A novel iheyamine A derivative L42 suppresses acute myeloid leukemia via dual regulation of the PI3K/AKT/FOXO3a axis and TNF signaling pathway.

Acute myeloid leukemia (AML) is one of the most common hematopoietic malignancies and the development of new drugs is crucial for the treatment of this lethal disease. Iheyamine A is a nonmonoterpenoid azepinoindole alkaloid from the ascidian Polycitorella sp., and its anticancer mechanism has not been investigated in leukemias. Herein, we showed the significant antileukemic activity of L42 in AML cell lines HEL, HL-60 and THP-1. The IC50 values were 0.466±0.099 µM, 0.356±0.023 µM, 0.475±0.084 µM in the HEL, HL-60 and THP-1 cell lines, respectively, which were lower than the IC50 (2.594±0.271 µM) in the normal liver cell line HL-7702. Furthermore, L42 significantly inhibited the growth of peripheral blood mononuclear cells (PBMCs) from an AML patient. In vivo, L42 effectively suppressed leukemia progression in a mouse model induced by Friend murine leukemia virus (F-MuLV). Mechanistically, we showed that L42 induced cell cycle arrest and apoptosis in leukemia cell lines. RNA sequencing analysis of L42-treated THP-1 cells revealed that the differentially expressed genes (DEGs) were enriched in the cell cycle and apoptosis and predominantly enriched in the PI3K/AKT pathway. Accordingly, L42 decreased the expression of the phospho-PI3K (p85), phospho-AKT and phospho-FOXO3a. Docking and CETSA analysis indicated that L42 bound to the PI3K isoform p110α (PIK3CA), which was implicated in the suppression of the PI3K/AKT pathway. L42 was also shown to initiate the TNF signaling-mediated apoptosis. Moreover, L42 exhibited stronger anti-leukemia activity and sensitivity in IDH2-mutant HEL cells than in IDH2-wild-type control. In conclusion, L42 effectively suppresses cell proliferation and triggers apoptosis in AML cell lines in part through inhibition of the PI3K/AKT signaling pathway to restore FOXO3a expression and activation of the TNF signaling pathway. Thus, the iheyamine A derivative L42 represents a novel candidate for AML therapy.

Clinical study of Guishao Liujunzi Decoction with TCM mouthrinse for the treatment of Hp-associated gastritis / 中国现代医生

@#Objective To observe the clinical efficacy of Guishao Liujunzi Decoction combined with traditional Chinese medicine(TCM)mouthrinse in the treatment of helicobacter pylori(Hp)associated gastritis,and its effect on the Hp conversion rate.Methods Eighty patients with Hp-related gastritis were selected and randomly divided into the control group(standard quadruple therapy)and the treatment group(standard quadruple therapy combined with Guishao Liujunzi Decoction and TCM mouthrinse),with 40 patients in each group.The clinical efficacy,TCM syndrome scores,and Hp conversion rate of the two groups were observed.Results The total effective rate of the treatment group(95%)was higher than that of the control group(72.5%)(P<0.05).The Hp conversion rate in the treatment group(90%)was higher than that in the control group(72.5%)(P<0.05).After treatment,the main symptom scores and total scores of the two groups decreased compared to before treatment,and the treatment group was lower than the control group(P<0.05).Conclusion The combination of modified Guishao Liujunzi decoction and TCM mouthrinse in the treatment of Hp-related gastritis can significantly improve clinical efficacy and Hp negative conversion rate compared to conventional treatment.

Advances in acromelic dysplasia caused by FBN1 mutation / 国际儿科学杂志

The mutation of FBN1 gene results in the abnormality of its encoded fibrillin-1 protein, which affects musculoskeletal growth and results in two opposing phenotypes of tall and short stature, with clinical manifestations of Marfan syndrome and acromelic dysplasia.Acromelic dysplasia caused by FBN1 mutation includes acromicric dysplasia(AD), geleophysic dysplasia(GD)and Weill-Marchesani syndrome(WMS). As some FBN1 mutations have been reported to cause both AD and GD.The dysregulation of TGF-β signal pathway is the underlying mechanism of acromelic dysplasia.Currently, there is no specific treatment, mainly symptomatic treatment, early identification, diagnosis and treatment will improve prognosis of patients.This article will review the pathogenesis, clinical phenotype, treatment and follow-up of acromelic dysplasia caused by FBN1 mutation.

