Alzheimer's disease (AD) is the major form of dementia in the elderly and is closely related to the toxic effects of microglia sustained activation. In AD, sustained microglial activation triggers impaired synaptic pruning, neuroinflammation, neurotoxicity, and cognitive deficits. Accumulating evidence has demonstrated that aberrant expression of deubiquitinating enzymes is associated with regulating microglia function. Here, we use RNA sequencing to identify a deubiquitinase YOD1 as a regulator of microglial function and AD pathology. Further study showed that YOD1 knockout significantly improved the migration, phagocytosis, and inflammatory response of microglia, thereby improving the cognitive impairment of AD model mice. Through LC-MS/MS analysis combined with Co-IP, we found that Myosin heavy chain 9 (MYH9), a key regulator maintaining microglia homeostasis, is an interacting protein of YOD1. Mechanistically, YOD1 binds to MYH9 and maintains its stability by removing the K48 ubiquitin chain from MYH9, thereby mediating the microglia polarization signaling pathway to mediate microglia homeostasis. Taken together, our study reveals a specific role of microglial YOD1 in mediating microglia homeostasis and AD pathology, which provides a potential strategy for targeting microglia to treat AD.

BackgroundSchool bullying is a serious social issue. Non-suicidal self-injury （NSSI） is a highly prevalent behavior among adolescents with depression and is also becoming a great matter of concern. Previous studies have proved a very close correlation among school bullying， experiential avoidance， family functioning， and NSSI behavior. However， there is a considerable lack of research on the moderating role of family functioning in the relationship between school bullying and experiential avoidance in adolescents with depression in China. ObjectiveTo explore the mediating role of experiential avoidance in the relationship between school bullying and NSSI in adolescents with depressive disorder， and the moderating role of family functioning in the relationship between school bullying and experiential avoidance， so as to provide references for formulating intervention strategies for NSSI in adolescents with depressive disorder. MethodsFrom January to December 2024， 318 consecutive adolescent patients fulfilling the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5） diagnostic criteria for depression and attending the outpatient department of Weifang Mental Health Center were selected. All respondents completed the Delaware Bullying Victimization Scale-Student （DBVS-S）， Acceptance and Action Questionnaire-II （AAQ-II）， Family Assessment Device （FAD）， and Behavioral Questionnaire in the Adolescent Non-suicidal Self-injury Assessment Questionnaire （ANSAQ）. Pearson correlation was used to examine the relationship among variables. SPSS Process Macro v4.1 package program was utilized to seek the mediating and moderating effects. ResultsData were collected from 306 valid respondents （96.23%）. In adolescent with depressive disorder， DBVS-S score was positively correlated with both the behavioral questionnaire score in the ANSAQ and the AAQ-II score （r=0.357， 0.558， P<0.01）. AAQ-II score was positively correlated with the behavioral questionnaire score in the ANSAQ （r=0.380， P<0.01）. Experiential avoidance partially mediated the relationship between school bullying and NSSI in adolescents with depressive disorder， and the mediating effect value was 0.142 （95% CI： 0.081~0.204）. Family functioning moderated the relationship between school bullying and experiential avoidance， and the moderated mediation value was 0.096 （95% CI： 0.042~0.165）. ConclusionMediation is found from school bullying to NSSI behavior through experiential avoidance in adolescents with depressive disorder， and family functioning plays a moderating role in the relationship between school bullying and experiential avoidance.

