[Genotype-environment interaction on arterial stiffness: A pedigree-based study].

OBJECTIVE: To utilized the baseline data of the Beijing Fangshan Family Cohort Study, and to estimate whether the association between a healthy lifestyle and arterial stiffness might be modified by genetic effects. METHODS: Probands and their relatives from 9 rural areas in Fangshan district, Beijing were included in this study. We developed a healthy lifestyle score based on five lifestyle behaviors: smoking, alcohol consumption, body mass index (BMI), dietary pattern, and physical activity. The measurements of arterial stiffness were brachial-ankle pulse wave velocity (baPWV) and ankle-brachial index (ABI). A variance component model was used to determine the heritability of arterial stiffness. Genotype-environment interaction effects were performed by the maximum likelihood methods. Subsequently, 45 candidate single nucleotide polymorphisms (SNPs) located in the glycolipid metabolism pathway were selected, and generalized estimated equations were used to assess the gene-environment interaction effects between particular genetic loci and healthy lifestyles. RESULTS: A total of 6 302 study subjects across 3 225 pedigrees were enrolled in this study, with a mean age of 56.9 years and 45.1% male. Heritability of baPWV and ABI was 0.360 (95%CI: 0.302-0.418) and 0.243 (95%CI: 0.175-0.311), respectively. Significant genotype-healthy diet interaction on baPWV and genotype-BMI interaction on ABI were observed. Following the findings of genotype-environment interaction analysis, we further identified two SNPs located in ADAMTS9-AS2 and CDH13 might modify the association between healthy dietary pattern and arterial stiffness, indicating that adherence to a healthy dietary pattern might attenuate the genetic risk on arterial stiffness. Three SNPs in CDKAL1, ATP8B2 and SLC30A8 were shown to interact with BMI, implying that maintaining BMI within a healthy range might decrease the genetic risk of arterial stiffness. CONCLUSION: The current study discovered that genotype-healthy dietary pattern and genotype-BMI interactions might affect the risk of arterial stiffness. Furthermore, we identified five genetic loci that might modify the relationship between healthy dietary pattern and BMI with arterial stiffness. Our findings suggested that a healthy lifestyle may reduce the genetic risk of arterial stiffness. This study has laid the groundwork for future research exploring mechanisms of arterial stiffness.

[Venous thromboembolism risk and prophylaxis status of cancer inpatient].

Objective: To determine the risk profile of venous thromboembolism (VTE) and evaluate VTE prophylaxis implementation of the hospitalized cancer patients in the DissolVE 2 study. Methods: The data of hospitalized cancer patients in the DissolVE 2 study were analyzed. The risk distribution of VTE, preventive measures and in-hospital VTE events of hospitalized patients with tumors were described by percentage and 95% confident interval (CI). Results: A total of 1 535 cancer patients were included. According to the Padua score, 826 (53.8%) patients were at low risk of VTE, while 709 (46.2%) patients were at high VTE risk. VTE events occurred in 4 low-risk patients (0.5%; 95%CI: 0.1%, 1.2%) and 5 high-risk patients (0.7%; 95%CI: 0.2%, 1.6%). The overall incidence was 0.6% (9/1 535, 95%CI: 0.3%, 1.1%). Among patients with high VTE risk, 666 (93.9%) did not receive any VTE prophylaxis, and only 11 (1.6%) patients received appropriate VTE prophylaxis. Among patients who received VTE prevention, no VTE event was observed. Conclusions: Nearly half of the hospitalized cancer patients are at high risk of VTE, but most of them don't receive VTE prophylaxis. The results reflect the insufficient management of VTE risk for hospitalized cancer patients in China, and improvement of awareness and practice of VTE prophylaxis is urgently needed.

[Research progression in clinical treatment of gastric cancer in 2020].

