OBJECTIVE: To explore the pathogenic mechanism of a child with Waardenburg syndrome type 4C due to a c.661_664dup (p.P222Lfs*60) variant of SOX10 gene through in vitro experiments. METHODS: A child diagnosed at the Handan First Hospital was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples were collected from the child and his parents. Following extraction of genomic DNA, trio-whole exome sequencing was carried out. Pathogenicity of candidate variant was determined by bioinformatic analysis and reference to the guidelines from the American College of Medical Genetics and Genomics (ACMG). Candidate variant was verified by Sanger sequencing. Expression plasmids of wild-type SOX10 and the c.661_664dup (p.P222Lfs*60) variant were constructed and transiently transfected into 293T cells to determine the expression at the RNA and protein levels. The 293T cells transiently transfected with the wild-type/mutant SOX10 were treated with 10 ug/mL cycloheximide (CHX) for 0, 4, 8, 24 h, respectively, and the degradation rate of target protein was detected by Western blotting assay. This study has been approved by the Ethics Committee of Handan First Hospital (Ethics No. HDYY-LW-25053). RESULTS: The child was found to harbor a heterozygous c.661_664dup (p.P222Lfs*60) variant of the SOX10 gene, which was unreported previously. The variant did not significantly alter the expression of SOX10 at the mRNA level but the protein level. After the CHX treatment, the degradation of mutant SOX10 protein had slowed down. CONCLUSION The mutant SOX10 may affect the expression of downstream genes by affecting the degradation rate of its protein product.
Humans ; HEK293 Cells ; Mutation ; SOXE Transcription Factors/metabolism* ; Waardenburg Syndrome/genetics* ; Child

Objective To explore the application effect of foot massage based on the brain-gut axis theory in patients with spleen-kidney yang deficiency syndrome undergoing maintenance hemodialysis and suffering from insomnia,and to provide references for improving patients' sleep quality and gastrointestinal symptoms.Methods A total of 88 patients with spleen-kidney yang deficiency syndrome undergoing maintenance hemodialysis and suffering from insomnia,who were treated at a Blood Purification Center of a tertiary-A general hospital in Hangzhou,Zhejiang Province from April to September 2024,were selected as a study subjects.They were randomly divided into an experimental group and a control group using the random number table method,with 44 cases in each group.The experimental group received foot massage based on the guidance of the brain-gut axis theory in addition to conventional treatment and nursing care,while the control group received conventional treatment and nursing care only.The intervention lasted for 3 months.The differences in the Pittsburgh Sleep Quality Index(PSQI)scores,Gastrointestinal Symptom Rating Scale(GSRS)scores,traditional Chinese medicine(TCM)syndrome scores,and serum 5-hydroxytryptamine and melatonin levels between the 2 groups before and after the intervention were compared.Results During the study period,no cases were lost in the experimental group,while 5 cases were lost in the control group.Ultimately,44 cases were included in the experimental group and 39 cases in the control group.After the intervention,the PSQI scores,GSRS scores,and TCM syndrome scores in both groups were lower than those before the intervention,and those in the experimental group were lower than those in the control group.The serum 5-hydroxytryptamine and melatonin levels were higher than those before the intervention,and the levels in the experimental group were higher than those in the control group,with statistically significant differences(all P＜0.001).Conclusion Foot massage based on the brain-gut axis theory can improve gastrointestinal symptoms and TCM syndromes in patients with spleen-kidney yang deficiency syndrome undergoing maintenance hemodialysis and suffering from insomnia,and enhance their sleep quality.

