C634Y mutation in RET-induced multiple endocrine neoplasia type 2A:A case report

BACKGROUND Multiple endocrine neoplasia type 2(MEN2)is a rare,autosomal dominant endocrine disease.Currently,the RET proto-oncogene is the only gene implicated in MEN2A pathogenesis.Once an RET carrier is detected,family members should be screened to enable early detection of medullary thyroid carcinoma,pheochromocytoma,and hyperparatitity.Among these,medullary thyroid carcinoma is the main factor responsible for patient mortality.Accordingly,delineating strategies to inform clinical follow-up and treatment plans based on genes is paramount for clinical practitioners.CASE SUMMARY Herein,we present RET proto-oncogene mutations,clinical characteristics,and treatment strategies in a family with MEN2A.A family study was conducted on patients diagnosed with MEN2A.DNA was extracted from the peripheral blood of family members,and first-generation exon sequencing of the RET protooncogene was conducted.The C634Y mutation was identified in three family members spanning three generations.Two patients were sequentially diagnosed with pheochromocytomas and bilateral medullary thyroid carcinomas.A 9-yearold child harboring the gene mutation was diagnosed with medullary thyroid carcinoma.Surgical resection of the tumors was performed.All family members were advised to undergo complete genetic testing related to the C634Y mutation,and the corresponding treatments administered based on test results and associated clinical guidelines.CONCLUSION Advancements in MEN2A research are important for familial management,assessment of medullary thyroid cancer invasive risk,and deciding surgical timing.

Value of shear wave elastography with maximal elasticity in differentiating benign and malignant solid focal liver lesions

BACKGROUND It is important to differentiate benign and malignant focal liver lesions(FLLs)accurately.Despite the wide use and acceptance of shear wave elastography(SWE),its value for assessing the elasticity of FLLs and differentiating benign and malignant FLLs is still investigational.Previous studies of SWE for FLLs used mean elasticity as the parameter to reflect the stiffness of FLLs.Considering the inhomogeneity of tumor stiffness,maximal elasticity(Emax)might be the suitable parameter to reflect the stiffness of FLLs and to differentiate malignant FLLs from benign ones.AIM To explore the value of SWE with Emax in differential diagnosis of solid FLLs.METHODS We included 104 solid FLLs in 95 patients and 50 healthy volunteers.All the subjects were examined using conventional ultrasound(US)and virtual touch tissue quantification(VTQ)imaging.A diagnosis of benign or malignant FLL was made using conventional US.Ten VTQ values were acquired after 10 consecutive measurements for each FLL and each normal liver,and the largest value was recorded as Emax.RESULTS There were 56 cases of malignant FLLs and 48 cases of benign FLLs in this study.Emax of malignant FLLs(3.29±0.88 m/s)was significantly higher than that of benign FLLs(1.30±0.46 m/s,P<0.01)and that of livers in healthy volunteers(1.15±0.17 m/s,P<0.01).The cut-off point of Emax was 1.945,and the area under the curve was 0.978.The sensitivity and specificity of Emax were 92.9%and 91.7%,respectively,higher(but not significantly)than those of conventional US(80.4%for sensitivity and 81.3%for specificity).Combined diagnosis of conventional US and Emax using parallel testing improved the sensitivity to 100%with specificity of 75%.CONCLUSION SWE is a convenient and easy method to obtain accurate stiffness information of solid FLLs.Emax is useful for differential diagnosis of FLLs,especially in combination with conventional US.