Gastric cancer is a common type of malignant tumors, but its clinical prognosis remains unsatisfactory. Up to 2020, a growing number of high-quality clinical researches has provided reliable evidence for clinical practice. Evidences from surgery, perioperative treatment and immunotherapy, such as changes in surgical methods, improvement of perioperative chemotherapy and combination of immune and chemotherapy strategy, provided the possibility to improve the clinical efficacy of gastric cancer. In our clinical practice, gastrointestinal surgeons need to integrate the current research progression and develop individualized strategy for different patients, which is expected to further improve the prognosis and quality of life for patients with gastric cancer.

[Clinicopathological features and prognosis of 59 patients with platelet-derived growth factor α-mutant gastrointestinal stromal tumor].

Objective: Platelet-derived growth factor α (PDGFRA)-mutant gastrointestinal stromal tumor (GIST) is a relatively rare disease, whose clinicopathological characteristics and prognosis have been poorly studied. In this paper, the clinicopathological features and prognostic factors of PDGFRA-mutant GIST are investigated to provide more data for its understanding and treatment. Methods: A retrospective case-control study was used to collect the medical records of patients with GIST who underwent surgical resection in Zhongshan Hospital of Fudan University from January 2015 to August 2019. Patients with PDGFRA-mutant GIST were enrolled, and those with synonymous PDGFRA mutations, non-tumor-related deaths, and lack of clinicopathological data were excluded. The clinicopathological data were collected and the risk factors associated with prognosis were analyzed. Results: Among the enrolled 59 patients, there were 41 males (69.5%) and 18 females (30.5%) with the median age of 60 (25-79) years. All tumors originated from the stomach. The tumor size was 5 (3-7) cm, and the mitotic count was 2 (1-4)/50 high-power fields (HPF). According to the modified NIH risk stratification, 8 cases were classified as very low risk (13.6%), 25 cases as low risk (42.4%), 14 cases as moderate risk (23.7%), and 12 cases as high risk (20.3%). There were 7 cases of exon 12 mutation and 52 cases of exon 18 mutation (including 36 cases of D842V mutation). A comparison of clinicopathological features between the D842V mutation group and the non-D842V mutation group showed no statistically significant difference (all P>0.05). During a median follow-up of 21 (0-59) months, the 1- and 3-year relapse-free survival (RFS) rates of all the patients were 96.6% and 91.5%, respectively. There were 8 cases of recurrence and 3 cases of death. Six GIST patients with D842V mutation had tumor recurrence after operation, of whom 4 cases achieved varying degrees of tumor remission after being treated with dasatinib or avapritinib. Log-rank analysis showed that the overall survival (OS) of male was better than that of female (100% vs. 83.3%, P=0.046), but there was no significant difference in OS among patients with different risk grades (P=0.057). The RFS and OS of patients with D842V mutation and non-D842V mutation, exon 12 and exon 18 mutation were similar (all P>0.05). Univariate Cox analysis showed that RFS was associated with gender (P=0.010), tumor size (P=0.042), mitotic count (P=0.003), and the modified NIH risk stratification (P=0.042), while multivariate analysis revealed that higher risk grade was an independent risk factor for recurrence of PDGFRA-mutant GIST (HR=12.796, 95%CI: 1.326-123.501, P=0.028). Gender was an independent factor for recurrence, and the risk of recurrence in males was lower than that in females (HR=0.154, 95%CI: 0.028-0.841, P=0.031). Conclusions: Gender and the modified NIH risk stratification are independent risk factors for recurrence of PDGFRA-mutant GIST, while patients with D842V and non-D842V mutation, and exon 12 and exon 18 mutation have a similar risk of recurrence and death.

Clinical outcomes of different therapeutic modalities for rectal gastrointestinal stromal tumor: Summary of 14-year clinical experience in a single center.

