Hedgehog （Hh） signaling pathway plays an important regulatory role in the process of cell proliferation， differentiation and tissue formation. Proper intensity and action time of Hh signal are crucial for the normal development of various tissues of the body， and its abnormal activation will lead to the occurrence and development of most malignant tumors， including breast cancer， liver cancer， pancreatic cancer， and lung cancer， which makes Hh signaling pathway an ideal target for anti-tumor drug research and development. At present， the main targets of Hh signaling pathway inhibitors include Hh ligand， receptor Smoothened （Smo） and transcription factor Gli. Among them， the compounds that depend on the Hh ligand pathway still remain at the stage of laboratory research because they cannot act on the non-classical Hh signaling pathway. The special structure of Smo protein enables it to combine with drugs efficiently and selectively， which is a powerful and effective drug target. Therefore， Smo selective inhibitors have been an active field of related research， and many Smo inhibitors have entered the clinical use or trial stage. Gli can regulate multiple carcinogenic genes， promote abnormal cell proliferation and lead to tumor， and can also cause feedback inhibition to Hh signaling pathway. Therefore， the development of drugs that can inhibit the activity of Gli has broad prospects. In the future， a combination of multiple pathway inhibitors can be designed to avoid drug resistance and other side effects.

Objective:To explore the potential facilitators and barriers to healthy behavior among stroke patients.Methods:Semi-structured interviews were conducted among 16 stroke patients from September 2022 to March 2023 using an objective sampling method.The interview guide was developed using the theoretical domain framework(TDF). Interviews were transcribed and refined the theme using directed content and induction analysis.Using the TDF as the initial coding framework, the themes were then merged into the most relevant domains.Finally, the correspondence between theoretical domains and the healthy behavior of stroke patients was determined based on the frequency and relationship between themes.Results:This study identified nine theoretical domains that affected the healthy behavior of stroke patients: knowledge, skills, motivation and goals, social influences, social/professional role and identity, environment context and resources, belief about capability, consequence belief and behavioral regulation.Conclusion:The healthy behavior of stroke patients is complex and influenced by several factors.The nine theoretical domains identified in this study will provide recommendations for future healthy behavior interventions for stroke patients.

Autoimmune diseases of the nervous system are a group of diseases caused by the body′s immune system attacking its own nervous system, resulting in structural damage and functional impairment of the corresponding tissues. Interventional clearance of pathogenic auto-antibodies has been shown to be effective in reducing immune damage, inhibiting disease progression and improving prognosis through extensive basic research and long-term clinical practice. The neonatal Fc receptor (FcRn)-mediated circulating protection mechanism of IgG contributes to the long half-life and high plasma levels of IgG. FcRn inhibitors are able to target and block the binding of FcRn to IgG, accelerating IgG clearance and reducing IgG levels. Therefore, the use of FcRn inhibitors in the treatment of autoimmune diseases of the nervous system could theoretically help to accelerate the clearance of pathogenic IgG, achieve good clinical efficacy and have promising applications. Research in this area has made considerable progress in recent years and this article will review this.

OBJECTIVE: To explore the genetic basis for a Chinese patient suspected for Canavan disease. METHODS: Whole exome sequencing (WES) was carried out for the proband, and candidate variants were verified by Sanger sequencing of the proband, her parents and brother. Prenatal diagnosis was provided to her mother by chorionic villi sampling (CVS) upon her subsequent pregnancy. RESULTS: The proband, a 4-month-old female infant, had manifested drowsiness, hypotonia and apathy. Urine metabolism screening showed elevated N-acetylaspartic acid. Cranial magnetic resonance imaging revealed abnormal myelination and multiple abnormal signals in large brain areas. WES revealed that the proband has harbored compound heterozygous variants of the ASPA gene, namely c.187A>G (p.Arg63Gly) in exon 1 and c.634+1G>A (P.?) in exon 4. Sanger sequencing confirmed that the c.187A>G (p.Arg63Gly) and c.634+1G>A (p.?) variants were respectively inherited from her mother and father. Her phenotypically normal brother has carried a heterozygous c.634+1G>A (p.?) variant. Prenatal diagnosis by CVS indicated that the fetus was a heterozygous carrier of the c.187A>G variant. CONCLUSION WES can facilitate the diagnosis of Canavan disease, particularly for those lacking specific phenotypes of the disease. The compound heterozygous variants of the ASPA gene probably underlay the Canavan disease in this patient, and the result has enabled prenatal diagnosis for this family.
Canavan Disease/genetics* ; China ; Female ; Humans ; Male ; Mutation ; Pedigree ; Pregnancy ; Prenatal Diagnosis

