Objective:To explore the clinical characteristics and genetic etiology of a child with Neurofibromatosis-Noonan syndrome (NFNS).Methods:A child with NFNS who was treated at the Department of Endocrinology of Hangzhou Children′s Hospital in January 2024 was selected as the study subject. Clinical data of the child was collected by retrospective analysis method. Peripheral venous blood samples (2 mL each) were collected from the child and his parents. Genomic DNA was extracted, and trio whole exome sequencing (Trio-WES) of the family was carried out. Sanger sequencing was used to perform family verification on the candidate variants. The identified variants were classified for pathogenicity according to the Standards and Guidelines for the Interpretation of Sequence Variants established by the American College of Medical Genetics and Genomics (ACMG) (hereafter referred to as the " ACMG guidelines" ). This study has been approved by the Medical Ethics Committee of Hangzhou Children′s Hospital (Ethics No. 2021-06).Results:The child was a 7-year and 4-month-old male. He has short stature, numerous café-au-lait spots on the neck and trunk, and special facial features such as a full forehead, wide interpupillary distance, a low nasal bridge, and low-set ears.The results of Trio-WES showed that he has harbored a NF1 gene c. 3773G>T (p.W1258L) mutation, which was verified by Sanger sequencing to be de novo in origin. The NF1 gene child was associated with NFNS, which was an autosomal dominant inheritance. According to the ACMG guidelines, this variant was judged to be a likely pathogenic variant (PS2+ PM2+ PP3+ PP2). No pathogenic variant in genes associated with Noonan syndrome, such as those in PTPN11, SOS1, RAF1, RIT1, and KRAS, was found. Conclusion:The child with NFNS has clinical features such as short stature, special facial features, and café-au-lait spots. The c. 3773G>T (p.W1258L) variation in the NF1 gene may be the genetic etiology of the NFNS child in this study. The results of this study has enriched the variation spectrum of the NF1 gene.

Objective:To construct a prior based on the inherent properties of PET to accurately segment the lesion areas.Methods:A network framework for PET tumor segmentation driven by geodesic priors was proposed (geodesic network for short). Specifically, partial differential equations were constructed to characterize the geodesic distances between different regions in PET images. Tumor marker points identified by CT labeling were used as the initial conditions for the equations. To enhance the contrast between areas of lung or breast tumors and normal tissues, a smooth Heaviside function was utilized to map the geodesic distances. The network framework adopted a dual-branch architecture, using geodesic priors to assist in PET image segmentation.Results:The proposed method achieved a Dice coefficient of 94.92% in lung cancer segmentation and 90.12% in breast cancer segmentation. With the addition of geodesic priors in the Unet, the Dice coefficient for breast cancer increased by 32.37% (from 42.50% to 74.87%).Conclusion:Geodesic priors can significantly improve segmentation outcomes and enhance the generalization capability of the network.

OBJECTIVE: To explore the clinical characteristics and genetic etiology of a child with Neurofibromatosis-Noonan syndrome (NFNS). METHODS: A child with NFNS who was treated at the Department of Endocrinology of Hangzhou Children's Hospital in January 2024 was selected as the study subject. Clinical data of the child was collected by retrospective analysis. Peripheral venous blood samples (2 mL each) were collected from the child and his parents. Genomic DNA was extracted, and trio-whole exome sequencing (Trio-WES) of the family was carried out. Sanger sequencing was used to perform family verification on the candidate variants. The identified variants were classified for pathogenicity according to the Standards and Guidelines for the Interpretation of Sequence Variants established by the American College of Medical Genetics and Genomics (ACMG) (hereafter referred to as the "ACMG guidelines"). This study has been approved by the Medical Ethics Committee of Hangzhou Children's Hospital (Ethics No. 2021-06). RESULTS: The child was a 7-year and 4-month-old male. He has short stature, numerous café-au-lait spots on the neck and trunk, and special facial features such as a full forehead, wide interpupillary distance, a low nasal bridge, and low-set ears. The results of Trio-WES showed that the he had harbored the NF1 gene c.3773G>T (p.W1258L) mutation, which was verified by Sanger sequencing to be de novo in origin. The NF1 gene was associated with NFNS, which has an autosomal dominant inheritance. According to the ACMG guidelines, this variant was judged to be a likely pathogenic variant (PS2+PM2+PP3+PP2). No pathogenic variant in genes associated with Noonan syndrome, such as PTPN11, SOS1, RAF1, RIT1, and KRAS, was found. CONCLUSION The child with NFNS has clinical features such as short stature, special facial features, and café-au-lait spots. The c.3773G>T (p.W1258L) variation in the NF1 gene may be the genetic etiology of the NFNS child in this study. The results of this study has enriched the variation spectrum of the NF1 gene.
Child ; Humans ; Male ; Exome Sequencing ; Mutation ; Neurofibromatosis 1/genetics* ; Neurofibromin 1/genetics* ; Noonan Syndrome/genetics*

