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Pulsatile gonadotropin-releasing hormone therapy is associated with earlier spermatogenesis compared to combined gonadotropin therapy in patients with congenital hypogonadotropic hypogonadism

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Asian Journal of Andrology 2017年第6期19卷 680-685页

作者： Jiang-Feng Mao Zhao-Xiang Liu Min Nie Xi Wang Hong-Li Xu Bing-Kun Huang Jun-Jie Zheng Le Min Ursula Brigitte Kaiser Xue-Yan Wu Department of Endocrinology Peking Union Medical College Hospital Key Laboratory of Endocrinology Ministry of Health Beijing 100730 China Internal Department Division of Endocrinology Diabetes and Hypertension Brigham and Women's Hospital Harvard Medical School Boston MA 02115 USA.

Both pulsatile gonadotropin-releasing hormone （GnRH） infusion and combined gonadotropin therapy （human chorionic gonadotropin and human menopausal gonadotropin [HCG/HMG]） are effective to induce spermatogenesis in male patients with congenital hypogonadotropic hypogonadism （CH H）. However, evidence is lacking as to which treatment strategy is better. This retrospective cohort study included 202 patients with CHH： twenty had received pulsatile GnRH and 182 had received HCG/HMG. Patients had received therapy for at least 12 months. The total follow-up time was 15.6 ± 5.0 months （range： 12-27 months） for the GnRH group and 28.7 ± 13.0 months （range： 12-66 months） for the HCG/HMG group. The median time to first sperm appearance was 6 months （95% confidence interval [CI]： 1.6-10.4） in the GnRH group versus 18 months （95% Ch 16.4-20.0） in the HCG/HMG group （P〈 0.001）. The median time to achieve sperm concentrations 〉5 x 106 m1-1 was 14 months （95% Ch 5.8-22.2） in the GnRH group versus 27 months （95% Ch 18.9-35.1） in the HCG/HMG group （P 〈 0.001）, and the median time to concentrations 〉10 x 106 m1-1 was 18 months （95% Ch 10.0-26.0） in the GnRH group versus 39 months （95% CI unknown） in the HCG/HMG group. Compared to the GnRH group, the HCG/HMG group required longer treatment periods to achieve testicular sizes of 〉4 ml, 〉8 ml, 〉12 ml, and 〉16 ml. Sperm motility （a ＋ b ＋ c percentage） evaluated in semen samples with concentrations 〉1 × 106 ml-1 was 43.7% ± 20.4% （16 samples） in the GnRH group versus 43.2% ± 18.1% （153 samples） in the HCG/HMG group （P= 0.921）. Notably, during follow-up, the GnRH group had lower serum testosterone levels than the HCG/HMG group （8.3 ±4.6 vs 16.2 ± 8.2 nmol 1-1, P 〈 0.001）. Our study found that pulsatile GnRH therapy was associated with earlier spermatogenesis and larger testicular size compared to combined gonadotropin therapy. Additional prospective randomized studies would be required to confirm these findings.

关键词： combined gonadotropin therapy congenital hypogonadotropic hypogonadism pulsatile GnRH therapy spermatogenesis

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Surgical treatment of hepatocellular carcinoma with inferior vena cava tumor thrombus: a new classification for surgical guidance

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Hepatobiliary & Pancreatic Diseases International 2013年第3期12卷 263-269页

作者： Ai-Jun Li Wei-Ping Zhou Chuan Lin Xi-Long Lang Zhen-Guang Wang Xiao-Yu Yang Qing-He Tang Ran Tao Meng-Chao Wu division of Special treatment Ⅱ Eastern Hepatobiliary Surgery Hospital Second Military Medical University division of Hepatic Surgery Third Eastern Hepatobiliary Surgery Hospital Second Military Medical University Department of Cardiothoracic Surgery Changhai Hospital Second Military Medical University Center for Organ Transplantation and Department of General Surgery Ruijin Hospital