OBJECTIVE: The optimal treatment for gastrointestinal stromal tumor (GIST) of the rectum is controversial due to the extremely low incidence of the disease. The aim of the present study was to compare the clinical outcomes of different treatment modalities for rectal GIST by reviewing the 14-year experience in our center. METHOD: Medical records of rectal GIST patients who received surgical treatment in our center between January 2004 to December 2017 were reviewed retrospectively. Overall survival (OS) and recurrence-free survival (RFS) were used as the observation endpoints. RESULTS: Included in this study were 71 GIST patients, including 42 patients who underwent local excision (LE) and 29 patients who underwent segmental resection (SR). There were differences in tumor size (P = 0.001) and malignant risk grade (P = 0.007). The LE approach achieved a lower rate of R0 resection than SR (29/42 vs.27/29, P = 0.015) and shorter hospital stay (P = 0.004). Preoperative imatinib mesylate (IM) therapy improved the rate of sphincter-sparing surgery for patients with tumors in the very low segment of the rectum (P = 0.012) and offered better R0 resection margins (P = 0.027). Multivariate analysis showed that the resection margin status (P = 0.014), risk stratification (P = 0.001) and IM therapy (P = 0.042) were independent factors affecting RFS of rectal GIST patients but not the surgical modalities (LE vs. SR, P = 0.802). Multivariate analysis showed no significant impact of these variables on OS. CONCLUSION: Selection of surgical modalities has no significant impact on the prognosis. Local excision is the preferred surgical modality for resectable rectal GIST by virtue of less injury and shorter hospital stay. IM therapy has proved to be associated with improved RFS for rectal GIST patients.

[The shift of the treatment strategy of gastrointestinal stromal tumor from the surgical perspective].

As tumors originated from mesenchymal tissue, gastrointestinal stromal tumors (GIST) has its own typical history. For the idea of treatment for GIST at different historical periods, the role and value of surgery for the treatment of GIST keep changing. Laparoscopy and endoscopy will have the role they deserved. With the understanding of pathogenesis of GIST, targeted chemotherapy will be more and more accurate and individualized. How to improve the overall therapeutic effect of GIST, especially for the patients with the high risk and drug-resistance, is the dilemma and challenges for the surgeons.

[Retrospect of 2019: focus on the research progress of gastric neoplasm].

Gastric carcinoma, gastrointestinal stromal tumor and gastric neuroendocrine tumor are the most common gastric neoplasms. A series of researches in 2019 showed that the safety and efficacy of laparoscopic gastrectomy in the treatment of both early and advanced gastric cancer patients are similar to open surgeries, providing a high-level evidence-based medical basis for the promotion of laparoscopic surgery in the treatment for gastric cancer. In multidisciplinary treatment and perioperative chemoradiotherapy, major research results have also been published, and clinical researches in China are gradually gaining international recognition and attention. Although the application of targeted therapy and immunotherapy has made progress, the first-line therapy after gastric cancer surgery has not been established. In the field of gastrointestinal stromal tumors, laparoscopic surgery has gradually been recognized, and surgical treatment of patients with advanced drug resistance still has its value. In terms of gastric neuroendocrine tumors, the latest researches showed that surgical methods should be selected according to tumor characteristics, and gastric adenocarcinoma with neuroendocrine components may have a worse prognosis.

[Construction of 3ß-HSD gene silencing cell line and its effects on apoptosis induced by DEHP].

