Objective: To explore the clinical phenotypes and the genetic causes for a 5 years old boy with unexplained growth retardation, developmental delay, special face, and hypothyroidism. Methods: Routine G-banding was performed to analyze the karyotype of the patient and his parents. In addition, whole exome sequencing and low-coverage massively parallel CNV sequencing (CNV-seq) were used to determine the potentially pathogenic variants as well as the copy number variations (CNVs). Results: The child′s karyotype was 46, XY, and his parents′ karyotypes were normal.However, CNV-seq identified a heterozygous deletion of 1.56 Mb on chromosome region 7q11.23 in the patient, including 24 protein-coding genes, which were associated with Williams-Beuren syndrome. His parents′ results of CNV-seq were normal, indicating a de novo CNVs. Conclusion A Williams-Beuren syndrome child presenting with hypothyroidism was diagnosed by CNV-seq, which would contribute to further understanding the clinical phenotypes and pathogenesis of this disease.

Objective: To study the role of corticotropin-releasing hormone (CRH) system in locus ceruleus (LC) in irritable bowel syndrome (IBS) and to explore its molecular mechanism. Methods: The IBS rat was established by maternal separation following with postnatal stress. The tissues sample of LC was obtained by micropunched nuclei. The expression of c-Fos, CRH and its receptors including corticotropin-releasing hormone receptor (CRHR) 1 and CRHR2 of rats’ LC tissues of control group and IBS group was detected by quantitative polymerase chain reaction(PCR). The expression of DNA methyltransferase (DNTM) 1, DNMT3a and DNMT3b at the mRNA level were also measured. In addition, the expression of histone methyltransferase ASH2-like protein (ASH2L) and SET and MYND domain containing 2 (SMYD2) was determined by Western blotting. T test was used for statistical analysis. Results: The rectal pneumatic pressure of IBS group was lower than that of control group ((69.82±5.47) mmHg vs. (86.86±5.98) mmHg; 1 mmHg=0.133 kPa), however compared with that of control group, the expression of c-Fos at the mRNA level increased (2.11±0.44 vs.1.00±0.19), and the differences were statistically significant (t=6.215 and 2.321, P<0.01 and 0.05). In addition, compared with that of control group, the expression of CRH at the mRNA level increased (1.99±0.35 vs.1.00±0.13), and the difference was statistically significant (t= 2.797, P<0.05). Compared with that of control group, the expression of SMYD2 at the protein level up-regulated (1.04±0.21 vs. 0.61±0.12), and the difference was statistically significant (t=4.451, P<0.01). However, there were no statistically significant differences in the expression of CRHR-1, CRHR2, DNMT1, DNMT3a, DNMT3b at the mRNA level, and the expression of ASH2L between IBS group and control group (0.96±0.13 vs. 1.00±0.26, 1.35±0.63 vs. 1.00±0.43, 1.40±0.61 vs.1.00±0.19, 1.39±0.58 vs. 1.00±0.21, 1.45±0.71vs.1.00±0.39 and 0.80±0.19 vs. 1.05±0.26, respectively; all P>0.05). Conclusions Maternal separation combined with postnatal stress affect the transcription of Crh gene in LC and cause the activation of the stress regulation network CRH and norepinephrine system, resulting in the increase of the visceral sensitivity of rats. The abnormal transcription of Crh gene may be related with SMYD2-mediated histone H3K36 methylation, but not related with the modification of DNA methylation.