Objective:To explore the clinical characteristics and genetic etiology of a child with Neurofibromatosis-Noonan syndrome (NFNS).Methods:A child with NFNS who was treated at the Department of Endocrinology of Hangzhou Children′s Hospital in January 2024 was selected as the study subject. Clinical data of the child was collected by retrospective analysis method. Peripheral venous blood samples (2 mL each) were collected from the child and his parents. Genomic DNA was extracted, and trio whole exome sequencing (Trio-WES) of the family was carried out. Sanger sequencing was used to perform family verification on the candidate variants. The identified variants were classified for pathogenicity according to the Standards and Guidelines for the Interpretation of Sequence Variants established by the American College of Medical Genetics and Genomics (ACMG) (hereafter referred to as the " ACMG guidelines" ). This study has been approved by the Medical Ethics Committee of Hangzhou Children′s Hospital (Ethics No. 2021-06).Results:The child was a 7-year and 4-month-old male. He has short stature, numerous café-au-lait spots on the neck and trunk, and special facial features such as a full forehead, wide interpupillary distance, a low nasal bridge, and low-set ears.The results of Trio-WES showed that he has harbored a NF1 gene c. 3773G>T (p.W1258L) mutation, which was verified by Sanger sequencing to be de novo in origin. The NF1 gene child was associated with NFNS, which was an autosomal dominant inheritance. According to the ACMG guidelines, this variant was judged to be a likely pathogenic variant (PS2+ PM2+ PP3+ PP2). No pathogenic variant in genes associated with Noonan syndrome, such as those in PTPN11, SOS1, RAF1, RIT1, and KRAS, was found. Conclusion:The child with NFNS has clinical features such as short stature, special facial features, and café-au-lait spots. The c. 3773G>T (p.W1258L) variation in the NF1 gene may be the genetic etiology of the NFNS child in this study. The results of this study has enriched the variation spectrum of the NF1 gene.

Objective:To construct a prior based on the inherent properties of PET to accurately segment the lesion areas.Methods:A network framework for PET tumor segmentation driven by geodesic priors was proposed (geodesic network for short). Specifically, partial differential equations were constructed to characterize the geodesic distances between different regions in PET images. Tumor marker points identified by CT labeling were used as the initial conditions for the equations. To enhance the contrast between areas of lung or breast tumors and normal tissues, a smooth Heaviside function was utilized to map the geodesic distances. The network framework adopted a dual-branch architecture, using geodesic priors to assist in PET image segmentation.Results:The proposed method achieved a Dice coefficient of 94.92% in lung cancer segmentation and 90.12% in breast cancer segmentation. With the addition of geodesic priors in the Unet, the Dice coefficient for breast cancer increased by 32.37% (from 42.50% to 74.87%).Conclusion:Geodesic priors can significantly improve segmentation outcomes and enhance the generalization capability of the network.

