OBJECTIVE: To investigate the clinical phenotypic and genetic characteristics of three children with Paroxysmal kinesigenic dyskinesia (PKD) and Self-limited familial infantile epilepsy (SeLIE) caused by PRRT2 gene mutation. METHODS: Three children with PKD and SeLIE caused by PRRT2 gene mutation (children 1-3) who were treated in the First Affiliated Hospital of Zhengzhou University from November 2022 to August 2023 were selected as the research subjects. A retrospective study was conducted to collect the clinical and family history data of the three children. 2 mL of peripheral venous blood from children 1-3 and parents of children 1-2 were collected (parents of children refused to undergo genetic testing and no blood samples were collected), genomic DNA was extracted, whole exome sequencing (WES) was performed, and Sanger sequencing method was used for verification. According to the Classification Standards and Guidelines for Genetic Variants formulated by the American Society of Medical Genetics and Genomics (ACMG) (hereinafter referred to as the "ACMG Guidelines"), the pathogenicity of the variant loci detected in three children was rated, and the detrimental loci of the variant loci were analyzed by multiple bioinformatics software. This study has been approved by the Ethics Committee of the First Affiliated Hospital of Zhengzhou University (Ethics No. 2024-KY-0881-002). RESULTS: The clinical data and genetic test results of the three children in this study are as follows. Child 1: female, age of onset of 4 months and 10 days, with seizures, manifested as sudden cessation of movements, staring in both eyes, cyanosis of the lips, paleness, and stiffness and shaking of limbs. The results of genetic testing showed that child 1 had maternal PRRT2 gene c.583_584dup (p.P196Afs*34) frameshift variant, which was rated as a pathogenic variant (PVS1 PM2_Supporting PP4) according to ACMG guidelines. According to the clinical manifestations and genetic test results of child 1, he was diagnosed with SeLIE and took oral sodium valproate [0.5 mL/(kg.d)], and was still taking medication at the follow-up of 2 years old, and did not have seizures again after 5 months of age. Child 2: male, age of onset of 10 years old, manifested as dystonia after sudden movement. The results of genetic testing showed that child 2 had PRRT2 gene mutations: paternal c.649dupC (p.R217Pfs*8) frameshift variant and maternal c.445C>A (p.Q149K) mutation. Among them, c.649dupC was a reported pathogenic variant, and according to ACMG guidelines, c.445C>A variant was rated as a variant of unknown clinical significance (PM2_Supporting), with a high probability of benignness. According to the clinical manifestations and genetic test results of the child 2, he was diagnosed with PKD, and was followed up with oral oxcarbazepine 9 mg/(kg.d) until 12 years and 2 months, and was still on the drug, and there was no recurrence of the seizure of the form of dyskinesia after taking the drug. Child 3: male, age of onset of 11 years old, manifested by dystonia after sudden exercise. The results of genetic testing showed that child 3 had a missense variant of PRRT2 gene c.904G>C (p.D302H), and his parents refused genetic testing, and the source of the mutation was unknown, and the variant was rated as a variant of unknown clinical significance (PM2_Supporting+PP3_Moderate+PP4) according to ACMG guidelines. According to the clinical manifestations and genetic test results of child 3, he was diagnosed with PKD, and was treated with oral oxcarbazepine 10 mg/(kg.d) for 1 year and then discontinued on his own, and was followed up at the age of 17, and there was no recurrence of the seizure of the form of movement disorder after taking the drug. CONCLUSION One case of SeLIE and two cases of PKD caused by PRRT2 gene mutations responded well to anti-seizure drugs. In this study, four variant loci of PRRT2 gene were found: c.583_584dup, c.904G>C, c.649dupC, c.445C>A, among which c.583_584dup were new variants, enriching the variant spectrum of PRRT2 gene.
