Objective To investigate the regulation of synaptic plasticity by cannabinoid receptor 1(CB1R)and its effects on autism spectrum disorder(ASD)-like behavior.Methods CB1R-knockout(KO)mice and valproic acid(VPA)-induced ASD model mice(VPA mice)were used as study subjects.Behavioral experiments were used to assess the effects of CB1R on ASD-like behavior in mice,neuronal structural integrity and dendritic density were detected by microtubule-associated protein 2(MAP2)staining experiments,and the expression of synapse-associated proteins was detected by Western blot,to assess the effects of CB1R on synaptic plasticity.Results Behavioral result showed that VPA mice demonstrated significant ASD-like behavior,while CB1R-/-mice spent a significantly smaller proportion of residence time in the central region of the open field(P＜0.0001),showed significant increases in the number of marbles buried and self-grooming time(P＜0.01),significantly less time spent socializing with unfamiliar mice 2 and exploring unfamiliar objects(P＜0.001),and significantly more time exploring old objects(P＜0.05).The relative dwelling time was significantly reduced in CB1R+/-mice(P＜0.001),and the number of marbles buried and self-grooming time were significantly increased(P＜0.05).Synaptic plasticity assays revealed significant synaptic plasticity impairment in VPA mice.Hippocampal MAP2-positive neuron densities were significantly reduced in CB1R-/-and CB1R+/-mice,and expression levels of synapsin-1 were significantly increased(P＜0.05).Conclusions CB1R KO leads to ASD-like behavior such as anxiety and repetitive stereotyped behavior,social and cognitive impairments,as well as neuronal damage,dendritic dysplasia and disrupted synaptic protein expression in mice,suggesting that CB1R is involved in regulating synaptic plasticity as a pathological mechanism for the development of ASD-like behavior.

Objective:Comparative study on the application value of bronchial ultrasound combined with different biopsy methods under thin-layer CT navigation in the diagnosis of malignant peripheral lung lesions.Methods:A retrospective analysis of patients with suspected malignant peripheral lung lesions identified by chest CT from January 2019 to September 2024 at the Cancer Hospital of the Chinese Academy of Medical Sciences and Peking Union Medical College, and Xianyang Central Hospital, who underwent routine bronchoscopy with negative results (209 cases). These patients were diagnosed using bronchial ultrasound under thin-layer CT navigation. The cases were divided into a cryobiopsy group (127 cases) and a conventional forceps biopsy group based on the biopsy method (82 cases). The diagnostic rates of the two groups were statistically analyzed, along with factors influencing the diagnostic rates. The tissue size obtained from both groups was compared, and the occurrence of complications was summarized.Results:This study included 209 cases with 216 peripheral lung lesions. A total of 209 cases with 210 lesions were successfully located through thin-slice CT guidance, resulting in a guiding success rate of 97.2% (210/216). Among the 130 lesions in the cryobiopsy group, 78 lesions were diagnosed as lung malignancies, with a diagnostic rate of 82.1% (64/78) for cryobiopsy in lung malignant lesions. In the forceps biopsy group, 46 of the 86 lesions were diagnosed as lung malignancies, with a diagnostic rate of 87.0% (40/46) for forceps biopsy in lung malignant lesions. There was no statistically significant difference between the two diagnostic rates ( P=0.473). The average longest diameter of tissue obtained by cryobiopsy was (6.11±0.23) mm, while the average longest diameter of tissue obtained by forceps biopsy was (1.58±0.43) mm. There was a statistically significant difference in tissue longest diameter between the two groups ( P＜0.001). When the distance from the bronchoscopic tip to the lesion was ≥3 cm and the most distal bronchus visible under bronchoscopy was ≤5th generation, the diagnostic rate of forceps biopsy was higher [83.3%(25/30) and 94.1%(32/34)] than that of cryobiopsy [79.3%(23/29) and 78.0%(46/59)], and the difference was statistically significant ( P＜0.05). Regarding complications, one case (1.3%, 1/78) of clinically significant complications occurred in the cryobiopsy group, while no complications occurred in the forceps biopsy group. Conclusions:Under thin-layer CT navigation, bronchial ultrasound combined with different biopsy methods demonstrates a high diagnostic rate for malignant peripheral lung lesions and is safe to operate. Cryobiopsy allows for the collection of larger tissue specimens.

