Objective:To summarize the clinical phenotype and genetic features of patients with relapsing encephalopathy with cerebellar ataxia (RECA) caused by ATP1A3 gene R756 variants. Methods:A retrospective analysis was performed on patients carrying the ATP1A3 gene R756 variants, identified by whole-exome sequencing of family members, at Capital Center for Children′s Health, Capital Medical University and Children's Medical Center, Peking University First Hospital from August 2005 to February 2024. Their clinical, laboratory, neuroimaging, electrophysiological and genetic characteristics were summarized. Results:A total of 13 RECA patients were enrolled in this study, including 8 males and 5 females. The age of onset was 8 months to 5 years, with a median age of onset of 18 months. All of 13 patients presented paroxysmal episodes of neurological decompensations triggered by fever and residual symptoms following the acute phase. During acute attack stage, ataxia was observed in all 13 cases, muscle weakness in 12 cases, dysarthria in 12 cases, altered consciousness in 10 cases, dysphagia in 10 cases, dystonic episodes in 4 cases, abnormal eye movement in 2 cases, choreoathetosis in 2 cases, and epileptic seizures in 1 case. All 13 patients had residual symptoms during the nonparoxysmal period, of whom 9 patients had ataxia, 9 patients had dysarthria, 4 patients had dystonia, 3 patients had cognitive disorders, and 1 patient had epileptic seizures. All 13 cases had ATP1A3 missense variants, and variant c.2266C>T/p.R756C was found in 6 cases, c.2267G>A/p.R756H in 5 cases, and c.2267G>T/p.R756L in 2 cases. Nine cases carried de novo variants, 4 with inherited variants. Conclusions:RECA caused by variants of ATP1A3 in residue 756 typically presents with an acute onset during infancy or early childhood, precipitated by febrile episodes and characterized by recurrent episodes of ataxia, with bulbar paralysis, muscle weakness and altered consciousness. Recurrence is common, and the most common persistent symptoms are cerebellar ataxia and dysarthria. A few patients have cognitive impairment. Three types of ATP1A3 gene variants R756C, R756H and R756L are related with RECA, and R756C is the most common variant.

Radiation induced lung injury is a common complication of radiation therapy, typically characterized by the involvement of lung parenchyma.The radiation sensitivity of the trachea and bronchi is lower than that of the lung parenchyma, and the damage to the airways is usually not apparent for most patients using the standard radiation dose. The escalation of radiotherapy dose and the utilization of stereotactic body radiotherapy (SBRT) have been shown to enhance local tumor control. However, there is a growing concern regarding the development of radiation-induced airway disease (RIAD), which encompasses central airway stenosis, atelectasis, obstructive pneumonia, airway-wall necrosis, severe airway toxicity, and potentially life-threatening complications. This article presents the latest research advancements regarding the incidence, pathophysiological alterations, injury classification, preventive strategies, and treatment approaches of RIAD.

Objective:To summarize the clinical phenotype and genetic features of patients with relapsing encephalopathy with cerebellar ataxia (RECA) caused by ATP1A3 gene R756 variants. Methods:A retrospective analysis was performed on patients carrying the ATP1A3 gene R756 variants, identified by whole-exome sequencing of family members, at Capital Center for Children′s Health, Capital Medical University and Children's Medical Center, Peking University First Hospital from August 2005 to February 2024. Their clinical, laboratory, neuroimaging, electrophysiological and genetic characteristics were summarized. Results:A total of 13 RECA patients were enrolled in this study, including 8 males and 5 females. The age of onset was 8 months to 5 years, with a median age of onset of 18 months. All of 13 patients presented paroxysmal episodes of neurological decompensations triggered by fever and residual symptoms following the acute phase. During acute attack stage, ataxia was observed in all 13 cases, muscle weakness in 12 cases, dysarthria in 12 cases, altered consciousness in 10 cases, dysphagia in 10 cases, dystonic episodes in 4 cases, abnormal eye movement in 2 cases, choreoathetosis in 2 cases, and epileptic seizures in 1 case. All 13 patients had residual symptoms during the nonparoxysmal period, of whom 9 patients had ataxia, 9 patients had dysarthria, 4 patients had dystonia, 3 patients had cognitive disorders, and 1 patient had epileptic seizures. All 13 cases had ATP1A3 missense variants, and variant c.2266C>T/p.R756C was found in 6 cases, c.2267G>A/p.R756H in 5 cases, and c.2267G>T/p.R756L in 2 cases. Nine cases carried de novo variants, 4 with inherited variants. Conclusions:RECA caused by variants of ATP1A3 in residue 756 typically presents with an acute onset during infancy or early childhood, precipitated by febrile episodes and characterized by recurrent episodes of ataxia, with bulbar paralysis, muscle weakness and altered consciousness. Recurrence is common, and the most common persistent symptoms are cerebellar ataxia and dysarthria. A few patients have cognitive impairment. Three types of ATP1A3 gene variants R756C, R756H and R756L are related with RECA, and R756C is the most common variant.