Objective To explore the application of low dose of radiation combined with low concentration of contrast medium in the energy spectrum CT of the coronary artery angiography.Methods 60 patients with suspected diagnosis of coronary heart disease were randomly divided into A,B two groups,30 cases in each group.Group A with 350 mg I/mL contrast agent,undergoing conventional CT scanning;Group B using 300 mg I/mL contrast agent,the gems energy spectrum CT scanning with low-dose.Two groups both adopted forward-looking heart switch control scanning mode.After scanning,group A reconstructed conventional images of 40% ASiR sequence,group B rebuilded axial surface images of single energy 65 keV and 40% ASiR sequence,all the reconstruction images were introduced to AW4.6 workstations used for analysis.Double-blind subjective rating was done by two experienced doctors to measure CT values and SD of aortic sinus (AS),left main (LMA),the left anterior descending branch proximal (LAD-p),left circumflex branch proximal (LCX-p), right coronary artery proximal (RCA-p)and pericardial fat,AS the noise (SD),to calculate the signal-to-noise ratio (SNR)and contrast to noise ratio (CNR),to calculate the effective doses of radiation(ED)by recording CTDI and DLP,and to record iodine intake.By using two independent samples t test to compare two groups of patients’the effective radiation doses,iodine intake,the average CT value,SD,SNR and CNR.Results The subjective image quality score differences and coronary measuring section CT values between the two groups had no statistical significance.In the aspects of effective radiation dose,group B reduced about 29% compared to group A,the difference was statistically significant.Iodine intake in group B decreased about 16% than in group A.Conclusion In coronary artery CT imaging, spectral scanning with low dose of radiation and reconstruction images with single energy can effectively reduce the radiation dose and iodine intake,at the same time it can obtain the approximate image quality like conventional scanning.

Objective To explore a surgical method for the treatment of lumbosacral spinal tuberculosis by combination of one-stage focus debridement with anterolateral incision, bone graft fusion with titanium mesh cage and internal fixation with double pedicle crew system.Methods From Sep.2009 to Dec.2012, a total of 8 patients with lumbosacral spinal tuberculosis which included 5 cases of male, 3 cases of female.The age ranged from 20 to 65 years, with a mean of 51.6 years.All patients presented with persistent back pain, 4 patients with radiating pain of unilateral lower limb, 3 with weakness and numbness and 5 with constitutional symptoms including low-grade fever and weight loss.All patients were not associated with active tuberculosis in oth er parts of the body.The patients were given regular anti-TB treatment for at least 4 weeks.By anterolateral incision, common iliac and iliac arteries and veins were dissociated extraperitoneally.The focus was completely debrided through the inferior part of vessels.Then the bone graft fusion was performed with the titanium mesh cage and the internal fixation with a double pedicle crew system was accomplished.After the surgery, patients were treated with continuous anti-TB drugs and with antibiotics to prevent infection.Patients were allowed to move with the protection of waist early and regular follow-up.Results Operation time was 180-360 min, with an average of 225 min.Operative blood loss was 624 ml and drainage volume was 150 ml on average.All cases were cured after surgery.No severe complications were observed during the surgeries.After follow-up of 8 to 30 months (averaged 12months), no recurrence of the tuberculosis was found.The lumbocrural pain improved in all the patients.Complications such as migration, loosening and breaking of the implants were not observed.The vertebral bodies were fused in all patients with an average time of 8.3 months.No case occurred angiemphraxis or internal bleeding.Conclusion The method debrids the focus of lumbosacral spinal tuberculosis thoroughly and implements titanium mesh cage and double pedicle crew system simultaneously.The pedicle screw system is implemented in anterior lumbosacral vertebrae through the inferior part of iliac arteries and veins, which will not lead to angiemphraxis or vascular injuries.The early term outcome is encouraging.This technique is safe and effective to treat severe lumbosacral spinal tuberculosis.

BACKGROUND:Bisphosphonates that can suppress osteoclast activity strongly is a powerful inhibitor for bone resorption, which has been reported to have good effects in the treatment of fibrous dysplasia.
OBJECTIVE:To evaluate the clinical effect of surgical treatment combined with bisphosphonate therapy in the treatment of fibrous dysplasia.
METHODS: Fifteen patients with fibrous dysplasia of the long bone were subjected to surgical treatment and oral bisphosphonate therapy postoperatively. Limb pain, limb function, local X-ray manifestations and blood alkaline phosphatase activity were observed before and at 3, 6, 12, 24 months after treatment. The therapeutic effects were evaluated using modified Macnab standards.
RESULTS AND CONCLUSION:Al the 15 patients were folowed up for more than 24 months, and their pain symptoms were significantly relieved after the combined treatment of surgery and bisphosphonates, excelent in 12 cases and effective in 1 case, and the total efficiency was 100%. X-ray films showed that the density slightly decreased in operation areas after 3 months, but at 6 months after treatment, the cortical bone was thickened and the marrow cavity density increased in the operation areas, and non-focal zone was continuously enlarged. No fractures and recurrence were found in al patients. At 6 months after treatment, the serum alkaline phosphatase activity decreased significantly (P < 0.05). The results suggest that surgical operation with bisphosphonate treatment for bone fibrous dysplasia can effectively inhibit the bone resorption, promote bone formation, increase the intensity of the lesion, reduce fractures and recurrence rate, so as to achieve a better therapeutic effect in clinic.

