Objective:To investigate the risk factors associated with post-prematurity respiratory disease (PPRD) in very preterm infants.Methods:A prospective cohort study was conducted, enrolling 369 very preterm infants who were admitted to the neonatal intensive care unit of Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, within one week of birth from January 2019 to June 2023. Data on maternal and infant clinical characteristics, neonatal morbidities, and treatments during hospitalization were collected. The very preterm infants were divided into 2 groups based on whether they developed PPRD. Continuous variables were compared using Mann-Whitney U test, while categorical variables were compared using χ2 tests or continuity correction χ2 test. Multivariate Logistic regression analysis was used to identify the independent risk factors for PPRD in very preterm infants. Results:Among the 369 very preterm infants, 217 cases(58.8%) were male, with a gestational age of 30 (28, 31) weeks at birth and a birth weight of 1 320 (1 085, 1 590) g. Of these, 116 cases (31.4%) developed PPRD, while 253 cases (68.6%) did not. The very preterm infants in the PPRD group had a lower gestational age and lower birth weight (both, P<0.001). The PPRD group also had a higher proportion of males, lower Apgar scores at the 1 th minute after birth and the 5 th minutes after birth, a higher rate of born via cesarean delivery, and a higher incidence of bronchopulmonary dysplasia, more pulmonary surfactant treatment, longer durations of mechanical ventilation, longer total oxygen therapy, and lower Z-score for weight at discharge (all P<0.05). Multivariate Logistic regression analysis showed that gestational age ( OR=0.85, 95% CI 0.73-0.99, P=0.037), born via cesarean delivery ( OR=2.23, 95% CI 1.21-4.10, P=0.010), a duration of mechanical ventilation ≥7 days ( OR=2.51, 95% CI 1.43-4.39, P=0.001), and a Z-score for weight at discharge ( OR=0.82, 95% CI 0.67-0.99, P=0.040) were all independent risk factors for PPRD in very preterm infants. Conclusion:Very preterm infants with a small gestational age, born via cesarean section, mechanical ventilation ≥7 days, and a low Z-score for weight at discharge should be closely monitored for PPRD, and provided with standardized respiratory management after discharge.

Objective:To explore the clinical characteristics and therapeutic effect of perioral myoclonia with absences (PMA), in order to improve the clinicians′ understanding of the disease.Methods:The clinical manifestations during seizures, as well as interictal and ictal electroencephalogram (EEG) features of 3 PMA patients admitted to the Epilepsy Unit, Neurology Center, Beijing Tiantan Hospital, Capital Medical University from May to October 2024 were analyzed. The clinical manifestations, EEG characteristics, differential diagnosis, treatment experience of PMA patients were summarized by retrospective analysis combined with previous literature review.Results:The onset age of these 3 PMA cases was 15, 15, and 7 years, respectively. The prominent manifestation of seizure was perioral myoclonus without disturbance of consciousness. The duration of seizures was brief, less than 10 seconds. PMA can occur several times a day and was prone to present as continuous state of perioral myoclonus. Three patients had rare generalized tonic-clonic seizures (GTCS). The seizures could be controlled by sodium valproate, lamotrigine, levetiracetam, or combined treatment. Fifteen literatures about PMA were retrieved (4 in Chinese and 11 in English). A total of 31 patients (including these 3 patients) were included in the study, of whom 17 were males and 14 were females. The onset age was from 9 months to 34 [7.63 (2.19, 11.00)] years. Perioral myoclonus with varying degrees of disturbance of consciousness was the main seizure type, and 12 patients exhibited continuous state of perioral myoclonus, 24 patients had GTCS. Eight patients had a history of fever convulsion, 6 patients had mental or learning disabilities, and 11 patients had a family history of epilepsy or febrile convulsion. The ictal EEG showed around 3 Hz generalized spike-wave/multiple spike-wave discharges accompanied with synchronous myoelectric bursts. There were no specific abnormalities in physical examination of nervous system and cranial imaging in all the patients. Ten patients were initially diagnosed as focal epilepsy. Nine patients′ seizures were increased or worsened due to improper medication. Valproate, lamotrigine and levetiracetam were the main treatments of PMA, and the seizures of 21 patients were effectively controlled.Conclusions:PMA is clinically characterized by perioral myoclonia with varying degrees of disturbance of consciousness and is easy to be misdiagnosed as focal epilepsy, so it is necessary to use video EEG combined with synchronous electromyography to confirm the diagnosis. PMA should be treated with broad-spectrum antiseizure drugs.

