Objective:To explore the efficacy and safety of tislelizumab combined with zanubrutinib in the treatment of refractory diffuse large B-cell lymphoma (DLBCL).Methods:A prospective observational study was conducted. A total of 10 patients with refractory DLBCL admitted to Beijing Chaoyang District Third Ring Cancer Hospital, a specialist medical consortium of Cancer Hospital Chinese Academy of Medical Sciences from November 2020 to February 2023 were prospectively collected. All the 10 refractory DLBCL patients at least received first-line systemic therapy containing rituximab; and they were given tislelizumab 200 mg, intravenous infusion, on day 1 and zanubrutinib 160 mg, orally, twice a day, day 1-day 21, with 21 days as 1 cycle; 6 patients received second-line therapy and 4 patients received ≥ third-line therapy. Subsequent regimens were added with rituximab (375 mg/m 2, intravenous infusion on day 1). The primary endpoint will be reached 12 months after enrollment if there was no disease progression or other events that were scheduled to withdraw from the study. The therapeutic efficacy was summarized at the end of the follow-up in March 2023. Kaplan-Meier method was used to make survival analysis and the adverse reactions were summed up. Results:There were 6 males and 4 females, all at stage Ⅲ-Ⅳ; and age [ M ( Q1, Q3)] was 55 years (50 years, 69 years). All 10 patients completed 90 cycles of treatment with tislelizumab and zanubrutinib, with the cycle number of 8 cycles (2 cycles, 24 cycles). The follow-up time was 19 months (11 months, 28 months); 4 cases achieved complete remission, 3 cases achieved partial remission and 1 case had the stable disease. The progression-free survival was 8.5 months (1.3 months, 27.0 months); the median remission duration time and median overall survival time were not reached. Treatment-related adverse reactions included 2 cases of neutropenia, 1 case of anemia, and 1 case of elevated alanine aminotransferase and aspartate aminotransferase, all of which were grade 1-2. Conclusions:Tislelizumab combined with zanubrutinib has good clinical efficacy and safety in the treatment of refractory DLBCL.

【Objective】 To analyze the effect of extensively hydrolyzed formula(eHF) in the treatment of feeding intolerance in preterm infants and the effect on hospital infection, in order to provide reference for the clinical treatment of feeding intolerance in preterm infants. 【Methods】 A total of 208 cases of preterm infants with feeding intolerance diagnosed and treated in Shandong Heze Municipal Hospital from April 2017 to February 2020 were selected into the clinical trial for eligibility assessment, then were randomly assigned into study group(n=100) and control group(n=100) after screening and exclusion. Children in the control group were fed with standard preterm formula, while children in the study group were fed with eHF. Feeding tolerance indicators, including daily milk intake, time to meconium evacuation, time to full gastrointestinal nutrition, total gastric residual counts(GRV1) in the 7-d period after resumption of breastfeeding, ratio of all-day gastric residual counts/all-day estimated milk intake after resumption of breastfeeding(GRV2) were compared between the two groups, and growth indicators(body weight growth rate, head dimension growth rate), complication incidence [necrotizing enterocolitis(NEC), pathological jaundice, positive fecal occult blood or blood in stool] and incidence of hospital-acquired infections. 【Results】 The daily milk intake(t=5.037) of the study group was higher than that of the control group, and the time of foetal excretion(t=9.217), the time to reach full gastrointestinal nutrition(t=15.833), GRV1(t=6.737), GRV2(t=9.956) were lower than those of the control group, and the differences were all statistically significant(P<0.05). The rate of weight gain(t=2.454) and head dimension growth(t=5.469) in the study group was significantly higher than those of the control group(P<0.05). The incidence of the three complications of NEC, pathological jaundice and positive fecal occult blood or blood in stool(χ²=4.310) and the incidence of hospital infections(χ²=4.688) were significantly lower in the study group than in the control group(P<0.05). 【Conclusions】 Compared with the standard formula milk for preterm infants, eHF can significantly improve the feeding intolerance of preterm infants, promote growth and development, and reduce the occurrence of hospital-acquired infections. Therefore, eHF can be widely used in clinic for preterm infants with feeding intolerance.