Objective: To construct 3ß-HSD gene shRNA lentivirus interference vecto, then transfect into human MCF-7 cells, and construct cell line with 3ß-HSD gene silencing, finally to study the effects of 3ß-HSD on apoptosis induced by di- (2-ethylhexyl) phthalate (DEHP) . Methods: According to the mRNA sequence of 3ß-HSD gene provided by GenBank, three interference sequences were designed and connected to PLVX-shRNA2-puro after annealing. The recombinant lentivirus vector was transfected into 293FT cells, the virus supernatants were collected and infected with MCF-7 cells. After puromycin screening, MCF-7 cells with 3ß-HSD gene silencing were constructed. The cells with 3ß-HSD gene silencing were identified by real-time quantitative PCR and western blot. Then the 3ß-HSD gene silencing cells and MCF-7 cells were treated at various doses of DEHP for 24 hours to detect the gene expression and protein expression of apoptosis genes including Bax, Caspase-3 and Caspase-8. Results: The interference sequence of 3ß-HSD gene inserted into lentivirus vector PLVX-shRNA2-puro is consistent with the designed sequence. 3ß-HSD gene expression level in MCF-7 cells with 3ß-HSD gene silencing was 77% lower than than that of control MCF-7 cells. 3ß-HSD protein level in MCF-7 cells with 3ß-HSD gene silencing was 74% lower than that of control MCF-7 cells. After DEHP treatment in MCF-7 cells with 3ß-HSD gene silencing and control MCF-7 cells, qRT-PCR results showed that Bax gene expression levels increased by 28%-54%, Caspase-3 gene increased by 13%-49%, Caspase-8 gene increased by 21%-70% in MCF-7 cells when compared with the control group. Additionally, in the 3ß-HSD gene silencing cells, Bax gene expression level decreased by 11%-28%, Caspase-3 gene expression decreased by 12%-23%, Caspase-8 gene expression decreased by 11%-34%, compared with the same treatment group of MCF-7 cells. Western blot results showed that Bax protein expression level increased by 28%-61%, Caspase-3 protein expression level increased by 40%-48%, Caspase-8 protein increased by 31%-84% in MCF-7 cells when compared with the control group. In 3ß-HSD gene silencing cells, Bax protein expression level increased by 11%-27%, Caspase-3 protein increased by 21%-40%, Caspase-8 protein increased by 12%-25%, compared with the same treatment group of MCF-7 cells. Conclusion: The stable 3ß-HSD gene silencing cell line are successfully constructed in this study. DEHP can induce increased expression of apoptotic gene and protein. Silencing of 3ß-HSD gene can inhibit the activation of apoptotic gene by DEHP in a certain degree.

[Preparation and evaluation of blank and doxorubicin loaded poly (acrylic acid) microspheres for embolization].

OBJECTIVE: To prepare ion exchange doxorubicin-loaded poly (acrylic acid) microspheres (DPMs) and evaluate the properties of these chemoembolic agents. METHODS: Poly (acrylic acid) microspheres (PMs) without drug were prepared by inverse suspension polymerization method and then doxorubicin was loaded by ion exchange mechanism to prepare DPMs. Optical microscope was used to investigate the morphology and particle size distribution of PMs and DPMs; fluorescence microscope and confocal microscope were used to observe the distribution of doxorubicin after drug loading. Elasticities of both the microspheres were evaluated by texture analyzer. High performance liquid chromatography (HPLC) method was established to determine the drug loading behavior of PMs and releasing behavior of DPMs. The in vivo embolic property was evaluated by embolizing the hepatic artery of a rabbit with 0.1 mL of DPMs. RESULTS: PMs and DPMs were both spherical in shape, smooth in surface and dispersed well. Doxorubicin was mainly in the outer area inside of DPMs and distributed evenly. The average particle size of PMs and DPMs were (283±136) µm and (248±149) µm, respectively. PMs and DPMs both had good compression ability with the Young's modulus of (62.63±1.65) kPa and (93.94±1.10) kPa separately. PMs reached the drug loading balance at 12 h, and the entrapment efficiency was greater than 99%. Drug loading of PMs in doxorubicin solution at the concentration of 5.0 g/L and 12.5 g/L was (19.78±0.27) g/L and (49.45±0.37) g/L, respectively. Doxorubicin released slowly from DPMs in PBS and the accumulative release percentages of DPMs with corresponding drug loading were 6.82%±0.02% and 2.83%±0.10% after 24 h, respectively. Arterial angiograms showed that the hepatic artery of the rabbit was successfully embolized with DPMs. CONCLUSION: DPMs with good performance of loading doxorubicin could be a potential embolic agent for transcatheter arterial chemoembolization.

[KRAS mutations analysis in mucinous epithelial lesions of the endometrium].

