The patient is a male neonate born at term. He was admitted 16 minutes after birth due to stridor and inspiratory respiratory distress. Physical examination revealed a cleft palate, and a grade II systolic ejection murmur was audible at the left sternal border. Whole exome sequencing identified a heterozygous variant in the SON gene, c.5753-5756del (p.Val1918GlufsTer87), which was absent in either parent, indicating a de novo mutation. According to the guidelines of the American College of Medical Genetics and Genomics, this was classified as a "pathogenic variant" leading to a diagnosis of Zhu-Tokita-Takenouchi-Kim (ZTTK) syndrome. Upon admission, symptomatic supportive treatment was provided. Follow-up at the age of 8 months revealed persistent stridor; the infant could only consume small amounts of milk and was unable to sit steadily. This patient represents the youngest reported case to date, and his symptoms expand the clinical spectrum of the disease, providing valuable insights for clinical diagnosis and treatment.
Humans ; Infant, Newborn ; Male ; Minor Histocompatibility Antigens/genetics* ; DNA-Binding Proteins/genetics* ; Rare Diseases/genetics* ; Neurodevelopmental Disorders/genetics*

OBJECTIVES: To investigate the molecular epidemiology of children with phenylketonuria (PKU) in Gansu, China, providing foundational data for intervention strategies. METHODS: A retrospective analysis was conducted on 1 159 PKU families who attended Gansu Provincial Maternity and Child Care Hospital from January 2012 to December 2024. Sanger sequencing, multiplex ligation-dependent probe amplification, whole exome sequencing, and deep intronic variant analysis were used to analyze the PAH gene. RESULTS: For the 1 159 children with PKU, 2 295 variants were identified in 2 318 alleles, resulting in a detection rate of 99.01%. The detection rates were 100% (914/914) in 457 classic PKU families, 99.45% (907/912) in 456 mild PKU families, and 96.34% (474/492) in 246 mild hyperphenylalaninemia families. The 2 295 variants detected comprised 208 distinct mutation types, among which c.728G>A (14.95%, 343/2 295) had the highest frequency, followed by c.611A>G (4.88%, 112/2 295) and c.721C>T (4.79%, 110/2 295). The cumulative frequency of the top 23 hotspot variants reached 70.28% (1 613/2 295), and most variant alleles were detected in exon 7 (29.19%, 670/2 295). CONCLUSIONS Deep intronic variant analysis of the PAH gene can improve the genetic diagnostic rate of PKU. The development of targeted detection kits for PAH hotspot variants may enable precision screening programs and enhance preventive strategies for PKU.
Humans ; Phenylketonurias/epidemiology* ; Female ; Male ; Retrospective Studies ; Phenylalanine Hydroxylase/genetics* ; Mutation ; Child, Preschool ; China/epidemiology* ; Child ; Infant

