Objective:To summarize the clinical characteristics of focal cerebral arteriopathy (FCA) in children, and to analyze its influencing factor of prognosis.Methods:A retrospective cohort study was conducted. Clinical data from 40 children with FCA who were hospitalized at the Department of Neurology, Beijing Children′s Hospital, Capital Medical University, from September 2015 to August 2024 were collected. A centralized follow-up was conducted in October 2024 via outpatient clinics or the internet. The pediatric stroke outcome measure (PSOM) was used to evaluate their outcomes. Based on the PSOM, the children were further divided into a group with normal neurological function and another group with abnormal neurological function. Differences between groups were analyzed using the Mann-Whitney U test and Fisher exact test. Univariate Logistic regression analysis was performed to identify the influencing factors for neurological outcomes in children with FCA. Results:A total of 40 children were included, with 20 males and 20 females, and the onset age of 9.2 (6.8, 12.5) years. Among them, 12 cases (30%) had a history of varicella within 1 year before onset. There were 23 cases (58%) presenting with transient ischemic attack (TIA) or recurrent fluctuating symptoms of onset, while 3 cases (8%) developed progressive stroke within the first month of onset. The M1 segment of the middle cerebral artery was the most commonly affected vascular site, with a total of 16 cases (40%). Arterial occlusion occurred in 8 cases (20%). Lumbar puncture was completed in 36 children, and white blood cell counts in cerebrospinal fluid was increased in 6 cases. All 23 patients who completed magnetic resonance vessel wall imaging (VWI) showed circular enhancement of the arterial wall. A total of 28 patients (70%) received antiplatelet or anticoagulation therapy, and 16 patients (40%) received hormone therapy. At admission, the pediatric National Institute of Health Stroke Scale (PedNIHSS) score was 6.0 (2.0, 8.8) points, which decreased to 0.5 (0, 3.0) points at discharge. The follow-up duration was 1.6 (0.8, 4.9) years, with 1 case lost to follow-up. There was 1 case presenting with recurrence course manifesting as TIA. Among the 39 cases who completed the follow-up, 23 cases (59%) were assessed as neurologically normal by PSOM, while 16 cases (41%) were assessed as neurologically abnormal. Among the 29 cases who completed the imaging review, magnetic resonance angiography (MRA) review in 23 cases indicated stability or improvement in the original arterial stenosis, with 6 cases experiencing transient worsening of arterial stenosis early in the disease course (within 2 months), which later improved. Arterial stenosis progression occurred in 6 cases at the final review of 29 cases who completed the imaging review, with 1 case developing progressive cerebral arteriopathy. The proportion of patients with headache, altered consciousness, and aphasia in the abnormal neurological function group, as well as the PedNISS scores at admission and discharge, were all higher than those in the normal neurological function group (all P<0.05). Univariate Logistic regression analysis revealed that only a PedNISS score>6 points at onset was an influencing factor for abnormal neurological function ( OR=20.58, 95% CI 3.93-107.70, P<0.001). Conclusions:Childhood FCA often presents with fluctuating onset, and the proximal segment of the middle cerebral artery is frequently affected. Progression of arterial stenosis is common within 2 months of the disease course, but clinical progression and new ischemic lesions are uncommon. Most patients have a favorable long-term prognosis. PedNIHSS score>6 points at admission is related to abnormal neurological function outcomes.