Humans ; Male ; Nerve Tissue Proteins/genetics* ; Female ; Membrane Proteins/genetics* ; Mutation ; Child, Preschool ; Infant ; Phenotype ; Dystonia/genetics* ; Retrospective Studies ; Child

OBJECTIVE: To analyze the clinical characteristics and genetic etiology of a child with Christianson syndrome (CS). METHODS: A 1-year-and-5-month-old boy with CS diagnosed at the First Affiliated Hospital of Zhengzhou University in April 2021 was selected as the study subject. Clinical data were retrospectively analyzed. Peripheral blood samples were obtained from the child and his parents, followed by genomic DNA extraction and whole exome sequencing (WES). Candidate variant was validated by Sanger sequencing. This study has been approved by the Medical Ethics Committee of the Hospital of Zhengzhou University (Ethics No. 2024-KY-1103-001). RESULTS: The child has manifested with seizures, microcephaly, and global developmental delay. WES revealed that he has harbored a novel de novo hemizygous nonsense variant of the SLC9A6 gene, namely c.1014G>A (p.W338*). Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was rated as pathogenic. CONCLUSION The hemizygous c.1014G>A nonsense variant of the SLC9A6 gene probably underlay the pathogenesis in this child. Above discovery has expanded mutational spectrum of the SLC9A6 gene and enabled definite diagnosis of the child.
Humans ; Male ; Infant ; Microcephaly/genetics* ; Spasms, Infantile/genetics* ; Sodium-Hydrogen Exchangers/genetics* ; Exome Sequencing ; Intellectual Disability/genetics* ; Genetic Diseases, X-Linked/genetics* ; Mutation ; Seizures/genetics* ; Ataxia ; Epilepsy ; Ocular Motility Disorders

Aromatherapy refers to the method of using the aromatic components of plants in appropriate forms to act on the entire body or a specific area to prevent and treat diseases. Essential oils used in aromatherapy are hydrophobic liquids containing volatile aromatic molecules， such as limonene， linalool， linalool acetate， geraniol， and citronellol. These chemicals have been extensively studied and shown to have a variety of functions， including reducing anxiety， relieving depression， promoting sleep， and providing pain relief. Terpenoids are a class of organic molecules with relatively low lipid solubility. After being inhaled， they can pass through the nasal mucosa for transfer or penetrate the skin and enter the bloodstream upon local application. Some of these substances also have the ability to cross the blood-brain barrier， thereby exerting effects on the central nervous system. Currently， the academic community generally agrees that products such as essential oils and aromatherapy from aromatic plants have certain health benefits. However， the process of extracting a single component from it and successfully developing it into a drug still faces many challenges. Its safety and efficacy still need to be further verified through more rigorous and systematic experiments. This article systematically elaborated on the efficacy of aromatic substances， including plant extracts and natural small molecule compounds， in antibacterial and antiviral fields and the regulation of nervous system activity. As a result， a deeper understanding of aromatherapy was achieved. At the same time， the potential of these aromatic substances for drug development was thoroughly explored， providing important references and insights for possible future drug research and application.

OBJECTIVE To systematically investigate the changes of volatile components in Euphorbia wallichii after milk and wine processing， and preliminarily elucidate the material basis for reducing toxicity. METHODS Using headspace gas chromatography-mass spectrometry technology， the volatile components in raw E. wallichii， milk-processed E. wallichii， and wine- processed E. wallichii were isolated and identified， and the relative percentage content of each component was calculated by the peak area normalization method. Combining chemometric methods such as principal component analysis and orthogonal partial least- squares discriminant analysis， changes in volatile components in samples after milk and wine processing were compared. Differential components were screened. RESULTS A total of 66 volatile components were identified from the three samples， with the types of compounds primarily comprising alkanes， olefins， heterocycles and esters， among others. A total of 39， 24 and 36 volatile components were identified from raw E. wallichii， milk-processed E. wallichii， and wine-processed E. wallichii， respectively， with 10 components common to all three preparations. Compared with raw E. wallichii， the relative percentage of other components in milk-processed E. wallichii decreased， except for alkanes and esters. The relative percentage of alkanes， olefins， aldehydes and esters in wine-processed E. wallichii increased， but the contents of heterocyclic compounds， ketones， ethers and alcohols decreased. The results of chemometric analysis showed that the volatile components of raw and processed products were significantly different. A total of 5 kinds of differential components in milk-processed products and 3 kinds of differential components in wine-processed products were screened out. Among them， the relative percentage of potential toxic components such as linalool， octanal and 3-pentanone decreased significantly after processing（P＜0.05）. CONCLUSIONS Milk and wine processing may exert a toxicity-reducing effect by reducing the contents of toxic components such as linalool， octanal and 3-pentanonein E. wallichii.