B-cell lymphomas account for 70％-80％of non-Hodgkin lymphomas(NHL)and exhibit significant heterogeneity in genetic profiles,phenotypic characteristics,and clinical manifestations,posing substantial challenges for clinical management.The B-cell receptor(BCR)is a transmembrane receptor on the surface of B cells that plays a central regulatory role in B-cell development,activation,and adaptive immune responses.As a core mechanism driving malignant transformation in various B-cell malignancies,aberrant activation of the BCR signaling pathway,plays a pivotal role in B lymphoma pathogenesis.Dysregulated BCR signaling not only promotes tumor cell proliferation,survival,and anti-apoptotic capacity but also accelerates malignant progression.Consequently,researchers are vigorously exploring therapeutic strategies targeting BCR and its downstream pathways,including inhibitors of Bruton's tyrosine kinase(BTK)and PI3K,as well as direct BCR-targeted approaches.The central role of BCR signaling in lymphoma pathogenesis and treatment underscores its potential as a critical focus for future therapeutic development,offering new directions and hope for improved clinical outcomes.

B-cell lymphomas account for 70％-80％of non-Hodgkin lymphomas(NHL)and exhibit significant heterogeneity in genetic profiles,phenotypic characteristics,and clinical manifestations,posing substantial challenges for clinical management.The B-cell receptor(BCR)is a transmembrane receptor on the surface of B cells that plays a central regulatory role in B-cell development,activation,and adaptive immune responses.As a core mechanism driving malignant transformation in various B-cell malignancies,aberrant activation of the BCR signaling pathway,plays a pivotal role in B lymphoma pathogenesis.Dysregulated BCR signaling not only promotes tumor cell proliferation,survival,and anti-apoptotic capacity but also accelerates malignant progression.Consequently,researchers are vigorously exploring therapeutic strategies targeting BCR and its downstream pathways,including inhibitors of Bruton's tyrosine kinase(BTK)and PI3K,as well as direct BCR-targeted approaches.The central role of BCR signaling in lymphoma pathogenesis and treatment underscores its potential as a critical focus for future therapeutic development,offering new directions and hope for improved clinical outcomes.

Objective:To explore the clinical characteristics and therapeutic effect of perioral myoclonia with absences (PMA), in order to improve the clinicians′ understanding of the disease.Methods:The clinical manifestations during seizures, as well as interictal and ictal electroencephalogram (EEG) features of 3 PMA patients admitted to the Epilepsy Unit, Neurology Center, Beijing Tiantan Hospital, Capital Medical University from May to October 2024 were analyzed. The clinical manifestations, EEG characteristics, differential diagnosis, treatment experience of PMA patients were summarized by retrospective analysis combined with previous literature review.Results:The onset age of these 3 PMA cases was 15, 15, and 7 years, respectively. The prominent manifestation of seizure was perioral myoclonus without disturbance of consciousness. The duration of seizures was brief, less than 10 seconds. PMA can occur several times a day and was prone to present as continuous state of perioral myoclonus. Three patients had rare generalized tonic-clonic seizures (GTCS). The seizures could be controlled by sodium valproate, lamotrigine, levetiracetam, or combined treatment. Fifteen literatures about PMA were retrieved (4 in Chinese and 11 in English). A total of 31 patients (including these 3 patients) were included in the study, of whom 17 were males and 14 were females. The onset age was from 9 months to 34 [7.63 (2.19, 11.00)] years. Perioral myoclonus with varying degrees of disturbance of consciousness was the main seizure type, and 12 patients exhibited continuous state of perioral myoclonus, 24 patients had GTCS. Eight patients had a history of fever convulsion, 6 patients had mental or learning disabilities, and 11 patients had a family history of epilepsy or febrile convulsion. The ictal EEG showed around 3 Hz generalized spike-wave/multiple spike-wave discharges accompanied with synchronous myoelectric bursts. There were no specific abnormalities in physical examination of nervous system and cranial imaging in all the patients. Ten patients were initially diagnosed as focal epilepsy. Nine patients′ seizures were increased or worsened due to improper medication. Valproate, lamotrigine and levetiracetam were the main treatments of PMA, and the seizures of 21 patients were effectively controlled.Conclusions:PMA is clinically characterized by perioral myoclonia with varying degrees of disturbance of consciousness and is easy to be misdiagnosed as focal epilepsy, so it is necessary to use video EEG combined with synchronous electromyography to confirm the diagnosis. PMA should be treated with broad-spectrum antiseizure drugs.

