10.3969/j.issn.2095-4344.2013.24.007

Objective To investigate the influence of anti-angiogenesis therapy on proliferation and apoptosis of fibroblasts derived from keloids. Methods Thirty pieces of keloids from a patient were implanted into subcutaneous tissue of the nude mice, 24 pieces of which survived were divided into three groups which were treated with perilesional injection of vascular endothelial growth factor( VEGF) (0.4 mg/0.2 mL) , Endostar(0.125 g/0.2 mL) and physiological saline (0.2 mL)on the 21 d, 23 d, 25 d, 27 d after implantation. Sample were collected on the 10th day after perilesional injection, the proliferating fibroblasts in keloid tissue were immunohistochemically detected by proliferating cell nuclear antigen (PCNA) expression. The apoptotic cell was detected by terminal deoxynucleotidyl transferase dUTP-nick end labeling (TUNEL) staining. Results IHC staining indicated that PCNA expression of fibroblasts was significantly increased in keloid tissue after VEGF injection, PCNA expression of fibroblasts was significantly reduced in keloid tissue after Endostar injection,TUNEL assay revealed lower apoptotic cells expression in the keloid tissue after VEGF injection and higher in the Endostar group than control group. The rate of proliferative index (PI) , apoptotic index(AI) and AI/PI of fibroblasts in keloid after VEGF (PI:41.13 ±2.29,AI:5.75 ±1.28,AI/PI: 0.14 ± 0.04)or Endostar injection (PI:27.25 ±2.61,AI:11.00±1.31,AI/PI:0.41 ±0.09)and control group (PI: 34.75 ±3.62,AI:7. 88 ± 1.64,AI/PI:0. 23 ±0.07) showed statistical differences. Conclusion Anti-angiogenesis therapy is shown to induce keloid regression through suppression of keloid fibroblast proliferation,induction of apoptosis, which may be a new approach for the treatment of keloids.

Objective To evaluate the dosimetry accuracy and clinical efficacy of 125I radioactive seed implantation using coplanar template (CPT) in the treatment of metastatic or recurrent chest wall tumor.Methods Thirty-one patients with metastasis or recurrence of chest wall tumor,who had been diagnosed with pathology between July 2005 and July 2015,were retrospectively studied.All patients underwent CPT-assisted 125I radioactive seed implantation.Brachytherapy radiation treatment planning system (BTPS) was used to make preoperative plans,and the prescribed dose (PD) was 110 Gy.CPT was used to assist CT guided 125I radioactive seeds implantation.Dose evaluation was performed immediately after implantation.The difference of dose parameters was compared between preoperation and postoperation,including Dg0,D100,V90,V100 and the numbers of seeds.Postoperative chest CT was conducted regularly to assess the treatment efficacy based on the response evaluation criteria in solid tumors (RECIST Version 1.1).The patients were followed up till July 2016.Results All patients went through implantation procedure successfully and there was no significant statistical difference between preoperative and postoperative dose parameters (P ＞ 0.05).The conformal index (CI) was 0.951 ± 0.13,external index(EI) was 6.5％ ±0.9％.Six months after implantation,CR,PR,SD and PD were 25.8％ (8/31),51.6％ (16/31),6.5％ (2/31) and 16.1％ (5/31),respectively.The effective rate was 77.4％,and local control rate was 83.9％ (26/31).Skin pigmentation occurred in 13 patients during the follow-up period,without any special treatment.Conclusions The auxiliary of CPT in the treatment of metastatic or recurrent chest wall tumor under the guiding of CT could achieve quality control,safety and effectiveness.

Objective To compare the planned radiation dose and the actual dose received after 125I radioactive seeds implantation supported by coplanar template (CPT) in lung cancer patients with mediastinal node metastases 4R,and to evaluate the clinical efficacy.Methods Totally 32 patients with lung cancer with mediastinal lymph node metastases 4R who had been diagnosed via cellular pathology studies were selected from January 2008 to December 2014.The mediastinal lymph node metastases were treated by CPT-assisted 125I radioactive seed implantation.Digital imaging and communications in medicine (DICOM) data were acquired by chest CT scan before implantation,brachytherapy radiation treatment planning system (BTPS) was introduced to carry out the plan,and the prescribed dose(PD) was 120 Gy.CPT was used to control the precision of needle penetration and implantation of radioactive seeds.Computer tomography (CT) was used to ensure the correct position of needles and radioactive seeds.Dose evaluation was performed immediately after implantation and was compared with planned dose using paired t-test.The 6-months postoperative chest CT was conducted to evaluate treatment efficacy according to response evaluation criteria in solid tumors(RECIST Version 1.1).Results All patients went through implantation procedure successfully.Dose evaluation after implantation was as followed.The average dose received (231.9 ±29.6)Gy,the dose received by 90％ of the target(D90) (150.8 ± 16.6) Gy,the dose received by 100％ of the target(D100) (100.4 ± 12.6)Gy,the volume of 100％PD covering the target(V100)(94.1 ± 2.6) ％,the volume of 200％ PD covering the target(V200) (33.0 ± 5.7) ％,the conformal index (CI) 0.75 ±0.06,the external index(EI) (22.7 ± 5.8)％,the average dose received by the superior vena cava (19.3 ± 7.2)Gy,and the average dose received by aorta (12.1 ± 5.1)Gy.Efficacy was followed for 6 months after implantation and the effective rate was 84.37％.There was no serious complications (such as radioactive lung injury,major vascular injury,bleeding,and et al.) occurred in follow-up period.Conclusions CPT assisted CT guided 125I radioactive seed imnplantation in treating mediastinal node metastases 4R can achieve preoperative BTPS,minimize major vascular or organ injury.It is an accurate,effective and safe treatment approach and may be of great value to standardize the procedure of radioactive seed implantation in mediastinal metastases.