PURPOSE: Venous thromboembolism (VTE) is a major health issue among hip fracture patients. This study aimed to develop an information platform based on a mobile application and then evaluate whether information platform-based nursing could improve patient's drug compliance and reduce the incidence of VTE in hip fracture patients. METHODS: This study retrospectively analyzed hip fracture patients who were treated with conventional prevention and intervention methods for VTE (control group) between January 2008 and November 2012, and prospectively analyzed hip fracture patients who were treated with nursing intervention based on the information platform (study group) between January 2016 and September 2017. All the patients included in the both groups were hip fracture patients who had an age over 50 years, treated with surgery, and hospitalized ≥ 48 h. Patients were excluded if they admitted to hospital due to old fractures, had a severe bleeding after 72 h of admission, diagnosed with any type of VTE, or refused to participate in the study. The information platform was divided into medical, nursing, and patient interface. Based on the information platform, medical practitioners and nurses could perform risk assessments, monitoring management and early warnings, preventions and treatments, health educations, follow-up, and other aspects of nursing interventions for patients. This study compared essential characteristics, drug compliance, VTE occurrence, and mean length of hospitalization between the two groups. Besides, a subgroup analysis was performed in the study group according to different drug compliances. SPSS 18.0 software (IBM Corp., NY, and USA) was used for statistical analysis. RESULTS: Altogether 1177 patients were included in the control group, and 491 patients in the study group. Regarding baseline data, patients in the study group had more morbidities than those in the control group (p < 0.05). The difference of drug compliance between the two groups was statistically significant (p < 0.001): 761 (64.7%) of the patients in the control group and only 30 (6.1%) patients in the study group had poor drug compliance. In terms of VTE, 10.7% patients (126/1177) in the control group had VTE, and the rate in the study group was 7.1% (35/491), showing a statistically significant difference (p = 0.02). Moreover, the average length of hospitalization in the study group was also significantly lower than that in the control group (10.4 days vs. 13.7 days, p < 0.001). Subgroup analyses of the study group showed that the incidence of VTE in patients with poor, partial, and good compliances were 56.7% (17/30), 5.8% (10/171), and 2.8% (8/290), respectively, revealing a significantly huge difference (p < 0.001). CONCLUSIONS Poor drug compliance leads to higher VTE occurrence. The information platform-based nursing can effectively improve the compliance of hip fracture patients and thus considerably reduce the incidence of VTE. The mobile application may be an effective tool to prevent VTE in hip fracture patients.
Humans ; Middle Aged ; Venous Thromboembolism/epidemiology* ; Retrospective Studies ; Risk Factors ; Hip Fractures/surgery* ; Incidence

Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Child ; China/epidemiology* ; Cryptorchidism/genetics* ; Disorders of Sex Development/genetics* ; Female ; Genital Diseases, Male ; Genotype ; Humans ; Hypospadias/genetics* ; Male ; Membrane Proteins/genetics* ; Penis/abnormalities* ; Phenotype ; Retrospective Studies ; Steroid 21-Hydroxylase/genetics*

ObjectiveTo observe the efficacy and safety of Fuzheng Huayu tablets （FHT） for treating pulmonary inflammation in patients with coronavirus disease 2019 （COVID-19）. MethodA total of 70（4 cases were lost to follow-up, and 66 cases were finally completed） COVID-19 patients were recruited from February 1 to April 15 in 2020. They were assigned to a control group （35 patients） and a FHT group （31 patients）. The patients in the control group received routine treatment alone and those in the FHT group received FHT in addition to routine treatment. The primary outcome was the ratio of patients showing improvement in chest computed tomographic manifestations after 14 days. The secondary outcome measures included remission rate or progression rate of critical illness， clinical remission rate of respiratory symptoms， routine blood examination， C-reactive protein （CPR） level， procalcitonin （PCT） level， and blood oxygen saturation （SPO₂）. The safety was assessed based on liver and kidney functions and adverse events. ResultAfter the 14-day treatment， the ratio of patients showing improvement in the FHT group （100%） was higher than that in the control group （77.1%） （χ²=8.063，P<0.01）. The ratio of disease stages after treatment showed no significant difference between two groups. In the FHT group， the symptoms including cough， dyspnea， and fatigue were alleviated after treatment （P<0.01）. In the control group， the symptoms including fever， cough， and dyspnea were alleviated （P<0.01）， while the fatigue was not relieved after treatment. No significant difference was observed in the clinical symptoms between the two groups after treatment. After treatment， the FHT group showed decreased white blood cell （WBC） count and neutrophil-to-lymphocyte ratio （NLR） （P<0.01）， elevated platelet （PLT） level （P<0.05）， lowered CRP level （P<0.05）， and no significant difference in lymphocyte （LYM）， hemoglobin （Hb）， SPO₂ or PCT level. The control group showed decreased NLR （P<0.05） and WBC count （P<0.01）， elevated PCT level （P<0.05）， and no significant change in LYM， Hb， PLT， SPO₂ or CRP level after treatment. Furthermore， the FHT group had higher PLT level than the control group （P<0.05） after treatment， and other indicators had no significant differences between the two groups. The liver and kidney functions had no significant difference between the two groups after treatment. ConclusionFHT can safely promote the absorption of acute pulmonary inflammation in COVID-19 patients.