Advances in biomarkers related to multi-omics of idiopathic short stature / 国际儿科学杂志

Idiopathic short stature(ISS)is a group of short stature with unclear etiology and pathogenesis, of which the cause is heterogeneous and complex, primarily due to a combination of genetic and environmental factors.ISS is generally exclusionary diagnosis due to the lack of specific symptoms, signs and biomarkers.Recently, with the development of various high-throughput detection technologies, the study of transcriptomics, proteomics, metabolomics, and microbiomics related to ISS has gradually become a hot topic, providing new ideas for elucidating the etiology, making an early diagnosis, and guiding treatment of ISS.In this paper, advances in the pathogenesis and early diagnosis of ISS by biomarkers associated with multi-omics are reviewed.

Discussion on the indications and timing of targeted therapy and immunotherapy before and after liver transplantation for hepatocellular carcinoma / 器官移植

Liver transplantation is one of the main treatments of early hepatocellular carcinoma (HCC). The recurrence of HCC after liver transplantation severely affects the long-term survival rate of the recipients. Targeted therapy and immunotherapy play a critical role in HCC downstaging, preventing disease progression, reducing recurrence rate, prolonging the survival and improving the quality of life. However, no consensus has been reached on the application of targeted therapy and immunotherapy in recipients undergoing liver transplantation for HCC, including indications, timing and dosage. In this article, clinical research progresses on the indications and timing of targeted therapy and immunotherapy before and after liver transplantation for HCC were reviewed, aiming to provide reference for prolonging the survival of recipients after liver transplantation for HCC.

Progress of prognostic nutritional index in prognostic assessment after radical resection of colorectal cancer / 肿瘤研究与临床

The prognostic nutritional index (PNI) is an immune-nutritional index that contains both albumin and lymphocytes. The use of PNI to investigate the nutritional and immune status of patients before surgery to predict postoperative complications, prognosis and recurrence of colorectal cancer has important clinical significances. This review summarizes the application value of PNI in prognostic assessment after radical resection of colorectal cancer.

Clinical analysis of Epstein-Barr virus-associated lymphoproliferative disease in children / 国际儿科学杂志

Objective:To investigate the clinical features of Epstein-Barr virus associated lymphoproliferative disease in children and to improve the understanding of this disease.Methods:This study included the children with Epstein-Barr virus associated lymphoproliferative disease admitted to the First Affiliated Hospital of College of Medicine of Zhejiang University from January 2014 to December 2018.Data of these children were collected, including age, clinical manifestations, laboratory results, treatment and outcome.The clinical features and therapeutic effects were analyzed.Results:A total of 114 cases(mean age 6 years, 0~17 years)were enrolled in this study, including 53 males and 61 females.There were 107 cases(93.86%) in the mild group (38 cases of EBV infection and 69 cases of infectious mononucleosis) and 7 cases in the severe group (6.14%). Six cases of the severe group were T cell or NK cell proliferation.Compared with the mild group, the load of EBV-DNA was higher in the severe group, but there was no significant difference( χ2=0.957, P>0.05). The IgM in severe group was significantly lower( Z=-2.041, P<0.05). But the differences in the level of immune function including IgA, IgG, CD4 + cell and CD8 + cell between the severe group and the mild group were not significant.The cases in the mild group had improved after antiviral treatments.Among the severe group, 3 cases survived after treatment, another 1 case was diagnosed as hydroa vacciniforme-like EBV-related proliferative disease (HV-like LPD). After antiviral treatment, the effect was not good, then after high-dose IVIG treatment and Bortezomib combined with methylprednisolone treatment, the EBV-DNA load decreased and the condition improved.While 1 case lost to follow-up, there were 2 cases with EBV-associated hemophagocytic syndrome and 1 case with EBV-associated lymphoma died after chemotherapy or transplantation. Conclusion:EBV-associated lymphoproliferative disease may manifest as a condition similar to infectious mononucleosis.High IgE, low IgM or high DNA load may indicate poor prognosis.Immune function after EBV infection may have different effects on prognosis.When the infected lymphocyte types are NK or T cells, it may indicate poor prognosis.The efficacy of transplantation and chemotherapy in severe cases is still uncertain.