Objective: To investigate the frequency of KRAS mutation in mucinous epithelial lesions of the endometrium, and analyze the correlation between KRAS mutation and the clinicopathologic features. Methods: The cohort included forty-three cases of mucinous epithelial lesions of the endometrium selected from July 2015 to October 2017 from Beijing Obstetrics and Gynecology Hospital, and 22 control cases. Genomic DNA was extracted from formalin-fixed paraffin-embedded tissue sections. Polymerase chain reaction amplification for KRAS exons 2 and 3 was performed, followed by sequencing using capillary electrophoresis. The Fisher exact test was used to compare the prevalence of KRAS mutation among the different groups. Results: The patients'age ranged from 33 to 77 years [mean (55.12±9.34) years, median 55 years]. None of the eight cases of endometrial hyperplasia with mucinous differentiation without atypia showed KRAS mutation. The frequency of KRAS mutations was 1/10 in endometrial atypical hyperplasia, 1/12 in endometrioid carcinoma, 4/11 in endometrial atypical hyperplasia with mucinous differentiation (EAHMD), 6/15 in endometrioid carcinoma with mucinous differentiation (ECMD) and 8/9 in mucinous carcinoma (MC), respectively. The differences were statistically significant between MC versus EC (P<0.01) and MC versus ECMD (P<0.05). Conclusion: The high frequency of KRAS mutation in EAHMD, ECMD and MC indicates that KRAS mutational activation is implicated in the pathogenesis of endometrial mucinous carcinoma.

[Clinical application of STR genotyping diagnosis for hydatidiform mole and nonmolar gestation].

Objective: To investigate the value of short tandem repeat (STR) genotyping in the diagnostic workup of molar and non-molar gestations with correlation of histological characteristics. Methods: Six hundred and fifty-six cases were selected based on clinically suspected hydropic abortion and/or molar pregnancy from July 2015 to September 2017 at Beijing Obstetrics and Gynecology Hospital. DNA was extracted from dissected chorionic villi and paired maternal endometrial FFPE tissue samples by Simplex OUP™ FFPE DNA Tissue Kit. STR genotyping was performed by PowerPlex 16 HS system. Results: DNA genotyping was informative in 649 of 656 cases, leading to identification of 215 hydatidiform mole gestations and 434 non-molar gestations. Most of non-molar gestations (375 cases, 86.4%) were diploid hydropic abortion. Various trisomy syndromes were found (53 cases, 12.2%), including trisomy 2, 3, 4, 7, 8, 13, 16 and 21. Only 2(0.5%) digynic triploid gestations were detected. Moreover, 4 cases (0.9%) of uniparental disomies (homologous or heterologous) were found. There were 196 cases with histologic diagnostic suspicious of hydatidiform moles were accurate sub-classified. Among them, 59 cases hydatidiform moles were under-diagnosed as diploid hydropic abortions, and 28 cases diploid hydropic abortions were over-diagnosed as hydatidiform moles.Compared with partial moles(PHM), there were no specific histomorphological features between the various types of non-molar gestations and partial moles for definitive diagnostic separation. There was no significant difference in the expression of p57(kip2) among PHM, trisomy and diploid hydropic abortions group (P=0.247). Conclusions: STR genotyping can distinguish non-molar gestations from early hydatidiform moles, and efficiently avoid misdiagnosis based only on histological evaluation. Therefore, using STR genotyping, not only can the overdiagnosis of non-molar pregnancy be avoided, but also individualized management can be offered to patients including monitoring of serum hCG.

[Future trends and prospect of surgery of gastrointestinal cancer in China].

With the development of medical concepts and technology, the surgical treatment of gastrointestinal cancer is gradually moving towards a new era. Chinese gastrointestinal surgeons are building up our own high-level evidence in evidence-based medicine, with tremendous clinical trials carrying out in gastrointestinal cancers. Besides, standardized procedure of diagnosis and treatment should be promoted. More personalized schemes are needed. The model of multidisciplinary team can be more widely and deeply applied. And the concept of enhanced recovery after surgery should be more operable. To keep pace with the times, the gastrointestinal surgeons have to seek for innovative technology and new ideas.