Objective To observe the value of prenatal ultrasound graded management of Sylvian fissure for diagnosing fetal lissencephaly.Methods Totally 39 fetuses with MRI diagnosed lissencephaly who underwent prenatal ultrasound examination were retrospectively enrolled and divided into non-graded management group(n=20)and graded management group(n=19)according to prenatal ultrasound examination before or after the application of prenatal ultrasound graded management of Sylvian fissure(i.e.prenatal ultrasound routine screening for fetal Sylvian fissure morphology).The diagnosis of prenatal ultrasound were compared and analyzed between groups,and the diagnostic value of graded management was evaluated.Results Among 20 fetuses in non-graded management group,prenatal ultrasound showed lissencephaly in 4 fetuses,but only other structural abnormalities in 16 fetuses.Then the latter were re-evaluated based on prenatal ultrasound graded management of Sylvian fissure,among which 4 fetuses could not be evaluated since not standard ultrasonic section,2 fetuses with severe hydrocephalus and Sylvian fissure could not be seen,while Sylvian fissure morphology did not match the corresponding gestational week in 4 fetuses,and type Ⅰ(no platform type)and type Ⅴ(Z-shaped)were noticed in 5 and 1 fetus,respectively.In graded management group,prenatal ultrasound indicated 15 fetuses with lissencephaly,including Sylvian fissure morphology did not match the corresponding gestational week in 6 fetuses,type Ⅰ(no platform type),type Ⅲ(linear type)and type Ⅴ(Z-shaped)were detected in 7,1 and 1 fetus,respectively,while no clear diagnosis was obtained in 4 fetuses.Prenatal ultrasound detection rate of fetal lissencephaly in graded management group(15/19,78.95％)was significantly higher than that in non-graded management group(4/20,20.00％)(P＜0.01).Conclusion Based on graded management of Sylvian fissure could improve the efficiency of prenatal ultrasound for diagnosing fetal lissencephaly.

Objective To explore the effects of Jingling Oral Liquid(mainly composed of Polygoni Multiflori Radix,Polygonati Rhizoma,Platycladi Semen,Nelumbinis Semen,Ligustri Lucidi Fructus,Poria,and Lilii Bulbus)as an adjunctive therapy on cognitive,motor,and social abilities in children with global developmental delay(GDD).Methods A total of 120 children with GDD who visited the Department of Neurological Rehabilitation at Hebei Children's Hospital from July 2021 to November 2023 were selected as the study subjects.The children were randomly divided into a control group and a trial group using a random number table,with 60 children in each group.The control group received conventional comprehensive rehabilitation training,while the trial group received Jingling Oral Liquid as an adjunctive therapy in addition to the control group's treatment.The treatment course lasted 12 weeks.Before and after treatment,the changes in Gesell Developmental Scale(GDS)scores,Peabody Developmental Motor Scales(PDMS)scores,motor function scores,and language ability scores in both groups were observed to evaluate the cognitive,motor,and social abilities of the children.Results(1)After treatment,the scores of all dimensions of the GDS,including adaption,developmental quotient of fine motor,language developmental quotient,and personal-social developmental quotient,were significantly increased in both groups compared to those before treatment(P＜0.01),and the improvement of GDS scores in the trial group was significantly superior to that in the control group(P＜0.01).(2)After treatment,the scores of all dimensions of the PDMS,including fine developmental quotient score,standardized score of visual-motor integration,and standardized score of grasping,were significantly increased in both groups compared to those before treatment(P＜0.01),and the improvement of PDMS scores in the trial group was significantly superior to that in the control group(P＜0.01).(3)After treatment,the scores of motor function indicators of fine motor quotient(FMQ),gross motor quotient(GMQ),and total motor quotient(TMQ)were significantly increased in both groups compared to those before treatment(P＜0.01),and the improvement of motor function scores in the trial group was significantly superior to that in the control group(P＜0.01).(4)After treatment,the language ability scores were significantly increased in both groups compared to those before treatment(P＜0.01),and the improvement of language ability scores in the trial group was significantly superior to that in the control group(P＜0.01).Conclusion The combination of Jingling Oral Liquid with conventional comprehensive rehabilitation training can effectively improve the cognitive,motor,and social abilities of children with GDD.