Objective:To explore the pathogenic mechanism of a child with Waardenburg syndrome type 4C due to a c. 661_664dup (p.P222Lfs*60) variant of SOX10 gene through in vitro experiments. Methods:A child diagnosed at the Handan First Hospital was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples were collected from the child and his parents. Following extraction of genomic DNA, trio-whole exome sequencing was carried out. Pathogenicity of candidate variant was determined by bioinformatic analysis and reference to the guidelines from the American College of Medical Genetics and Genomics (ACMG). Candidate variant was verified by Sanger sequencing. Expression plasmids of wild-type SOX10 and the c. 661_664dup (p.P222Lfs*60) variant were constructed and transiently transfected into 293T cells to determine the expression at the RNA and protein levels. The 293T cells transiently transfected with the wild-type/mutant SOX10 were treated with 10 μg/mL cycloheximide (CHX) for 0, 4, 8, 24 h, respectively, and the degradation rate of target protein was detected by Western blotting assay. This study has been approved by the Ethics Committe of Handan First Hospital(Ethics No.HDYY-LW-25053). Results:The child was found to harbor a heterozygous c. 661_664dup (p.P222Lfs*60) variant of the SOX10 gene, which was unreported previously. The variant did not significantly alter the expression of SOX10 at the mRNA level but the protein level. After the CHX treatment, the degradation of mutant SOX10 protein had slowed down. Conclusion:The mutant SOX10 may affect the expression of downstream genes by affecting the degradation rate of its protein product.

Objective To explore the application effect of foot massage based on the brain-gut axis theory in patients with spleen-kidney yang deficiency syndrome undergoing maintenance hemodialysis and suffering from insomnia,and to provide references for improving patients' sleep quality and gastrointestinal symptoms.Methods A total of 88 patients with spleen-kidney yang deficiency syndrome undergoing maintenance hemodialysis and suffering from insomnia,who were treated at a Blood Purification Center of a tertiary-A general hospital in Hangzhou,Zhejiang Province from April to September 2024,were selected as a study subjects.They were randomly divided into an experimental group and a control group using the random number table method,with 44 cases in each group.The experimental group received foot massage based on the guidance of the brain-gut axis theory in addition to conventional treatment and nursing care,while the control group received conventional treatment and nursing care only.The intervention lasted for 3 months.The differences in the Pittsburgh Sleep Quality Index(PSQI)scores,Gastrointestinal Symptom Rating Scale(GSRS)scores,traditional Chinese medicine(TCM)syndrome scores,and serum 5-hydroxytryptamine and melatonin levels between the 2 groups before and after the intervention were compared.Results During the study period,no cases were lost in the experimental group,while 5 cases were lost in the control group.Ultimately,44 cases were included in the experimental group and 39 cases in the control group.After the intervention,the PSQI scores,GSRS scores,and TCM syndrome scores in both groups were lower than those before the intervention,and those in the experimental group were lower than those in the control group.The serum 5-hydroxytryptamine and melatonin levels were higher than those before the intervention,and the levels in the experimental group were higher than those in the control group,with statistically significant differences(all P＜0.001).Conclusion Foot massage based on the brain-gut axis theory can improve gastrointestinal symptoms and TCM syndromes in patients with spleen-kidney yang deficiency syndrome undergoing maintenance hemodialysis and suffering from insomnia,and enhance their sleep quality.

Objective:To explore the pathogenic mechanism of a child with Waardenburg syndrome type 4C due to a c. 661_664dup (p.P222Lfs*60) variant of SOX10 gene through in vitro experiments. Methods:A child diagnosed at the Handan First Hospital was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples were collected from the child and his parents. Following extraction of genomic DNA, trio-whole exome sequencing was carried out. Pathogenicity of candidate variant was determined by bioinformatic analysis and reference to the guidelines from the American College of Medical Genetics and Genomics (ACMG). Candidate variant was verified by Sanger sequencing. Expression plasmids of wild-type SOX10 and the c. 661_664dup (p.P222Lfs*60) variant were constructed and transiently transfected into 293T cells to determine the expression at the RNA and protein levels. The 293T cells transiently transfected with the wild-type/mutant SOX10 were treated with 10 μg/mL cycloheximide (CHX) for 0, 4, 8, 24 h, respectively, and the degradation rate of target protein was detected by Western blotting assay. This study has been approved by the Ethics Committe of Handan First Hospital(Ethics No.HDYY-LW-25053). Results:The child was found to harbor a heterozygous c. 661_664dup (p.P222Lfs*60) variant of the SOX10 gene, which was unreported previously. The variant did not significantly alter the expression of SOX10 at the mRNA level but the protein level. After the CHX treatment, the degradation of mutant SOX10 protein had slowed down. Conclusion:The mutant SOX10 may affect the expression of downstream genes by affecting the degradation rate of its protein product.

