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*

OBJECTIVE: To distinguish the ambiguous genotyping results of human leukocyte antigen (HLA), identify a novel HLA-B allele and analyze the nucleotide sequence. METHODS: A total of 2 076 umbilical core blood samples from the Zhejiang Cord Blood Bank in 2022 were detected using the next generation sequencing technology (NGS) based on the Ion Torrent S5 platform. Among these a rare HLA-B allele with ambiguous combination result containing a base mutation was identified, and was further confimed by the third-generation sequencing (TGS) based on the nanopore technology. RESULTS: The NGS typing result of HLA-B locus showed HLA-B* 46:18, 54:06 or HLA-B*46:01, 54:XX (including a base mutation), and nanopore sequencing confirmed the typing as HLA-B*46:01, 54:XX (including a base mutation). Compared with HLA-B*54:01:01:01, the HLA-B*54:XX allele showed one single nucleotide substitution at position 1014 T>C in exon 6, with no amino acid change. The nucleotide sequence of the novel HLA-B*54:XX has been submitted to the GenBank nucleotide sequence database and the accession number OP853532 was assigned. CONCLUSION A ambiguous genotyping of the HLA-B Locus detected by NGS was distinguished by nanopore sequencing and a new HLA-B allele was successfully identified, which was officially named as HLA-B*54:01:11 by the World Health Organization Nomenclature Committee for Factors of the HLA System.
Humans ; High-Throughput Nucleotide Sequencing ; Alleles ; HLA-B Antigens/genetics* ; Genotype ; Mutation ; Sequence Analysis, DNA ; Base Sequence

OBJECTIVE: To explore and quantify the association of hot night exposure during the sperm development period (0-90 lag days) with semen quality. METHODS: A total of 6,640 male sperm donors from 6 human sperm banks in China during 2014-2020 were recruited in this multicenter study. Two indices (i.e., hot night excess [HNE] and hot night duration [HND]) were used to estimate the heat intensity and duration during nighttime. Linear mixed models were used to examine the association between hot nights and semen quality parameters. RESULTS: The exposure-response relationship revealed that HNE and HND during 0-90 days before semen collection had a significantly inverse association with sperm motility. Specifically, a 1 °C increase in HNE was associated with decreased sperm progressive motility of 0.0090 (95% confidence interval [ CI]: -0.0147, -0.0033) and decreased total motility of 0.0094 (95% CI: -0.0160, -0.0029). HND was significantly associated with reduced sperm progressive motility and total motility of 0.0021 (95% CI: -0.0040, -0.0003) and 0.0023 (95% CI: -0.0043, -0.0002), respectively. Consistent results were observed at different temperature thresholds on hot nights. CONCLUSION Our findings highlight the need to mitigate nocturnal heat exposure during spermatogenesis to maintain optimal semen quality.
Humans ; Male ; Semen Analysis ; Adult ; Sperm Motility ; Hot Temperature/adverse effects* ; China ; Middle Aged ; Spermatozoa/physiology* ; Young Adult

Objective To investigate the current status of pelvic floor muscle training(PFMT)adherence for preventing low anterior resection syndrome(LARS)in rectal cancer patients with prophylactic ostomy and analyze its influencing factors.Methods A total of 247 patients who underwent preventive stoma reversal surgery after sphincter-preserving rectal cancer resection between January 2024 and February 2025 at 22 tertiary hospitals in the Beijing-Tianjin-Hebei region were recruited in this study.Their clinical data were collected through a general information questionnaire,a LARS Knowledge-Attitude-Practice and Needs questionnaire,a PFMT Self-Efficacy Scale,and a PFMT Adherence Questionnaire.Univariate analysis,correlation analysis,LASSO regression,and random forest importance ranking were applied to screen the variables,and multiple linear regression analysis was conducted to analyze the significant variables.Results The overall PFMT adherence score was 14.52±4.18 among the 247 patients.The random forest algorithm identified 7 key predictors when the minimum error was achieved at a λ value of 2.293.The top 7 variables in importance ranking were PFMT self-efficacy,total knowledge-attitude-practice(KAP)score,education level,primary caregiver,tumor location,stoma reversal time,and chemoradiotherapy.Multiple linear regression analysis revealed that PFMT self-efficacy(P<0.001,β=0.007,95%CI:0.004～0.009),total KAP score(P<0.001,β=0.052,95%CI:0.035～0.070),stoma reversal time(P<0.030,β=-0.539,95%CI:-1.025～-0.053),and chemoradiotherapy(P<0.045,β=-0.451,95%CI:0.010～0.892)were significant related factors of PFMT adherence(P<0.05).Conclusion PFMT adherence for LARS prevention is at a moderate level in rectal cancer patients with prophylactic ostomy.Key factors such as PFMT self-efficacy,total KAP score,stoma reversal time,and chemoradiotherapy are significantly correlated with PFMT adherence.

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.