Objective:To detect the biological markers related to Alzheimer's disease(AD)in the peripheral blood of AD patients,and to explore the activities and levels of the antioxidant function indexes and the expressions of related genes and proteins in the blood of AD patients and the changes after intervention of selenium-rich food.Methods:The Mini-Mental State Examination(MMSE)combined with electroencephalogram or brain CT and clinician diagnosis were used for screening AD.Fifty-six elderly patients with AD aged 75-90 years old were selected.Among them,28 cases were selected as normal diet group for AD(AD group),and 28 cases were selected as dietary selenium intervention group(Se-AD group).The patients in Se-AD group were given daily dietary selenium supplementation(increaseing dietary selenium by 15-20 μg per day)for 3 months.Meanwhile,30 people with the same age were selected as healthy control group.The activities of serum superoxide dismutase(SOD),cholinesterase(CHE),and glutathione peroxidase(GSH-Px)and the levels of serum malondialdehyde(MDA),homocysteine(Hcy),and nitric oxide(NO)as well as reagent kit the levels of serum β-amyloid protein(Aβ),and microtubule-associated protein(Tau)and phosphorylated microtubule-associated protein(p-Tau)of the subjects in various groups were detected by and enzyme-linked immunosorbent assay(ELISA)method;the expression levels of apolipoprotein E4(ApoE4),presenilin 1(PS1),presenilin 2(PS2),cysteinyl aspartate specific proteinase 3(Caspase3),sorting associated protein receptor 1(SORL1),β-site amyloid precursor protein cleaving enzyme 1(BACE1),hypoxia-inducible factor 1(HIF1),nuclear factor-kappa B(NF-κB),β-amyloid precursor protein(APP),protein kinase C(PKC),and Aβ mRNA in peripheral blood of the subjects various groups were detected by real-time fluorescence quantitative PCR(RT-qPCR)method.Results:Compared with healthy control group,the serum SOD activities of the patients in Se-AD group and AD group were significantly decreased(P＜0.05),while serum CHE activity and the levels of MDA and Hcy were significantly increased(P＜0.05);the serum GSH-Px activity of the patients in AD group was significantly decreased(P＜0.05),and the level of NO was significantly increased(P＜0.05).Compared with Se-AD group,serum CHE activity and the level of Hcy of the patients in AD group were significantly increased(P＜0.05).The expression levels of ApoE4,PS1,Caspase3,BACE1,NF-κB and APP mRNA of the patients in Se-AD group and AD group were significantly increased(P＜0.05),and the expression levels of PKC mRNA were significantly decreased(P＜0.05);the expression level of PS2 mRNA of the patients in AD group was significantly increased(P＜0.05),and the expression levels of Aβ mRNA of the patients in Se-AD group and AD group were significantly increased(P＜0.05).Conclusion:The activities of serum SOD,GSH-Px and CHE and the levels of MDA,Hcy and NO,the levels of Aβ,Tau and p-Tau proteins,and the expression levels of ApoE4,PS1,Caspase3,BACE1,NF-κB,PKC,PS2,Aβ and APP mRNA in peripheral blood of the AD patients may vary and can be used for clinical diagnosis of the AD patients.Selenium-rich food can improve AD to some extent,and its mechanism is related to reducing the oxidative damage of brain tissue and decreasing the expression of AD related genes PS2 and Aβ.

Yi Dagen was a famous physician of Xujiang School in Ming Dynasty.In the process of syndrome differentiation and treatment,Yi Dagen attached great importance to pulse diagnosis and paid attention to the influence of time factors.His theory was based on"Yin and Yang having time rules and coordinating with pulse"in Basic Questions:The subtlety of pulse diagnosis,emphasizing the mutual reference of pulse and time,reflecting the fundamental principle of"correspondence between nature and man"in traditional Chinese medicine.The thought of mutual reference of pulse and time is mainly reflected in two levels:one is to guide syndrome differ-entiation,which can be summarized as referring to midnight-midday ebb flow to identify the location of the disease,referring to the four-season and five-viscus pulse method to identify the cause of the disease,referring to the north-south governance to identify the nature of the disease,and choosing the time to diagnose the pulse to identify the disease situation;the second is the whole process of syndrome differentiation and treatment,including pulse and time diagnosis and treatment according to the time.The idea of mutual ref-erence of pulse and time plays an important guiding role in current clinical work.In the future,wearable pulse diagnosis equipment and intelligent monitoring technology can be combined to build a dynamic pulse analysis system to realize the real-time and precise applica-tion of the"mutual reference of pulse and time"theory.