ObjectiveTo investigate related factors for stone recurrence after endoscopic minimally invasive gallbladder-preserving cholecystolithotomy, and to establish a nomogram model for predicting the risk of stone recurrence after surgery based on independent risk factors. MethodsA retrospective analysis was performed for the clinical data of 144 patients with gallstones who underwent endoscopic minimally invasive gallbladder-preserving cholecystolithotomy in Qinghai University Affiliated Hospital from January 2012 to January 2018, and according to postoperative stone recurrence, the patients were divided into non-recurrence group and recurrence group. The chi-square test was used for comparison of categorical data between two groups. LASSO and logistic regression analyses were used to analyze independent risk factors for postoperative stone recurrence, and the corresponding nomogram prediction model was plotted according to regression coefficient. The calibration curve was plotted to evaluate the reliability of the predictive nomogram; Harrell consistency index was used to quantify the discriminatory performance of the predictive nomogram; the receiver operating characteristic (ROC) curve was used to evaluate the sensitivity, specificity, and area under the ROC curve (AUC) of this predictive nomogram. ResultsAll 144 patients underwent successful endoscopic minimally invasive gallbladder-preserving cholecystolithotomy, among whom 14 patients (9.7%) experienced stone recurrence after surgery. The multivariate analysis showed that family history (odds ratio ［OR］= 3.245, 95% confidence interval ［CI］: 0.752-13567, P=0.104), regular diet (OR=3.752, 95% CI: 1.067-14.141, P=0.041), stone homogeneity (OR=5.871, 95% CI: 1636-25.390, P=0.010), and medication compliance (OR=0.225, 95% CI: 0.057-0.799, P=0.024) were independent risk factors for recurrence. The nomogram model had an index of concordance (C-index) of 0.835 (95% CI: 0.732-0.938) in the modeling sample and 0.7925 in the verification sample, suggesting that the nomogram model in this study had good accuracy and discrimination. The predictive nomogram had an AUC of 0.835, suggesting that this nomogram had a relatively high predictive value. ConclusionFamily history, regular diet, stone homogeneity, and medication compliance are independent risk factors for stone recurrence after endoscopic minimally invasive gallbladder-preserving cholecystolithotomy, and the nomogram constructed based on these independent risk factors may help to predict the risk of postoperative stone recurrence.

OBJECTIVE: To analyze characteristics and related factors of the plantar pressure during the level walking and single leg standing in the chronic ankle instability (CAI) individuals. METHODS: From April 2019, 75 CAI individuals and 40 healthy individuals were enrolled in this study. Both of the static and dynamic plantar pressure were measured during six times level walking and three times single leg standing testing. The data including peak force, time to peak force in various foot contact areas and the time to boundary (TTB) and velocity of center of pressure (COP) were measured and compared between the affected side and the unaffected side and between the CAI cases and the healthy individuals. The correlations between the plantar pressure and the gender, Beighton score, affected side and body mass index (BMI) were analyzed. RESULTS: The characteristics of plantar pressure distribution in the CAI individuals included: (1) During the level walking, the affected side showed the similar pressure contribution as the unaffected side (P>0.05). While compared with healthy individuals, there was a significantly higher peak force in the 5th metatarsal area (t=-3.86, P=0.03) of the affected side, lower peak force in the 1st (t=2.99, P=0.02), 2nd metatarsal head areas (t=2.09, P=0.01) of the affected side, medial hindfoot areas of both sides (affected, t=2.33, P=0.01; unaffected, t=3.74, P=0.02) and toes areass of both sides (affected, t=2.23, P=0.01; unaffected, t=3.28, P=0.02) and a delay to peak force in the 4th metatarsal head area (t=3.33, P=0.01) of the affected side. (2) During the single leg standing, the CAI individuals showed significantly worse balance control in the anterior/posterior direction (P < 0.05) and lateral/medial direction (P < 0.05) compared with the healthy controls, and the affected side had more severe balance control deficit in the lateral/medial direction (P < 0.05). (3) The women (P < 0.05) and the individuals with higher Beighton scores (P < 0.05) showed worse balance control deficit in the lateral/medial direction. CONCLUSION CAI individuals showed significantly a more lateral shifted plantar distribution during the level walking compared with the healthy individuals and the tendency was worse on the affected sides, and showed worse balance control in the anterior/posterior direction and lateral/medial direction during the single leg standing. The women and those with generalized ligament laxity showed significantly worse balance control.
Ankle ; Ankle Joint ; Case-Control Studies ; Female ; Foot ; Humans ; Joint Instability