Objective:To explore the value of high frequency ultrasound scoring combined with serum levels of interleukin-6 (IL-6), C-reactive protein (CRP), and procalcitonin (PCT) in evaluating the prognosis of neonatal respiratory distress syndrome (NRDS) in children.Methods:A total of 106 children with NRDS who were treated at Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University from March 2021 to December 2022 were selected. According to the discharge outcome, NRDS patients were divided into a poor prognosis group ( n=11) and a good prognosis group ( n=95), and the clinical data differences between the two groups were compared. At the same time, NRDS patients were divided into mild to moderate group ( n=75) and severe group ( n=31) based on the severity of the disease. The differences in high-frequency ultrasound scores of the lungs and serum levels of IL-6, CRP, and PCT were analyzed in children with different disease severity levels of NRDS. Logistic multiple regression analysis was used to identify the influencing factors of prognosis; receiver operating characteristic (ROC) curve analysis of lung high-frequency ultrasound score, IL-6, and their combination predicted the prognostic value of NRDS in children. Results:The gestational age, birth weight, and high-frequency ultrasound scores of the lungs in the poor prognosis group were significantly lower than those in the good prognosis group (all P<0.05); The proportion of diabetes in pregnancy, the proportion of severe disease, the first use time of pulmonary surfactant (PS) and the level of IL-6 in the poor prognosis group were significantly higher than those in the good prognosis group (all P<0.05). The serum levels of IL-6, CRP, and PCT in severe children were significantly higher than those in mild to moderate children (all P<0.05); The high-frequency ultrasound score of the lungs in severe children was significantly lower than that in mild to moderate children ( P<0.05). Logistic regression analysis showed that gestational age, pulmonary high-frequency ultrasound score, gestational diabetes, disease severity, and IL-6 were the influencing factors for poor prognosis of children with NRDS (all P<0.05). The area under the ROC curve for predicting poor prognosis in children with NRDS using high-frequency ultrasound score, IL-6, and their combination were 0.745, 0.802, and 0.786, respectively. Conclusions:The severity of NRDS in children is related to the high-frequency ultrasound score of the lungs and serum levels of IL-6, CRP, and PCT. At the same time, the high-frequency ultrasound score of the lungs and IL-6 are related to the prognosis of NRDS children, and have certain application value in predicting the prognosis of children.

Malocclusion,identified by the World Health Organization(WHO)as one of three major oral diseases,profoundly impacts the dental-maxillofacial functions,facial esthetics,and long-term development of～260 million children in China.Beyond its physical manifestations,malocclusion also significantly influences the psycho-social well-being of these children.Timely intervention in malocclusion can foster an environment conducive to dental-maxillofacial development and substantially decrease the incidence of malocclusion or reduce the severity and complexity of malocclusion in the permanent dentition,by mitigating the negative impact of abnormal environmental influences on the growth.Early orthodontic treatment encompasses accurate identification and treatment of dental and maxillofacial morphological and functional abnormalities during various stages of dental-maxillofacial development,ranging from fetal stages to the early permanent dentition phase.From an economic and societal standpoint,the urgency for effective early orthodontic treatments for malocclusions in childhood cannot be overstated,underlining its profound practical and social importance.This consensus paper discusses the characteristics and the detrimental effects of malocclusion in children,emphasizing critical need for early treatment.It elaborates on corresponding core principles and fundamental approaches in early orthodontics,proposing comprehensive guidance for preventive and interceptive orthodontic treatment,serving as a reference for clinicians engaged in early orthodontic treatment.