PurposeTo explore the feasibility of personalized energy spectrum scanning in upper abdomen CT by comparing the image quality and radiation dose of optimizing choice spectrum scanning protocol with conventional 120 kVp scan.Material and Methods Sixty patients undergoing abdominal CT scan with and without contrast enhancement were prospectively collected and randomly assigned into two groups. Group A (30 patients) underwent conventional 120 kVp scan and spectral enhancement scanning; group B (30 patients) underwent spectrum scan and 120 kVp enhancement scanning. Spectral scanning protocol was based on individual choice with conventional 120 kVp NI10-5 mm average mAs scan for every patient. The CT dose index of volume (CTDIvol) and effective dose (ED) during non-contrast phase and portal venous phase were recorded. The CT value, standard deviation (SD), signal noise ratio (SNR) and contrast noise ratio (CNR) were measured in the liver parenchyma, spleen parenchyma and portal venous trunk.Results The CTDIvol and ED of spectrum scanning were less than 120 kVp scan but there was no statistical difference (P>0.05). The SD of group B GSI imaging was less than group A 120 kVp (P<0.05), while the SNR was greater than group A. The SD of group A GSI portal venous phase in the liver, spleen and portal vein was less than group B 120 kVp (P<0.05).ConclusionThe optimized energy spectrum scanning protocol can reduce radiation dose with quality of single energy image from the energy spectrum equal to or better than the conventional 120 kVp scanning protocol. Personalized energy spectrum scan protocol provides multi-parameter diagnosis and multi-application platform and can be used routinely in the upper abdomen scan.

Objective To investigate the role of human herpesvirus type 7 (HHV-7) in the development of drug eruptions.Methods Venous blood samples were collected from 35 patients with mild drug eruptions at acute stage,15 patients with severe drug eruptions at both acute stage and remission stage,as well as 50 healthy human controls.PCR was performed to detect HHV-7 DNA in peripheral blood mononuclear cells (PBMCs),and enzymelinked immunosorbent assay (ELISA) to determine the titer of anti-HHV-7 IgM antibody in serum.Statistical analysis was carried out by t test,one way analysis of variance,Chi-square test and q test.Results The detection rate of HHV-7 DNA was significantly higher in these patients with drug eruptions than in the healthy controls (82.00％ (41/50) vs.62.00％ (31/50),x2 =4.96,P ＜ 0.05),different among patients with severe drug eruptions (93.33％ (14/15)),patients with mild drug eruptions (77.14％ (27/35)) and the healthy controls (x2 =6.32,P ＜ 0.05),higher in the patients with severe drug eruptions than in the healthy controls (q =3.50,P ＜ 0.05),but not significantly different between the patients with severe drug eruptions at acute stage and those at remission stage (73.33％(11/15),P ＞ 0.05).The anti-HHV-7 IgM antibody titer was significantly increased in the patients with drug eruptions compared with the healthy controls ((69.319 0 ± 25.289 7) ng/L vs.(59.785 3 ± 22.438 2) ng/L,t =1.99,P ＜ 0.05),but no significant difference was observed among the patients with severe drug eruptions (74.340 7 ±31.411 2) ng/L),patients with mild drug eruptions ((65.479 1 ± 21.326 1) ng/L) and healthy controls (P ＞ 0.05) or between HHV-7 DNA-positive patients ((63.748 1 ± 27.239 1) ng/L) and-negative patients ((65.580 2 ± 36.258 4) ng/L,P ＞ 0.05).Conclusions Active HHV-7 infection exists in patients with drug eruptions,and may be associated with the development and aggravation of this entity.