Objective:To investigate the risk factors and prognosis of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis following herpes simplex virus encephalitis (HSE) in children.Methods:A retrospective cohort study was conducted on 83 children with HSE hospitalized at Beijing Children′s Hospital, Capital Medical University, from January 2013 to June 2023. The clinical data, including demographics, clinical manifestations, Glasgow coma scale (GCS) scores, auxiliary examinations, and treatment regimens, were collected. The prognoses of these children were evaluated using the modified Rankin scale (mRS), pediatric cerebral performance category (PCPC) scale, and pediatric quality of life inventory (PedsQL). These children were divided into 2 groups: those who developed secondary anti-NMDAR encephalitis and those who did not. Non-parametric tests were used for intergroup comparisons, and Logistic regression models were applied to identify risk factors for secondary anti-NMDAR encephalitis.Results:Among the 83 children with HSE, 23 children developed secondary anti-NMDAR encephalitis. The secondary anti-NMDAR encephalitis group exhibited a later age of onset compared to the non-secondary group (4.0 (2.2, 7.1) vs. 1.6 (0.8, 5.4) years, Z=2.19, P=0.028), lower GCS scores (8.0 (5.5, 11.5) vs. 14.0 (9.8, 15.0) points, Z=3.74, P<0.001), and worse prognostic outcomes as measured by mRS, PCPC scale and PedsQL (3.0 (2.0, 5.0) vs. 1.0 (0.3, 3.0) points, 3.0 (2.0, 4.0) vs. 2.0 (1.0, 4.0) points, 52.0 (17.0, 67.0) vs. 86.5 (53.3, 97.5) points, Z=3.48, 3.36, 3.09, all P<0.01). Logistic regression analysis identified lower GCS scores during HSE as an independent risk factor for the secondary anti-NMDAR encephalitis ( OR=0.82, 95% CI 0.72-0.94, P=0.003). Conclusion:For the children with HSE who present low GCS scores, regular follow-ups are imperative in order to monitor for the potential development of anti-NMDAR encephalitis, thus facilitating early intervention and improving clinical outcomes.

Objective:To summarize the clinical characteristics of focal cerebral arteriopathy (FCA) in children, and to analyze its influencing factor of prognosis.Methods:A retrospective cohort study was conducted. Clinical data from 40 children with FCA who were hospitalized at the Department of Neurology, Beijing Children′s Hospital, Capital Medical University, from September 2015 to August 2024 were collected. A centralized follow-up was conducted in October 2024 via outpatient clinics or the internet. The pediatric stroke outcome measure (PSOM) was used to evaluate their outcomes. Based on the PSOM, the children were further divided into a group with normal neurological function and another group with abnormal neurological function. Differences between groups were analyzed using the Mann-Whitney U test and Fisher exact test. Univariate Logistic regression analysis was performed to identify the influencing factors for neurological outcomes in children with FCA. Results:A total of 40 children were included, with 20 males and 20 females, and the onset age of 9.2 (6.8, 12.5) years. Among them, 12 cases (30%) had a history of varicella within 1 year before onset. There were 23 cases (58%) presenting with transient ischemic attack (TIA) or recurrent fluctuating symptoms of onset, while 3 cases (8%) developed progressive stroke within the first month of onset. The M1 segment of the middle cerebral artery was the most commonly affected vascular site, with a total of 16 cases (40%). Arterial occlusion occurred in 8 cases (20%). Lumbar puncture was completed in 36 children, and white blood cell counts in cerebrospinal fluid was increased in 6 cases. All 23 patients who completed magnetic resonance vessel wall imaging (VWI) showed circular enhancement of the arterial wall. A total of 28 patients (70%) received antiplatelet or anticoagulation therapy, and 16 patients (40%) received hormone therapy. At admission, the pediatric National Institute of Health Stroke Scale (PedNIHSS) score was 6.0 (2.0, 8.8) points, which decreased to 0.5 (0, 3.0) points at discharge. The follow-up duration was 1.6 (0.8, 4.9) years, with 1 case lost to follow-up. There was 1 case presenting with recurrence course manifesting as TIA. Among the 39 cases who completed the follow-up, 23 cases (59%) were assessed as neurologically normal by PSOM, while 16 cases (41%) were assessed as neurologically abnormal. Among the 29 cases who completed the imaging review, magnetic resonance angiography (MRA) review in 23 cases indicated stability or improvement in the original arterial stenosis, with 6 cases experiencing transient worsening of arterial stenosis early in the disease course (within 2 months), which later improved. Arterial stenosis progression occurred in 6 cases at the final review of 29 cases who completed the imaging review, with 1 case developing progressive cerebral arteriopathy. The proportion of patients with headache, altered consciousness, and aphasia in the abnormal neurological function group, as well as the PedNISS scores at admission and discharge, were all higher than those in the normal neurological function group (all P<0.05). Univariate Logistic regression analysis revealed that only a PedNISS score>6 points at onset was an influencing factor for abnormal neurological function ( OR=20.58, 95% CI 3.93-107.70, P<0.001). Conclusions:Childhood FCA often presents with fluctuating onset, and the proximal segment of the middle cerebral artery is frequently affected. Progression of arterial stenosis is common within 2 months of the disease course, but clinical progression and new ischemic lesions are uncommon. Most patients have a favorable long-term prognosis. PedNIHSS score>6 points at admission is related to abnormal neurological function outcomes.

