1.Screening of specific binding peptide targeting blood vessel of human esophageal cancer in vivo in mice.
Min ZHI ; Kai-chun WU ; Zhi-ming HAO ; Chang-cun GUO ; Jia-yin YAO
Chinese Medical Journal 2011;124(4):581-585
BACKGROUNDCancer of the esophagus and gastroesophageal junction remains a virulent malignancy with poor prognosis. Rapid progresses were made in chemotherapeutic agents and the development of molecular markers allowed better identification of candidates for targeted therapy. This study aimed to identify the candidate peptides used for anti-angiogenic therapy of esophageal cancer by in vivo screening C7C peptide library for peptides binding specifically to blood vessels of human esophageal cancer.
METHODSThe phage displayed C7C peptide library was injected intravenously into mice bearing human esophageal tumor xenografts under renal capsule. After 5 rounds of screening, 13 clones were picked up individually and sequenced. During each round of screening, titers of phage recovery were calculated from tumor xenograft and control tissues. Homing of these 9 peptides to tumor vessel was detected by calculating phage titers in the tumor xenograft and control tissues (lung and spleen) after each phage was injected into mice model, and compared with the distribution of phage M13 and VIII-related antigen in tumor xenograft by immunohistochemical staining. Comparisons among groups of data were made using one-way analysis of variance (ANOVA), followed by the Bonferroni multiple comparisons test.
RESULTSThe number of phage recovered from tumor tissue of each round increased gradually in tumor group while decreased in control groups (P < 0.01 in tumor and spleen, P < 0.05 in lung). Immunohistochemical staining showed similar staining pattern with M13 antibody or VIII-related antigen antibody, suggesting that phages displaying the selected peptides could home to blood vessel of human esophageal cancer. According to their DNA, 9 corresponding peptide sequences were deduced. And the homing ability to blood vessel of phages displaying the selected peptides was confirmed by comparing with their recovery in tumor and control tissues. Two motifs, YSXNXW and PXNXXN, were also obtained by analyzing the homology of these peptide sequences. The staining distribution of phage with the sequence of PNPNNST was similar to that of the blood vessel marker factor VIII-related antigen staining. After sequencing, each phage with the selected peptide of PNPNNST with 1.0 × 10(11) pfu/ml was injected intravenously into mice. The homing ability to tumor vessel of these 9 kinds of peptides in the xenograft was higher than control tissues (lung and spleen).
CONCLUSIONNine peptides obtained from in vivo screening homed to the blood vessel of human esophageal cancer, and the two motifs of YSXNXW and PXNXXN are the possible biochemical recognition units binding to vascular endothelial cells of esophageal cancer.
Animals ; Antineoplastic Agents ; therapeutic use ; Endothelial Cells ; drug effects ; Esophageal Neoplasms ; blood supply ; drug therapy ; metabolism ; Humans ; Immunohistochemistry ; Mice ; Mice, Inbred BALB C ; Peptide Library ; Peptides ; therapeutic use
2.Expression of Smads in keloid scarring.
Bing TANG ; Bin ZHU ; Liang-Kuan BI ; Chun-Li XUE ; Hao CAI ; Jia-Yuan ZHU
Chinese Journal of Surgery 2009;47(12):941-943
OBJECTIVETo investigate the differential expression of different types of Smads in keloids, normal scars and normal skins and its possible clinicopathological significance.
METHODSRT-PCR and Western blot methods were used to examine the expression of Smads mRNA and proteins level in 10 cases of keloid, in 10 cases of normal scar and in 10 cases of normal skin tissues and fibroblasts. Fibroblasts of keloid, normal scar and normal skin were cultured in vitro. The expression difference were compared and analyzed by t-test, there was statistical difference when P < 0.05.
RESULTSThe mRNA and protein expression of inhibitory Smad7 were significantly down regulated in keloid compared with normal scar (P < 0.05) and normal skin (P < 0.05). However, no significant difference of the mRNA and protein expression of Smad2, 3 and the protein expression of phosphorylation of Smad2, 3 in keloid, normal scar, normal skin tissues and fibroblasts.
CONCLUSIONSThe decreased expression of Smad7 in keloid might play a significant role in the increased TGF-beta1/Smads signal transduction, which can not be terminated by autologous negative feedback cycle.
Adolescent ; Adult ; Female ; Humans ; Keloid ; metabolism ; Male ; Middle Aged ; RNA, Messenger ; genetics ; Signal Transduction ; Smad Proteins ; genetics ; metabolism ; Transforming Growth Factor beta1 ; metabolism ; Young Adult
3.Laparoscopy-assisted combined radical resection for synchronous rectal and gastric cancer in elderly patients: report of two cases.
Jia-feng FANG ; Hong-bo WEI ; Tu-feng CHEN ; Yong HUANG ; Bo WEI ; Zong-heng ZHENG ; Jiang-long HUANG ; Hao-zhong XU
Chinese Journal of Gastrointestinal Surgery 2012;15(2):149-151
OBJECTIVETo investigate the safety and feasibility of laparoscopy-assisted combined radical resection for synchronous rectal and gastric cancer in elderly patients.
