Objective:To investigate the clinical and genetic variation characteristics of a child with autosomal dominant lateral temporal lobe epilepsy caused by de novo variation of the MICAL1 gene. Methods:Clinical data of the patient with autosomal dominant lateral temporal lobe epilepsy caused by MICAL1 gene variation diagnosed in Children′s Hospital of Soochow University in August 2019 were collected. The whole exome sequencing was performed on the core members of the family, and the characteristics of gene variations were analyzed. Results:The proband, a 10 years and 5 months old boy, was admitted to the hospital because of "intermittent convulsions for 7 years". The clinical manifestations included focal or generalized tonic-clonic seizures and hearing aura, with normal language and intellectual development. No abnormalities were found in the T 1 and fluid attenuated inversion recovery sequences of the cranial 3.0 T magnetic resonance imaging and 3D thin-slice magnetic resonance imaging.Long-range video electroencephalogram showed the distribution of spinous and slow spinous waves in the left frontal and temporal areas. The results of whole exome gene sequencing in the core family members showed heterozygous de novo missense variation in the MICAL1 gene of the proband (NM_022765): c.763G>T(exon6)(p.Val255Leu) that had not been reported. According to American College of Medical Genetics and Genomics and Association for Molecular Pathology guidelines (2015), the mutation was considered potentially pathogenic. The application of antiepileptic drugs was effective in controlling epileptic seizures. Conclusions:Auditory symptoms are main clinical manifestations for the child with autosomal dominant lateral temporal lobe epilepsy. Antiepileptic drugs can effectively control epileptic seizures of the child, and the MICAL1 gene c.763G>T (p.Val255Leu) mutation is the genetic cause of the proband.

Objective:To summarize the clinical characteristics of 5 children with developmental epileptic encephalopathy type 17 (DEE17) caused by GNAO1 gene variants confirmed by whole-exome sequencing and analyze the features of their genetic variants. Methods:A retrospective analysis was conducted on the clinical data of 5 children diagnosed with GNAO1-related DEE17 in the Department of Neurology, Children′s Hospital of Soochow University from January 2019 to October 2024. Their clinical features, genetic testing results, neuroimaging findings, electroencephalogram (EEG) results, and treatment regimens were summarized. Follow-up was performed via telephone or outpatient visits. Results:Among the 5 diagnosed children (3 males, 2 females), the age of onset ranged from 2 days to 2 years, and the age at diagnosis ranged from 2 days to 6 years. Four children presented with seizures in the neonatal or infantile period, manifesting as hypotonia, developmental delay, and seizure types including generalized tonic-clonic, myoclonic, and epileptic spasms. One child had a later onset at 2 years, presenting with language delay, intellectual disability, and involuntary movements, followed by seizures at 6 years, including focal and generalized tonic-clonic seizures. Genetic testing revealed de novo heterozygous missense variants in GNAO1 in all 5 cases: c.119G>C (p.G40A), c.808A>C (p.N270H), c.808A>G (p.N270D), c.118G>C (p.G40R), and c.17G>T (p.S6I). Among these variants, c.119G>C and c.17G>T were previously unreported pathogenic variants. Neuroimaging showed nonspecific changes in 3 children (widened frontal-temporal subarachnoid space, delayed myelination) and abnormal white matter signals in 2 cases. Long-term video-EEG revealed abnormal discharges and background slowing in all cases: multifocal discharges in 4 cases and focal epileptiform discharges (left mid-temporal) in 1 case. Clinical seizures were captured in 3 cases: 1 with a burst-suppression pattern and 2 with hypsarrhythmia. All patients received 3 or more antiseizure medications. Four cases (cases 1-4) responded well to topiramate combination therapy, with 2 cases (cases 1, 2) achieving complete seizure freedom and 2 cases (cases 3, 4) experiencing more than a 50% reduction in seizures. One child (case 3) achieved seizure control with an adjunctive ketogenic diet. The late-onset case (case 5) required a combination of levetiracetam, oxcarbazepine, and valproate for seizure management. Conclusions:GNAO1 variants can lead to DEE17 with diverse seizure types, often requiring multiple antiseizure medications, among which topiramate is effective. Early-onset cases typically present with seizures and developmental delay, while late-onset cases may exhibit language delay, intellectual disability, movement disorders, and refractory epilepsy. Genetic testing should be performed early for timely diagnosis.