Objective:To investigate the risk factors and prognosis of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis following herpes simplex virus encephalitis (HSE) in children.Methods:A retrospective cohort study was conducted on 83 children with HSE hospitalized at Beijing Children′s Hospital, Capital Medical University, from January 2013 to June 2023. The clinical data, including demographics, clinical manifestations, Glasgow coma scale (GCS) scores, auxiliary examinations, and treatment regimens, were collected. The prognoses of these children were evaluated using the modified Rankin scale (mRS), pediatric cerebral performance category (PCPC) scale, and pediatric quality of life inventory (PedsQL). These children were divided into 2 groups: those who developed secondary anti-NMDAR encephalitis and those who did not. Non-parametric tests were used for intergroup comparisons, and Logistic regression models were applied to identify risk factors for secondary anti-NMDAR encephalitis.Results:Among the 83 children with HSE, 23 children developed secondary anti-NMDAR encephalitis. The secondary anti-NMDAR encephalitis group exhibited a later age of onset compared to the non-secondary group (4.0 (2.2, 7.1) vs. 1.6 (0.8, 5.4) years, Z=2.19, P=0.028), lower GCS scores (8.0 (5.5, 11.5) vs. 14.0 (9.8, 15.0) points, Z=3.74, P<0.001), and worse prognostic outcomes as measured by mRS, PCPC scale and PedsQL (3.0 (2.0, 5.0) vs. 1.0 (0.3, 3.0) points, 3.0 (2.0, 4.0) vs. 2.0 (1.0, 4.0) points, 52.0 (17.0, 67.0) vs. 86.5 (53.3, 97.5) points, Z=3.48, 3.36, 3.09, all P<0.01). Logistic regression analysis identified lower GCS scores during HSE as an independent risk factor for the secondary anti-NMDAR encephalitis ( OR=0.82, 95% CI 0.72-0.94, P=0.003). Conclusion:For the children with HSE who present low GCS scores, regular follow-ups are imperative in order to monitor for the potential development of anti-NMDAR encephalitis, thus facilitating early intervention and improving clinical outcomes.

