watching TV.The analysis results show that there is a two-way causal relationship between different exercise intensity and osteoarthritis risk.

Neurofibromas are benign peripheral nerve sheath tumors. It is more common in neurofibromatosis type Ⅰ. However, isolated vagal nerve neurofibroma（VNN） of the neck is extremely rare, and only a few case reports have been reported. Its etiology and pathogenesis are not clear. The diagnosis is mainly based on pathological examination and immunohistochemistry, and surgical resection is the main treatment. This study reports a rare case of giant solitary vagus neurofibroma in the neck. The patient was a 29-year-old female who was found to have a mass on the right side of the neck by physical examination, which was considered to be a vagus nerve tumor by neck ultrasound and imaging examination. The tumor was completely removed during the operation, with the size of about 10.0 cm×2.5 cm, and the patient had no special discomfort. Postoperative pathology and immunohistochemistry confirmed neurofibroma. After surgery, the patient had right vocal cord paralysis, hoarseness, choking and paroxysmal cough. After swallowing function training and voice rehabilitation treatment in the department, the patient recovered satisfactorily. There was no complication and recurrence during the follow-up of 1 year. This article reviews the literature to improve the diagnosis and treatment of solitary vagus neurofibroma in the neck by combining its medical history, imaging features, pathology and immunohistochemistry, and surgical treatment.
Humans ; Female ; Adult ; Neurofibroma ; Vagus Nerve/pathology* ; Neck ; Cranial Nerve Neoplasms

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

Tracheostomy is a very common airway procedure in the treatment of critically ill neurological patients. At present, the traditional tracheal cannula fixation belt is easy to be contaminated, difficult to disinfect, and needs to be replaced regularly. It is prone to infection, skin injury, unplanned extubation and other adverse events, which cannot meet the clinical treatment effect and patient safety management. In order to overcome the above problems, the medical staff of the neurology intensive care unit of Henan Provincial People's Hospital designed a new type of tracheal cannula fixation belt to increase patient comfort and reduce complications, and obtained a National Utility Model Patent of China (ZL 2022 2 0855188.8). The main structure of the device includes a following shaped bending plate, a fastening belt, a locking pin, and a distance adjustment hole. The left and right sides of the shaped bending plate are equipped with fastening belts with breathable and anti-wear pads. The inner side of the left fastening belt is equipped with two sets of locking pins, and the outer surface of the right fastening belt and breathable and anti-wear pad is equipped with multiple sets of distance adjustment holes. Additionally, the back of the shaped bending plate is equipped with breathable buffer pads. The fastening belt can drive the following bending plate to stick tightly to the patient's neck. The operator installs the locking pin card into the distance adjustment hole according to the "one back" principle, and the fastening belts on both sides fix the device with the cooperation of the locking pin, greatly reducing the probability of excessive displacement of the tracheal tube during use, effectively improving the fixation effect of the device, strengthening the adaptability of the device to different personnel, and thus enhancing the practicality of the device. The new type of tracheal cannula fixation band is convenient, safe and efficient, which can increase patient comfort, reduce complications. It has certain clinical value and is suitable for clinical promotion.

Objective To explore the clinical effects of hypoglycemic drugs on depression degree in patients with type 2 diabetes mellitus(T2DM).Methods A total of 160 newly diagnosed T2DM patients or T2DM patients who have not used hypoglycemic drugs in the past 3 months with mild to moderate depressive episodes and visited our outpatient department were enrolled in this study from January to December 2022.All the participants HbA1c were ranged from 7%to 9%.They were randomly divided into four groups:Metformin treatment group(Met,n=40),Met combined with sulfonylurea treatment group(Met+SUs,n=40),Met combined with DPP-4i treatment group(Met+DPP-4i,n=40),and Met combined with GLP-1 receptor agonist treatment group(Met+GLP-1RA,n=40).All the patients were scored with the Hamilton Depression Rating Scale(HAMD)and the Hamilton Anxiety Rating Scale(HAMA)in each group.Results The Met+DPP-4i and Met+GLP-1RA groups showed the most significant decrease in HAMD and HAMA scores after treatment(P<0.05),while the proportion of moderate depression and significant anxiety in HAMD decreased(P<0.05).Pearson correlation analysis showed that?HAMD,?HAMA were positively correlated with ?HbA1c in the Met+GLP-1RA group(P<0.05).Conclusion The combination of Met with DPP-4i and GLP-1RA has the most significant effect on improving the degree of depression in patients with T2DM and depression.