Objective:To investigate the clinical and genetic variation characteristics of a child with autosomal dominant lateral temporal lobe epilepsy caused by de novo variation of the MICAL1 gene. Methods:Clinical data of the patient with autosomal dominant lateral temporal lobe epilepsy caused by MICAL1 gene variation diagnosed in Children′s Hospital of Soochow University in August 2019 were collected. The whole exome sequencing was performed on the core members of the family, and the characteristics of gene variations were analyzed. Results:The proband, a 10 years and 5 months old boy, was admitted to the hospital because of "intermittent convulsions for 7 years". The clinical manifestations included focal or generalized tonic-clonic seizures and hearing aura, with normal language and intellectual development. No abnormalities were found in the T 1 and fluid attenuated inversion recovery sequences of the cranial 3.0 T magnetic resonance imaging and 3D thin-slice magnetic resonance imaging.Long-range video electroencephalogram showed the distribution of spinous and slow spinous waves in the left frontal and temporal areas. The results of whole exome gene sequencing in the core family members showed heterozygous de novo missense variation in the MICAL1 gene of the proband (NM_022765): c.763G>T(exon6)(p.Val255Leu) that had not been reported. According to American College of Medical Genetics and Genomics and Association for Molecular Pathology guidelines (2015), the mutation was considered potentially pathogenic. The application of antiepileptic drugs was effective in controlling epileptic seizures. Conclusions:Auditory symptoms are main clinical manifestations for the child with autosomal dominant lateral temporal lobe epilepsy. Antiepileptic drugs can effectively control epileptic seizures of the child, and the MICAL1 gene c.763G>T (p.Val255Leu) mutation is the genetic cause of the proband.

Objective:To summarize the clinical characteristics of 5 children with developmental epileptic encephalopathy type 17 (DEE17) caused by GNAO1 gene variants confirmed by whole-exome sequencing and analyze the features of their genetic variants. Methods:A retrospective analysis was conducted on the clinical data of 5 children diagnosed with GNAO1-related DEE17 in the Department of Neurology, Children′s Hospital of Soochow University from January 2019 to October 2024. Their clinical features, genetic testing results, neuroimaging findings, electroencephalogram (EEG) results, and treatment regimens were summarized. Follow-up was performed via telephone or outpatient visits. Results:Among the 5 diagnosed children (3 males, 2 females), the age of onset ranged from 2 days to 2 years, and the age at diagnosis ranged from 2 days to 6 years. Four children presented with seizures in the neonatal or infantile period, manifesting as hypotonia, developmental delay, and seizure types including generalized tonic-clonic, myoclonic, and epileptic spasms. One child had a later onset at 2 years, presenting with language delay, intellectual disability, and involuntary movements, followed by seizures at 6 years, including focal and generalized tonic-clonic seizures. Genetic testing revealed de novo heterozygous missense variants in GNAO1 in all 5 cases: c.119G>C (p.G40A), c.808A>C (p.N270H), c.808A>G (p.N270D), c.118G>C (p.G40R), and c.17G>T (p.S6I). Among these variants, c.119G>C and c.17G>T were previously unreported pathogenic variants. Neuroimaging showed nonspecific changes in 3 children (widened frontal-temporal subarachnoid space, delayed myelination) and abnormal white matter signals in 2 cases. Long-term video-EEG revealed abnormal discharges and background slowing in all cases: multifocal discharges in 4 cases and focal epileptiform discharges (left mid-temporal) in 1 case. Clinical seizures were captured in 3 cases: 1 with a burst-suppression pattern and 2 with hypsarrhythmia. All patients received 3 or more antiseizure medications. Four cases (cases 1-4) responded well to topiramate combination therapy, with 2 cases (cases 1, 2) achieving complete seizure freedom and 2 cases (cases 3, 4) experiencing more than a 50% reduction in seizures. One child (case 3) achieved seizure control with an adjunctive ketogenic diet. The late-onset case (case 5) required a combination of levetiracetam, oxcarbazepine, and valproate for seizure management. Conclusions:GNAO1 variants can lead to DEE17 with diverse seizure types, often requiring multiple antiseizure medications, among which topiramate is effective. Early-onset cases typically present with seizures and developmental delay, while late-onset cases may exhibit language delay, intellectual disability, movement disorders, and refractory epilepsy. Genetic testing should be performed early for timely diagnosis.