Differential diagnosis of different types of solid focal liver lesions using two-dimensional shear wave elastography

BACKGROUND The clinical management and prognosis differ between benign and malignant solid focal liver lesions(FLLs),as well as among different pathological types of malignant FLLs.Accurate diagnosis of the possible types of solid FLLs is important.Our previous study confirmed the value of shear wave elastography(SWE)using maximal elasticity(Emax)as the parameter in the differential diagnosis between benign and malignant FLLs.However,the value of SWE in the differential diagnosis among different pathological types of malignant FLLs has not been proved.AIM To explore the value of two-dimensional SWE(2D-SWE)using Emax in the differential diagnosis of FLLs,especially among different pathological types of malignant FLLs.METHODS All the patients enrolled in this study were diagnosed as benign,malignant or undetermined FLLs by conventional ultrasound.Emax of FLLs and the periphery of FLLs was measured using 2D-SWE and compared between benign and malignant FLLs or among different pathological types of malignant FLLs.RESULTS The study included 32 benign FLLs in 31 patients and 100 malignant FLLs in 96 patients,including 16 cholangiocellular carcinomas(CCCs),72 hepatocellular carcinomas(HCCs)and 12 liver metastases.Thirty-five FLLs were diagnosed as undetermined by conventional ultrasound.There were significant differences between Emax of malignant(2.21±0.57 m/s)and benign(1.59±0.37 m/s)FLLs(P=0.000),and between Emax of the periphery of malignant(1.52±0.39 m/s)and benign(1.36±0.44 m/s)FLLs(P=0.040).Emax of liver metastases(2.73±0.99 m/s)was significantly higher than that of CCCs(2.14±0.34 m/s)and HCCs(2.14±0.46 m/s)(P=0.002).The sensitivity,specificity and accuracy were 71.00%,84.38%and 74.24%respectively,using Emax>1.905 m/s(AUC 0.843)to diagnose as malignant and 23 of 35(65.74%)FLLs with undetermined diagnosis by conventional ultrasound were diagnosed correctly.CONCLUSION Malignant FLLs were stiffer than benign ones and liver metastases were stiffer than primary liver carcinomas.2D-SWE with Emax was a useful complement to conventional ultrasound for the differential diagnosis of FLLs.

Antenatal Diagnosis and Outcome of 12 Congenital Cystic Adenomatoid Malformation of Lung

Objective To investigate the ultrasonic detection probability, type, prenatal diagnosis, and outcome of congenital cystic adenomatoid malformation of lung （CCAM）. Methods In this retrospective study, all 12 cases which were diagnosed with suspected prenatal CC,4M over the period in the hospital were analyzed. Information on diagnosis time, types and progression of the lesions during pregnancy, the additional abnormalities, and the outcome of pregnancies were recorded.Results The positive rate of ultrasonic detection of CCAM was about 1.01‰ （1/11 124） before 28 gestation weeks. There were 1 case of type Ⅰ （8%）, 2 cases of type Ⅱ （17%） and 9 cases of type Ⅲ （75%）. Nine pregnancies were terminated and 2 cases were confirmed by pathology. Three neonates were alive and without any symptom now. Conclusions Type Ⅲ is the major type. Ultrasound examination during 20-28 weeks and following up, prenatal consultation, chromosome examination offetus, delivery with a pediatrician standing by, and all suspected neonates being investigated are recommended.

Novel hydroxymethylbilane synthase gene mutation identified and confirmed in a woman with acute intermittent porphyria:A case report

BACKGROUND Acute intermittent porphyria(AIP)is a rare autosomal dominant porphyrin metabolic disease caused by a mutation in the hydroxymethylbilane synthase(HMBS)gene.This study aimed to explore the clinical manifestations of a patient with AIP,to identify a novel HMBS gene mutation in the proband and some of her family members,and to confirm the pathogenicity of the variant.CASE SUMMARY A 22-year-old Chinese woman developed severe abdominal pain,lumbago,sinus tachycardia,epileptic seizure,hypertension,and weakness in lower limbs in March,2018.Biochemical examinations indicated hypohepatia and hyponatremia.Her last menstrual period was 45 d prior to admission,and she was unaware of the pregnancy,which was confirmed by a pregnancy test after admission.Sunlight exposure of her urine sample for 1 h turned it from yellow to wine red.Urinary porphyrin test result was positive.Based on these clinical manifestations,AIP was diagnosed.After increasing her daily glucose intake(250–300 g/d),abdominal pain was partially relieved.Three days after hospitalization,spontaneous vaginal bleeding occurred,which was confirmed as spontaneous abortion;thereafter,her clinical symptoms completely resolved.Genetic testing revealed a novel heterozygous splicing variant of the HMBS gene in exon 10(c.648_651+1delCCAGG)in the proband and four other family members.The pathogenicity of the variant was verified through bioinformatic methods and a minigene assay.CONCLUSION We identified a novel HMBS gene mutation in a Chinese patient with AIP and confirmed its pathogenicity.