Objective To mine the adverse drug events(ADE)signal of avatrombopag,an effective drug for thrombocytopenia treatment,based on real world data in order to provide reference for its clinical safety application.Methods The OpenVigil2.1 pharmacovigilance platform was used to obtain the ADE report data of avatrombopag from May 2018 to March 2023 in the database of FDA adverse event reporting system(FAERS).The ADE signals were classified and described by the system organ class(SOC)and preferred term(PT)of the ADE terminology set in the Medical Dictionary for Regulatory Activities(MedDRA),and reporting odds ratio(ROR)and UK Medicines and Healthcare Products Regulatory Agency(MHRA)comprehensive standard were used to detect the positive ADE signals.Results A total of 1 879 ADE reports related to avatrombopag were obtained,24 SOCs were involved,and 28 positive ADE signals were detected at PT level.Among these signals,the strongest ones were renal vein thrombosis,portal vein thrombosis and graft versus host disease,while the reports accounting for the largest numbers were headache,fatigue and asthenia.There were 8 ADE signals discovered newly,that is,seasonal allergy,back disorder,musculoskeletal discomfort,flatulence,hypersomnia,rash macular,emotional disorder,and rhinorrhoea.Conclusion For clinical use of avatrombopag,clinicians should not only concern the risk of thrombosis,but also pay close attention to ADE signals such as seasonal allergy,back disorder,musculoskeletal discomfort,flatulence,hypersomnia,rash macular,emotional disorder,and rhinorrhoea that are not documented in the instructions.

Thyroid cancer is the most common malignant tumor of the head and neck, among which papillary thyroid carcinoma is the most common. Papillary thyroid carcinoma with a diameter of ≤ 1.0 cm is called thyroid micropapillary carcinoma. In recent years, thermal ablation technology for the treatment of thyroid micropapillary carcinoma has developed rapidly at home and abroad. At present, many guidelines, consensus and clinical studies related to thermal ablation treatment of thyroid micropapillary carcinoma have been published at home and abroad. Based on the existing literature, guidelines and clinical studies, this article summarizes, discusses and analyzes the advantages, indications, efficacy, safety, and existing problems of thermal ablation therapy for thyroid cancer.

Objective:To summarize the clinical features and pregnancy outcomes of fetal micrognathia.Methods:This retrospective study enrolled 52 cases of fetal micrognathia diagnosed at Shandong Provincial Maternal and Child Health Hospital Affiliated to Qingdao University and Affiliated Maternity and Child Health Care Hospital of Nantong University from January 2014 to December 2022. Clinical features, genetic testing results, and pregnancy outcomes of the cases were summarized. These cases were divided into two groups based on whether they were complicated by other system anomalies: non-isolated micrognathia (49 cases) and isolated micrognathia (three cases). The non-isolated micrognathia cases were further divided into two subgroups: cleft palate group (21 cases) and non-cleft palate group (28 cases). Clinical features were compared between different groups. Statistical analysis was performed using two independent samples t-test, Chi-square test, or Fisher's exact test. Results:(1) The non-isolated micrognathia cases were complicated by one to six system anomalies, with the most common being facial anomalies (59.2%, 29/49), followed by circulatory system (51.0%, 25/49), musculoskeletal system (44.9%, 22/49), nervous system (34.7%, 17/49), digestive system (12.2%, 6/49), and urinary system anomalies (8.2%, 4/49). (2) Among 52 cases, nine non-isolated micrognathia cases received genetic testing, and the results indicated six with genetic abnormalities. (3) Forty-seven cases chose to terminate the pregnancies, while the other five cases continued the pregnancies (all fetuses were non-isolated micrognathia) and resulted in live births. Treatment was withdrawn in one live birth due to multiple anomalies, and the other four neonates required mechanical ventilation (two died after withdrawal of treatment; two underwent surgeries after birth and the prognosis of them was good during a one-year outpatient follow-up). (4) The proportion of women with polyhydramnios [28.6% (6/21) vs. 3.6% (1/28), Fisher's exact test, P=0.033] and the proportion of fetuses with confirmed Pierre Robin sequence [85.7% (18/21) vs. 7.1% (2/28), Fisher's exact test, P<0.001] were higher in the cleft palate group than those in the non-cleft palate group. Conclusions:Fetal micrognathia cases revealed by prenatal ultrasound should undergo a comprehensive screening for other system anomalies, especially cleft palate. Fetuses with micrognathia and multiple system anomalies often have a poor prognosis. Besides, it is recommended to take genetic testing. For fetuses with micrognathia, preparations for neonatal resuscitation at birth are essential to avoid adverse outcomes due to breathing difficulties.