Autophagy， a mechanism of cell self-protection and self-renewal， is associated with the occurrence and development of lung cancer. Favorable autophagy can slow down the progression of lung cancer， while unfavorable autophagy can promote the progression. Therefore， regulating the level of autophagy is of great significance in the treatment of lung cancer. Healthy Qi deficiency and pathogenic Qi stagnation is an extension of the theory of deficiency and Qi stagnation proposed by the Academician WANG Yongyan. It refers to the pathological process that the abnormal body fluid metabolism caused by Qi deficiency of lung， spleen， and kidney results in phlegm and blood stasis. Lung cancer has the root cause of Qi deficiency of lung， spleen， and kidney and the syndrome of phlegm and blood stasis. The autophagy in lung cancer is interconnected with healthy Qi deficiency and pathogenic Qi stagnation. The Qi deficiency of lung， spleen， and kidney is the key factor for the weakening of favorable autophagy in lung cancer， which inhibits the apoptosis of tumor cells and leads to the accumulation of harmful substances. Phlegm and blood stasis is a direct factor enhancing the unfavorable autophagy in lung cancer， which promotes the autophagic death of normal cells， weakens the immunosuppressive effect of immune cells on tumor cells， and leads to the proliferation and migration of tumor cells. The combination of healthy Qi deficiency and pathogenic Qi stagnation results in the development of autophagy in an unfavorable direction and finally leads to the continuous progression of lung cancer. Therefore， the traditional Chinese medicine （TCM） treatment of lung cancer should follow the principle of reinforcing healthy Qi and expelling pathogenic Qi， removing phlegm and resolving stasis， so as to enhance favorable autophagy while inhibiting unfavorable autophagy. Such therapy can inhibit the proliferation and migration of tumor cells and promote the remission of lung cancer. According to the existing literature， Chinese medicine monomers are mainly used to treat lung cancer by regulating autophagy. The Chinese medicine intervention of autophagy in lung cancer mainly aims to promote the activation of autophagy. This may be because the favorable autophagy weakening caused by the Qi deficiency of lung， spleen， and kidney is the fundamental reason for the development of lung cancer.

During coronavirus disease 2019 epidemic, the treatment of severe trauma has been impacted. The Consensus on emergency surgery and infection prevention and control for severe trauma patients with 2019 novel corona virus pneumonia was published online on February 12, 2020, providing a strong guidance for the emergency treatment of severe trauma and the self-protection of medical staffs in the early stage of the epidemic. With the Joint Prevention and Control Mechanism of the State Council renaming "novel coronavirus pneumonia" to "novel coronavirus infection" and the infection being managed with measures against class B infectious diseases since January 8, 2023, the consensus published in 2020 is no longer applicable to the emergency treatment of severe trauma in the new stage of epidemic prevention and control. In this context, led by the Chinese Traumatology Association, Chinese Trauma Surgeon Association, Trauma Medicine Branch of Chinese International Exchange and Promotive Association for Medical and Health Care, and Editorial Board of Chinese Journal of Traumatology, the Chinese expert consensus on emergency surgery for severe trauma and infection prevention during coronavirus disease 2019 epidemic ( version 2023) is formulated to ensure the effectiveness and safety in the treatment of severe trauma in the new stage. Based on the policy of the Joint Prevention and Control Mechanism of the State Council and by using evidence-based medical evidence as well as Delphi expert consultation and voting, 16 recommendations are put forward from the four aspects of the related definitions, infection prevention, preoperative assessment and preparation, emergency operation and postoperative management, hoping to provide a reference for severe trauma care in the new stage of the epidemic prevention and control.