The Janus kinase/signal transducers and activators of transcription (JAK-STAT) control natural killer (NK) cells development and cytotoxic functions, however, whether long non-coding RNAs (lncRNAs) are involved in this pathway remains unknown. We found that miR155HG was elevated in activated NK cells and promoted their proliferation and effector functions in both NK92 and induced-pluripotent stem cells (iPSCs)-derived NK (iPSC-NK) cells, without reliance on its derived miR-155 and micropeptide P155. Mechanistically, miR155HG bound to miR-6756 and relieved its repression of JAK3 expression, thereby promoting the JAK-STAT pathway and enhancing NK cell proliferation and function. Further investigations disclosed that upon cytokine stimulation, STAT3 directly interacts with miR155HG promoter and induces miR155HG transcription. Collectively, we identify a miR155HG-mediated positive feedback loop of the JAK-STAT signaling. Our study will also provide a power target regarding miR155HG for improving NK cell generation and effector function in the field of NK cell adoptive transfer therapy against cancer, especially iPSC-derived NK cells.

Objective:Comparative study on the application value of bronchial ultrasound combined with different biopsy methods under thin-layer CT navigation in the diagnosis of malignant peripheral lung lesions.Methods:A retrospective analysis of patients with suspected malignant peripheral lung lesions identified by chest CT from January 2019 to September 2024 at the Cancer Hospital of the Chinese Academy of Medical Sciences and Peking Union Medical College, and Xianyang Central Hospital, who underwent routine bronchoscopy with negative results (209 cases). These patients were diagnosed using bronchial ultrasound under thin-layer CT navigation. The cases were divided into a cryobiopsy group (127 cases) and a conventional forceps biopsy group based on the biopsy method (82 cases). The diagnostic rates of the two groups were statistically analyzed, along with factors influencing the diagnostic rates. The tissue size obtained from both groups was compared, and the occurrence of complications was summarized.Results:This study included 209 cases with 216 peripheral lung lesions. A total of 209 cases with 210 lesions were successfully located through thin-slice CT guidance, resulting in a guiding success rate of 97.2% (210/216). Among the 130 lesions in the cryobiopsy group, 78 lesions were diagnosed as lung malignancies, with a diagnostic rate of 82.1% (64/78) for cryobiopsy in lung malignant lesions. In the forceps biopsy group, 46 of the 86 lesions were diagnosed as lung malignancies, with a diagnostic rate of 87.0% (40/46) for forceps biopsy in lung malignant lesions. There was no statistically significant difference between the two diagnostic rates ( P=0.473). The average longest diameter of tissue obtained by cryobiopsy was (6.11±0.23) mm, while the average longest diameter of tissue obtained by forceps biopsy was (1.58±0.43) mm. There was a statistically significant difference in tissue longest diameter between the two groups ( P＜0.001). When the distance from the bronchoscopic tip to the lesion was ≥3 cm and the most distal bronchus visible under bronchoscopy was ≤5th generation, the diagnostic rate of forceps biopsy was higher [83.3%(25/30) and 94.1%(32/34)] than that of cryobiopsy [79.3%(23/29) and 78.0%(46/59)], and the difference was statistically significant ( P＜0.05). Regarding complications, one case (1.3%, 1/78) of clinically significant complications occurred in the cryobiopsy group, while no complications occurred in the forceps biopsy group. Conclusions:Under thin-layer CT navigation, bronchial ultrasound combined with different biopsy methods demonstrates a high diagnostic rate for malignant peripheral lung lesions and is safe to operate. Cryobiopsy allows for the collection of larger tissue specimens.

Objective To investigate the regulation of synaptic plasticity by cannabinoid receptor 1(CB1R)and its effects on autism spectrum disorder(ASD)-like behavior.Methods CB1R-knockout(KO)mice and valproic acid(VPA)-induced ASD model mice(VPA mice)were used as study subjects.Behavioral experiments were used to assess the effects of CB1R on ASD-like behavior in mice,neuronal structural integrity and dendritic density were detected by microtubule-associated protein 2(MAP2)staining experiments,and the expression of synapse-associated proteins was detected by Western blot,to assess the effects of CB1R on synaptic plasticity.Results Behavioral result showed that VPA mice demonstrated significant ASD-like behavior,while CB1R-/-mice spent a significantly smaller proportion of residence time in the central region of the open field(P＜0.0001),showed significant increases in the number of marbles buried and self-grooming time(P＜0.01),significantly less time spent socializing with unfamiliar mice 2 and exploring unfamiliar objects(P＜0.001),and significantly more time exploring old objects(P＜0.05).The relative dwelling time was significantly reduced in CB1R+/-mice(P＜0.001),and the number of marbles buried and self-grooming time were significantly increased(P＜0.05).Synaptic plasticity assays revealed significant synaptic plasticity impairment in VPA mice.Hippocampal MAP2-positive neuron densities were significantly reduced in CB1R-/-and CB1R+/-mice,and expression levels of synapsin-1 were significantly increased(P＜0.05).Conclusions CB1R KO leads to ASD-like behavior such as anxiety and repetitive stereotyped behavior,social and cognitive impairments,as well as neuronal damage,dendritic dysplasia and disrupted synaptic protein expression in mice,suggesting that CB1R is involved in regulating synaptic plasticity as a pathological mechanism for the development of ASD-like behavior.