METHODSClinical data of two elderly patients undergoing laparoscopy-assisted combined radical resection for synchronous rectal and gastric cancer were analyzed retrospectively.
RESULTSThe two cases were 78 and 75 years old respectively. Both were complicated with many medical conditions. One case suffered from stage II cancer in the gastric body and stage IB rectal cancer, and the other suffered from stage IIIA gastric cancer and stage IB rectal cancer. Both cases had received laparoscopy-assisted combined radical resection for synchronous rectal and gastric cancer, with 5 cm of incision. The operative time was 260 and 255 min and the intraoperative bleeding was 60 and 80 ml respectively. No complication occurred intraoperatively. Time to resume oral intake was 4 and 5 days and length of postoperative hospital stay was 13 and 14 days respectively. No postoperative complication occurred. The patients were followed up for 13 and 12 months and no postoperative recurrence or metastasis was noticed.
CONCLUSIONLaparoscopy-assisted combined radical resection for elderly synchronous rectal and gastric cancer is safe and feasible when performed by surgeons with plentiful experience in laparoscopic technology, and associated with less injury and faster recovery.
Aged ; Female ; Humans ; Laparoscopy ; methods ; Rectal Neoplasms ; complications ; surgery ; Retrospective Studies ; Stomach Neoplasms ; complications ; surgery ; Treatment Outcome
4.Autologous buccal mucosal graft pre-transplantation for urethral reconstruction of complicated hypospadias.
Hao WANG ; Sen-Kai LI ; Ming-Yong YANG ; Yang-Qun LI ; Li-Qiang LIU ; Qiang LI ; Wen CHEN ; Jia-Jie XU ; Yong-Qian WANG ; Yi-Guang WU
Chinese Journal of Plastic Surgery 2005;21(5):360-363
OBJECTIVEApplicate autologous buccal mucosal graft pre-transplantation for urethral reconstruction of complicated hypospadias by staging.
METHODSFrom 1999 to 2003, 40 patients have been treated by method of autologous buccal mucosal graft pre-placing. There were two models: graft onlay and graft-tube for urethral reconstruction, and the 2rd operation was accomplished half year later.
RESULTSAll patients healed without urethral fistula.
CONCLUSIONThe method is valuable for treatment of complicated hypospadias.
Adolescent ; Adult ; Child ; Child, Preschool ; Humans ; Hypospadias ; surgery ; Male ; Mouth Mucosa ; transplantation ; Reconstructive Surgical Procedures ; methods ; Surgical Flaps ; Urethra ; surgery ; Young Adult
5.Suppression of experimental abdominal aortic aneurysm by saturated hydrogen saline: a preliminary study with rats.
Feng CHEN ; Jiang XIONG ; Wei GUO ; Xiu-jie PAN ; Tao ZHANG ; Yu-xiang SONG ; Sen-hao JIA ; Jie LIU
Chinese Journal of Surgery 2013;51(5):437-441
OBJECTIVETo investigate the effects of saturated hydrogen saline on the prevention of abdominal aortic aneurysm (AAA) induced by calcium chloride in a rat model.
METHODSIn healthy male Sprague-Dawley rats, AAA was induced by infiltration of abdominal arota with 0.5 mol/L calcium chloride. Saturated hydrogen saline (5 ml·kg(-1)·d(-1)) or saline was administred intraperitoneally once daily. Twenty-eight days later, the diameter of the aorta was measured, and the aortic tissue was exercised for histological examination. Pro-inflammatory cytokines (tumor necrosis factor α (TNF-α), IL-1β) in AAA tissue were detected with ELISA. The protein expression and mRNA expression of matrix metalloproteinase 2 (MMP-2) and MMP-9 in AAA tissue were observed by immunohistochemistry staining and real-time PCR.
RESULTThe aorta diameter of the experiment group and control group were (2.2 ± 0.3) mm and (3.4 ± 0.5) mm, the tissue IL-1β levels were (81 ± 29) ng/L and (165 ± 51) ng/L, the tissue TNF-α levels were (109 ± 46) ng/L and (360 ± 51) ng/L, the relative mRNA expressions were 2.4 ± 1.0 and 11.8 ± 2.9, the relative mRNA expressions were 2.9 ± 0.6 and 6.7 ± 1.0 (t = 4.055 to 10.406, P < 0.05). Compared with the control group, the infiltration of inflammation, the injury of elastic fibers in the vessel wall, and the positive expression of MMP-2 and 9 protein of the experiment group were all reduced.
CONCLUSIONSSaturated hydrogen saline prevents the degradation of elastin in vessel wall and ameliorates the formation and development of AAA, which may be associated with its anti-inflammatory effects, thereby reduces the MMP-2 and 9 mRNA and protein expression.
