Objective To evaluate the long-term results and prognostic factors in 582 nasopharyngeal carcinoma ( NPC ) patients treated by intensity modulated radiotherapy ( IMRT ) . Methods 582 newly diagnosed NPC patients treated by IMRT in Sichuan cancer hospital from Jan. 2001 to Dec. 2004were reviewed. According to 2002UICC staging system, there were 36 stage Ⅰ , 144 stage Ⅱ , 224 stage Ⅲ, 178 stage Ⅳa. The Kaplan-Meier method was used to calculate the survival rate.Acute and late toxicities were graded according to the radiation therapy oncology group (RTOG) radiation morbidity scoring criteria. Results The follow up rate was 93.5％. The 5-year local control, regional control, distant metastasis-free survival, disease free survival, disease specific survival and overall survival rate was 89. 8％,95. 2％, 74. 1％, 69.6％, 83.2％ and 77. 1％. There were 29, 13 and 117 patients who had developed local, regional and distant recurrence respectively. The incidence of grade 3 acute ( salivary gland、 oral mucosa and skin) and late toxicity was 44. 5％ and 4. 2％. No grade 4 acute and late toxicity reaction was found. Multivariate analysis showed that clinical stage, N stage, radiotherapy interruption, age, HGB and weight loss were the independent prognostic factors for the overall survival. ConclusionsNPC treated with IMRT could get good long-term survival with high quality of life. The clinical stage and N stage were the main prognostic factors for the overall survival. The acute and late toxicities were mainly grade 1 and 2.Distant metastasis is the main cause of treatment failure.

OBJECTIVE: To explore the clinical characteristics and genetic etiology of a patient with adolescent-onset hypomyelinated leukodystrophy with atrophy of basal ganglia and cerebellum (H-ABC). METHODS: A patient who was diagnosed with H-ABC in March 2018 at the First Affiliated Hospital of Nanjing Medical University was selected as the study subject. Clinical data was collected. Peripheral venous blood samples of the patient and his parents were collected. The patient was subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing. RESULTS: The patient, a 31-year-old male, had manifested with developmental retardation, cognitive decline and abnormal gait. WES revealed that he has harbored a heterozygous c.286G>A variant of the TUBB4A gene. Sanger sequencing confirmed that neither of his parents has carried the same variant. Analysis with SIFT online software indicated the amino acid encoded by this variant is highly conserved among various species. This variant has been recorded by the Human Gene Mutation Database (HGMD) with a low population frequency. The 3D structure constructed by PyMOL software showed that the variant has a harmful effect on the structure and function of the protein. According to the guidelines formulated by the American College of Medical Genetics and Genomics (ACMG), the variant was rated as likely pathogenic. CONCLUSION The c.286G>A (p.Gly96Arg) variant of the TUBB4A gene probably underlay the hypomyelinating leukodystrophy with atrophy of basal ganglia and cerebellum in this patient. Above finding has enriched the spectrum of TUBB4A gene variants and enabled early definitive diagnosis of this disorder.
Male ; Humans ; Adolescent ; Adult ; Magnetic Resonance Imaging ; Basal Ganglia/pathology* ; Cerebellum ; Atrophy/pathology* ; Mutation ; Tubulin/genetics*

Objective:To analyze and evaluate the equity of children's health in countries along the"the Belt and Road",promote further attention to children's health in countries along the route,and promote cooperation and exchanges on children's health between China and countries along the"the Belt and Road".Methods:Using concentration index and concentration curve to measure overall equity,and using the Thiel index for intraregional and interregional euqity measurement.Results:The under-five mortality concentration index is 0.349 7,the concentration curve is below the absolute fair line.The Thiel index shows that inequality in low-income countries,lower-middle-income countries,upper-middle-income countries and high-income countries is the leading cause of child health inequities in the"the Belt and Road"countries.Conclusion:There is inequity in the health of children in countries along"the Belt and Road Initiative",countries along the"the Belt and Road"should take comprehensive measures to reduce the under-five mortality rate,at the same time strengthen international cooperation to further promote equity in children's health in"Belt and Road"countries.