OBJECTIVE: To summarize the genetic diagnosis, low-depth copy number variation sequencing (CNV-seq) and prenatal finding in 7 fetuses with 2p16.3 deletions only involving the NRXN1 gene. METHODS: The 7 fetuses have all been found to have loss of heterozygosity at 2p16.3 by CNV-seq, which were verified by quantitative real-time PCR (qPCR). Specific regions of NRXN1 gene deletions were identified, and the CNVs were verified in their parents. Outcome of the pregnancies were followed up. RESULTS: Among 16 502 prenatal samples, 7 fetuses were found to harbor a 120 kb ~ 900 kb microdeletion in the 2p16.3 region, which yielded a prevalence of 0.424‰. The deleted region mainly involved 50 200 000-51 880 000 positions of chromosome 2 and involved only the NRXN1 gene. All of the 7 fetal CNVs were confirmed by qPCR, including 2 cases with heterozygous deletion of exons 1 to 6, 1 with heterozygous deletion of exons 1 to 19, 1 with heterozygous deletion of exons 19 to 22, and 3 with heterozygous deletion of introns 6 to 7 of the NRXN1 gene. Verification in the parents had found that one deletion was inherited from the father, 1 was from the mother, 2 cases were de novo in origin, whilst the remaining 3 had refused parental verification. After genetic counseling, one couple had elected induced abortion, 1 case has not been born yet, whilst the other 5 cases were born healthy. Follow up had identified no mental abnormalities among the children. CONCLUSION Seven fetuses with heterozygous 2p16.3 deletions only involving the NRXN1 gene were detected by CNV-seq. The specific deletion of the NRXN1 gene was verified by qPCR. Prenatal genetic counseling and fertility guidance has been provided to the particular family by combining the results of CNV testing, pedigree analysis and pregnancy outcome.
Female ; Humans ; Pregnancy ; Calcium-Binding Proteins/genetics* ; Cell Adhesion Molecules, Neuronal/genetics* ; DNA Copy Number Variations ; Nerve Tissue Proteins/genetics* ; Neural Cell Adhesion Molecules/genetics* ; Prenatal Diagnosis ; Real-Time Polymerase Chain Reaction ; Infant, Newborn

Objective To investigate the correlation between HLA-DM gene polymorphism and antibody response induced by poliomyelitis vaccine.Methods 355 healthy infants aged 2 to 3 months in Guangxi Zhuang Autonomous Region were selected as the study objects,and 10 SNPs of DMA exon 3 and DMB exon 2/3 were genotyped by Sanger sequencing.The correlation between DMA and DMB genes and poliomyelitis vaccine-induced antibody response was analyzed at allele,genotype and haplotype levels.Results In the type Ⅰ antibody response induced by polio vaccine,the frequencies of DMA*01:02,DMB*01:01,DMB*01:01/DMB*01:01 and DMA*01:02-DMB*01:01 were higher in the non-seroconversion group than in the seroconversion group(P<0.05).In the polio type Ⅱ antibody response,the frequencies of DMA*01:02,DMA*01:02/DMA*01:02,DMB*01:01/DMB*01:01 and DMA*01:02-DMB*01:01 were higher in the non-seroconversion group than in the seroconversion group(P<0.05).Conclusion Alleles DMA*01:02 and DMB*01:01 may be associated with type Ⅰ and type Ⅱ antibody responses induced by poliomyelitis vaccine.

Objective To explore the therapeutic effect of radioactive 125I seeds combined with chemotherapy on the treatment of inoperative pancoast tumor by CT-guided percutaneous implantation of treatment planning system (TPS).Methods From December 2002 to December 2010,36 patients with pancoast tumor were confirmed by imaging and pathology.Among them,26 cases suffered from squamous cell carcinoma and 10 cases with adenocarcinoma.At 1 week after radioactive 125I implantation,chemotherapy was administered as intravenous 1 000 mg / m2 gemcitabine at 1 and 8 d and intravenous cisplatin 75 mg/ m2 at 1 d for 4 consecutive cycles.The prescribed dose (PD) was 120 Gy,and the median activity of the seeds was 0.7 mCi (2.59 × 107 Bq) with the range of 0.68-0.82 mCi (2.52 × 107-3.03 × 107 Bq).The patients were followed-up and the median follow-up time was 48 months.The survival rate was observed.Results The mPD of the target tumor was (118.7 ± 7.2) Gy,D90(126 ± 4.7) Gy,D90 ＞ mPD.The rate of CR (11 cases) was 63.6％,and the effective rate (CR + PR) was 83.4％.The follow-up last till December 1st,2016.1-,3-and 5-year local control rates were 92％,83％,and 67％,respectively.1-,3-and 5-year cumulative survival rate were 84.1％,56.7％,and 36.8％,respectively.Median survival was 38 months.Conclusions Chemotherapy combined with tissue radioactive 125I seed implantation is a minimally invasive and effective method for the treatment of pancoast tumor.