[Effects of 3ß-HSD gene silence or overexpression on DEHP induced oxidative damage in MCF-7 cells].

Objective: To study the oxidative damage of di- (2-ethylhexyl) phthalate (DEHP) on MCF-7 cells, and to investigate the effects of 3ß-hydroxysteroid dehydrogenase (3ß-HSD) gene silence or overexpression on DEHP-induced oxidative damage. Methods: MCF-7 cells, 3ß-HSD gene silencing cells and 3ß-HSD gene overexpression cells were treated with different doses of DEHP (0,0.05,0.1,0.2,0.4,0.8 mmol/L) for 24h, then intracellular oxidative damage index such as MDA, SOD, GSH, GSH-PX were detected, DNA repair gene hOGG1, hMTH1 mRNA expression were tested by Q-PCR, hOGG1, hMTH1 protein expression were detected by western blot. Results: After MCF-7 cells were treated by DEHP, MDA levels increased; SOD activity, GSH content, GSH-PX activity decreased, hOGG1 and hMTH1 mRNA expression levels increased, hOGG1 and hMTH1 protein expression levels increased, the differences were statistically significant when compared with control (P<0.05 or P<0.01) . In 3ß-HSD gene silencing cells which were treated by DEHP, when compared with the same dose group of MCF-7 cells, MDA content increased, SOD activity, GSH content, GSH-PX activity decreased, hOGG1 and hMTH1 mRNA expression levels decreased, hOGG1 and hMTH1 protein expression levels decreased, the difference were statistically significant (P<0.05 or P<0.01) . In 3ß-HSD gene overexpression cells which were treated by DEHP, when compared with the same dose group of MCF-7 cells, MDA content decreased; SOD activity, GSH content, GSH-PX activity increased, of hOGG1 and hMTH1 mRNA expression levels increased, hOGG1 and hMTH1 protein expression levels increased, the difference were statistically significant (P<0.05 or P<0.01) . Conclusion: DEHP could cause oxidative damage in MCF-7 cells, induce the changes of related genes and proteins, 3ß-HSD plays an antioxidant role in the process of DEHP ox-idative damage.

Alpha1,2-fucosyl transferase gene, the key enzyme of Lewis y synthesis, promotes Taxol resistance of ovarian carcinoma through apoptosis-related proteins.

We aimed to investigate the role of FUT1 gene in Taxol resistance and to explore its mechanism in epithelial ovarian cancer. Three ovarian cancer cell lines, ES-2, SK-OV-3 and OVCAR-3 were selected from epithelial ovarian cancer in this experiment. Western blot was used to validate the protein expression level of FUT1 and the apoptosis proteins. The expression level of the corresponding carrier was validated by RT-PCR. Transfection and isolation of stable transfectants were carried out to establish the cell line models. The different concentrations of Taxol on the inhibition of cell growth rate was measured by MTT, in which Taxol resistance profiling in ovarian cancer cells was determined by IC50 data. Flow cytometry was conducted to compare cell apoptosis ability. Caspase-3 activity and the apoptosis proteins were measured by colorimetry and western blot, respectively, to further compare the cell apoptosis ability in different groups. To demonstrate the inhibition of miR-FUT1 combined with Taxol therapy against ovarian cancer, xenograft assay was carried out for the in vivo effect. The western blot results indicate that FUT1 is expressed in all of the ovarian cancer cells with different expression level: ES-2 > SK-OV-3 > OVCAR-3. Besides, FUT1 siRNA was used in the maximum expression of FUT1 cell line ES-2, or over-expression plasmid was used in the minimum expression of FUT1 cell line OVCAR-3, to establish stable expression cell lines. After the treatment with Taxol, the inhibition rate of Taxol was obviously decreased with the established cell model above, and the IC50 level was significantly increased in the FUT1 over-expression + Taxol group (p Keywords: FUT1, Lewis y, Taxol resistance, ovarian cancer, apoptosis.