Yi Dagen was a famous physician of Xujiang School in Ming Dynasty.In the process of syndrome differentiation and treatment,Yi Dagen attached great importance to pulse diagnosis and paid attention to the influence of time factors.His theory was based on"Yin and Yang having time rules and coordinating with pulse"in Basic Questions:The subtlety of pulse diagnosis,emphasizing the mutual reference of pulse and time,reflecting the fundamental principle of"correspondence between nature and man"in traditional Chinese medicine.The thought of mutual reference of pulse and time is mainly reflected in two levels:one is to guide syndrome differ-entiation,which can be summarized as referring to midnight-midday ebb flow to identify the location of the disease,referring to the four-season and five-viscus pulse method to identify the cause of the disease,referring to the north-south governance to identify the nature of the disease,and choosing the time to diagnose the pulse to identify the disease situation;the second is the whole process of syndrome differentiation and treatment,including pulse and time diagnosis and treatment according to the time.The idea of mutual ref-erence of pulse and time plays an important guiding role in current clinical work.In the future,wearable pulse diagnosis equipment and intelligent monitoring technology can be combined to build a dynamic pulse analysis system to realize the real-time and precise applica-tion of the"mutual reference of pulse and time"theory.

Objective To observe the value of prenatal ultrasound graded management of Sylvian fissure for diagnosing fetal lissencephaly.Methods Totally 39 fetuses with MRI diagnosed lissencephaly who underwent prenatal ultrasound examination were retrospectively enrolled and divided into non-graded management group(n=20)and graded management group(n=19)according to prenatal ultrasound examination before or after the application of prenatal ultrasound graded management of Sylvian fissure(i.e.prenatal ultrasound routine screening for fetal Sylvian fissure morphology).The diagnosis of prenatal ultrasound were compared and analyzed between groups,and the diagnostic value of graded management was evaluated.Results Among 20 fetuses in non-graded management group,prenatal ultrasound showed lissencephaly in 4 fetuses,but only other structural abnormalities in 16 fetuses.Then the latter were re-evaluated based on prenatal ultrasound graded management of Sylvian fissure,among which 4 fetuses could not be evaluated since not standard ultrasonic section,2 fetuses with severe hydrocephalus and Sylvian fissure could not be seen,while Sylvian fissure morphology did not match the corresponding gestational week in 4 fetuses,and type Ⅰ(no platform type)and type Ⅴ(Z-shaped)were noticed in 5 and 1 fetus,respectively.In graded management group,prenatal ultrasound indicated 15 fetuses with lissencephaly,including Sylvian fissure morphology did not match the corresponding gestational week in 6 fetuses,type Ⅰ(no platform type),type Ⅲ(linear type)and type Ⅴ(Z-shaped)were detected in 7,1 and 1 fetus,respectively,while no clear diagnosis was obtained in 4 fetuses.Prenatal ultrasound detection rate of fetal lissencephaly in graded management group(15/19,78.95％)was significantly higher than that in non-graded management group(4/20,20.00％)(P＜0.01).Conclusion Based on graded management of Sylvian fissure could improve the efficiency of prenatal ultrasound for diagnosing fetal lissencephaly.