Objective:To explore the prevalence, clinical features, genetic characteristics and prognosis of Citrin deficiency in Henan province of China.Methods:A total of 986 565 neonates screened by tandem mass spectrometry at the Third Affiliated Hospital of Zhengzhou University from January 2013 to December 2021 were retrospectively analyzed. Analysis of SLC25A13 gene variants and parental verification were carried out for neonates suspected for Citrin deficiency by next-generation sequencing. The clinical, biochemical and genetic characteristics of Citrin deficiency patients were integrated to guide the diet treatment and follow up the growth and development. Paired- t test was used to compare the amino acid levels in the peripheral blood samples before and after the treatment. Results:Nine cases of Citrin deficiency were diagnosed among the 986 565 neonates. Specific elevation of citrulline was observed in all of the 9 cases. Six variants were detected by genetic sequencing, among which c. 852_855delTATG, c. 615+ 5G>A, c. 550C>T and IVS16ins3kb were known pathogenic variants, whilst c. 1111_1112delAT and c. 837T>A were unreported previously. The detection rate for c. 852_855delTATG was the highest (61.6%, 11/18), followed by IVS16ins3kb (16.7%, 3/18). The clinical symptoms of all patients were relieved after the treatment, and the blood amino acid profile and biochemical parameters were significantly improved by gradually falling within the normal range. By June 2022, all patients had shown a good prognosis.Conclusion:The prevalence of Citrin deficiency among neonates from Henan Province by tandem mass spectrometry is 1/109 618, and the carrier rate for the pathogenic variants of the SLC25A13 gene was 1/166. The c. 852_855delTATG may be a hot spot variant among the patients. Discovery of the novel variants has enriched the mutational spectrum of the SLC25A13 gene. Above results have provided a basis for the early diagnosis, treatment, prognosis and genetic counseling for the affected families.

Objective:To explore the genetic etiology of a fetus with short limbs identified by prenatal ultrasonography.Methods:A fetus detected with short limb malformations at Shengjing Hospital Affiliated to China Medical University on October 25, 2021 was selected as the study subject. Prenatal ultrasound and post-abortion imaging were carried out to determine the phenotypic characteristics of the fetus. Amniotic fluid sample of the fetus and peripheral blood samples of its parents were collected. Following extraction of genomic DNA, whole-exome sequencing was carried out. Candidate variants were verified by Sanger sequencing. Online software was used to predict the structural changes of the mutant proteins.Results:Prenatal ultrasound showed that the fetus had a small bell-shaped thorax, markedly shortened limbs, flat midface, a small nose with anteriorly tilted nostrils, and a small mandible. Post-abortion CT showed typical short and wide fetal ribs, cupped metaphyses at both ends, short long bones with wide metaphyses, resulting in a dumbbell-shaped appearance and curved thoracic vertebrae. Whole-exome sequencing revealed that the fetus had harbored compound heterozygous variants of the COL11A1 gene, namely c. 2251G>T and c. 3790G>T, both of which were predicted to alter the important Gly-X-Y structure of collagen protein. Sanger sequencing confirmed that the variants were respectively inherited from its parents. Conclusion:A rare fetus with Fibrochondrogenesis type 1 due to compound heterozygous variants of the COL11A1 gene has been diagnosed. Above finding has enabled genetic counseling and reproductive guidance for this family.