Objective:To summarize the electroclinical characteristics of patients with epilepsy with myoclonic absence（EMA）and analyze the relationship with prognosis.Methods:Clinical data of 25 patients with EMA monitored at the pediatric EEG monitoring centers of Peking University People's Hospital and Peking University First Hospital between January 2012 and December 2022 were retrospectively analyzed and divided into three groups according to development before and after the onset of the disease to analyze the electroclinical characteristics and the relationship with prognosis.Results:There were 14 males and 11 females in 25 cases，and the median age of epilepy onset was 48（26，74）months.Sixteen cases in the group with normal development before and after the onset of epilepsy（group A），5 cases in the group with normal development before the onset of epilepsy but retarded development after the onset of epilepsy（group B），and 4 cases in the group with retarded development before and after the onset of epilepsy（group C）.The median age at onset was 62（36，82）months，34（21，66）months，and 26（20，32）months in the three groups，with 3，3，and 4 cases of early onset in each group，respectively.The EEG background activity slowed down in 10 cases，with 6，1 and 3 cases in the three groups，respectively.Interictal EEG was normal in 1 and abnormal in 24 cases，which showed generalized discharges，of which 11 cases showed coexisting focal discharges and generalized discharges.Among the focal discharges，there were cases in all three groups，involving the anterior-posterior，temporal and Rolandic regions.Fifteen cases had myoclonic absence（MA）induced by hyperventilation，with 10 cases in group A，4 cases in group B and 1 case in group C.The most prevalent concomitant seizure was myoclonic seizure（MS），with 9，3 and 2 cases in each group respectively.Statistically significant differences were seen in early onset and refractory EMA among the three groups（both P<0.05）.In further two by two comparisons，the proportion of early onset and drug refractory cases was greater in children in group C than in group A，with statistically significant differences（both P<0.017），and the difference in concomitant MS among the three groups was not statistically significant（ P>0.05）. Conclusions:The MA seizures in children with EMA are sensitive to hyperventilation.The common accompanying seizure is MS.Some children with EMA present with early onset and refractory epilepsy，with a tendency towards developmental epileptic encephalopathy.

Objective To explore the clinical effect of endoscopic sclerosing agent injection combined with ligation in the treatment of third degree internal hemorrhoids.Methods 100 patients with internal hemorrhoids from January 2019 to August 2022 were prospectively selected and divided into control group(50 patients,treated with ligation)and study group(50 patients,treated with endoscopic sclerosing agent injection combined with ligation).Clinical data of patients were collected,and the clinical efficacy,postoperative recovery related indicators,resting anal pressure,anal canal maximum systolic pressure(AMSP),degree of hemorrhoid prolapse and the incidence of postoperative complications were compared between the two groups.Results The total effective rate of the study group was higher than that of the control group,and the difference was statistically significant(P<0.05);After surgery,the pain score,wound bleeding score,degree of hemorrhoid prolapse score,and anal edema score in the study group were lower than those in the control group,and the differences were statistically significant(P<0.05).After operation,the resting anal pressure and AMSP in both groups were obviously reduced,and the study group was lower than the control group(P<0.05).Conclusion The combination of endoscopic sclerosing agent injection combined with ligation for the treatment of internal hemorrhoids has a significant effect,which can improve the recovery of surgical and postoperative related indicators,improve the anal and intestinal dynamics,reduce the score of hemorrhoid prolapse,and have good safety.