Objective:To analyze the clinical features and outcomes of paroxysmal supraventricular tachycardia (PSVT) in neonates without structural heart disease.Methods:A retrospective study was conducted on PSVT neonates without structural heart disease who were treated and followed up at the Women and Children's Hospital, Qingdao University, from January 2019 to June 2022. Clinical data, including the prenatal history of PSVT, the time at first onset of PSVT after birth, anti-arrhythmic treatment, and follow-up outcomes, were collected and analyzed. These patients were divided into two groups based on the presence and absence of fetal PSVT history. Differences in the clinical data between the two groups were compared, including the time at first onset of PSVT, the proportion of patients with persistent tachycardia at initial diagnosis, and hospitalization frequency. Statistical analysis was performed using t-test, Mann-Whitney U test, or Pearson's Chi-square test. Results:A total of 72 neonates with PSVT were included, with an average gestational age at delivery of (38.8±1.8) weeks and an average birth weight of (3 260±330) g. There were 26 (36.1%) cases with a prenatal history of PSVT, while 46 (63.9%) cases without. The median time at the first onset of PSVT after birth was 2.1 (0.3-13.7) d. Anti-arrhythmic drugs used for the patients included propafenone (44 cases, 61.1%), amiodarone (28 cases, 38.9%), and cedilanid (14 cases, 19.4%). There were 44 cases (61.1%) received single drug therapy, 26 (36.1%) receiving dual therapy, and only two (2.8%) receiving triple therapy. Prophylactic drugs were administered to 38 patients (52.8%) for six months, and 20 (27.8%) for 12 months. Fourteen cases (19.4%) still exhibited tachycardia during follow-up and continued their drug therapy. No major illnesses or deaths occurred in the 72 patients during a 12-month follow-up. Compared with the patients without a history of fetal PSVT, those with a history of fetal PSVT had an earlier onset of PSVT after birth [0.2 d (0.0-0.7 d) vs. 12.0 d (2.2-15.0 d), Z=－4.83, P<0.001], a high rate of persistent tachycardia at first diagnosis [76.9% (20/26) vs. 39.1% (18/46), χ2=4.76, P=0.029], more hospitalizations [4.0 times(3.0-7.0 times) vs. 1.0 times (1.0-1.0 times), Z=－3.52, P<0.001], and longer duration of preventive anti-arrhythmic treatment [12.0 months (10.5-21.0 months) vs. 6.0 months (3.0-6.0 months), Z=－4.17, P<0.001]. Conclusion:Attention should be given to PSVT screening in neonates without structural heart disease, particularly for those with a history of fetal PSVT, who tend to have an early onset of PSVT after birth, persistent tachycardia at first diagnosis with high rates of recurrence and require longer preventive anti-arrhythmic treatment.

Objective:To summarize the prenatal ultrasound features of fetal cleidocranial dysplasia (CCD) and provide references for clinical consultation.Methods:A retrospective analysis was conducted on the prenatal ultrasound features, genetic testing results, and prognosis of a CCD fetus diagnosed at Qingdao Women and Children's Hospital in June 2023. Relevant literature on CCD was retrieved from the CNKI, Yiigle, Wanfang, and PubMed databases including cases confirmed by genetic testing or postnatal clinical phenotype and imaging with relatively complete prenatal ultrasound information. The prenatal ultrasound features of CCD fetuses were summarized using descriptive statistical analysis.Results:(1) In this case, prenatal ultrasound at 25 weeks of gestation indicated widened cranial sutures with clear near-field intracranial structures, absence of the nasal bone, shortened and rigid bilateral clavicles, and mildly shortened bilateral femurs and humeri. Chromosomal karyotyping and chromosomal microarray analysis showed no abnormalities, but whole exome sequencing detected a RUNX2 gene mutation, leading to a diagnosis of CCD combined with the ultrasound phenotype. At 36 weeks of gestation, the mother experienced premature rupture of membranes and delivered a male infant vaginally. Bedside X-rays indicated bilateral wet lungs and bilateral clavicular dysplasia in the newborn. Telephone follow-up at 9 months showed no abnormalities in growth and development. (2) Literature review: Thirteen cases from 13 articles were included, along with this case, totaling 14 CCD fetuses. The main ultrasound phenotypes of CCD fetuses were clavicular dysplasia (12/14), incomplete cranial ossification (10/14), absence of the nasal bone (8/14), and shortening of the femur (12/14). Other ultrasound phenotypes included scapular dysplasia, short ribs, and increased interocular distance. Conclusion:Clavicular dysplasia and incomplete cranial ossification are the most specific signs of fetal CCD, while absence of the nasal bone and mild femoral shortening are secondary features of CCD.