Objective:To investigate the clinical phenotypic and genetic characteristics of three children with Paroxysmal kinesigenic dyskinesia (PKD) and Self-limited familial infantile epilepsy (SeLIE) caused by PRRT2 gene mutation. Methods:Three children with PKD and SeLIE caused by PRRT2 gene mutation (children 1-3) who were treated in the First Affiliated Hospital of Zhengzhou University from November 2022 to August 2023 were selected as the research subjects. A retrospective study was conducted to collect the clinical and family history data of the three children. 2 mL of peripheral venous blood from children 1-3 and parents of children 1-2 were collected (parents of children refused to undergo genetic testing and no blood samples were collected), genomic DNA was extracted, whole exome sequencing (WES) was performed, and Sanger sequencing method was used for verification. According to the Classification Standards and Guidelines for Genetic Variants formulated by the American Society of Medical Genetics and Genomics (ACMG) (hereinafter referred to as the " ACMG Guidelines" ), the pathogenicity of the variant loci detected in three children was rated, and the detrimental loci of the variant loci were analyzed by multiple bioinformatics software. This study has been approved by the Ethics Committee of the First Affiliated Hospital of Zhengzhou University (Ethics No. 2024-KY-0881-002). Results:The clinical data and genetic test results of the three children in this study are as follows. ①Child 1: female, age of onset of 4 months and 10 days, with seizures, manifested as sudden cessation of movements, staring in both eyes, cyanosis of the lips, paleness, and stiffness and shaking of limbs. The results of genetic testing showed that child 1 had maternal PRRT2 gene c. 583_584dup (p. P196Afs*34) frameshift variant, which was rated as a pathogenic variant (PVS1 PM2_Supporting PP4) according to ACMG guidelines. According to the clinical manifestations and genetic test results of child 1, he was diagnosed with SeLIE and took oral sodium valproate [0.5 mL/(kg.d)], and was still taking medication at the follow-up of 2 years old, and did not have seizures again after 5 months of age. ②Child 2: male, age of onset of 10 years old, manifested as dystonia after sudden movement. The results of genetic testing showed that child 2 had PRRT2 gene mutations: paternal c. 649dupC (p.R217Pfs*8) frameshift variant and maternal c. 445C>A (p.Q149K) mutation. Among them, c. 649dupC was a reported pathogenic variant, and according to ACMG guidelines, c. 445C>A variant was rated as a variant of unknown clinical significance (PM2_Supporting), with a high probability of benignness. According to the clinical manifestations and genetic test results of the child 2, he was diagnosed with PKD, and was followed up with oral oxcarbazepine 9 mg/(kg.d) until 12 years and 2 months, and was still on the drug, and there was no recurrence of the seizure of the form of dyskinesia after taking the drug. ③Child 3: male, age of onset of 11 years old, manifested by dystonia after sudden exercise. The results of genetic testing showed that child 3 had a missense variant of PRRT2 gene c. 904G>C (p.D302H), and his parents refused genetic testing, and the source of the mutation was unknown, and the variant was rated as a variant of unknown clinical significance (PM2_Supporting+ PP3_Moderate+ PP4) according to ACMG guidelines. According to the clinical manifestations and genetic test results of child 3, he was diagnosed with PKD, and was treated with oral oxcarbazepine 10 mg/(kg.d) for 1 year and then discontinued on his own, and was followed up at the age of 17, and there was no recurrence of the seizure of the form of movement disorder after taking the drug. Conclusion:One case of SeLIE and two cases of PKD caused by PRRT2 gene mutations responded well to anti-seizure drugs. In this study, four variant loci of PRRT2 gene were found: c. 583_584dup, c. 904G>C, c. 649dupC, c. 445C>A, among which c. 583_584dup were new variants, enriching the variant spectrum of PRRT2 gene.

