Objective To explore the clinical and genetic characteristics of 17 cases with glucose-6-phosphate dehydrogenase(G6PD) deficiency in Guizhou,China.Methods The clinical features of 17 patients with G6PD deficiency were analyzed,DNA samples were obtained from the patients and some mothers,and the exons and flanking intronic sequences of the G6PD gene were analyzed by the polymerase chain reaction and sequencing.Results The cases had diverse phenotypes,these patients had acute haemolytic anaemia triggered by eating broad beans,infections,ingestion of specific drugs or the neonatal period and chronic nonspherocytic haemolytic anaemia.Three cases of the patients had concomitant diseases for α Mediterranean anemia,acute myeloid leukemia M2 type and neonatal anal membrane stenosis,respectively.G1376T,G1388A and A95G were the commonest G6PD variants in patients in Guizhou,China.G1376T,G1388A and A95G mutations were observed in 82.4％ cases.Two patients had only compound variants(c.1311 C ＞ T,IVS11 nt 93 T ＞ C).One case in the Rongjiang County,Guizhou Province had novel compound variants (c.G1388A,IVS10-10 T ＞ G) in the world.A patient's mother in the Guiyang City,Guizhou Province,China had compound variants (c.1376 G ＞ T,1311 C ＞ T,IVS11 nt 93 T ＞ C) as a carrier.Conclusions G6PD deficiency has a wide range of clinical heterogeneity.A novel G6PD compound variant haplotype c.G1388A,IVS10-10 T ＞ G was first found in the world,and the SNP spectrum of G6PD was enlarged.There may be a G6PD compound variant haplotype c.1376 G ＞ T,1311 C ＞ T,IVS11 nt 93 T ＞ C in Guizhou.

Objective To evaluate the differences of toxicities,therapeutic efficacy and immune function between induction chemotherapy followed by sinusoidal chrono-modulated infusion and flat intermittent infusion of cisplatin (DDP)with intensity-modulated radiotherapy (IMRT) in patients with locoregionally advanced nasopharyngeal carcinoma (NPC).Methods Seventy patients with biopsydiagnosed stages Ⅲ and Ⅳ B NPC (according to the 2010 UICC staging system) were treated with two-cycle induction chemotherapy before chemoradiotherapy in Guizhou Cancer Hospital.The TPF chemotherapy regimen was administered as follows:The TXT and DDP with the dose of 75 mg/m2 was carried out by bolus infusing for the first day,the 5-FU with 750 mg · m-2 · d-1 was carried out by continuous intravenous pumping for the first day to fifth day(120 h).The induction chemotherapy was 21 days per cycle,for two cycles.After that all patients were randomly treated with 2-3 cycles of sinusoidal chronomodulated infusion or flat intermittent constant rate infusion of DDP with IMRT.Using a multi-channel programmed pump,the patients were given 12 h continuous infusions of DDP (100 mg/m2) for day one,repeated every 3 weeks for 2-3 cycles.DDP was administered from 10:00 am to 10:00 pm.Concurrent radiotherapy regimen was administered as follows:GTVnx 69.96-73.92 Gy/33 f,PTVnx 69.96 Gy/33 f,PTVnd 69.96 Gy/33 f,PTV1 60.06 Gy/33 f,PTV2 50.96 Gy/28 f.Results The main toxicities of chemoradiotherapy in the group of sinusoidal chrono-modulated infusion were bone marrow suppression:leukocytes,and then nausea,oral mucositis and hemoglobin.The main toxicities of chemoradiotherapy in the group of flat intermittent constant rate infusion were bone marrow suppression:hemoglobin,leukocytes,and then nausea,oral mucositis.No significant differences were observed for toxicities(P ＞ 0.05).After concurrent chemoradiotherapy,the complete response rate (CR),partial response rate (PR),stable disease rate(SD),progressive disease rate (PD) and overall response rate (ORR) were 11.4％,85.7％,2.9％,0 and 97.1％ in the group of sinusoidal chrono-modulated infusion.The CR,PR,SD,PD,ORR in the group of flat intermittent constant rate infusion were 22.9％,74.2％,2.9％,0,97.1％,respectively.However,there was no significant differences of effect in the two Arms (P ＞ 0.05).For sinusoidal ehrono-modulated infusion and flat intermittent infusion group,the 2-year overall survival(OS) were 82.9％ and 94.3％ respectively,the 2-year progression-free survival(PFS) were 77.1％,91.4％ respectively,and the 2-year distant metastasis free survival (DMFS) were 82.9％,91.4％ respectively.The value of CD3 + in the group of sinusoidal chrono-modulated infusion was higher than the group of flat intermittent constant rate infusion after therapy (Z =3.254,P ＜ 0.05).The value of CD4 +,CD8 +,CD16 + CD56 +,CD19 +,and CD4 +/CD8 + had no differences in two Arms (P ＞ 0.05).Conclusions No significance differences on the toxicities,therapeutic efficacy and survival were observed between the two groups,but immune function might be improved in the sinusoidal chrono-modulated infusion group.