BACKGROUND: Hepatic resection is the main treatment modality for hepatic tumors. Advances in diagnostic technique, preoperative preparation, surgical technique, and postoperative management increased the success rate. The present study aimed to evaluate hepatectomy and resection of inferior vena cava tumor thrombus (IVCTT) in patients with hepatocellular carcinoma, and the relationship between IVCTT classification and selection of surgical technique. METHODS: We retrospectively reviewed 13 patients with hepatocellular carcinoma who had undergone hepatectomy with IVCTT resection between May 1997 and August 2009. Age, gender, diagnosis, findings of physical examination, results of preoperative laboratory investigations, radiological examination, criteria for resection, postoperative pathological results, incisions, operative technique, intraoperative transfusion, drains, and intraoperative and postoperative complications were evaluated for all patients. RESULTS: Type Ⅰ IVCTT (10 patients) was posterior to the liver and below the diaphragm; type Ⅱ IVCTT (2 patients) was above the diaphragm but still outside the atrium; and type Ⅲ IVCTT (1 patient) was above the diaphragm and in the right atrium. Type Ⅰ was treated by radical hepatectomy and removal of IVCTT with total hepatic vascular exclusion. Type Ⅱ was treated by radical hepatectomy and removal of IVCTT by incision of the diaphragm. Type Ⅲ was treated by hepatectomy and resection of the thrombus from the right atrium under cardiopulmonary bypass. There were no surgical complications and one patient has been survived for 4 years with cancer-free status. The median survival time was 18.2 months, and the 1-and 2-year survival rates were 53.8% and 15.4%, respectively. CONCLUSION: Surgical treatment is safe and feasible for treatment of IVCTT in patients with hepatocellular carcinoma, and surgical resectability can be judged according to the classification of tumor thrombus.

关键词： liver tumor inferior vena cava hepatectomy tumor thrombus total hepatic vascular exclusion

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Remote ischemic perconditioning prevents liver transplantation-induced ischemia/reperfusion injury in rats: Role of ROS/RNS and e NOS

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World Journal of Gastroenterology 2017年第5期23卷 830-841页

作者： Ning He Jun-Jun Jia Jian-Hui Li Yan-Fei Zhou Bing-Yi Lin Yi-Fan Peng Jun-Jie Chen Tian-Chi Chen Rong-Liang Tong Li Jiang Hai-Yang Xie Lin Zhou Shu-Sen Zheng Key Lab of Combined Multi-Organ Transplantation Ministry of Public Health Collaborative Innovation Center for Diagnosis and treatment of Infectious Diseases division of Hepatobiliary and Pancreatic Surgery Department of SurgeryFirst Affiliated HospitalZhejiang University School of Medicine

AIM To investigate the underlying mechanisms of the protective role of remote ischemic perconditioning (RIPerC) in rat liver transplantation. METHODS Sprague-Dawley rats were subjected to sham, orthotopic liver transplantation (OLT), ischemic postconditioning (IPostC) or RIPerC. After 3 h reperfusion, blood samples were taken for measurement of alanine aminotransferase, aspartate aminotransferase, creatinine (Cr) and creatinine kinase-myocardial band (CK-MB). The liver lobes were harvested for the following measurements: reactive oxygen species (ROS), H2O2, mitochondrial membrane potential (Delta psi m) and total nitric oxide (NO). These measurements were determined using an ROS/H2O2, JC1 and Total NOx Assay Kit, respectively. Endothelial NO synthase (eNOS) was analyzed by reverse transcription-polymerase chain reaction (RTPCR) and western blotting, and peroxynitrite was semiquantified by western blotting of 3-nitrotyrosine. RESULTS Compared with the OLT group, the grafts subjected to RIPerC showed significantly improved liver and remote organ functions (P < 0.05). ROS (P < 0.001) including H2O2 (P < 0.05) were largely elevated in the OLT group as compared with the sham group, and RIPerC (P < 0.05) reversed this trend. The collapse of Delta psi m induced by OLT ischemia/reperfusion (I/R) injury was significantly attenuated in the RIPerC group (P < 0.001). A marked increase of NO content and phosphoserine eNOS, both in protein and mRNA levels, was observed in liver graft of the RIPerC group as compared with the OLT group (P < 0.05). I/R-induced 3-nitrotyrosine content was significantly reduced in the RIPerC group as compared with the OLT group (P < 0.05). There were no significant differences between the RIPerC and IPostC groups for all the results except Cr. The Cr level was lower in the RIPerC group than in the IPostC group (P < 0.01). CONCLUSION Liver graft protection by RIPerC is similar to or better than that of IPostC, and involves inhibition of oxidative stres

关键词： Liver transplantation Ischemia/reperfusion injury Remote ischemic perconditioning Endothelial nitric oxide synthase Reactive oxygen species