Objective:To analyze the clinical characteristics and genetic etiology of a child with Christianson syndrome (CS).Methods:A 1-year-and-5-month-old boy with CS diagnosed at the First Affiliated Hospital of Zhengzhou University in April 2021 was selected as the study subject. Clinical data were retrospectively analyzed. Peripheral blood samples were obtained from the child and his parents, followed by genomic DNA extraction and whole exome sequencing (WES). Candidate variant was validated by Sanger sequencing. This study has been approved by the Medical Ethics Committee of the Hospital (Ethics No. 2024-KY-1103-001).Results:The child has manifested with seizures, microcephaly, and global developmental delay. WES revealed that he has harbored a novel de novo hemizygous nonsense variant of the SLC9A6 gene, namely c. 1014G>A (p.W338*). Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was rated as pathogenic. Conclusion:The hemizygous c. 1014G>A nonsense variant of the SLC9A6 gene probably underlay the pathogenesis in this child. Above discovery has expanded mutational spectrum of the SLC9A6 gene and enabled definite diagnosis of the child.

Objective:To investigate the clinical phenotypic and genetic characteristics of three children with Paroxysmal kinesigenic dyskinesia (PKD) and Self-limited familial infantile epilepsy (SeLIE) caused by PRRT2 gene mutation. Methods:Three children with PKD and SeLIE caused by PRRT2 gene mutation (children 1-3) who were treated in the First Affiliated Hospital of Zhengzhou University from November 2022 to August 2023 were selected as the research subjects. A retrospective study was conducted to collect the clinical and family history data of the three children. 2 mL of peripheral venous blood from children 1-3 and parents of children 1-2 were collected (parents of children refused to undergo genetic testing and no blood samples were collected), genomic DNA was extracted, whole exome sequencing (WES) was performed, and Sanger sequencing method was used for verification. According to the Classification Standards and Guidelines for Genetic Variants formulated by the American Society of Medical Genetics and Genomics (ACMG) (hereinafter referred to as the " ACMG Guidelines" ), the pathogenicity of the variant loci detected in three children was rated, and the detrimental loci of the variant loci were analyzed by multiple bioinformatics software. This study has been approved by the Ethics Committee of the First Affiliated Hospital of Zhengzhou University (Ethics No. 2024-KY-0881-002). Results:The clinical data and genetic test results of the three children in this study are as follows. ①Child 1: female, age of onset of 4 months and 10 days, with seizures, manifested as sudden cessation of movements, staring in both eyes, cyanosis of the lips, paleness, and stiffness and shaking of limbs. The results of genetic testing showed that child 1 had maternal PRRT2 gene c. 583_584dup (p. P196Afs*34) frameshift variant, which was rated as a pathogenic variant (PVS1 PM2_Supporting PP4) according to ACMG guidelines. According to the clinical manifestations and genetic test results of child 1, he was diagnosed with SeLIE and took oral sodium valproate [0.5 mL/(kg.d)], and was still taking medication at the follow-up of 2 years old, and did not have seizures again after 5 months of age. ②Child 2: male, age of onset of 10 years old, manifested as dystonia after sudden movement. The results of genetic testing showed that child 2 had PRRT2 gene mutations: paternal c. 649dupC (p.R217Pfs*8) frameshift variant and maternal c. 445C>A (p.Q149K) mutation. Among them, c. 649dupC was a reported pathogenic variant, and according to ACMG guidelines, c. 445C>A variant was rated as a variant of unknown clinical significance (PM2_Supporting), with a high probability of benignness. According to the clinical manifestations and genetic test results of the child 2, he was diagnosed