Radiation induced lung injury is a common complication of radiation therapy, typically characterized by the involvement of lung parenchyma.The radiation sensitivity of the trachea and bronchi is lower than that of the lung parenchyma, and the damage to the airways is usually not apparent for most patients using the standard radiation dose. The escalation of radiotherapy dose and the utilization of stereotactic body radiotherapy (SBRT) have been shown to enhance local tumor control. However, there is a growing concern regarding the development of radiation-induced airway disease (RIAD), which encompasses central airway stenosis, atelectasis, obstructive pneumonia, airway-wall necrosis, severe airway toxicity, and potentially life-threatening complications. This article presents the latest research advancements regarding the incidence, pathophysiological alterations, injury classification, preventive strategies, and treatment approaches of RIAD.

Objective To determine the correlation and agreement of sacral ratio(SR)measured by lateral and anteroposterior radiographs in patients with anorectal malformation(ARM).Methods A retrospective analysis was conducted on the anteroposterior and lateral radiographs images of the sacral vertebrae of patients with ARM.All SR values were measured by three radiologists.Pearson's correlation coefficient were used to assess the correlation between the SR measured by lateral and anteroposterior radiographs.A weighted Kappa statistic was used to measure the agreement between how the anteroposterior and lateral SR categorized observations into risk groups.Results Of the 385 ARM patients,25 patients whose radiographs image quality was insufficient to calculate SR value were excluded.For a given pair of measurements,the mean lateral SR value was 0.08 units greater than the anteroposterior SR value[95%confidence interval(CI)0.06-0.09,P<0.01].Anteroposterior and lateral images had a moderate positive correlation(r=0.79,95%CI 0.73-0.79,P<0.01)and moderate agreement in risk categorization(Kappa=0.62,P<0.01).Anteroposterior and lateral readings conducted by all three radiologists had excellent inter-rater reliability with intraclass correlation coefficient(ICC)for anteroposterior and lateral SR of 0.88 and 0.84,respectively.Conclusion Even though the anteroposterior and lateral SR values have moderate positive correlation,the mean SR value determined by images in the lateral is 0.08 units greater than the anteroposterior.Anteroposterior and lateral SR value conclude different risk categories relatively often.The SR values measured by lateral sacral radiographs are more clinically significant than those measured by anteroposterior radiographs.

Background::With an increasing number of patients with hematological malignancies being treated with umbilical cord blood transplantation (UCBT), the correlation between immune reconstitution (IR) after UCBT and graft-versus-host disease (GVHD) has been reported successively, but reports on double-negative T (DNT) cell reconstitution and its association with acute GVHD (aGVHD) after UCBT are lacking.Methods::A population-based observational study was conducted among 131 patients with hematological malignancies who underwent single-unit UCBT as their first transplant at the Department of Hematology, the First Affiliated Hospital of USTC, between August 2018 and June 2021. IR differences were compared between the patients with and without aGVHD.Results::The absolute number of DNT cells in the healthy Chinese population was 109 (70-157)/μL, accounting for 5.82 (3.98-8.19)% of lymphocytes. DNT cells showed delayed recovery and could not reach their normal levels even one year after transplantation. Importantly, the absolute number and percentage of DNT cells were significantly higher in UCBT patients without aGVHD than in those with aGVHD within one year ( F = 4.684, P = 0.039 and F = 5.583, P = 0.026, respectively). In addition, the number of DNT cells in the first month after transplantation decreased significantly with the degree of aGVHD increased, and faster DNT cell reconstitution in the first month after UCBT was an independent protective factor for aGVHD (HR = 0.46, 95% confidence interval [CI]: 0.23-0.93; P = 0.031). Conclusions::Compared to the number of DNT cells in Chinese healthy people, the reconstitution of DNT cells in adults with hematological malignancies after UCBT was slow. In addition, the faster reconstitution of DNT cells in the early stage after transplantation was associated with a lower incidence of aGVHD.