OBJECTIVE: To explore the genetic basis for child with congenital cataract. METHODS: The child was subjected to next-generation sequencing. Candidate variant was verified by Sanger sequencing of his family members. RESULTS: The proband was found to harbor novel heterozygous variants of c.855del and c.872dup of the GJA8 gene, which were inherited from his father and mother, respectively. Neither of these two variants has been reported. Based on the American College of Medical Genetics and Genomics (ACMG) guidelines, the c.855del and c.872dup variants were classified as likely pathogenic (PVS1_S+PM2+PP4) and pathogenic (PVS1_S+PM2+PM3+PP4), respectively. CONCLUSION The c.855del and c.872dup variants of the GJA8 gene probably underlay the congenital cataract in this patient.
Child ; Humans ; Cataract/congenital* ; Family ; Heterozygote ; High-Throughput Nucleotide Sequencing ; Mutation ; Pedigree

With in-depth research and development of dermoscopy, the dermoscopic features including perifollicular pigments, perilesional pigments, pigment network structure, satellite phenomenon and "tapioca sago" appearance, micro-Koebner phenomenon and comet tail-like phenomenon have provided a basis for the evaluation of vitiligo activity. This review summarizes progress in the evaluation of vitiligo activity with dermoscopy in recent years, aiming to promote the application of dermoscopy in the assessment of vitiligo activity.

OBJECTIVE: To explore the genetic basis for a pedigree affected with Nance-Horan syndrome. METHODS: Clinical manifestation of the patients was analyzed. Genomic DNA was extracted from peripheral blood samples of the pedigree members and 100 unrelated healthy controls. A panel of genes for congenital cataract was subjected to next-generation sequencing (NGS), and candidate variant was verified by Sanger sequencing and bioinformatic analysis based on guidelines of American College of Medical Genetics and Genomics (ACMG). mRNA expression was determined by reverse transcriptase-PCR (RT-PCR). Linkage analysis based on short tandem repeats was carried out to confirm the consanguinity. RESULTS: A small insertional variant c.766dupC (p.Leu256Profs*21) of the NHS gene was identified in the proband and his affected mother, but not among unaffected members and the 100 healthy controls. The variant was unreported in Human Gene Mutation Database (HGMD) and other databases. Based on the ACMG guideline, the variant is predicted to be pathogenic (PVS1+PM2+PM6+PP4). CONCLUSION The novel variant c.766dupC of the NHS gene probably underlay the X-linked dominant Nance-Horan syndrome in this pedigree.
Cataract/genetics* ; Genetic Diseases, X-Linked ; Humans ; Mutation ; Pedigree ; State Medicine ; Tooth Abnormalities

OBJECTIVE: To explore the genetic basis for a patient with tuberous sclerosis complex. METHODS: Genomic DNA was extracted from peripheral blood samples from members of his family and 100 unrelated healthy controls. The proband was subjected to next-generation sequencing, and candidate variant was confirmed by multiple ligation-dependent probe amplification (MLPA) and Sanger sequencing. Reverse transcription-PCR (RT-PCR) was carried out to determine the relative mRNA expression in the proband. RESULTS: The patient was found to harbor a c.2355+1G>C splicing variant of the TSC2 gene. Sequencing of cDNA confirmed that 62 bases have been inserted into the 3' end of exon 21, which has caused a frameshift producing a truncated protein. CONCLUSION The novel splicing variant c.2355+1G>C of the TSC2 gene probably underlay the TSC in the proband. Above finding has expanded the variant spectrum of TSC2 and provided a basis for preimplantation genetic testing and/or prenatal diagnosis.
Female ; Humans ; Mutation ; Pregnancy ; RNA Splicing/genetics* ; Tuberous Sclerosis/genetics* ; Tuberous Sclerosis Complex 1 Protein/genetics* ; Tuberous Sclerosis Complex 2 Protein/genetics*

OBJECTIVE: To detect potential variants of MECP2 gene in three pedigrees affected with Rett syndrome (RTT). METHODS: All exons and their flanking regions of the MECP2 gene were subjected to Sanger sequencing and multiplex ligation-dependent probe amplification assay. RESULTS: The probands of pedigrees 1 and 2 have respectively carried a c.965C>G and a c.1157_1197del41 variant of the MECP2 gene, while the proband of pedigree 3 carried a heterozygous deletional variant in exon 4 of the MECP2 gene. CONCLUSION Variants of the MECP2 gene probably underlay the RTT in the three pedigrees. Above finding has enriched the spectrum of MECP2 gene variants, and provided a guidance for the patients upon preimplantation genetic testing and prenatal diagnosis.