Objective:To explore the prognostic value of epidermal growth factor receptor (EGFR) co-mutation status in patients with advanced lung adenocarcinoma.Methods:Clinical data of patients with stage ⅢB-Ⅳ lung adenocarcinoma who were first diagnosed in the Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Hebei North University from January 2019 to December 2022 were collected prospectively. Patients were divided into EGFR mutation group ( n=82) and EGFR co-mutation group ( n=74) according to whether EGFR was combined with other gene mutations. The level of circulating tumor DNA (ctDNA) in peripheral blood was measured by real time fluorescence quantitative PCR. Objective response rate (ORR), disease control rate (DCR), the levels of ctDNA in peripheral blood, and progression-free survival (PFS) were compared between two groups of patients before and after 1 month of treatment. The univariate and multivariate analyses were conducted by Cox proportional hazards regression model. Results:In the EGFR mutation group, there were 45 cases of EGFR19 deletion mutation and 37 cases of EGFR21 mutation. In the EGFR co-mutation group, there were 41 cases of EGFR19 deletion mutation, 33 cases of EGFR21 mutation, 46 cases of TP53 mutation, 16 cases of RB1 mutation, 6 cases of PTEN mutation, 2 cases of MET amplification, 1 case of ERBB2 mutation, 1 case of KRAS mutation, 1 case of RET rearrangement, and 1 case of ALK rearrangement. There were statistically significant differences between the EGFR mutation group and the EGFR co-mutation group in the maximum tumor diameter ( χ2=5.04, P=0.025) and stage ( χ2=3.92, P=0.048). The ORRs of the two groups were 64.63% (53/82) and 37.84% (28/74), respectively, with a statistically significant difference ( χ2=11.19, P<0.001). The DCRs were 96.34% (79/82) and 86.49% (64/74), respectively, with a statistically significant difference ( χ2=4.95, P=0.026). The ctDNA levels in the EGFR mutation group and EGFR co-mutation group after one month of treatment decreased compared to before treatment[2.63 (1.83, 3.30) ng/μl vs. 4.73 (3.92, 5.49) ng/μl, Z=-7.06, P<0.001; 4.26 (2.26, 6.07) ng/μl vs. 5.28 (4.37, 6.09) ng/μl, Z=-5.15, P<0.001], the ctDNA levels in the EGFR co-mutation group were higher than those in the EGFR mutation group before treatment and after 1 month of treatment ( Z=-2.47, P=0.013; Z=-4.29, P<0.001). In the EGFR co-mutation group, the ctDNA levels in peripheral blood of patients who were effectively treated with targeted therapy decreased after 1 month of treatment compared to before treatment [(2.03±0.63) ng/μl vs. (3.92±0.82) ng/μl, t=42.94, P<0.001], the levels of ctDNA in peripheral blood of ineffectively treated patients before and after 1 month of treatment were higher than those of effectively treated patients [(5.84±0.57) ng/μl vs. (3.92±0.82) ng/μl, t=-11.91, P<0.001; (5.87±1.64) ng/μl vs. (2.03±0.63) ng/μl, t=-14.43, P<0.001]. The median PFS of the EGFR mutation group and the EGFR co-mutation group of patients were 10.4 and 8.3 months, respectively, with a statistically significant difference ( χ2=22.28, P<0.001). Univariate analysis suggested that the maximum tumor diameter ( HR=0.10, 95% CI: 0.06-0.16, P<0.001), performance status (PS) score ( HR=0.09, 95% CI: 0.06-0.15, P<0.001), stage ( HR=0.09, 95% CI: 0.05-0.14, P<0.001), pre-treatment ctDNA level ( HR=12.04, 95% CI: 8.21-17.65, P<0.001), ctDNA level after 1 month of treatment ( HR=3.75, 95% CI: 3.10-4.54, P<0.001) and EGFR co-mutations ( HR=2.21, 95% CI: 1.57-3.12, P<0.001) were found to be significant factors affecting the PFS of stage ⅢB-Ⅳ lung adenocarcinoma patients receiving targeted therapy; Multivariate analysis demonstrated that PS score ( HR=0.25, 95% CI: 0.14-0.47, P<0.001), stage ( HR=0.49, 95% CI: 0.24-0.98, P=0.044), pre-treatment ctDNA level ( HR=4.73, 95% CI: 3.08-7.28, P<0.001), ctDNA level after 1 month of treatment ( HR=2.15, 95% CI: 1.65-2.80, P<0.001), and EGFR gene co-mutation ( HR=2.26, 95% CI: 1.40-3.64, P<0.001) were independent risk factors for PFS in stage ⅢB-Ⅳ lung adenocarcinoma patients receiving targeted therapy. Conclusion:Both the EGFR mutation group and EGFR co-mutation group show a decrease in ctDNA levels after targeted therapy for one month compared to before treatment. The median PFS of EGFR co-mutation patients is shorter than that of patients with a single EGFR mutation. PS score, stage, ctDNA levels before and after treatment, and EGFR gene co-mutation are all independent factors affecting PFS in stage ⅢB-Ⅳ lung adenocarcinoma patients after targeted therapy.