Objective: To investigate the expression and clinical significance of PD-1 molecule in tumor cells (T-ALL cells) derived from the patient with T-cell acute lymphoblastic leukemia (T-ALL). Methods: T-ALL cells from one patient and PBMCs from four healthy volunteers provided by the Department of Hematology in Jiangsu Provincial Hospital of Traditional Chinese Medicine in December 2015, and human 293T/PD-1 cells provided by Persongen Bio Therapeutics (Suzhou) Co., Ltd. were used for this study. The mouse T-ALL xenograft model was constructed by injecting T-ALL cells into tail vein of B-NDG mice, and flow cytometry was used to verify whether the cells obtained from the spleen of transplanted mice were mainly consisted of T-ALL cells. Flow cytometry was used to study the protein expression of PD-1 in T-ALL cells, and RT-PCR was applied to further verify the mRNA expression of PD-1 in T-ALL cells. The PD-1 gene in T-ALL cells was sequenced by SNP genotyping to detect whether the DNA sequence of PD-1 gene changed. PD-1 inhibitor was used in vitro to study their effects on proliferation, apoptosis, and the mRNA expression levels of related factors in T-ALL cells. Results: The mouse T-ALL xenograft model was successfully constructed and verified by flow cytometry as T-ALL. PD-1 was highly expressed at both mRNA and protein levels in T-ALL cells (all P<0.01). A C-to-T mutation was detected in the fifth exon of the PD-1 gene. PD-1 inhibitor had no significant effect on proliferation and apoptosis of T-ALL cells in vitro; PD-1 inhibitor up-regulated the mRNA expression of tumor-suppressor protein IGFBP3 and decreased the mRNA expression of oncoprotein SULT1A3 (all P<0.01). Conclusion: PD-1 is highly expressed in T-ALL cells, and PD-1 could be used as a target for clinical diagnosis and treatment for T-ALL.

ObjectiveTo investigate the efficacy and safety of camrelizumab monoclonal antibody combined with molecular-targeted therapy in elderly patients with unresectable or advanced hepatocellular carcinoma （HCC）. MethodsA retrospective analysis was performed for the patients with unresectable/advanced HCC who attended six hospitals from January 1， 2019 to March 31， 2021， and all patients received camrelizumab monoclonal antibody treatment， among whom 84.8% also received targeted therapy. According to the age of the patients， they were divided into elderly group （≥65 years） and non-elderly group （<65 years）. The two groups were assessed in terms of overall survival （OS）， progression-free survival （PFS）， objective response rate （ORR）， disease control rate （DCR）， and immune-related adverse events （irAE）. The chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups； the independent samples t-test was used for comparison of normally distributed continuous data， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups. The Kaplan-Meier method was used for survival analysis， and the log-rank test was used for comparison of survival curves. Univariate and multivariate Cox proportional hazards regression analyses were used to determine the independent influencing factors for PFS and DCR at 6 months. ResultsA total of 99 HCC patients were enrolled， with 27 in the elderly group and 72 in the non-elderly group. The elderly group had an OS rate of 67.8%， an ORR of 44.4%， and a DCR of 74.1% at 12 months and a median PFS of 6.4 （95% confidence interval ［CI］： 3.0‍ ‍—‍ ‍12.4） months， with no significant differences compared with the non-elderly group （all P>0.05）. The median OS was unavailable for the elderly group， while the non-elderly group had an OS of 18.9 （95%CI： 13.0‍ ‍—‍ ‍24.8） months； there was no significant difference between the two groups （P=0.485）. The univariate and multivariate Cox regression analyses showed that major vascular invasion （MVI） was an independent risk factor for PFS （hazard ratio ［HR］=2.603， 95%CI： 1.136‍ ‍—‍ ‍5.964， P=0.024） and DCR （HR=3.963， 95%CI： 1.671‍ ‍—‍ ‍9.397， P=0.002） at 6 months， while age， sex， etiology of HBV infection， presence of extrahepatic metastasis， Child-Pugh class B， and alpha-fetoprotein>400 ng/mL were not associated with PFS or DCR at 6 months. For the elderly group， the incidence rates of any irAE and grade 3/4 irAE were 51.9% and 25.9%， respectively， with no significant differences compared with the non-elderly group （P>0.05）， and skin disease was the most common irAE in both groups （39.4%）. ConclusionCamrelizumab monoclonal antibody combined with molecular-targeted therapy has similar efficacy and safety in patients with unresectable/advanced HCC aged ≥65 years and those aged <65 years. MVI is associated with suboptimal response to immunotherapy and poor prognosis.