with PKD, and was followed up with oral oxcarbazepine 9 mg/(kg.d) until 12 years and 2 months, and was still on the drug, and there was no recurrence of the seizure of the form of dyskinesia after taking the drug. ③Child 3: male, age of onset of 11 years old, manifested by dystonia after sudden exercise. The results of genetic testing showed that child 3 had a missense variant of PRRT2 gene c. 904G>C (p.D302H), and his parents refused genetic testing, and the source of the mutation was unknown, and the variant was rated as a variant of unknown clinical significance (PM2_Supporting+ PP3_Moderate+ PP4) according to ACMG guidelines. According to the clinical manifestations and genetic test results of child 3, he was diagnosed with PKD, and was treated with oral oxcarbazepine 10 mg/(kg.d) for 1 year and then discontinued on his own, and was followed up at the age of 17, and there was no recurrence of the seizure of the form of movement disorder after taking the drug. Conclusion:One case of SeLIE and two cases of PKD caused by PRRT2 gene mutations responded well to anti-seizure drugs. In this study, four variant loci of PRRT2 gene were found: c. 583_584dup, c. 904G>C, c. 649dupC, c. 445C>A, among which c. 583_584dup were new variants, enriching the variant spectrum of PRRT2 gene.

Objective:To analyze the clinical characteristics and genetic etiology of a child with Christianson syndrome (CS).Methods:A 1-year-and-5-month-old boy with CS diagnosed at the First Affiliated Hospital of Zhengzhou University in April 2021 was selected as the study subject. Clinical data were retrospectively analyzed. Peripheral blood samples were obtained from the child and his parents, followed by genomic DNA extraction and whole exome sequencing (WES). Candidate variant was validated by Sanger sequencing. This study has been approved by the Medical Ethics Committee of the Hospital (Ethics No. 2024-KY-1103-001).Results:The child has manifested with seizures, microcephaly, and global developmental delay. WES revealed that he has harbored a novel de novo hemizygous nonsense variant of the SLC9A6 gene, namely c. 1014G>A (p.W338*). Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was rated as pathogenic. Conclusion:The hemizygous c. 1014G>A nonsense variant of the SLC9A6 gene probably underlay the pathogenesis in this child. Above discovery has expanded mutational spectrum of the SLC9A6 gene and enabled definite diagnosis of the child.

Objective:To investigate the clinical value of ultrasound-guided thoracic paravertebral block (TPVB) combined with bronchial blocker (BB) placement in thoracoscopic surgery.Methods:A randomized controlled study was conducted involving 60 patients scheduled for thoracoscopic surgery at The First Affiliated Hospital of Xiamen University from November to December 2023. These patients were classified as American Society of Anesthesiologists (ASA) I-II. They were divided into an observation group (BB placement) and a control group (double-lumen bronchial blocker placement) using the random number table method, with 30 patients in each group. Preoperatively, TPVB was performed under ultrasound guidance. After the induction of general anesthesia, a single-lumen tracheal tube was inserted, followed by the placement of a BB in the observation group, while a corresponding type of double-lumen bronchial tube was inserted in the control group. A fiberoptic bronchoscope was used for positioning and fixation in both groups, and anesthesia was maintained with intravenous anesthesia. The following parameters were assessed in each group: positioning time for intubation; number of cases with tube displacement; number of cases of postoperative pharyngeal pain; hemodynamic parameters [mean arterial pressure (MAP) and heart rate (HR)] before and after intubation; and blood gas analysis [partial pressure of oxygen (PaO 2) and carbon dioxide (PaCO 2)]. Additionally, the surgical field