Objective: To investigate the safety and feasibility of proximal partial gastrectomy with Cheng's Giraffe esophagogastric reconstruction for the treatment of early Siewert II adenocarcinoma of esophagogastric junction (AEG). Methods: Indication of Cheng's Giraffe esophagogastric reconstruction: (1) Siewert II AEG or Siewert III AEG with diameter < 4 cm; (2) preoperative staging as cT1-2N0M0. A descriptive case series study was carried out. Clinical data of 34 patients with Siewert II AEG undergoing proximal partial gastrectomy and Cheng's Giraffe esophagogastric reconstruction at Department of Abdominal Surgery of Zhejiang Cancer Hospital and Department of Gastrointestinal Surgery, The First Affiliated Hospital of Zhejiang University of Traditional Chinese Medicine from February to July 2018 were retrospectively collected and analyzed, including 14 cases in IA stage, 11 cases in IIA stage and 8 cases in IIB stage. Brief procedure of Cheng's Giraffe esophagogastric reconstruction was as follows: Firstly, 12 cm long tubular stomach was formed by longitudinal incision 4 cm away from the great curvature of the stomach. Secondly, the gastric fundus and His angle were formed. Finally, the distance from His angle to esophagal-tubular gastric anastomosis should be more than 5 cm. The reflux disease questionare (RDQ) scores, radionuclide gastric emptying scintigraphy, and 24-hour multichannel intraluminal (MII)-pH monitoring technology were used to evaluate postoperative gastric emptying and gastroesophageal reflux. Result: All 34 patients successfully completed proximal partial gastrectomy with Cheng's Giraffe esophagogastric reconstruction, including 13 cases by open surgery and 21 cases by laparoscopic surgery. The operation time was (144.6±39.8) minutes, the blood loss during operation was (35.4±17.2) ml. No laparoscopic case was converted to open surgery and no postoperative complication was observed. The postoperative hospital stay was (8.4±2.5) days. The postoperative RDQ score was 4.4±3.1 one month after operation, and 3.3±2.5 six months after operation. Gastric-half emptying time was (67.0±21.5) minutes, and the residual ratio was (52.2±7.7)% in 1 hour, (36.4±3.1)% in 2 hours and (28.8±3.6)% in 3 hours at postoperative 1-month. The 24-hour MII-pH monitoring at postoperative 2-month revealed the frequency of acid reflux was (12.6±7.9) times, frequency of non-acid reflux was (19.6±9.7) times, DeMeester score was 5.8±2.9. Conclusion Cheng's Giraffe esophagogastric reconstruction is safe and feasible in the treatment of Siewert type II AEG, and has good dynamic and anti-reflux effects.

Objective To evaluate the feasibility of replacing the fixed jaw 2.5 cm mode with dynamic jaw 5.0 cm for mid-esophageal cancer after the upgrade of helical tomotherapy (TOMO).Methods A total of 10 patients with locally advanced esophageal cancer were planned with radical intent using 2.5 cm fixed jaw (FJ2.5),2.5 cm dynamic jaw (DJ2.5) and 5.0 cm dynamic jaw (DJ 5.0) modes respectively on TOMO.Dose conformity index (CI),dose homogeneity index (HI) and dose to OARs were analyzed to evaluate the plan quality.Treatment time and monitor units were used to assess efficiency.Results CI and HI met clinical requirement for all plans.D J5.0 plans showed significant improvement over FJ2.5 plans in terms of V5 and mean dose to lungs,the V5,V10 and mean dose to normal tissues (t =9.751,4.163,11.840,10.321,3.745,P＜0.05).DJ2.5 plans were superior to DJ5.0 plans in the aspects of the V30,V40 and mean dose to heart,the V20 and mean dose to normal tissues (-2.454,-3.275,-4.192,-6.435,-4.139,-6.431,P＜0.05).Compared with DJ2.5 plans,the V5,V20,V30 and mean dose to lungs,the V4 0and mean dose to heart,maximum dose to cord and cord PRV,the V5,V10,V20 and mean dose to normal tissues of FJ2.5 plans were worse (t=8.289,6.142,3.137,8.895,3.597,4.565,3.782,5.429,16.421,12.496,8.286,11.933,P＜0.05).The beam-on time of DJ5.0 plans was significantly reduced by 43.9％ and 42.8％ compared with FJ2.5 and DJ2.5 plans respectively,and the machine monitor unit was reduced by 42.8％ and 43.8％ respectively.Conclusions The dynamic jaw of 5.0 cm technique is recommended for treatment of mid-esophageal cancer for sake of plan quality and efficiency.It does not only shorten the treatment time and improve radiation efficiency compared with fixed and dynamic jaw of 2.5 cm technique,but also provides a dosimetric advantage in terms of lung and normal tissue sparing in comparison with fixed jaw of 2.5 cm.When only improving plan quality is concerned,the dynamic jaw of 2.5 cm technique is more recommendable.