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Injectable hydrogel-based drug delivery systems for enhancing the efficacy of radiation therapy:A review of recent advances

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Chinese Chemical Letters 2024年第8期35卷 128-137页

作者： Ningyue Xu Jun Wang Lei Liu Changyang Gong division of Head&Neck Tumor Multimodality treatment Cancer CenterWest China HospitalSichuan UniversityChengdu 610041China Department of Biotherapy Cancer Center and State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China

Radiotherapy(RT)is a crucial treatment for cancer;however,its effectiveness is limited by adverse effects on normal tissues,radioresistance,and tumor *** overcome these challenges,hydrogels have been employed for delivery of radiosensitizers and other therapeutic *** review summarizes recent advancements in the application of hydrogel-based local drug delivery systems for improving the therapeutic efficacy of RT in cancer ***,we introduce the classification and properties of ***,we detail hydrogel-based platforms designed to enhance both external beam radiation therapy and *** also discuss hydrogels used in combination therapy involving RT and ***,we highlight the challenges that hydrogels face in *** surveying the latest developments in hydrogel applications for RT,this review aims to provide insights into the development of more effective and targeted cancer therapies.

关键词： Radiotherapy Drug delivery systems Hydrogel Radiation sensitization Combination therapy

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Role of [18F] fludeoxyglucose positron emission tomography in the selection of liver transplantation candidates in patients with hepatocellular carcinoma

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Hepatobiliary & Pancreatic Diseases International 2017年第3期16卷 257-263页

作者： Yu-Fu Ye Wei Wang Ting Wang Jun Yu Lei Geng Song-Feng Yu Sheng Yan Shu-Sen Zheng division of Hepatobiliary and Pancreatic Surgery First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 China Key Laboratory of Combined Multi-organ Transplantation Ministry of Public Health Collaborative Innovation Center for Diagnosis treatment of Infectious Diseases Hangzhou 310003 China

BACKGROUND： The Milan criteria are widely accepted among many centers. However, patients with hepatocellular carcinoma beyond the Milan criteria might still benefit from liver transplantation （LT） when tumor itself is not aggressive. [18F] fluorodeoxyglucose positron emission tomography/computed tomography imaging could provide useful information of tumor behaviors, which is helpful to predict the prognosis for many tumors. METHOD： In order to determine its role in candidate selection for LT, we therefore retrospectively analyzed 103 recipients with preoperative positron emission tomography （PET） findings. RESULTS： Positive PET findings （PET＋） were significantly associated with tumor nodule numbers （P=0.013）, tumor grade （P=0.025）, macro- （P=0.002） and micro-vascular invasion （P=0.002）, as well as the Milan criteria （P=0.018）. PET＋ patients had significantly increased risk of tumor recurrence post-LT compared to PET negative （PET-） patients （P=0.007）. The 1-, 3-, and 5-year overall survival rate of PET- patients were 96.0%, 87.2% and 76.2%, compared to 74.7%, 55.4% and 49.9% in PET＋ patients, respectively （P〈0.05）. The 1-, 3-, and 5-year recurrence-free survival rate of PET- patients were 91.8%,81.9% and 76.0%, compared to 70.1%, 39.3% and 21.9% in PET＋ patients, respectively （P〈0.05）. Recipients within the Milan criteria showed comparable 1-, 3-, and 5-year survival rates in comparison with those beyond the Milan criteria with a PET- findings （1-, 3-, and 5-year overall survival rates, 97.5%, 83.3%, and 83.3% vs 90.0%, 80.0%, and 66.7%, P= 0.123; 1-, 3-, and 5-year recurrence-free survival rates, 95.1%, 73.1%, and 73.1% vs 90.0%, 78.8%, and 65.6%, P=0.148）. CONCLUSIONS： Certain patients with hepatocellular carcinoma and negative PET findings, who have exceeded the Milan criteria, are also eligible candidates for LT. Preoperative PET/CT imaging is an important marker, which should be incorporated in extended candidate selection criteria for LT.