OBJECTIVE: To assess the diagnostic value of copy number variation sequencing (CNV-seq) in the genetic etiology of fetuses with nasal bone dysplasia (NBD). METHODS: A total of 217 fetuses discovered with NBD from December 2017 to December 2020 were divided into the isolated NBD group and NBD combined with other anomalies group, for which copy number variations (CNVs) were analyzed. RESULTS: A total of 40 fetal abnormalities were detected in 217 cases, with an overall abnormal rate of 18.4%. These included 31 cases with aneuploidies (14.3%, 31/217) and 9 cases with genomic CNVs (4.1%, 9/217). Five cases of trisomy 21 (3.5%, 5/144) and two CNVs cases with unknown clinical significance (1.4%, 2/144) were detected in the isolated group. As for the combined NBD group, 26 aneuploidies (35.6%, 26/73), including 19 cases with trisomy 21, 6 cases with trisomy 18, 1 case with trisomy 13, 5 cases with pathogenic CNVs (6.8%, 5/73), and 2 cases with CNVs of unknown clinical significance (2.7%, 2/73) were detected. A significant difference was detected between the two groups (P < 0.01). CONCLUSION The detection rate of CNV-seq is high for chromosomal aneuploidies and pathogenic CNVs in fetuses with NBD, particularly in those combined with other ultrasonic abnormalities.
Aneuploidy ; Bone Diseases, Developmental ; Chromosome Aberrations ; DNA Copy Number Variations ; Down Syndrome/genetics* ; Female ; Fetus/abnormalities* ; Humans ; Pregnancy ; Prenatal Diagnosis ; Trisomy

Objective:To explore the genetic etiology of a child with delayed growth and development and carry out a literature review.Methods:A child suspected for Al Kaissi syndrome at the First Affiliated Hospital of Zhengzhou University on March 6, 2021 was selected as the study subject. Following extraction of genomic DNA, the child was subjected to copy number variation sequencing (CNV-seq) and whole exome sequencing (WES), and candidate variants were verified by PCR-agarose gel electrophoresis and quantitative real-time PCR (qPCR). Prenatal diagnosis was conducted on chorionic villi sample upon subsequent pregnancy.Results:The child, a 6-year-and-4-month-old boy, has dysmorphic features including low-set protruding ears and triangular face, delayed language and intellectual development, and ventricular septal defect. CNV-seq result has found no obvious abnormality, whilst WES revealed homozygous deletion of exons 1 and 2 of the CDK10 gene, which was confirmed by PCR -agarose gel electrophoresis and qPCR. Both of his parents were heterozygous carriers. Prenatal diagnosis using chorionic villi samples suggested that the fetus also carried the heterozygous deletion.Conclusion:The clinical features of Al Kaissi syndrome in this child can probably be attributed to the homozygous deletion of exons 1 and 2 of the CDK10 gene.

Objective:To explore the genetic etiology of a Chinese pedigree affected with Branchio-oculo-facial syndrome (BOFS) and summarize the prenatal phenotype of BOFS patients.Methods:A pedigree with BOFS which had presented at the Genetics and Prenatal Diagnosis Center of the First Affiliated Hospital of Zhengzhou University in December 2021 was selected as the study subject. Clinical data of the pedigree was collected. The fetus was subjected to routine prenatal ultrasound scan. Trio-whole exome sequencing (trio-WES) was carried out for the fetus and its parents, and candidate variant was verified by Sanger sequencing. Relevant literature was searched from the database to summarize the prenatal phenotype of BOFS patients. This study was approved by the First Affiliated Hospital of Zhengzhou University (Ethics No. KS-2018-KY-36).Results:Ultrasound exam suggested the fetus had cleft lip and palate. Its father had presented with high palatal arch, prematurely grayed hair, occult cleft lip, congenital preauricular fistula, red-green color blindness and unilateral renal agenesis. Its grandfather also had high palatal arch, prematurely gray hair, protruding ears, congenital preauricular fistula and hearing disorders. Trio-WES revealed that the fetus and its father had both harbored a heterozygous c. 890-1G>A variant of the TFAP2A gene. The same variant was not found in its mother. Sanger sequencing confirmed that its grandfather had also harbored the same variant. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was rated as likely pathogenic (PVS1+ PM2_Supporting). Combined with 36 similar cases retrieved from the literature, the prenatal phenotypes of BOFS patients had included growth restriction (25/37), renal abnormalities (10/37), cleft lip and palate (5/37) and oligohydramnios (5/37). Conclusion:The c. 890-1G>A variant of the TFAP2A gene probably underlay the pathogenesis of BOFS in this pedigree. Discovery of the novel variant has enriched the mutational spectrum of the TFAP2A gene. The common prenatal phenotypes of BOFS have included growth restriction, renal abnormalities, cleft lip and palate and oligohydramnios. Delineation of the intrauterine phenotype of BOFS may facilitate its prenatal diagnosis, clinical diagnosis, treatment and genetic counseling.