Objective:To analyze the genetic variations and clinical phenotypic characteristics of epilepsy associated with CSNK2B gene mutations. Methods:A case series summary study.Clinical data of 15 epileptic children with CSNK2B gene mutations diagnosed and treated at the Third Affiliated Hospital of Zhengzhou University and the Peking University First Hospital from February 2016 to October 2023 were retrospectively analyzed.The clinical manifestations, genotypes, and electroencephalography (EEG) results were summarized. Results:Among the 15 children (8 boys and 7 girls), 14 cases had de novo mutations in the CSNK2B gene, and 1 case had hereditary variations.There were 5 missense variants, 4 splice-site variants, 3 frameshift variants, and 3 nonsense variants.Ten mutation sites had not been previously reported (c.326G>A/p.Cys109Tyr, c.485A>G/p.His162Arg, c.368-1G>A, c.464A>C/p.Asp155Ala, c.301T>G/p.Tyr101Asp, c.342T>A/p.Cys114*, c.198del/p.Asn67Thrfs*5, c.292-10T>G, c.573-574del/p.Lys191Asnfs*54, and c. 11C>G/p.Ser4*).The age of onset of seizures ranged from 14 days to 6 years, with 13 cases starting within 2 years old.The types of seizures included focal seizures in 9 cases, generalized tonic-clonic seizure (GTCS) in 5 cases, myoclonic seizures in 1 case, atonic seizures in 1 case, atypical absence seizures in 1 case, and epileptic seizures in 1 case.Three cases had multiple seizures, and 4 cases had cluster seizures.The EEG showed slow background activity in 1 case.Epileptiform discharges were observed in 13 cases during the interictal phase, including generalized discharges in 6 cases, multifocal discharges in 3 cases, and focal discharges in 5 cases.Two cases had normal EEG findings.Brain magnetic resonance imaging results were normal in 10 cases.The age of the last follow-up ranged from 1 year and 1 month to 13 years and 10 months.Seizures were controlled in 12 cases treated with 1 or 2 antiepileptic drugs, while seizures persisted in 2 cases treated with multiple antiepileptic drugs, and 1 case suffered no seizures for 1 year and 3 months, without antiepileptic drug treatment.Oxcarbazepine was effective in 5 cases (5/7), Valproate sodium was effective in 6 cases (6/8), and Levetiracetam was effective in 3 cases (3/9). Conclusions:CSNK2B gene mutations are mainly de novo mutations, and epilepsy triggered by them typically starts within 2 years of age.GTCS and focal seizures are the most common types.The seizures of most children are easily controlled with the effective treatment of Oxcarbazepine, Valproate sodium, and Levetiracetam.

Objective:To summarize the genotype and clinical phenotype of children with WWOX gene related developmental and epileptic encephalopathy (DEE).Methods:Case series studies. The clinical data of 12 children with WWOX gene related DEE who were admitted to the Neurological Department of Children′s Medical Center, Peking University First Hospital from June 2019 to December 2023 were analyzed. The children′s characteristics of gene variation, clinical phenotype, auxiliary examination results, treatment and prognosis were analyzed.Results:Among 12 children with WWOX gene related DEE, there were 7 boys and 5 girls, the age of seizure onset ranged from 10 days to 6 months (median 1.8 months). Multiple seizure types were observed, including focal seizures in 10 cases, epileptic spasms in 9 cases, tonic seizures in 4 cases, myoclonic seizures in 1 case. Among 12 cases, 9 cases had multiple seizure types. All 12 cases showed microcephaly and global developmental delay. Video electroencephalography showed slowed background activity in 6 cases, hyperarrhythmia in 6 cases, multifocal discharges in 6 cases, and focal discharges in 1 case. Epileptic spasms were detected in 8 cases, tonic seizures in 4 cases and myoclonic seizures in 1 case. Brain magnetic resonance imaging showed bilateral frontotemporal subarachnoid space widening in 5 cases, deep sulci in 3 cases, bilateral ventricular enlargement in 2 cases, callosal hypoplasia in 5 cases, and delayed white matter myelination in 3 cases. The phenotypes of 12 cases were consistent with the diagnosis of DEE, and 8 of them were diagnosed with infantile epileptic spasm syndrome. All the WWOX gene variants in 12 cases were complex heterozygous variants, including 20 variants, 11 variants and 1 large intragenic WWOX gene deletion (p.Ala149Thr, p.Arg156Ser, p.R167Tfs*8, p.Leu186Val, c.605+5G>A, p.Trp218*, p.His263Arg, p.Leu275fs*19*1, p.N285Kfs*10, p.Ser304Tyr, p.Met326Arg, loss1 exon2-8) had not been reported previously. The age of last follow-up ranged from 11 months to 5 years and 3 months. During the follow-up, 1 case died at the age of 1 year and 10 months, 2 cases were seizure-free, and 9 cases still had seizures after multiple anti-seizure medications.Conclusions:The seizure onset age of children with WWOX gene related DEE is usually less than 6 months, and some of them in neonate. The common seizure types include focal seizures and epileptic spasms. Children usually have microcephaly and global developmental delay. WWOX gene related DEE usually has drug refractory epilepsy.