Advance in autoimmune diseases related to Turner syndrome / 国际儿科学杂志

Turner syndrome(TS)results from a sex-chromosomal anomaly characterized by presence of one normal X chromosome and the loss of the second X-chromosome in phenotypic females.The typical clinical manifestations of Turner syndrome are short stature, hypogonadal dysplasia, and special physical characteristics(such as neck web, shield chest, elbow valgus, etc.). And it is related to the risk of autoimmune diseases, such as autoimmune thyroiditis, celiac disease, type 1 diabetes, inflammatory bowel disease, alopecia areata or vitiligo.This review will address the autoimmune disorders associated with TS, their pathophysiologic mechanisms and clinical characteristics.

Advance in genetic research on Gitelman syndrome / 中华医学遗传学杂志

With an estimated incidence of 1/40 000 to 1/4000, Gitelman syndrome is the most common type of inherited renal tubular disease during adolescence or adulthood. Characteristic features of Gitelman syndrome include transient episodes of muscle cramps and fatigue, hypokalemia, hypomagnesemia, hypocalciuria, and metabolic alkalosis. Detection of SLC12A3 mutations, in conjunct with clinical manifestations, may confirm the diagnosis. Recent research suggested that CLCNKB may also be a candidate gene for Gitelman syndrome. Research on genotype-phenotype correlation has provided more information on the genetic etiology of Gitelman syndrome, which may facilitate the diagnosis and treatment for this syndrome and improve their prognosis.

The etiology and therapeutic strategies of premature ovarian insufficiency in children and adolescents / 国际儿科学杂志

Premature ovarian insufficiency(POI), previously known as premature ovarian failure(POF), is defined as the occurrence of premature ovarian failure in women under the age of 40 who may present with delayed puberty, primary or secondary(for 4 months or more)amenorrhea with two times and more of abnormal serum hormonal levels(low estradiol and raised gonadotrophins). And POI is not common in children and adolescents.It is generally believed that the etiologies of POI may be genetic, immunological, iatrogenic, etc.Hormone replacement therapy(HRT)is the primary treatment of POI in children and adolescents, and evaluation of therapeutic strategies to POI including cardiovascular, skeletal and emotional health is needed as well.Recently, the incidence of POI in children and adolescents has increased, therefore, early diagnosis and active treatment are urgent and necessary.Thus, this review will mainly be focused on the etiology and treatment of POI in children and adolescents.

Aromatase inhibitors combined with growth hormone in treatment of adolescent boys with short stature / 浙江大学学报·医学版

OBJECTIVE@#To assess the efficacy and safety of aromatase inhibitors (AIs) combined growth hormone in treatment of adolescent boys with short stature.@*METHODS@#One hundred and fifty-one short stature pubertal boys with age of 10-14 years and bone age of 13-15 years, who were admitted to the Department of Pediatrics, the First Affiliated Hospital, Zhejiang University School of Medicine, were included in this trial. According to their own or parents' intention, the children were divided into recombinant human growth hormone (rhGH)+AI group ( =108) and rhGH group ( =43). All children were injected subcutaneously with rhGH 0.15-0.2 IU·kg ·d , and those in rhGH+AI group were additionally given 2.5 mg/d letrozole or 1 mg/d anastrozole, orally for 12 months or longer. The children were followed-up every 3 months. During the follow-up visit, the predicted adult height (PAH), sex hormone level, glucose and lipid metabolism, and other indicators were measured, and adverse reactions were monitored.@*RESULTS@#After intervention, there were significant differences in ΔBA(bone age)/ΔCA(chronological age), ΔHtSDS (height standard deviation score based on bone age)and ΔPAH between rhGH+AI group and the rhGH group( < 0.05 or < 0.01). During follow-up, 63.9%of the children in the rhGH+AI group had elevated uric acid and 51.9%had decreased high-density lipoprotein (HDL); 25.9%showed severe acne, excitement, hyperactivity and irritability, 11.1%had knee pain; 4.6%had fracture; 2.8%had mild renal dysfunction; 1.9%had inactivity, drowsiness, memory loss and performance decline; 1.9%showed mild abnormal liver function; 0.9%showed impaired fasting glucose; 0.9%showed granulocytopenia. In the rhGH group, 11.6%of the children presented with knee pain and 2.3%with impaired fasting glucose.@*CONCLUSIONS@#AI combined with rhGH can delay the growth of BA and effectively improve the PAH of adolescent boys with larger bone age. However, the occurrence of adverse reactions of AI should be closely monitored during treatment.