Objective: To investigate the immunohistochemical staining of anaplastic lymphoma kinase (ALK; clone 1A4) in pediatric medulloblastoma (MB). Methods: Molecular subtyping was performed based on the NanoString and sequencing techniques for 44 pediatric MB cases at Children′s Hospital, Zhejiang University School of Medicine from 2014 to 2017. ALK expression was detected with EnVision immunhistochemistry using ALK clone 1A4 on whole section. Statistical analyses were performed to evaluate the correlation of protein expression with molecular subgroups. Results: The age ranged from 0.5 to 13.0 years with an average age of 5.8 years. There were 28 males and 16 females, and 31 classic, 5 desmoplastic nodular, 3 extensive nodular and 5 large cell/anaplastic MBs. Except three cases was unable classified, 41 MBs were classified into the four molecular groups: 5 in WNT group, 12 in SHH group, 9 in Group 3 and 15 in Group 4. Thirteen of 44 MB cases were positive staining for ALK, and the positive rate was 29.5%. Six cases were strong reaction, and 7 cases were weak. The expression of ALK at the protein level was associated with the WNT group (P<0.01). The characteristic perinuclear dot-like staining was only showed in WNT group. Conclusions The ALK immunhistochemistry using antibody clone 1A4 is a useful marker for the molecular subgroup detection of MB. The strong staining and perinuclear dot-like staining indicate as WNT group.

OBJECTIVETo explore the clinical features and genetic mutation in a family affected with non-syndrome X-linked intellectual disability (NS-XLID) using whole exome sequencing (WES).

METHODSMultiplex ligation-dependent probe amplification (MLPA) was applied to screen potential mutations of Fragile X syndrome (FXS). Whole exome sequencing (WES) and Sanger sequencing were screen for pathological mutations.

RESULTSFXS was excluded by MLPA analysis. WES has discovered in the proband an ARX gene mutation c.88G>T, which was confirmed by Sanger sequencing. Combining his clinical phenotype with information from the OMIM database, it was inferred that the ARX mutation probably underlies the NS-XLID in the proband. The same mutation was found in his mother and two uncles but not in his father and sister.

CONCLUSIONWES is capable of revealing the mutation underlying NS-XLID and can facilitate genetic counseling for the affected families.

Objective To study cellular immune responses induced by DNA vaccine against Chlamydia trachomatis (Ct) serotype E. Methods BALB/c mice were divided into three groups to be intramuscularly immunized by blank plasmid (negative control group), DNA vaccine against Ct serotype E (vaccine group), and inactivated Ct elementary body (positive control group), respectively. Two weeks after the last immunization,delayed-type hypersensitivity (DTH) response was evaluated; MTT assay was performed to detect the proliferation of spleen lymphocytes, ELISA to measure the serum level of interferon-γin mice. Some immunized mice underwent a genital challenge with Ct elementary body followed by isolation of Ct from exfoliated epithelial cells in genital tract and pathological examination of cervical tissue from the challenged mice. Results Compared to negative control group, vaccine group and positive control group experienced a stronger DTH response.The lymphocyte stimulating index and serum level of IFN-γwere highest in the positive control group (3.81 ±0.30, 2891.7 ± 1048.8 μg/L), followed by vaccine group (2.35 ± 0.25, 593.3 ± 342.6 μg/L) and negative control group (1.48 ± 0.15, 309.2 ± 157.9 μg/L), and significant difference was observed between the three groups (P ＜ 0.05 or 0.01 ). After Ct challenge, Ct was isolated from exfoliated epithelial cells and cervical tissue was damaged in the negative control group, while in the other two groups, Ct was undetected and genital tract tissue was intact. Conclusions The DNA vaccine against Ct serotype E could induce Ct-specific cellular immune responses to some extent, and offer a protection against vaginal challenge with Ct.