exposure score and the dosages of propofol and remifentanil administered during surgery were recorded. Levels of inflammatory markers [interleukin (IL)-2, IL-4, IL-6, IL-10, tumor necrosis factor (TNF) -α, and TNF-β] and Visual Analog Scale scores for pain at rest and during cough, recorded at 2, 4, 8, 10, 12, and 24 hours postoperatively were compared between the two groups. Results:The total amounts of propofol [(569.7 ± 29.2) mg] and remifentanil [(289.3 ± 46.3) μg] in the observation group were significantly lower than those in the control group [(612.6 ± 28.7) mg, (361.7 ± 40.6) μg, t = 5.74, 6.44, both P = 0.001]. The recovery time in the observation group [(31.8 ± 11.4) minutes] was significantly shorter than that in the control group [(37.5 ± 10.1) minutes, t = 2.10, P = 0.040]. There was no significant difference in positioning time for intubation between observation and control groups [(67 ± 13) seconds vs. (80 ± 36) seconds, t = 1.86, P = 0.068). There was no significant difference in percentage of cases who underwent tube displacement after intubation between observation and control group [23.3% (7/30) vs. 16.7% (5/30), χ2 = 0.58, P = 0.445]. The incidence of postoperative pharyngeal pain in the observation group was significantly lower than that in the control group [10.0% (3/30) vs. 33.3% (10/30), χ2 = 5.02, P = 0.025). There were no statistically significant differences between the two groups in terms of number of cases with tube displacement, hemodynamic parameters, blood gas analysis, inflammatory markers, surgical field exposure, and postoperative Visual Analog Scale scores between the two groups (all P > 0.05). Conclusion:Ultrasound-guided TPVB combined with BB placement during thoracoscopic surgery can reduce airway injury compared with the use of a double-lumen bronchial tube. It provides adequate sedation and analgesia during the procedure, facilitates rapid awakening, promotes early recovery of spontaneous breathing, and has fewer adverse reactions, making it worthy of clinical promotion.

Purpose: Molecular residual disease (MRD) is a promising biomarker in colorectal cancer (CRC) for prognosis and guiding treatment, while the whole-exome sequencing (WES) based tumor-informed assay is standard for evaluating MRD based on circulating tumor DNA (ctDNA). In this study, we assessed the feasibility of a fixed-panel for evaluating MRD in CRC. Materials and Methods: Seventy-five patients with resectable stage I-III CRC were enrolled. Tumor tissues obtained by surgery, and preoperative and postoperative day 7 blood samples were collected. The ctDNA was evaluated using the tumor-agnostic and tumor-informed fixed assays, as well as the WES-based and panel-based personalized assays in randomly selected patients. Results: The tumor-informed fixed assay had a higher preoperative positive rate than the tumor-agnostic assay (73.3% vs. 57.3%). The preoperative ctDNA status failed to predict disease-free survival (DFS) in either of the fixed assays, while the tumor-informed fixed assay-determined postoperative ctDNA positivity was significantly associated with worse DFS (hazard ratio [HR], 20.74; 95% confidence interval [CI], 7.19 to 59.83; p < 0.001), which was an independent predictor by multivariable analysis (HR, 28.57; 95% CI, 7.10 to 114.9; p < 0.001). Sub-cohort analysis indicated the WES-based personalized assay had the highest preoperative positive rate (95.1%). The two personalized assays and the tumor-informed fixed assay demonstrated same results in postoperative landmark (HR, 26.34; 95% CI, 6.01 to 115.57; p < 0.001), outperforming the tumor-agnostic fixed panel (HR, 3.04; 95% CI, 0.94 to 9.89; p=0.052). Conclusion Our study confirmed the prognostic value of the ctDNA positivity at postoperative day 7 by the tumor-informed fixed panel. The tumor-informed fixed panel may be a cost-effective method to evaluate MRD, which warrants further studies in future.