关键词： liver transplantation hepatocellular carcinoma positron emission tomography/computed tomography ,prognostic factors

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Influence of magnetically constricted arc traverse speed (MCATS) on tensile properties and microstructural characteristics of welded Inconel 718 alloy sheets

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Defence Technology（防务技术） 2021年第4期17卷 1395-1413页

作者： Tushar Sonar Visvalingam Balasubramanian Sudersanan Malarvizhi Thiruvenkatam Venkateswaran Dhenuvakonda Sivakumar Centre for Materials Joining and Research(CEMAJOR) Department of Manufacturing EngineeringAnnamalai UniversityAnnamalai Nagar608002Tamilnadu StateIndia Heat treatment and Welding Metallurgy division(HWMD) Materials and Metallurgy Group(MMG)Vikram Sarabhai Space Centre(VSSC)ISROThiruvananthpuram695022Kerala StateIndia

The magnetically constricted arc technique was implemented to mitigate the heat input related metallurgical problems in Gas Tungsten Arc Welding(GTAW)of Inconel 718 alloy particularly Nb segregation and subsequent laves phase evolution in fusion *** paper reports the direct effect of magnetically constricted arc traverse speed(MCATS)on bead profile,tensile properties and microstructural evolution of Inconel 718 alloy sheets joined by Gas Tungsten Constricted Arc Welding(GTCAW)*** mechanism amenable for the microstructural modification and corresponding influence on the tensile properties of joints is investigated both in qualitative and quantitative manner related to the mechanics of arc constriction and *** is correlated to the solidification conditions during *** relationship between MCATS and Arc Constriction Current(ACC)was *** interaction effect on the magnetic arc constriction and joint performance was *** showed that the joints fabricated using CATS of 70 mm/min exhibited superior tensile properties(98.39% of base metal strength with 31.50% elongation).It is attributed to the grain refinement in fusion zone microstructure leading to the evolution of finer,discrete laves phase in interdendritic areas.

关键词： GTCA welding Inconel 718 alloy Magnetically constricted arc traverse speed Tensile properties Microstructure Laves phase

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Immunotherapy in gastric cancer

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World Journal of Gastroenterology 2014年第7期20卷 1657-1666页

作者： Satoko Matsueda David Y Graham Cancer Vaccine Development division Research Center for Innovative Cancer TherapyKurume UniversityKurumeFukuoka 830-0011Japan Michael E DeBakey VA Medical Center Baylor College of MedicineHoustonTX 77030United States

Gastric cancer is the second most common of cancerrelated deaths *** the majority of cases gastric cancer is advanced at diagnosis and although medical and surgical treatments have improved,survival rates remain *** immunotherapy has emerged as a powerful and promising clinical approach for treatment of cancer and has shown major success in breast cancer,prostate cancer and ***,we provide an overview of concepts of modern cancer immunotherapy including the theory,current approaches,remaining hurdles to be overcome,and the future prospect of cancer immunotherapy in the treatment of gastric *** cell therapies,cancer vaccines,gene therapies,monoclonal antibody therapies have all been used with some initial successes in gastric ***,to date the results in gastric cancer have been disappointing as current approaches often do not stimulate immunity efficiently allowing tumors continue to grow despite the presence of a measurable immune ***,we discuss the identification of targets for immunotherapy and the role of biomarkers in prospectively identifying appropriate subjects or *** also discuss the molecular mechanisms by which tumor cells escape host immunosurveillance and produce an immunosuppressive tumor *** show how advances have provided tools for overcoming the mechanisms of immunosuppression including the use of monoclonal antibodies to block negative regulators normally expressed on the surface of T cells which limit activation and proliferation of cytotoxic T *** has greatly improved and is becoming an important factor in such fields as medical care and welfare for human *** has been rapid ensuring that the future of immunotherapy for gastric cancer is bright.

关键词： Gastric cancer Immune checkpoint Immune escape Adoptive cell therapy Cancer vaccine Antibody therapy Predictive biomarker

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Linking uric acid metabolism to diabetic complications

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World Journal of diabetes 2014年第6期5卷 787-795页

作者： Akifumi Kushiyama Kentaro Tanaka Shigeko Hara Shoji Kawazu division of diabetes and Metabolism The Institute for Adult DiseasesAsahi Life Foundation2-2-6