Objective:To evaluate the efficacy and safety of rituximab in pediatric myasthenia gravis (MG).Methods:Case series study. The clinical manifestations, laboratory tests, treatment plans and prognosis of 27 pediatric MG patients treated with rituximab from June 2013 to June 2023 at Children′s Medical Center of Peking University First Hospital were retrospectively collected.Results:There were 5 males and 22 females in 27 MG children. The onset age was 2.1 (1.6, 4.8) years, ranging from 8 months to 11 years. The clinical classification included 20 children (74%) of ocular MG and 7 children (26%) of generalized MG. Seventeen children (63%) had positive MG-related pathogenic antibodies, including 17 children of anti-AchR antibody and 1 of them also had anti-MuSK antibody. Rituximab was used as first-line immunosuppressant in 13 children, second-line immunosuppressant in 13 children and third-line immunosuppressant in 1 child. Immunosuppressants used before rituximab including 8 children of cyclosporine, 3 children of tacrolimus, 1 child of azathioprine, 1 child of mycophenolate mofetil and 1 child of cyclosporine combined with azathioprine. Rituximab was used for at least half a year with a follow-up period of more than 12 months. At the last follow-up after rituximab treatment, all children achieved improved or above, 14 children (52%) achieved complete stable remission, 7 children (26%) achieved pharmacologic remission, 1 child (4%) achieved minimal manifestations, and 5 children (18%) improved. After rituximab treatment, 27 children all could reduce the immunomodulation therapy and shorten the course of glucocorticoid therapy, and 22 children (81%) had stopped the glucocorticoid therapy. Among the 14 children with poor efficacy of other immunosuppressants, rituximab had complete stable remission of 7 children. The most common adverse reaction was respiratory infection (4 children (15%)). Only 2 children had allergic reaction to rituximab and got better after symptomatic treatment.Conclusions:Rituximab has good efficacy and tolerance in pediatric MG. Early application of rituximab can improve the prognosis and shorten the course of glucocorticoid treatment.

Objective:To summarize the clinical features of epilepsy and (or) developmental delay associated with KCNB1 gene variants in children.Methods:A case series study was conducted on 24 children with KCNB1 gene variants associated with epilepsy and (or) developmental delay who were treated at the Children′s Medical Center of Peking University First Hospital and the Department of Neurology of Shenzhen Children′s Hospital from July 2015 to June 2024. The manifestations of seizures, electroencephalogram (EEG) and genetic test results of those children were analyzed.Results:All the KCNB1 gene variants were de novo, involving 20 different variation, including 15 missense variations, 3 frameshift variations and 2 nonsense variations. There were 7 novel variations. Among the 24 developmental and epileptic encephalopathy children, there were 14 boys and 10 girls. The last follow-up age ranged from 9 months to 13 years and 9 months. Seizures were present in 21 children (88%), with onset ranging from 1 month to 7 years, and 76% (16/21) began before 2 years of age. The seizure types included focal seizures in 15 children (71%), epileptic spasms, myoclonic seizures, and generalized tonic-clonic seizures in 6 children respectively, atypical absence seizures in 4 children, and myoclonic atonic seizures in 1 child. Seventeen children (81%) had a cluster of seizures and 5 had a history of focal status epilepticus with impaired consciousness. All 24 children had varying degrees of developmental delay, with 3 presenting solely developmental delay. EEG abnormalities were present in all the 21 children with seizures, including focal or multifocal discharges in 20 children, generalized discharges in 10 children, hypsarrhythmia in 2 children, and electrical status epilepticus during sleep in 3 children. Magnetic resonance imaging abnormalities were found in 5 of the 24 children. Among the 21 children with seizures, 57% (12/21) achieved seizure control.Conclusions:KCNB1 gene variants are predominantly de novo missense variation. Most affected children present with epilepsy, though some may exhibit only developmental delay. Epilepsy often begins before 2 years of age, with focal seizures being the most common type. About 80% of patients experience clustered seizures. Although most patients achieve seizure control, they still exhibit varying degrees of developmental delay, consistent with developmental epileptic encephalopathy.