Reconsideration of the third-generation non-steroidal aromatase inhibitors in pediatrics / 浙江大学学报·医学版

Aromatase is the rate-limiting enzyme in estrogen biosynthesis. The third generation aromatase inhibitors (AIs), represented by letrozoleand and anastrozole, can combine with aromatase, effectively reducing the estrogen level in the body. Because of its high efficiency, selectivity and reversibility, it has been used in the treatment of McCune-Albright syndrome, familial male-limited precocious puberty, gynecomastia, and adolescent boy with short stature. The good efficacy and safety of AIs have been observed. However, so far the drug instructions of AIs usually do not show indications for children; there are risks of adverse reactions involving liver and kidney function, lipid metabolism, hyperandrogenemia and bone metabolism; especially the long-term effects on reproductive system and bone metabolism are still not clear. Therefore, it is necessary to prescribe it carefully and follow up closely. It was not recommended that AIs be routinely used to improve adult height of adolescent boy with short stature. And more clinical evidences are needed for the safety and effectiveness of AIs prescribed in pediatrics.

Mutation analysis of AAAS gene in a child with Allgrove syndrome / 中华内分泌代谢杂志

Objective To study the AAAS gene mutations in a child with autosomal recessive Allgrove syndrome. Methods Clinical data were collected and blood samples were obtained from the proband of Allgrove syndrome and her parents. Genomic DNA was extracted and sequenced by PCR amplification. Subclone sequencing was performed to validate the gene mutations. The disease-causing potentials of mutation genes were evaluated by the Mutation Taster, and the target protein tertiary structure was modelled by the Swiss Model. Results A new heterozygous insertion mutation(c. 1347_1348insG) of exon 15 in the proband was identified and firstly reported. Other two reported mutations were detected, which were the heterozygous mutation c. 688C>T in the patient and her mother, and the homozygous mutation c. 855C>T in the proband and her parents. In addition, it was confirmed that the novel compound heterozygous mutations(c. 688C>T, c. 1347_1348insG) in the AAAS gene of the proband were pathogenic mutation locus. Conclusion The heterozygous mutation(c. 1347_1348insG) of AAAS gene was firstly reported. In case of the patients being clinically misdiagnosed, related-gene detection should be performed for the patients who were diagnosed with primary adrenal insufficiency during the period of infants and young childhood.

Immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome in two cases / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To report on two cases affected with immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX).</p><p><b>METHODS</b>Two unrelated Chinese infants affected with IPEX were investigated. Case 1 was a 4-month-old boy with neonatal diabetes and severe enteropathy. Case 2 was a 6-day newborn boy with neonatal diabetes and ketoacidosis. DNA samples of the two infants and their parents were sequenced for FOXP3 gene mutations. Suspected mutations were verified among 100 unrelated healthy controls. The function of mutations was predicted with bioinformatics software.</p><p><b>RESULTS</b>Both infants had onset of the disease during neonatal period, and manifested insulin-dependent diabetes mellitus, persistent diarrhea, eczema and malnutrition. In case 1, a novel splice site mutation was identified in intron 9 (c.967+3A>T) of the FOXP3 gene, for which his mother was a carrier. For case 2, a missense mutation (c.1150G>A) was detected in exon 11 of the FOXP3 gene, for which his mother was also a carrier. The IVS9 c.967+3A mutation was not detected among the 100 healthy controls. As predicted with Human Splicing Finder software, the c.967+3A>T mutation may influence the splicing of mRNA and affect the function of protein.</p><p><b>CONCLUSION</b>Both cases had typical clinical manifestation of the IPEX syndrome, among whom a novel splice site mutation (IVS9 c.967+3A>T) and a missense mutation (c.1150G>A) of the FOXP3 gene were identified. The clinical manifestation of the IPEX syndrome may be variable and the mortality is high. FOXP3 gene sequencing is recommended when insulin-dependent diabetes mellitus is diagnosed during the neonatal period.</p>

Application of combination of intraoperative neuroelectrophysiological monitoring and neuronavigation multi-modal fusion technology in the glioma resection / 中国神经精神疾病杂志