Enrichment of trace bioactive constituents and metabolites from complex biological samples is chal-lenging. This study presented a one-pot synthesis of magnetic polydopamine nanoparticles (Fe3O4@-SiO2@PDA NPs) with multiple recognition sites for the magnetic dispersive solid-phase extraction (MDSPE) of ginsenosides from rat plasma treated with white ginseng. The extracted ginsenosides were characterized by combining an ultra-high-performance liquid chromatography coupled to a high-resolution mass spectrometry with supplemental UNIFI libraries. Response surface methodology was statistically used to optimize the extraction procedure of the ginsenosides. The reusability of Fe3O4@-SiO2@PDA NPs was also examined and the results showed that the recovery rate exceeded 80％ after recycling 6 times. Furthermore, the proposed method showed greater enrichment efficiency and could rapidly determine and characterize 23 ginsenoside prototypes and metabolites from plasma. In com-parison, conventional methanol method can only detect 8 ginsenosides from the same plasma samples. The proposed approach can provide methodological reference for the trace determination and charac-terization of different bioactive ingredients and metabolites of traditional Chinese medicines and food.

Objective:To compare the clinical effects of Zero-profile (Zero-p) intervertebral fusion and titanium plate combined with cage fusion in treating symptomatic adjacent segment disease (ASD) after anterior cervical discectomy and fusion (ACDF).Methods:Retrospective analysis was performed on 26 patients who underwent ACDF and readmission due to concurrent symptomatic ASD from October 2014 to June 2019. There were 17 males and 9 females, aged 54.15±8.60 (range 41-68) years. The index level included C 2, 3 1 case, C 3, 4 3 cases, C 4,5 9 cases, C 5, 6 6 cases, C 6, 7 7 cases. Twelve cases underwent anterior cervical decompression with Zero-p intervertebral fusion and fixation (Zero-p group), while 14 cases underwent anterior cervical decompression with titanium plate combined with cage fusion and fixation (titanium plate group). The following parameters, including operative duration, intraoperative blood loss, Japanese Orthopaedic Association (JOA) score, visual analogue score (VAS), neck disability index (NDI), dysphagia Bazaz grade, bone graft fusion Eck grade, C 2-C 7 Cobb angle, and related complications, were compared between the two groups. Results:The operation was performed successfully in all the patients. The patients were followed up for averagely 33.38±21.26 (range 12-71) months. The operation duration was 95.83±5.47 (range 89-105) min in the Zero-p group, which was shorter than 121.28±8.24 (range 106-131) min in the titanium plate group. The Bazaz classification of dysphagia in the Zero-p group was superior to the titanium plate group at 1 month after operation ( W=126.00, P=0.022). Neither group had dysphagia 3 months after surgery. The JOA score increased from preoperative 9.50±1.31 to 14.33±0.78, and VAS decreased from 5.33±1.67 to 0.83±0.72 in the Zero-p group. The NDI decreased from 43.62%±9.31% to 14.99%±3.26%, and C 2-C 7 Cobb changed from 8.26°±2.92° to 14.80°±4.18° in the Zero-p group. The JOA score increased from preoperative 9.14±1.79 to 14.71±0.73, and VAS decreased from 5.43±1.55 to 1.43±0.76 in the titanium plate group. The NDI decreased from 43.76%±8.47% to 14.22%±4.59%, and C 2-C 7 Cobb changed from 5.53°±9.04° to 14.68°±6.89° in the titanium plate group. No complication, such as screw loosening or breakage or esophageal injury, occurred during the follow-up. Conclusion:Both methods can achieve good clinical effects in treating symptomatic ASD and can restore the physiological curvature of the cervical spine to a certain extent. Furthermore, the advantages of Zero-p intervertebral fusion include shorter operation duration, reducing soft tissue injury and less postoperative dysphagia.