Hyperuricemia have been thought to be caused by the ingestion of large amounts of purines, and prevention or treatment of hyperuricemia has intended to prevent gout. Xanthine dehydrogenase/xanthine oxidase(XDH/XO) is rate-limiting enzyme of uric acid generation, and allopurinol was developed as a uric acid(UA) generation inhibitor in the 1950 s and has been routinely used for gout prevention since then. Serum UA levels are an important risk factor of disease progression for various diseases, including those related to lifestyle. Recently, other UA generation inhibitors such as febuxostat and topiroxostat were launched. The emergence of these novel medications has promoted new research in the field. Lifestyle-related diseases, such as metabolic syndrome or type 2 diabetes mellitus, often have a common pathological foundation. As such, hyperuricemia is often present among these patients. Many in vitro and animal studies have implicated inflammation and oxidative stress in UA metabolism and vascular injury because XDH/XO act as one of the major source of reactive oxygen species Many studies on UA levels and associated diseases implicate involvement of UA generation in disease onset and/or progression. Interventional studies for UA generation, not UA excretion revealed XDH/XO can be the therapeutic target forvascular injury and renal dysfunction. In this review, the relationship between UA metabolism and diabetic complications is highlighted.

关键词： Uric acid Xanthine dehydrogenase/xanthine oxidase diabetes mellitus Diabetic complications Xanthine oxidase inhibitor Metabolism

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The Short- and Long-Term Effect of Liraglutide on the Beta Cell Function in Type 2 Diabetic Patients

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Journal of diabetes Mellitus 2014年第4期4卷 334-340页

作者： Toshinobu Suzuki Koichi Hirai Yingchao Chen Kunihiko Hashimoto division of diabetes and Endocrinology Department of Internal Medicine NTT West Osaka Hospital Osaka Japan

Glucagon-like peptide 1 (GLP-1) is a hormone, inducing glucose-dependent stimulation of insulin secretion from beta cells. Liraglutide acts as a GLP-1 receptor agonist. To assess the effect of liraglutide on the beta cell function, we performed oral glucose tolerance tests in 7 subjects with type 2 diabetes before and after treatment of liraglutide. Moreover, we performed same study again in 4 subjects at 6 months after induction. Liraglutide significantly increased area under the Curve (AUC) of plasma insulin level after glucose loading and significantly decreased AUC of plasma glucose level, compared with before induction. HOMA-beta was significantly increased, whereas insulinogenic index was not changed. HOMA-R was not affected but Matsuda index was significantly decreased after induction of liraglutide. Disposition index was not altered significantly, but tendency of improvement was observed. Glucose tolerance tests revealed that those effects of liraglutide were continued for 6 months after induction. These results showed that treatment of liraglutide could improve insulin secretion but early phase of insulin secretion was not improved. The results suggest that liraglutide is likely to improve beta-cell function, but this effect is still inadequate by six-month treatment.

关键词： Glucagon-Like Peptide 1 Oral Glucose Tolerance Test Insulin Secretion Insulin Sensitivity Type 2 diabetes

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Unique cytologic features of thyroiditis caused by immune checkpoint inhibitor therapy for malignant melanoma

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Genes & Diseases 2018年第1期5卷 46-48页

作者： Trevor E.Angell Le Min Tad J.Wieczorek F.Stephen Hodi division of Endocrinology Diabetesand HypertensionBrigham and Women’s HospitalBostonMAUSA Department of Pathology Brigham and Women’s HospitalBostonMAUSA Department of Medical Oncology Dana-Farber Cancer InstituteBostonMAUSA

Blockade of immune checkpoint molecules to reverse cancer-induced immune suppression can improve anti-tumor immune responses in cancer *** antibodies targeting two such molecules,Programmed cell death protein 1(PD-1)and cytotoxic T-lymphocyte associated protein 4(CTLA-4)have shown clinical benefit in the treatment of advanced malignancies,including metastatic *** effects of these immune checkpoint inhibitors include immune-related adverse events(irAE),of which one of the most common is autoimmune *** thyroiditis is increasingly recognized,there are no reports of the pathological findings that occur in immunotherapy-induced *** present a case of immunotherapy-induced thyroiditis demonstrating its unique cytopathologic features.A 51-year-old woman with metastatic melanoma was found to have a suppressed TSH and elevated free thyroxine concentration 14 days after starting treatment with nivolumab(PD-1 antagonist)plus ipilimumab(CTLA-4 antagonist)therapy.A thyroid biopsy was performed based on ultrasound findings and cytopathology revealed unique features including abundant clusters of necrotic cells,lymphocytes and CD163-positive *** case reports cytopathologic features found in immune checkpoint inhibitor related *** appear to be unique findings and may help inform future research regarding the pathophysiology and mechanisms of this condition.

关键词： Thyroiditis PD-1 CTLA-4 Ipilimumab Nivolumab Cytology

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