Objectives:To investigate the prognostic value of soluble growth stimulation expressed gene 2 protein(sST2)combined with N-terminal pro-brain natriuretic peptide(NT-proBNP)in patients with ST-segment elevation myocardial infarction(STEMI)undergoing primary percutaneous coronary intervention(PCI). Methods:A total of 206 patients who were diagnosed with STEMI for the first time and underwent emergency PCI from August 2020 to February 2021 in the People's Hospital of Liaoning Province were enrolled.Patients were followed up for 3 years and divided into major adverse cardiac event(MACE,a composite endpoint event including cardiac death,stroke,heart failure,and ischemia-driven revascularization)group and MACE-free group.Multivariate cox analysis was performed to determine the independent risk factors for the prognosis of primary PCI in STEMI patients;the predictive value of sST2 and NT-proBNP for the occurrence of MACE in STEMI patients undergoing primary PCI was assessed by ROC analysis and the prediction of MACE by each factor by itself and the combined variables was analyzed with the Delong test. Results:There were 62 cases of MACE during the 3-year follow-up.Compared with the MACE-free group,patients in the MACE group had higher levels of sST2 and NT-proBNP,higher proportion of patients with left anterior descending branch lesions,anterior wall myocardial infarction,lower LVEF,and higher proportion of coronary artery slow flow(all P<0.05).Multivariate Cox analysis showed that sST2(HR=1.018,95%CI:1.012-1.024,P<0.001)and NT-proBNP(HR=1.001,95%CI:1.000-1.010,P<0.001)were independent predictors of MACE.According to the statistical analysis of ROC and Delong test,the AUC of combined sST2 and NT-proBNP in predicting MACE was 0.854,the sensitivity was 64.5%,the specificity was 93.1%,and the combined prediction of prognosis was better than that of individual prediction,with statistically significant difference(Z=2.119,P=0.034;Z=2.178,P=0.029). Conclusions:Serum sST2 and NT-proBNP are valuable predictors of MACE after emergency PCI in patients with STEMI,and the predictive efficacy increases with combined assessment of both sST2 and NT-proBNP.

Phospholipase Cζ (PLCζ) is composed of XY domain, EF-hand domains and a C2 domain, which specifically hydrolyzes phosphatidylinositol (4,5)-bisphosphate (PIP 2) in the oocyte cytoplasm but not on the plasma membrane through the classical PIP 2→(1,4,5)-inositol trisphosphate (IP 3)+diacylglycerol (DAG) signal transduction pathway, which causes oscillation of calcium ion in oocytes, and plays an irreplaceable role in activating oocytes and initiating gamete development. Clinical data have shown that the reduced or absent expression level of PLCζ can lead to the inability of sperm activating oocytes and are closely related to various sperm abnormalities, ultimately leading to male subfertility and even infertility. In summary, this article reviews the structure and biological functions of PLCζ, the clinical diseases caused by abnormal PLCζ and their following therapeutic progresses.

Phospholipase Cζ (PLCζ) is composed of XY domain, EF-hand domains and a C2 domain, which specifically hydrolyzes phosphatidylinositol (4,5)-bisphosphate (PIP 2) in the oocyte cytoplasm but not on the plasma membrane through the classical PIP 2→(1,4,5)-inositol trisphosphate (IP 3)+diacylglycerol (DAG) signal transduction pathway, which causes oscillation of calcium ion in oocytes, and plays an irreplaceable role in activating oocytes and initiating gamete development. Clinical data have shown that the reduced or absent expression level of PLCζ can lead to the inability of sperm activating oocytes and are closely related to various sperm abnormalities, ultimately leading to male subfertility and even infertility. In summary, this article reviews the structure and biological functions of PLCζ, the clinical diseases caused by abnormal PLCζ and their following therapeutic progresses.

Objective:To summarize the clinical phenotype and gene mutation characteristics of male patients with epilepsy caused by mosaic PCDH19 mutation. Methods:The clinical data of 3 male patients with epilepsy caused by mosaic PCDH19 mutation were analyzed.Microdroplet digital polymerase chain reaction (mDDPCR) was used for the detection of mosaicism in the three probands and their family members.Relevant literatures were reviewed. Results:The seizure onset age were 5 months, 9 months and 6 months of life respectively.Focal seizures occurred in 2 cases and multiple seizure types occurred in 1 case.Three patients presented with clusters of seizures.Fever sensitivity was observed in 2 cases out of the 3 cases.Two patients had intellectual disability and 1 patient had autistic manifestation.The clinical phenotype in 2 patient fulfilled the diagnosis of Dravet syndrome. PCDH19 mosaic mutations c. 317T>A(p.M106K), c.158dupT(p.D54Gfs*35) and c. 1639G>C(p.A547P) were detected respectively, and were identified as de novo after parental validation.Mutant allele fractions (MAF) in the blood samples were identified as 81.18%, 37.08%, 77.64%, respectively.The MAF of multiple tissues in 1 patient varied from 78.67% to 98.46%.Review of literature revealed that a total of 11 cases with mosaic PCDH19 mutation were reported.Among them, seizure onset occurred between 5 and 31 months of age.Focal seizures occurred in 9 cases, 3 cases of the 9 cases had only focal seizures.Generalized tonic clonic seizures occurred in 4 cases.Two or more seizures were observed in 6 cases.Clustering of seizures was found in all patient and sensitivity to fever was observed in 9 patients.Seven patients had mild to severe intellectual disability and 5 patients had autistic features. Conclusions:The clinical phenotypes of male patients with epilepsy caused by PCDH19 mosaic mutation are characterized by clustering of seizures, sensitivity to fever, focal seizures in most cases, varied degree of intellectual disability and autistic features in partial.