It is a common understanding that turbidity and precipitation of traditional Chinese medicine are easy to occur in the process of decocting. At present, our research group found that the cause of "multi-phase of traditional Chinese medicine decoction" mainly came from the interaction between the effective components of traditional Chinese medicine, especially the interaction of acid and base components. For example, the Liquorice and Rhizoma chinensis was a supramolecular system formed by a large number of active components in the decoction (>30%), and could stably exist in the decoction system. In this study, the supramolecular part was extracted, and the morphology of the supramolecular part was characterized by scanning electron microscopy and dynamic light scattering. It was observed that the supramolecular particles were uniform in size and regular in shape. The main components of supramolecular sites were identified by liquid mass spectrometry (LC-MSⁿ). The results of UV and IR spectra showed that the chemical components of Liquorice and Rhizoma chinensis in the co-decocting process collided with each other, and weak bonds were formed between the functional groups of the molecules, which then induced the aggregation to form supramolecules. Thereafter, Through the diarrhea model of mice, sensory evaluation and antibacterial activity evaluation found that Liquorice and Rhizoma chinensis decocted together enhanced the antibacterial activity of Rhizoma, and compatibility "reconcile" Rhizoma "big bitter cold" property compared with single decoction group and interval administration group. All animal experiments were approved by the Animal Ethics Committee of Beijing University of Chinese Medicine, and the relevant regulations of Beijing University of Chinese Medicine on experimental animals were strictly followed. In this study, supramolecular chemistry method was used to preliminarily discuss the scientific connotation of "increasing efficiency and decreasing toxicity" of Liquorice and Rhizoma chinensis combined decoction from three perspectives of "property, efficacy and taste", and provide new ideas for the basic research of "reconcile" compatibility of Liquorice.

Objective:To evaluate the effect of two kinds of anterior maxillary segmental osteotomies on nasal morphology.Methods:30 patients with bimaxillary protrusion were included at from Tianjin Stomatological Hospital Between January 2015 and December 2017. There were 8 males and 22 females aged from 19 to 32 years old, the patients were randomly divided into the traditional operation group and modified operation group according to the order of treatment. 20 patients underwent traditional anterior maxillary osteotomy while 10 patients underwent modified osteotomy. Pre- and post-operative 1-year CBCT data of 30 patients were imported in Proplan CMF software, to reconstruct the 3D model of the nose and select characteristic landmarks. Three locating planes and 3D point measurement system were established, Relevant indices consisted of nasolabial angle, upper and lower nasolabial angle, nasal tip angle, nasal tip inclination, nasal columella inclination, nasal height, depth of nasal tip, vertical nasal tip position, nasal alar base width, inner canthic diameter, nasal columella height, bilateral nasal axis angle, nostril area and the comparison between two groups were conducted using paired-samples t test, the effect of two surgical methods on nasal morphology were evaluated. Results:There were statistically significant differences between the nasolabial angle, nasal columella inclination, nasal height, nasal alar base width between preoperative group(113.74°±9.42°, 120.06°±7.73°)and postoperative group (121.93°±4.05°, 129.86°±7.63°), whereas no significant difference among nasal tip angle, nasal tip inclination, vertical nasal tip position, nasal columella height, bilateral nasal axis angle and nostril area in traditional operative group. However, in the modified operation group, there were statistically significant differences in the nasolabial angle, vertical nasal tip position between preoperative group [110.75°±1.67°and(11.87±1.39) mm] and postoperative group [122.42°±6.95° and(11.16±1.02) mm], whereas no significant difference among other measurement items.Conclusions:Compared with the traditional osteotomies, the modified method has little influence on the nasal morphology after operation, meanwhile achieve good surgical result. However, the modified surgical method has its own indications, flexible application can obtain the best surgical result and patient satisfaction.

Objective:To evaluate the effect of two kinds of anterior maxillary segmental osteotomies on nasal morphology.Methods:30 patients with bimaxillary protrusion were included at from Tianjin Stomatological Hospital Between January 2015 and December 2017. There were 8 males and 22 females aged from 19 to 32 years old, the patients were randomly divided into the traditional operation group and modified operation group according to the order of treatment. 20 patients underwent traditional anterior maxillary osteotomy while 10 patients underwent modified osteotomy. Pre- and post-operative 1-year CBCT data of 30 patients were imported in Proplan CMF software, to reconstruct the 3D model of the nose and select characteristic landmarks. Three locating planes and 3D point measurement system were established, Relevant indices consisted of nasolabial angle, upper and lower nasolabial angle, nasal tip angle, nasal tip inclination, nasal columella inclination, nasal height, depth of nasal tip, vertical nasal tip position, nasal alar base width, inner canthic diameter, nasal columella height, bilateral nasal axis angle, nostril area and the comparison between two groups were conducted using paired-samples t test, the effect of two surgical methods on nasal morphology were evaluated. Results:There were statistically significant differences between the nasolabial angle, nasal columella inclination, nasal height, nasal alar base width between preoperative group(113.74°±9.42°, 120.06°±7.73°)and postoperative group (121.93°±4.05°, 129.86°±7.63°), whereas no significant difference among nasal tip angle, nasal tip inclination, vertical nasal tip position, nasal columella height, bilateral nasal axis angle and nostril area in traditional operative group. However, in the modified operation group, there were statistically significant differences in the nasolabial angle, vertical nasal tip position between preoperative group [110.75°±1.67°and(11.87±1.39) mm] and postoperative group [122.42°±6.95° and(11.16±1.02) mm], whereas no significant difference among other measurement items.Conclusions:Compared with the traditional osteotomies, the modified method has little influence on the nasal morphology after operation, meanwhile achieve good surgical result. However, the modified surgical method has its own indications, flexible application can obtain the best surgical result and patient satisfaction.

Abstract　　Among myeloid leukemias, the acute promyelocytic leukemia (APL) was found to be specifically sensitive to all-trans retinoic acid (ATRA), almost all APL patients respond to ATRA therapy. The ATRA induces remission of APL patients by stimulating the differentiation of the leukemia cells. However, with the long-term application of ATRA alone, ATRA resistance has become one of the main causes of chemotherapy failure in the patients with acute promyelocytic leukemia. At present, the mechanism of ATRA-resistance is not completely clear, this review discusses the mechanism of drug-resistance in terms of signal pathways, genes, proteins and enzyme.
Antineoplastic Agents ; Cell Differentiation ; Humans ; Leukemia, Promyelocytic, Acute ; Tretinoin