Objective To analyze the application of intraoperative neurophysiological monitoring combined with neuronavigation multi-modal fusion technology in the brainstem glioma resection. Methods One hundred twenty patients with brainstem glioma were divided into observation group and control group. The control group was treated by traditional operation, while the observation group was treated by intraoperative nerve electrophysiological monitoring combined with neuronavigation multimodal fusion technology. The general condition, clinical efficacy, KPS score, complications and survival rate of the two groups were compared. Results The effect was significantly better in the observation group(76.66%)than in control group(53.33%)( x2=11.962,P=0.001).KPS scores were significantly higher in the observation group (27.91 ±1.98) than in the control group (12.11 ±2.13)(t=32.669, P<0.001). Conclusions Intraoperative nerve electrophysiological monitoring plus neuronavigation multimodality fusion technology can improve clinical efficacy and quality of life in patients with brainstem glioma.

Contrast-enhanced ultrasound predicts the long-term prognosis of chronic kidney disease patients / 中华肾脏病杂志

Objective To evaluate the ability of contrast-enhanced ultrasound (CEUS) as a prognostic indicator of renal function in chronic kidney disease (CKD) patients.Methods A total of 122 patients with CKD were collected,and patients with allergies to sulfur hexafluoride,pregnancy,cardiopulmonary insufficiency,urinary calculus and tumour were excluded.These patients were divided into estimated glomerular filtration rate [eGFR,ml·min1· (1.73 m2)-1] ≥60 group,eGFR 30-59 group and eGFR ＜ 30 group.CEUS was performed after an intravenous bolus injection of 1.5 ml SonoVue (BR1;Bracco Milan,Italy).Time-intensity curves (TICs) and quantitative indexes were created using QLAB quantification software.Followed up for 2 years,and patients with eGFR dropped 50％,double serum creatinine and end-stage renal disease (ESRD) were regarded as having kidney failure events.Risk factors related to kidney survival were investigated using a multivariate Cox regression model.Results One hundred patients were enrolled in the study,with 78％ patients in CKD 1-2 stages,16％ in CKD 3 stage and 6％ in CKD 4-5 stages.Patients were followed for a mean period of 14.1 months,ten (10％) patients exhibited composite kidney failure events.Among 3 groups,significant differences in the left kidney length derived peak intensity (DPI) were noted (P=0.014,P=0.010).Multivariate Cox regression analysis revealed that the DPI was an independent factor of progression of kidney disease.Multiple linear regression showed that age,basic eGFR,peak intensity were associated with eGFR decline rate.Patients with DPI ＜ 12.27 db were less to recover from kidney disease progression as compared with patients with DPI≥ 12.27 db (P=0.008).The area under the curve (AUC) for DPI was 0.778(95％ CI 0.612-0.944,P＜ 0.05),with a sensitivity of 64％ and a specificity of 88％.Conclusions The DPI might be the most valuable CEUS parameter for the evaluation of renal function.The DPI could serve as an independent predictor of the long-term prognosis of CKD patients.

miR-498 inhibits A549 cell migration and invasion by down-regulating FOXM1 / 西安交通大学学报(医学版)

Objective To verify whether miR-498 can inhibit A549 cell migration and invasion by down-regulating FOXM1.Methods miR-498 mimic and miR-NC were transfected into A549 cells.Wound healing and Transwell method were employed to test the migratory ability and invasion ability of A549 cells;Western blot was used to detect the expressions of COL1A1,COL1A5 and FOXM1 in A549 cells.Luciferase assay was used to confirm whether FOXM1 is the target gene of miR-498.Results Compared with those in the control group,the expressions of COL1A1,COL1A5 and FOXM1 were decreased,and the migration and invasion abilities of A549 cells were decreased in the miR-498 group (both P<0 .01 ).The luciferase activity of the FOXM1-3′-UTR plasmid was significantly suppressed by miR-498 (P<0 .05 );over-expression of FOXM1 could reverse the effect of miR-498 on A549 cells.Conclusion miR-498 inhibits A549 cell migration and invasion by down-regulating FOXM1.