ObjectiveTo analyze the status of and family-related factors associated with extracurricular screen time (ST) among the primary and middle school students in a district of Shanghai, and to provide a scientific basis for the development of targeted intervention measures. MethodsA total of 819 students and their parents from one primary school and one middle school were selected by stratified cluster sampling method from November to December 2022 in a district of Shanghai. A questionnaire survey was conducted to investigate the total extracurricular ST and entertainment ST during school days, weekends and summer and winter vacation, as well as the underlying family-related factors. Taking daily total extracurricular ST>2 h as excessive extracurricular ST and daily extracurricular entertainment ST>1 h as excessive extracurricular entertainment ST. ResultsAmong the 795 valid questionnaires, the proportions of excessive extracurricular ST during school day, weekend and summer and winter vacation were 10.9%, 42.1% and 51.1%, respectively, and the proportions of excessive extracurricular entertainment ST were 16.2%, 63.0% and 71.3%, respectively. The proportion of excessive extracurricular ST on weekend and summer and winter vacation was higher for middle school students than for primary school students, and the proportion of excessive extracurricular ST was higher for the students whose father’s educational level was high school and below than for those whose father’s educational level was junior college and above (both P<0.05). Multivariate logistic regression analysis after controlling confounding factors showed that the students with poor parent-child relationships (aOR=1.40‒1.96) and parental daily ST>2 h (aOR=1.83‒3.85) were more likely to have an excessive total extracurricular ST and entertainment ST. ConclusionThe proportion of excessive extracurricular ST for the primary and middle school students in Shanghai is relative high during weekend and summer and winter vacation, especially for entertainment purposes. Improving parent-child relationships and reducing parental excessive ST may be important intervention measures.

Objective: To develop an assessment questionnaire for screen based behaviors among primary and secondary school students, so as to provide a basis for comprehensive assessment among the population. Methods: Nineteen experts were invited to take part in this study from August to September 2022. The initial framework and item pool of the assessment questionnaire were developed based on literature review and a series of guidelines and standards issued by the national education and health authorities, as well as relevant domestic and foreign guidelines, and were combined with existing assessment tools that were used to evaluate screen based behavior among these age groups. Experts in related fields were selected for two rounds of Delphi consultation to determine the dimensions, items and corresponding weights of the assessment questionnaire. Results: The response rates from two rounds of consultation were 95.0% and 100.0% respectively, the opinion submission rates were 89.5% and 63.2% respectively, and the authority coefficient ( Cr ) was 0.87. An assessment questionnaire was finally designed, consisting in 44 items and four dimensions, namely screen use type and time, screen use related health behaviors, safety and civilization in screen use, and reasonable arrangement of screen and non screen activities. The coefficient of variation( CV ) of each item ranged from 0.00 to 0.19, and the Kendall s W increased from 0.22 to 0.34( P <0.01). Expert opinions were in agreement and credible. Conclusion The designed assessment questionnaire can be used to comprehensively evaluate screen based behavior among primary and middle school students, and provides a basis for subsequent intervention measures to improve screen based behavior among this population.

8-prenylnaringenin (8-PN) is a potent estrogen with high medicinal values. It also serves as an important precursor for many prenylated flavonoids. Microbial synthesis of 8-PN is mainly hindered by the low catalytic activity of prenyltransferases (PTS) and insufficient supply of precursors. In this work, a SfN8DT-1 from Sophora flavescens was used to improve the efficiency of (2S)-naringenin prenylation. The predicted structure of SfN8DT-1 showed that its main body is comprised of 9 α-helices and 8 loops, along with a long side chain formed by nearly 120 amino acids. SfN8DT-1 mutants with different side-chain truncated were tested in Saccharomyces cerevisiae. A mutant expressing the truncated enzyme at K62 site, designated as SfND8T-1-t62, produced the highest 8-PN titer. Molecular docking of SfN8DT-1-t62 with (2S)-naringenin and dimethylallyl diphosphate (DMAPP) showed that K185 was a potentially crucial residue. Alanine scanning within a range of 0.5 nm around these two substrates showed that the mutant K185A may decrease its affinity to substrates, which also indicated K185 was a potentially critical residue. Besides, the mutant K185W enhanced the affinity to ligands implied by the simulated saturation mutation, while the saturated mutation of K185 showed a great decrease in 8-PN production, indicating K185 is vital for the activity of SfN8DT-1. Subsequently, overexpressing the key genes of Mevalonate (MVA) pathway further improved the titer of 8-PN to 31.31 mg/L, which indicated that DMAPP supply is also a limiting factor for 8-PN synthesis. Finally, 44.92 mg/L of 8-PN was produced in a 5 L bioreactor after 120 h, which is the highest 8-PN titer reported to date.
Dimethylallyltranstransferase/metabolism* ; Flavonoids/metabolism* ; Molecular Docking Simulation ; Prenylation ; Saccharomyces cerevisiae/metabolism* ; Sophora/metabolism*