Objective:To explore the latent classes of health behavior and explore the predictive factors among stroke patients.Methods:A total of 1 250 participants were recruited using cluster random sampling in September 2022. The general information, the modified Rankin scale(mRS), stroke prevention knowledge questionnaire(SPKQ), health behavior scale for stroke patients (HBS-SP), and short form-health belief model scale (SF-HBMS) were administered in the cross-sectional survey. Mplus 8.3 software was used to conduct a latent class analysis (LCA) on the health behavior of stroke patients, and SPSS 27.0 software was used to carry out multinomial Logistic regression to analyze the predictive factors of different latent classes of health behavior of stroke patients.Results:The health behavior of stroke patients obtained three latent classes: low health behaviors-lack of health responsibility group (66.9%, n=794), moderate health behaviors-poor compliance group (11.9%, n=141), and good health behaviors-insufficient exercise group (21.2%, n=251). Compared with good health behaviors-insufficient exercise group, stroke patients with shorter duration education time ( B=-0.589, OR=0.555, P=0.036), hemorrhagic stroke ( B=0.082, OR=1.086, P<0.001), fewer comorbidities ( B=-0.022, OR=0.978, P=0.026), higher mRS score ( B=-0.046, OR=1.047, P=0.004), lower SPKQ score ( B=-0.055, OR=0.947, P=0.016), and lower SF-HBMS score ( B=-0.085, OR=0.919, P<0.001) were more likely to be included in moderate health behaviors-poor compliance group. However, stroke patients with shorter duration education time ( B=-0.026, OR=0.974, P=0.003), rural areas dwelling ( B=0.800, OR=2.225, P=0.004), fewer comorbidities ( B=-0.056, OR=0.945, P<0.001), lower SPKQ score ( B=-0.101, OR=0.904, P<0.001), and lower SF-HBMS score ( B=-0.071, OR=0.931, P<0.001) were more likely to be included in low health behaviors-lack of health responsibility group. Conclusion:The health behavior of stroke patients has three latent classes. A targeted intervention should be carried out according to the characteristics of different classes to improve their health behavior levels.

ObjectiveTo explore the action mechanism of Linggan Wuwei Jiangxintang on the treatment of lipopolysaccharide （LPS）-induced acute lung injury （ALI） in mice. MethodTraditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， GeneCards， DisGeNET， and Herb databases were combined with clinical data from Gene Expression Omnibus （GEO） to screen the key targets of Linggan Wuwei Jiangxintang in the treatment of ALI. The protein-protein interaction （PPI） network was constructed to screen the core targets， and gene ontology （GO） and Kyoto encyclopedia of genes and genomes （KEGG） pathway enrichment analyses were performed. The mouse ALI model was established by LPS induction to verify the effect and key targets of Linggan Wuwei Jiangxintang on the treatment of ALI. The expression levels of Toll-like receptor 4 （TLR4）， nuclear transcription factor-κB p65 （NF-κB p65）， and phosphorylated NF-κB p65 （NF-κB p-p65） in lung tissue were detected by Western blot. ResultThe analysis showed that the treatment of ALI with Linggan Wuwei Jiangxintang was related to 10 core targets such as interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， and JUN， involving TNF signaling pathway， Toll-like receptor signaling pathway， NF-κB signaling pathway， etc. The animal experimental results show that Linggan Wuwei Jiangxintang can reduce lung injury， improve the pathological state of ALI mice， significantly reduce the expression of TNF-α and IL-6 in serum， increase the activity of total superoxide dismutase （T-SOD） and catalase （CAT） in lung tissue， and reduce the expression levels of JUN， TLR4， NF-κB p65， and NF-κB p-p65 proteins in lung tissue. ConclusionLinggan Wuwei Jiangxintang can inhibit LPS-induced inflammation and oxidative damage in ALI mice， and its mechanism may be related to the inhibition of TLR4/NF-κB signaling pathway and the reduction of inflammatory factors such as TNF-α and IL-6.

Objective Using event-related potentials(ERPs),to study the effect and mechanism of negative emotion accumulation hepatic insufficiency on working memory in normal people.Methods Fifty subjects in each of the emotionally stable group and emotionally unstable group were given two load tasks(0-back and 1-back)in the N-back paradigm,the reaction time and correct rate were recorded,and the ERPs components N200 and P300 were detected.The latency and amplitude of P300 were analyzed statistically.Results ①Compared with the emotionally stable group,the emotionally unstable group had a longer reaction time(P<0.05).②Compared with the emotionally stable group,the subjects in the emotionally unstable group had prolonged N200 latency,decreased P300 amplitude significantly(P<0.05),and P300 latency had a tendency to extend(P<0.1).Conclusion Long-term accumulation of negative emotions and liver failure in normal people have the performance of decreased working memory,which may be related to the reduction of attention resource allocation and the impairment of cognitive processing function.