Objective To evaluate the clinical efficacy and prognostic factors of limited-stage small cell lung cancer ( LS-SCLC) treated with 125 I radioactive seed implantation guided by CT combined with systemic chemotherapy. Methods A total of 128 limited-stage small cell lung cancer patients were treated with 125 I radioactive seed implantation combined with chemotherapy from Jun 2008 to Jun 2012 in Tianjin Medical University Second Hospital. Theχ2 test was used to analyze the influencing factors of short-term efficacy. Survival rate was calculated by Kaplan-Meier method, single factor analysis was performed by Log-rank, and multivariate analysis was performed by Cox proportional hazard model. Results Totally 128 patients finished the treatment. The overall response rate was 86.7％ ( 111/128 ) after 6 months of treatment. The 1-, 2-and 3-year overall survival rate was 77.9％, 39.8％and 28.0％, respectively, and the median survival time was 21.0 months. The univariate analysis showed that the following factors were main prognostic factors:age, performance status ( PS) , hemoglobin≥120 g/L before treatment, smoking index, the maximum diameter of tumor, neuron-specific enolase before treatment, subscribe for prophylactic cranial irradiation ( PCI) , number of chemotherapy cycle, chemotherapy response, prescribed dose ( PD ) , postoperation dose covering 100％ volume ( D100 ) , remedial model. multivariate analysis revealed that age, PS, hemoglobin≥120 g/L before treatment and PD, the maximum diameter of tumor, number of chemotherapy cycle, chemotherapy response, and remedial model were the independent prognostic factors for survival. 29 patients of 128 suffered from aerothorax and the incidence rate of aerothorax was 27.7％. Totally 16 patients occurred hemoptysis and theincidence rate was 12.5％. Conclusions 125 I radioactive seed implantation therapy showed good effecacy in the treatment of LS-SCLC. Age, PS, hemoglobin≥120 g/L before treatment, the maximum diameter of tumor, number of chemotherapy cycle, chemotherapy response, and remedial model might be the main prognostic factors for LS-SCLC patients.

Here, we report a previously unrecognized syndromic neurodevelopmental disorder associated with biallelic loss-of-function variants in the RBM42 gene. The patient is a 2-year-old female with severe central nervous system (CNS) abnormalities, hypotonia, hearing loss, congenital heart defects, and dysmorphic facial features. Familial whole-exome sequencing (WES) reveals that the patient has two compound heterozygous variants, c.304C>T (p.R102*) and c.1312G>A (p.A438T), in the RBM42 gene which encodes an integral component of splicing complex in the RNA-binding motif protein family. The p.A438T variant is in the RRM domain which impairs RBM42 protein stability in vivo. Additionally, p.A438T disrupts the interaction of RBM42 with hnRNP K, which is the causative gene for Au-Kline syndrome with overlapping disease characteristics seen in the index patient. The human R102* or A438T mutant protein failed to fully rescue the growth defects of RBM42 ortholog knockout ΔFgRbp1 in Fusarium while it was rescued by the wild-type (WT) human RBM42. A mouse model carrying Rbm42 compound heterozygous variants, c.280C>T (p.Q94*) and c.1306_1308delinsACA (p.A436T), demonstrated gross fetal developmental defects and most of the double mutant animals died by E13.5. RNA-seq data confirmed that Rbm42 was involved in neurological and myocardial functions with an essential role in alternative splicing (AS). Overall, we present clinical, genetic, and functional data to demonstrate that defects in RBM42 constitute the underlying etiology of a new neurodevelopmental disease which links the dysregulation of global AS to abnormal embryonic development.
Female ; Animals ; Mice ; Humans ; Child, Preschool ; Intellectual Disability/genetics* ; Heart Defects, Congenital/genetics* ; Facies ; Cleft Palate ; Muscle Hypotonia

ABSTRACT: Meningiomas are the most common primary intracranial neoplasm with diverse pathological types and complicated clinical manifestations. The fifth edition of the WHO Classification of Tumors of the Central Nervous System (WHO CNS5), published in 2021, introduces major changes that advance the role of molecular diagnostics in meningiomas. To follow the revision of WHO CNS5, this expert consensus statement was formed jointly by the Group of Neuro-Oncology, Society of Neurosurgery, Chinese Medical Association together with neuropathologists and evidence-based experts. The consensus provides reference points to integrate key biomarkers into stratification and clinical decision making for meningioma patients. REGISTRATION Practice guideline REgistration for transPAREncy (PREPARE), IPGRP-2022CN234.
Humans ; Meningioma/pathology* ; Consensus ; Neurosurgical Procedures ; Meningeal Neoplasms/pathology*