[Preparation and characterization of citric acid-modified superparamagnetic iron oxide nanoparticles].

OBJECTIVE: To prepare and characterize citric acid (CA)-modified super paramagnetic iron oxide nanoparticles (SPIONs) for magnetic targeting, hyperthermia and magnetic resonance imaging (MRI). METHODS: CA-modified SPIONs (CA-SPIONs) were prepared by co-precipitation method and then the magnetic responsiveness, morphology, particle size, infrared feature, weight percentage of CA, magnetic property and X-ray diffraction pattern of CA-SPIONs were respectively characterized by magnet, transmission electron microscope, laser particle size analyzer, Fourier transform infrared (FT-IR) spectroscopy, thermogravimetry-differential thermal analyzer, vibrating sample magnetometer and X-ray diffractometer (XRD). The heating efficiency of the CA-SPIONs was investigated by a high frequency induction heater. The transverse relaxivity (r2) of the CA-SPIONs was evaluated by a 3.0 T MRI scanner. RESULTS: The CA-SPIONs prepared were dispersed well in water with a dark black color and had good magnetic responsiveness. The CA-SPIONs were spherical in shape and uniform in size with an average size around 12 nm. The hydrodynamic average size of the CA-SPIONs was (72.35±4.47) nm with a polydispersity index of 0.231 ± 0.029. The result of infrared spectrum indicated that CA was successfully modified to the surface of SPIONs. The result of thermogravimetric analysis showed that the weight percentage of CA modified on the CA-SPIONs was 9.0%. The result of magnetic property evaluation demonstrated that the CA-SPIONs exhibited excellent superparamagetism with a saturation magnetism of 63.58 emu/g. The XRD result indicated that the CA-SPIONs were in inverse spinel structure. The crystallite size of the CA-SPIONs was calculated to be 12.4 nm by Debye-Scherrer equation. Under the high frequency alternating electromagnetic field with electric current of 9 A and frequency ranging from 45 to 50 kHz, the CA-SPIONs exhibited excellent heating efficiency and the specific absorption rate (SAR) value was calculated to be 26 W/g. The r2 of the CA-SPIONs was assessed to be 338 (mmol/L)-1×s-1 by a 3.0 T MRI scanner, which suggested the excellent negative contrast enhancement effect of the CA-SPIONs. CONCLUSION: The CA-SPIONs are expected to be used as a promising agent for magnetic targeting, hyperthermia and MRI detection.

[Trend of development and prospect of gastrointestinal surgery in era of minimally invasive].

The development and popularization of minimally invasive treatment is gradually evolving in the course of human fighting against disease. Minimally invasive surgery has been widely accepted and carried out because of the advantages of smaller trauma, less pain, little impact on the body and physiological metabolism of the body. The evidence-based medicine makes it important to conduct clinical trials to confirm the technical and oncological safety. With the development of minimally invasive technologies, including three-dimensional laparoscopic, natural orifice transluminal endoscopic surgery, robotic surgery system, minimally invasive surgery are providing more opportunities and challenges for gastrointestinal diseases. The standard conduction of minimally invasive surgery in gastroenterology disease makes it important to improve surgical procedure safety and treatment effects.

[Analysis of clinical features and related genes variation in five patients with 46, XX male syndrome].