Objective:To summarize the clinical and prognostic features of children with opsoclonus-myoclonus-ataxia syndrome (OMAS).Methods:A total of 46 patients who met the diagnostic criteria of OMAS in the Department of Neurology, Beijing Children′s Hospital from June 2015 to June 2023 were retrospectively analyzed. Centralized online consultations or telephone visits were conducted between June and August 2023. The data of the children during hospitalization and follow-up were collected, including clinical manifestations, assistant examination, treatment and prognosis. According to the presence or absence of tumor, the patients were divided into two groups. The chi-square test or Mann-Whitney U test was used to compare the differences between the two groups. Univariate Logistic regression was used to analyze the factors related to OMAS recurrence and prognosis. Results:There were 46 patients, with 25 males and the onset age of 1.5 (1.2, 2.4) years. Twenty-six (57%) patients were diagnosed with neuroblastoma during the course of the disease, and no patients were categorized into the high-risk group. A total of 36 patients (78%) were followed up for≥6 months, and all of them were treated with first-line therapy with glucocorticoids, gammaglobulin and (or) adrenocorticotrophic hormone. Among the 36 patients, 9 patients (25%) were treated with second-line therapy for ≥3 months, including rituximab or cyclophosphamide, and 17 patients (47%) received chemotherapy related to neuroblastoma. At the follow-up time of 4.2 (2.2, 5.5) years, 10 patients (28%) had relapsed of OMAS. The Mitchell and Pike OMS rating scale score at the final follow-up was 0.5 (0, 2.0). Seven patients (19%) were mildly cognitively behind their peers and 6 patients (17%) were severely behind. Only 1 patient had tumor recurrence during follow-up. The history of vaccination or infection before onset was more common in the non-tumor group than in the tumor group (55%(11/20) vs. 23%(6/26), χ2=4.95, P=0.026). Myoclonus occurred more frequently in the non-tumor group (40%(8/20) vs. 4%(1/26), χ2=7.23, P=0.007) as the onset symptom. Univariate Logistic regression analysis showed that the tumor group had less recurrence ( OR=0.19 (0.04-0.93), P=0.041). The use of second-line therapy or chemotherapy within 6 months of the disease course had a better prognosis ( OR=11.64 (1.27-106.72), P=0.030). Conclusions:OMAS in children mostly starts in early childhood, and about half are combined with neuroblastoma. Neuroblastoma in combination with OMAS usually has a low risk classification and good prognosis. When comparing patients with OMAS with and without tumors, the latter have a more common infection or vaccination triggers, and myoclonus, as the onset symptom, is more common. Early addition of second-line therapy is associated with better prognosis in OMAS.

Abiotic stresses substantially affect the growth and development of plants. Plants have evolved multiple strategies to cope with the environmental stresses, among which transcription factors play an important role in regulating the tolerance to abiotic stresses. Basic leucine zipper transcription factors (bZIP) are one of the largest gene families. The stability and activity of bZIP transcription factors could be regulated by different post-translational modifications (PTMs) in response to various intracellular or extracellular stresses. This paper introduces the structural feature and classification of bZIP transcription factors, followed by summarizing the PTMs of bZIP transcription factors, such as phosphorylation, ubiquitination and small ubiquitin-like modifier (SUMO) modification, in response to abiotic stresses. In addition, future perspectives were prospected, which may facilitate cultivating excellent stress-resistant crop varieties by regulating the PTMs of bZIP transcription factors.
Basic-Leucine Zipper Transcription Factors/genetics* ; Protein Processing, Post-Translational ; Phosphorylation ; Transcription Factors/genetics* ; Stress, Physiological/genetics*