Tear film hyperosmolarity plays a core role in the development of dry eye disease (DED) by mediating the disruption of ocular surface homeostasis and triggering inflammation in ocular surface epithelium. In this study, the mechanisms involving the hyperosmolar microenvironment, glycolysis mediating metabolic reprogramming, and pyroptosis were explored clinically, in vitro, and in vivo. Data from DED clinical samples indicated that the expression of glycolysis and pyroptosis-related genes, including PKM2 and GSDMD, was significantly upregulated and that the secretion of IL-1β significantly increased. In vitro, the indirect coculture of macrophages derived from THP-1 and human corneal epithelial cells (HCECs) was used to discuss the interaction among cells. The hyperosmolar environment was found to greatly induce HCECs' metabolic reprogramming, which may be the primary cause of the subsequent inflammation in macrophages upon the activation of the related gene and protein expression. 2-Deoxy-d-glucose (2-DG) could inhibit the glycolysis of HCECs and subsequently suppress the pyroptosis of macrophages. In vivo, 2-DG showed potential efficacy in relieving DED activity and could significantly reduce the overexpression of genes and proteins related to glycolysis and pyroptosis. In summary, our findings suggested that hyperosmolar-induced glycolytic reprogramming played an active role in promoting DED inflammation by mediating pyroptosis.

Nucleotide excision repair was a complex biochemical process that involved in the repair of many kinds of DNA damage. Previous study suggested that xeroderma pigmentosum group C (XPC) gene played an important role in the process of DNA damage repair. This study aimed to explore the influence of XPC gene polymorphism on the prognosis of patients with colorectal cancer (CRC) who were treated with capecitabine-related adjuvant chemotherapy. METHODS: A total of 158 patients with CRC who received surgical resection and capecitabine-based adjuvant chemotherapy were included in this study consecutively. Baseline clinical characteristics of patients were collected and analyzed. Additionally, peripheral blood specimens of the patients were collected for polymorphism analysis of XPC gene and mRNA expression of XPC, respectively. The association analysis between XPC polymorphism and prognosis and mRNA expression was performed. Cox regression analysis was used for multivariate adjustment. RESULTS: Prognostic data in the 158 patients with CRC who received capecitabine-based adjuvant chemotherapy was collected retrospectively. The median follow-up duration of the patients was 5.0 years (range: 0.25-7.5 years). The median DFS and OS of the 158 patients with CRC was 4.5 years and 5.7 years, respectively. XPC polymorphism analysis suggested that rs2228001 was of clinical significance. The prevalence of rs2228001 polymorphism among CRC patients was: TT genotype 86 cases (54.4%), TG genotype 60 cases (38.0%) and GG genotype 12 cases (7.6%), resulting in a minor allele frequency of 0.27, which was in accordance with Hardy-Weinberg equilibrium (P=0.733). TG and GG genotypes were merged in the subsequent analysis. The prognostic results exhibited that the median DFS of patients with TT genotype and TG / GG genotype was 4.5 and 5.7 years, respectively (c