Objective To explore the blood group changes of two acute myeloid leukemia patients with suspected O type,and their relationship with the therapeutic effect.Methods Serological analysis of ABO blood group of patients was carried out by microcolumn gel method,tube method and absorption-elution test,ABO blood group genotyping was per-formed by microfluidic chip method.Exons E2 to E7 of ABO gene were amplified by PCR and sequenced by Sanger method.Results The forward typing of two cases were both O type,but the reverse typing were both A type.The absorption-elution test results all showed detection of antigen A.ABO gene phenotype of the two cases were both A,with genotyping results as A102/A102 and A102/O01,respectively.Sequencing results showed that SNP sites of ABO blood group were 467T/T,261G/delG and 467C/T,respectively.In one case,the intensity of anti-A agglutination reaction changed significantly from weak to strong with the progress of treatment.Conclusion For clinical samples of acute myeloid leukemia patients with ABO for-ward and reverse typing discrepancy and suspected O type,the result of reverse typing should be valued,and absorption-e-lution test should be performed to further confirm the ABO blood type combining the genetic test results,so as to develop ap-propriate blood transfusion strategies for patients.

Gorham-Stout disease(GSD)is a sporadic chronic disease characterized by progressive bone dissolution,absorption,and disappearance along with lymphatic vessel infiltration in bone-marrow cavities.Although the osteolytic mechanism of GSD has been widely studied,the cause of lymphatic hyperplasia in GSD is rarely investigated.In this study,by comparing the RNA expression profile of osteoclasts(OCs)with that of OC precursors(OCPs)by RNA sequencing,we identified a new factor,semaphorin 3A(Sema3A),which is an osteoprotective factor involved in the lymphatic expansion of GSD.Compared to OCPs,OCs enhanced the growth,migration,and tube formation of lymphatic endothelial cells(LECs),in which the expression of Sema3A is low compared to that in OCPs.In the presence of recombinant Sema3A,the growth,migration,and tube formation of LECs were inhibited,further confirming the inhibitory effect of Sema3A on LECs in vitro.Using an LEC-induced GSD mouse model,the effect of Sema3A was examined by injecting lentivirus-expressing Sema3A into the tibiae in vivo.We found that the overexpression of Sema3A in tibiae suppressed the expansion of LECs and alleviated bone loss,whereas the injection of lentivirus expressing Sema3A short hairpin RNA(shRNA)into the tibiae caused GSD-like phenotypes.Histological staining further demonstrated that OCs decreased and osteocalcin increased after Sema3A lentiviral treatment,compared with the control.Based on the above results,we propose that reduced Sema3A in OCs is one of the mechanisms contributing to the pathogeneses of GSD and that expressing Sema3A represents a new approach for the treatment of GSD.

Objective:To understand the negative experiences of male master of nursing students during their studies.Methods:In this qualitative study, totally 11 male master of nursing students from China Medical University and Wuhan University were selected by purposive sampling in March 2023 for semi-structured interviews, and the data were analyzed using the KJ method.Results:Four themes were extracted: research pressure, pressure of time and finances, confusion about the future and development, and lack of identification with the nursing profession.Conclusions:Male master of nursing students experience negative emotions during their studies. Nursing educators and administrators should pay attention to the emotional management of male master of nursing students and gradually improve the training methods for nursing graduate students.

Objective This study was performed to explore the use of intramuscular low-dose Zoletil(1.5 mg/kg)combined with isoflurane inhalation for tracheal intubation in miniature pigs while preserving spontaneous respiration by determining the 50％and 95％minimum alveolar concentrations effective inhaled(MAC EI50 and MAC EI95).The goal was to establish a safe anesthetic method for tracheal intubation in miniature pigs in which intubation is difficult.Methods Forty-four Bama miniature pigs underwent general anesthesia.Following sedation with an intramuscular injection of sufentanil,anesthetic induction was performed using mask inhalation of isoflurane with monitoring of the heart rate,blood pressure,respiration,body temperature,oxygen saturation,end-tidal carbon dioxide concentration,and end-tidal isoflurane concentration.The initial end-tidal isoflurane concentration was set at 2.0％.The tracheal intubation conditions and outcomes were evaluated using Cooper's scoring system,and the dose-response relationship was calculated using Dixon's up-and-down method.Probit regression was employed to calculate the MAC EI50 and MAC EI95 along with their 95％confidence intervals(CI).Results In tracheal intubation using direct laryngoscopy with induction by low-dose sufentanil combined with isoflurane inhalation in miniature pigs,the MAC EI50 was 3.10％(95％CI,2.79％～3.56％)and the MAC EI95 was 3.77％(95％CI,3.41％～6.42％).With proper monitoring and airway management planning in place,alveolar isoflurane concentrations ranging from 3.10％to 3.75％were able to maintain stable vital signs in the miniature pigs.Conclusions The use of Zoletil combined with isoflurane inhalation for tracheal intubation in miniature pigs,aimed at preserving spontaneous breathing,is a preferable and safe anesthetic method for oral airway management in miniature pigs with significant potential for widespread application.