Objective To evaluate the dosimetric penumbra and delivery accuracy of dynamic jaw delivery in tomotberapy.Methods The jaw positioning hardware and the beam model were updated.Mechanical alignments were verified after the upgrade of the jaw positioning hardware.PDDs and beam profiles were measured by a two-dimensional water tank and compared with the new beam model.Dose penumbras in the longitudinal direction were compared between the dynamic and fixed jaw plans for different field width.Delivery accuracy was evaluated by point dose measurements with A1SL chamber and gamma analysis on the dose distribution measured by ArcCheck detector array.Results Mechanical alignments were in tolerance and beam characteristics were tuned to match the dynamic jaw beam model.Differences in the field width between the measured results and reference data were ＜ 0.3％ for both symmetric and asymmetric profiles in the longitudinal direction.The dose penumbra in dynamic jaw delivery was reduced from 17.92 mm to 7.51 mm for 2.5 cm jaw,and from 33.73 mm to 6.97 mm for 5.0 cm jaw,close to the penumbra of the traditional 1.0 cm jaw.IMRT verification of clinical cases was performed by A1SL ion chamber and ArcCheck detector array.The mean point dose difference was 0.33％ ± 0.73％ between the calculated and meassured data.Gamma analysis of dose distributions revealed that approximately 99.8％ of the points satisfied the gamma criteria of 3％ dose difference and 3 mm distance-to-agreement and the mean passing rates remained 97.9％ even with tightest criteria of 2％/2 mm,and 100.0％ with the criteria of 4％/4 mm,respectively.Conclusions Dosimetric penumbra in the longitudinal direction is significantly improved by the dynamic jaw delivery.Both the mechanical alignment and treatment delivery are qualified,suggesting that this new treatment is accurate and reliable.

Objective To investigate the safety and efficacy of wide local excision surgery combined with 5-aminolaevulinic acid(ALA)-photodynamic therapy(PDT)in treating Paget's disease of the scrotum in elderly people.Methods Patients with an average age of 68.4 ± 4.7 years undergoing wide local excision surgery combined with ALA-PDT for Paget's disease of the scrotum from June 2014 to February 2018 were followed up.All patients underwent wide local excision surgical treatment first and were then enrolled in ALA-PDT study after the diagnosis of Paget's disease of the scrotum was confirmed.Four cases were eliminated as a result of two patients refusing photodynamictherapy for various reasons and two patients lost during follow-up after ALA-PDT.A total of 16 patients were included in the study,of whom 6 cases were in Ray stage A1,7 cases in stage A2 and 3 cases in stage B.Patients underwent 3 courses of ALA-PDT after operation.Then the efficacy,shortand medium-term complications were followed up.Results The duration of disease among the 16 patients ranged from 4 to 76 months before diagnosis,with an average of 35.7 months.Surgery was performed immediately after diagnosis.Ten patients underwent resection and suture and 6 patients were treated with skin flap transfers.Of the patients treated with surgery,3 patients received suspicious lymph node dissection and 1 patient underwent reoperation due to skin flap necrosis.Patients were followed up for 3 months to 3 years and 6 months after ALA-PDT.Recurrence and distant metastasis occurred in 2 cases,with 1 case of brain metastasis and 1 case of systemic metastasis,and the overall recurrence rate was 12.5％.During the follow-up,there were no other serious complications except for 1 case(6.3 ％)with lower limb movement disorders.Conclusions Wide local excision surgery combined ALA-PDT has good clinical outcomes,low recurrence rates and few complications for the treatment of Paget's disease of the scrotum in elderly people.

To explore the clinical significance of C1q tumor necrosis factor-related protein-9 (CTRP9) in patients with cerebral infarction.Our data showed that the serum CTRP9 was significantly lower than that of control group,especially in patients with large artery atherosclerotic cerebral infarction.CTRP9 was first decreased and even lower from day 4 to day 10,then gradually elevated.Logistic regression analysis suggested that high CTRP9 level was a protective factor for cerebral infarction.Thus,CTRP9 could be a factor for further classification of cerebral infarction and provides a potential option for disease prevention and treatment.