Discuss the TCM Noematic Way of Double Heart Disease From the View of Wu Zang Yi Ti / 浙江中医药大学学报

[Objective] To discuss treatment according to syndrome differention of TCM (traditional Chinese medicine) on double heart disease from the view of Wu Zang Yi Ti.[Method] Based on the theory of Wu Zang Yi Ti from Huangdi Nei Jing and many ancient doctors,discuss the relation between heart and sense,heart and the other four viscera,and treat double heart disease from the etiology and pathogenesis of liver,spleen,kidney,lung and the contact of emotion and five viscera.[Result] The heart is closely related with emotional changes and plays a key role in emotion and viscer.Emotional disorders can promote the progress of double heart disease.So we must base on the characteristics of clinical syndromes when we treat the double heart disease and determine treatment from liver,spleen,kidney and lung.[Conclusion] Discriminating and treating double heart disease from the view of Wu Zang Yi Ti can help us grasp the etiology and pathogenesis of double heart disease better and hold the essence of the disease,so we can achieve the goal of curing for disease roots,and treating both root causes and symptoms.It is helpful to improve the clinical curative effect and improve the quality of life of patients with double heart disease.

Association of PA X 4 R192S and R192H polymorphism with obesity in children and adolescents / 临床儿科杂志

Objective To investigate association of the paired box 4 (PA X 4) gene rs3824004 (574C>A; R192S) and rs2233580 (575G>A; R192H) polymorphism with obesity and metabolic markers in children and adolescents. Methods A total of 103 obese children were randomly selected, and an average age was (10.82±2.57) years, and body mass index (BMI) was (26.82±4.57) kg/m2. At the same period, 100 normal weight children were selected as the control group, and an average age of (10.60±2.84) years, and BMI was (16.79±2.13) kg/m2. The blood pressure, physical measurements, and blood metabolic parameters were measured and compared. The oral glucose tolerance test (OGTT) and insulin release test were performed in the obesity group. The homeostasis model insulin resistance index (HOMA-IR) and the overall insulin sensitivity index (WBISI) were calculated. PA X 4 rs3824004 and rs2233580 polymorphism were detected by PCR.The differences of allele frequency and genotype frequency of polymorphic loci were analyzed, and the correlation between different genotypes and metabolic indexes was analyzed. Results The height, weight, BMI, systolic blood pressure, diastolic blood pressure, waist circumference, hip circumference, waist to height ratio (WHtR), fasting blood glucose (FPG), total cholesterol (TC), low density lipoprotein (LDL), triacylglycerol (TG), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) in the obesity group were significantly higher than those in the control group, and the high density lipoprotein (HDL) was significantly lower than that in the control group (all P<0.05). The frequency of gene distribution was in accordance with the Hard-Weinberg balance. The frequencies of A allele of rs3824004 in obesity and control groups were 4.9% and 5.0%, respectively, and the frequencies of CA genotype were 9.7% and 10.0%, respectively, and there was no significant difference between two groups (P>0.05). The frequency of GA allele of rs2233580 in obesity group was 25.2%, which was significantly higher than that in control group (P<0.05). The BMI and waist in rs2233580 GA genotype were significantly higher than those in GG genotype (all P <0.05). However,logistic regression analysis showed that there was no correlation between PA X 4 rs2233580 genotype and metabolic markers (all P>0.05).There were no significantly differences in HOMA-IR and WBISI among different genotypes of PA X 4 rs2233580 in obesity group(all P>0.05).Conclusions PA X 4 rs2233580 affects children's BMI and waist circumference and may be involved in the development of childhood obesity, but it is not an independent risk factor for obesity in children and adolescents.

Iodine 131 joint radio frequency ablation treatment for child with hyperthyroidism goiter: one case report / 浙江大学学报·医学版

A 12-year-old girl presented with a history of cervical mass, and one week of throat discomfort and dyspnea. Five years ago, the patient was diagnosed as Hashimoto's thyroiditis and hyperthyroidism; she received antithyroid drug treatment, but the result was not satisfactory. B-ultrasonic showed that the size of thyroid gland was 8.1 cm×3.2 cm in the left and 8.2 cm×4.8 cm in the right. After iodine 131 combined with radiofrequency ablation (RFA) treatment, throat discomfort and recumbent breathing difficulties disappeared, and B-ultrasonic showed that the size of thyroid reduced to 2.3 cm×1.7 cm (left) and 2.8 cm×2.0 cm (right). No recurrence was observed during the two and a half years of follow-up.