The prognostic value of baseline circulating tumor cells in patients with metastatic breast cancer: a meta-analysis

Objective:The prognostic value of circulating tumor cells(CTCs)in metastatic breast cancer(MBC)patients was contentious.A meta-analysis was conducted to evaluate whether MBC patients’clinical outcomes could be predicted by CTCs detection.Methods:Relevant published studies were searched through electronic databases from January 1990 to February 2018,among which,those investigated the correlation between CTCs and clinical outcomes of progression-free survival and overall survival in MBC patients were involved.The hazard ratios(HR)and confidence intervals(CI)in the studies were extracted from the study using random or fixed effects model,and the meta-analysis was conducted.The prognostic value of tumor cells in patients with different subtypes was estimated by subgroup analysis.Results:Twenty-one eligible studies enrolling 3,837 patients were appropriate for pooled analysis.Progression-free survival(HR,1.66;95%CI,1.47–1.87;P=0.000)and overall survival(HR,2.51;95%CI,2.13–2.96;P=0.000)were worse in patients with CTCs-positive.Subtypes of hormone receptor(HorR)positive,human epidermal growth factor receptor-2(HER2)negative and triple negative with presence of CTCs showed a statistically significant worse PFS and OS.However,CTCs detection presented no prognostic value in patients with HorR-negative or HER2-positive subtypes.Conclusion:The enumeration of CTCs at baseline in patients with MBC subtypes of HorR-positive,HER2-negative and triple negative is connected with disease progression and poor survival,but inappropriate for HorR-negative and HER2-positive subtypes.

Implementing the communication for development strategy to improve knowledge and coverage of measles vaccination in western Chinese immunization programs:a before-and-after evaluation

Background:Communication for Development(C4D)is a strategy promoted by the United Nations Children’s Fund to foster positive and measurable changes at the individual,family,community,social,and policy levels of society.In western China,C4D activities have previously been conducted as part of province-level immunization programs.In this study,we evaluated the association of C4D with changes in parental knowledge of immunization services,measles disease,and measles vaccine,and changes in their children’s measles vaccine coverage.Methods:From April 2013 to April 2014,C4D activities were implemented as part of provincial immunization programs in the Inner Mongolia,Guangxi,Chongqing,Guizhou,Tibet,Shaanxi,Gansu,Ningxia,and Qinghai provinces.We used a before-and-after study design and employed face-to-face interviews to assess changes in parental knowledge and vaccination coverage.Results:We surveyed 2107 households at baseline and 2070 households after 1 year of C4D activities.Following C4D,95%of caregivers were aware of the vaccination record check requirement for entry into kindergarten and primary school;80%of caregivers were aware that migrant children were eligible for free vaccination;more than 70%of caregivers knew that measles is a respiratory infectious disease;and 90%of caregivers knew the symptoms of measles.Caregivers’willingness to take their children to the clinic for vaccination increased from 51.3%at baseline to 67.4%in the post-C4D survey.Coverage of one-dose measles-containing vaccine(MCV)increased from 83.8%at baseline to 90.1%after C4D.One-dose MCV coverage was greater than 95%in the Guangxi,Shaanxi,and Gansu provinces.Two-dose MCV coverage increased from 68.5 to 77.6%.House-to-house communication was the most popular C4D activity among caregivers(91.6%favoring),followed by posters and educational talks(64.8 and 49.9%favoring).Conclusions:C4D is associated with increased caregiver knowledge about measles,increased willingness to seek immunization services for their children,and increased measles vaccination coverage.Tailored communication strategies based on insights gained from these analyses may be able to increase vaccination coverage in hard-to-reach areas.C4D should be considered for larger scale implementation in China.