OBJECTIVE: To analyze variants of TSC1 and TSC2 genes in a Chinese patient with tuberous sclerosis complex (TSC). METHODS: Peripheral blood samples were collected from the patient and her parents with informed consent. Following extraction of genomic DNA, potential variants of the TSC1 and TSC2 genes was detected by using targeted capture next-generation sequencing (NGS) and Sanger sequencing. RESULTS: The patient was found to harbor a de novo mosaicism variant c.3295_3298delG (Val1100CysfsTer3) of the TSC2 gene, with the proportion of the mutant allele determined as 13.4%, which was confirmed by Sanger sequencing. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.3295_3298delG (Val1100CysfsTer3) variant was predicted to be pathogenic (PVS1+PS2+PM2). CONCLUSION The mosaicism heterozygous variant of c.3295_3298delG of the TSC2 gene, as detected by both NGS and Sanger sequencing, probably underlay the TSC2 in this patient.
Female ; Humans ; Mosaicism ; Mutation ; Tuberous Sclerosis/genetics* ; Tuberous Sclerosis Complex 1 Protein/genetics* ; Tuberous Sclerosis Complex 2 Protein/genetics*

Objective To investigate the efficacy,adverse reactions and immune function of time-adjusted chemotherapy combined with intensity-modulated radiation therapy (IMRT) and conventional chemotherapy combined with IMRT for locally advanced nasopharyngeal carcinoma.Methods Random number grouping method was used to divide 66 cases of locally advanced nasopharyngeal carcinoma into 2 groups,of which 36 cases in the time-adjusted chemotherapy group and 30 cases in the conventional group.Both of them received docetaxel + cisplatin + fluorouracil regimen to induce chemotherapy for 2 cycles.The time-adjusted chemotherapy group was treated with intravenous injection of electronic automatic injection pump,the conventional group was treated with conventional intravenous infusion,and both groups were treated with synchronous cisplatin combined with IMRT.Calculated survival rate was generated by Kaplan-Meier method and long-term adverse reactions was evaluated according to CTC 3.0 criteria.Results The 3-year overall survival (OS) rate was 86.1％ and 93.3％ in the time-adjusted chemotherapy group and the regular group,the 3-year progress-free survival (PFS) was 83.3％ and 93.3％,the 3-year RFS was 88.5％ and 93.3％,and the 3-year recurrence-free survival was 94.1％ and 100％ respectively with no statistically significant difference (P ＞ 0.05).The dryness and hearing loss of the time-adjusted chemotherapy group had a decreasing trend compared with the conventional group.However,CD3 +,CD3 + CD4 +,CD3 + CD4 + CD8 +,and CD4 +/CD8 + of the time-adjusted chemotherapy group had an increasing trend compared with the conventional group.Conclusions Both time-adjusted chemotherapy and conventional chemotherapy combined with IMRT had comparable mid-term efficacy,but the former had lower adverse reactions,improved quality of life and immune function.Trial registration Chinese clinical trial registry,ChiCTR1800016809

Objective:To analyze the clinical features of anti-neurofascin-155 (NF155) antibody positive autoimmune nodopathy in children.Methods:This was a case series study. A total of 6 children who were diagnosed accurately as anti-NF155 antibody positive autoimmune nodopathy by cell immunofluorescence assay at the Children′s Hospital of Fudan University from January 2020 to December 2023 were collected. This study retrospectively analyzed 6 pediatric children′s clinical manifestations, laboratory and electrophysiological examination results, and treatment outcomes.Results:Among 6 children with anti-NF155 antibody positive autoimmune nodopathy, there were 4 boys and 2 girls. The onset age of 6 children ranged from 3 years and 8 months to 12 years. All 6 children had extremity weakness (more severe in the distal and the lower extremities than in the upper extremities), 5 children had sensory deficits such as numbness or pain in the extremities, 4 children had tremors and ataxia, 3 children had cranial nerve involvement. Among the 6 children, 4 children had protein-cell separation in cerebrospinal fluid examinations. Among the 6 children, 1 child had central nervous system demyelination, the brain magnetic resonance imaging showed multiple abnormal signals in the bilateral cerebral hemispheres. Four children showed motor and sensory nerve damage in electrophysiological examination, and 2 children only showed motor nerve damage. Three children showed myelin and axonal damage, and 3 children only showed axonal damage. Among the 6 children, 5 children were treated with intravenous immunoglobulin and steroids. Among them, 2 children underwent plasma exchange due to poor efficacy, and subsequently, rituximab was added. There was 1 child changed the treatment with olfatomumab since the symptoms did not significantly improve after using rituximab. After treatment for 4-15 months, 2 children had no clinical symptoms, 1 child had improvement in clinical symptoms, 2 children had no significant improvement in clinical symptoms, and 1 child who did not receive the immunotherapy had no significant change in clinical symptoms.Conclusions:Anti-NF155 antibody positive autoimmune nodopathy in children presents with varying degrees of clinical manifestations. It is mainly characterized by extremity weakness, numbness and pain, often accompanied bytremorsand ataxia. Some pediatric patients may also have central nervous system demyelination. Cerebrospinal fluid and electrophysiological examination are important auxiliary examination methods. If steroid therapy is not effective, plasma exchange and rituximab treatment should be used as soon as possible.

Genetic epilepsy with febrile seizures plus(GEFS+)is a genetically related epilepsy syndrome, characterized by a distinctive pattern of phenotypic heterogeneity and genetic heterogeneity. An increasing number of studies illustrate that a variety of pathogenic variations participate in the pathogenesis of GEFS+,but the pathogenesis and genetic mechanisms are not fully understood,and most families can not find pathogenic genes. With the improve-ment of genetic techniques,the pathogenesis of GEFS+ will be better explained and a new basis will be provided for its diagnosis and precision treatment. This article discusses the clinical manifestation,genetic research,diagnosis and treat-ment of GEFS+,aiming at raising awareness of the disease.