Objective: To explore the clinical manifestations and molecular features of 46, XX male syndrome. Method: The clinical and molecular data of five 46, XX male syndrome cases treated in the Department of Pediatrics of Shanghai Ruijin Hospital form August 2010 to August 2014 were retrospectively analyzed. Result: The five patients were all sociopsychologically males and came to hospital respectively for short stature, ambiguous genitalia or gynecomastia. They were all below the normal male's average height, and their karyotype was all 46, XX. One case in five was verified as sex determining region of Y chromosome (SRY gene) positive revealed no abnormality in their external genitalia. He had short stature since childhood, whose SRY gene fragments were shown by FISH transferred to the ends of X chromosome. Three cases in four were SRY gene negative with ambiguous genitalia of cryptorchidism and testicular dysplasia to different degrees. The copy number variations of SOX9 gene was found in one case, the loss of heterozygosity area in DHH gene of one case. Another SRY gene negative patient who had normal male external genitalia, came to the hospital due to puberty gynecomastia, that of SOX9 gene and its upstream gene both increased. Conclusion: The main clinical characteristics of 46, XX male syndrome are male phenotype, 46, XX karyotype, gonad of testis or ovotestis and no uterus. In addition, short stature, ambiguous genitalia or gynecomastia can be one reason for hospital visits. SRY gene translocation, SOX9 gene and its upstream gene copy number increase all can lead to 46, XX male syndrome. The cause of some may play an important role in 46, XX male syndrome, but has not yet been determined.

CTLA-4 polymorphisms and haplotype correlate with survival in ALL after allogeneic stem cell transplantation from related HLA-haplotype-mismatched donor.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been established as an effective treatment for patients with hematological malignancies. Disease relapse remains a major cause of transplant failure. T cell homeostasis is critical to determine the potency of the GVT effect. Recent studies have shown the association of the CTLA-4 polymorphisms with the outcome after HLA-identical sibling allogeneic HSCT. METHODS: In this study, we focused on four CTLA-4 polymorphisms, and analyzed the impact of donor genotypes and haplotypes on the conditions of 152 acute leukemia patients (ALL 83) after related HLA-haplotype- mismatched transplantation. The four SNP genotypes (-1661, -318, CT60 and +49) were determined by TaqMan SNP genotyping assays. RESULTS: ALL recipients of donors with +49 GG showed significantly lower OS (67.7 vs. 90.3 %, P = 0.015) than those with GA+AA. Multivariate analyses showed that +49 GG was an independent risk factor for OS (HR: 0.306, 95 % CI 0.111-0.842, P = 0.022) .23 ALL patients receiving mDLI showed significantly lower OS with +49 GG donor than those with GA+AA (30.0 vs. 83.1 %, P = 0.003). The haplotype analysis revealed only three haplotypes in the donor population -1661/-318/CT60/+49 i.e., ACGG, ACAA and GTGA, the frequencies were 64.1, 19.4 and 16.5 %, respectively. Donors with and without the ACGG/ACGG haplotype had the same effect on transplant outcomes as those with +49 GG and +49 GA+AA. CONCLUSION: In summary, the CTLA-4 +49 GG and the haplotype ACGG/ACGG reduced the overall survival in ALL after allo-HSCT from the related HLA-haplotype-mismatched donor, knowledge of the CTLA-4 polymorphism and haplotype may provide useful information for donor selection and individual application of immunosuppressive agents and immunotherapy.

[Current status and prospect of perioperative thrombus management in gastrointestinal cancer].

Thanks to the progress of surgical theory and skills, as well as the application of modern medical devices in general surgery, both the occurrence of perioperative complications and mortality of gastrointestinal surgery have significantly reduced recently. However, it is still far from optimal in terms of the perioperative venous thromboembolism (VTE) management in gastrointestinal cancer, and what is responsible for that? This paper aims at finding out the reasons contributing to the current status, giving suggestions for how to make improvement at both disease level and hospital management level. At the same time, while paying attention for the prophylaxis of VTE, there have been more and more patients receiving antithrombotic treatment require elective or emergent surgery in clinical practice, due to aging and increased incidence of cardiovascular disease year by year. How to balance the bleeding and thrombosis risk for these patients during perioperative periods is also a question we are going to discuss. In conclusion, as to the issue of the management of perioperative thrombosis, there will be a long way for Chinese doctors to go. Our peers should pay more attention to this problem and take more efforts, so that the thrombotic complications in surgical patients can be reduced.