Objective Human milk of mothers with positive hepatitis B surface antigen (HBsAg) contains hepatitis B virus (HBV). However, breastfeeding does not increase the risk of mother-to-infant transmission of HBV. Previous investigations demonstrated that breast milk has a property of binding with HBsAg. This study aimed to identify the component in human milk that can bind to HBsAg. Methods This study was performed in Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, from June 2015 to February 2017. Human milk samples from two postpartum women with negative HBV markers and two control samples of cow milk and goat milk were analyzed by Far-Western blot, in which highly purified recombinant yeast HBsAg was used to bind with whey proteins. Based on the results of mass-spectrum analysis, competition inhibition test was used to confirm the functioning component. Results Far-Western blot showed remarkable protein bands at the relative molecular weight of about 80 000 in both lanes of human milk, but none in the lane of cow or goat milk. Mass-spectrum analysis of the protein band indicated there were proteins sharing 28.4%-93.4% homology in amino acid sequences with five proteins with the highest homology to lactoferrin (93.4%). Further Far-Western blot with purified recombinant lactoferrin showed that lactoferrin could bind to the recombinant HBsAg. Competition inhibition test suggested that the purified recombinant lactoferrin inhibited the binding of HBsAg to its antibody in a dose-dependent manner. Conclusions This study confirms the capability of lactoferrin in human milk to combine with HBsAg, suggesting that lactoferrin can bind to HBV. Further study on whether lactoferrin can inhibit the infectivity of HBV would be valuable to clarify the reason for not increasing the risk of mother-to-infant transmission of HBV by breastfeeding.

Objective To investigate the effect of hyperbaric-oxygen therapy on osteoprotegerin (OPG) and integrin β1 (Itgβ1 ) expression during mandibular distraction osteogenesis .Methods Forty New-Zealand rabbits were used .The animals were randomly divided into two groups (experimental group and control group) with 20 animals each ;after accomplished osteotomy and implant distraction devices on mandible bilaterally for 3 days of latency period ,the device was activated at the rate of 0 .8 mm per day for 10 days .All animals in the experimental group were subjected to hyperbaric oxy -gen for 90 minutes once a day since the beginning of distraction ,and lasted for four weeks .In control group ,all the distractors were activated following the same distraction protocol as the experimental group ,but without hyperbaric oxygen therapy .Five animals of each group were sacrificed at 10th day after distraction ,7th ,14th and 28th day of consolidation , respectively .The lengthened mandibles were harvested and processed for immunohistochemical examinations to detect OPG and Itg β1 expres-sion in the distraction gap .Semi-quantitative analysis was carried out by image analysis software . Results OPG staining was mainly located in the membrane and cytoplasm of osteoprogenitor cells and osteoblasts in the distraction zones .The expression of OPG increased after distraction accomplished and reached to the peak at 7th day of consolidation ,and then decreased gradually .At every time point , the level of expression of OPG in the experimental group was remarkably higher than those in control group .There were significant differences between the experimental group and control group ( P <0 .01) .Itgβ1 mainly located in actively proliferating osteoblasts ,fibroblasts and mesenchymal cells . The expression of Itgβ1 decreased significantly after reached to the peak at the 10th day distraction .At 10th day distraction ,7th and 14th day of consolidation ,Itgβ1 expressed more strongly than that in the experimental group ,which was remarkably higher than those in control group .There were significant differences between experimental group and control group (P < 0 .05) .At 28th day of consolidation , Itgβ1 expressed weakly ; there was no significant difference between the two groups ( P > 0 .05 ) . Conclusions Hyperbaric oxygen therapy can up-regulate the expression of OPG and Itgβ1 in the dis-traction gap ,which may promote osteoblast differentiation ,proliferation ,enhance osteoblast func-tion ,and new bone formation in distraction gap .

Objective To learn the intention and demand of nurses of cancer hospitals to train abroad, so as to promote international exchange and management of nursing work. Methods Investigation was carried out by self-designed questionnaires among the nurses at the cancer hospital.The questionnaire covered the basic information of the nurses, the intention and demand of studying abroad, and information of those who have completed study abroad. The differences among different age groups were compared by descriptive statistics and χ2 test. Results Of the 700 people surveyed, 71.7% (502/700) of the nurses expect to study and train abroad.Their main purpose was to learn new nursing skills, new knowledge and nursing supervision methods.Nurses expect to study and train abroad for updating their concepts, promoting nursing skills, improving their command of a foreign language, and enhancing knowledge update ability. 54.9% (384/700)of the respondents were found with concerns for studying abroad.67.4% (33/49) of the respondents had the assessments after returning home. And 69.4% (34/49) of the respondents had more opportunities after their return. Conclusions It is important for nurses to study and train abroad.To this end, a gradient and hierarchical platform should be developed for nurses to go abroad for study under an institutionalized framework. It is also necessary to build an international communication platform and to establish a long-term evaluation and assessment mechanism.