Animals ; Aorta, Abdominal ; pathology ; Aortic Aneurysm, Abdominal ; prevention & control ; Disease Models, Animal ; Hydrogen ; pharmacology ; Interleukin-1beta ; metabolism ; Male ; Matrix Metalloproteinase 2 ; metabolism ; Matrix Metalloproteinase 9 ; metabolism ; Rats ; Rats, Sprague-Dawley ; Sodium Chloride ; pharmacology ; Tumor Necrosis Factor-alpha ; metabolism
6.Anatomy of mesoesophagus in esophagectomy with minimally invasive three-fields lymphadenectomy.
Hao-sheng ZHENG ; Jun-hui FU ; Ze-sen DU ; Chun-peng ZHENG ; Zhuo-yi LI ; Jia-jie LI
Chinese Journal of Gastrointestinal Surgery 2013;16(9):853-856
OBJECTIVETo explore the anatomic features of mesoesophagus in combined thoracoscopic and laparoscopic esophagectomy with three-fields lymphadenectomy.
METHODSClinical data of 67 patients undergoing thoracoscopic and laparoscopic esophagectomy with three-fields lymphadenectomy from July 2011 to September 2012 were analyzed retrospectively. All the patients underwent three-fields lymphadenectomy. Proper surgical planes were selected according to anatomy of mesoesophagus. Thoracoscopic surgical space was bounded on azygotic vein and divided into upper and low esophageal triangle. Pancreas was the key anatomical mark for laparoscopic gastric dissection, and peripancreatic space was the natural laparoscopic surgical plane. Prevertebral fascia was bottom surface of neck dissection and carotid sheath was the boundary of two sides.
RESULTSThe median operative time was 251.6 min (range, 220 to 320 min). The median operative blood loss was 105.6 ml (range, 40 to 320 ml). The median number of lymph nodes dissected was 29.1 (range, 13 to 46, totally 1949). There was no perioperative death. Sixty-six patients were followed up with a mean follow-up time of 8.2 months (range, 2 to 14 months). Postoperative complications included reflux esophagitis in 10 and anastomotic stenosis in 3 cases.
CONCLUSIONIt is safe and more radical for minimally invasive esophagectomy that overall concept of minimally invasive anatomy of mesoesophagus is applied to identify the anatomic plane and landmark during operation.
Aged ; Esophageal Neoplasms ; pathology ; surgery ; Esophagectomy ; Esophagus ; anatomy & histology ; pathology ; Female ; Humans ; Lymph Node Excision ; Male ; Middle Aged ; Retrospective Studies
7. Mechanism of 1,2-dichloroethane-induced toxicity in SH-SY5Y Cells
Si LI ; Hong-Ling LI ; Na ZHAO ; Xiang-Rong SONG ; Hao-Zhong LIU ; Jia-Bin CHEN ; Long-Yuan JIANG ; Yong-Shun HANG ; Hai-Lan WANG
China Occupational Medicine 2016;43(06):652-661
OBJECTIVE: To establish the cell model of human neuroblastoma cell( SH-SY5Y cell) exposed to1,2-dichloroethane( 1,2-DCE) in vitro and to explore the mechanism of 1,2-DCE-induced toxicity in SH-SY5Y cells.METHODS: SH-SY5Y cells were collected in their logarithmic growth phase and cultured in complete medium that had final concentrations of 1,2-DCE in 0,10,20,30,40,50,60,70 and 80 mmol / L for 24 hours. Cell morphology was observed and cell survival rate was examined by CCK-8 assay. Using chemical colorimetric method, the activity of lactic dehydrogenase( LDH) in the cell culture supernatant,and the intracellular level of malondialdehyde( MDA),the intracellular activities of superoxide dismutase( SOD) and adenosine triphosphate( ATP) enzymes were detected. RESULTS: With the increasing exposure concentrations of 1,2-DCE,the cell density of SH-SY5Y cells gradually decreased,the synapse became shorter,the membrane ruptured,cytoplasm condensed and cytoplasmic contents overflowed increased.With the increasing concentration of 1,2-DCE,the cell survival rate decreased( P < 0. 01),the activity of LDH in the cell culture supernatant increased( P < 0. 01). These changes had a dose-effect correlation. Intracellular MDA level,and activities of SOD,Na~+-K~+-ATP enzyme,Ca~(2+)-Mg~(2+)-ATP enzyme and total ATP enzyme increased at first and then decreased. The activity of LDH in the cell culture supernatant and cell survival rate was negatively correlated( the correlation coefficient is- 0. 907,P < 0. 01). CONCLUSION: 1,2-DCE could inhibit the proliferation of SH-SY5Y cells.The mechanism may be related to the permeability change of cell membrane,cellular damage from excessive free radicals,the decrease of free radical scavenging capacity,ATP enzyme activity and calcium overloading. SH-SY5Y cells can be used as a common cell line for 1,2-DCE cytotoxicity analysis.
8.Diagnostic Evaluation of CT Enhanced Thin-section Scan Technique for Small Pulmonary Carcinoma
Zhen-Feng ZHANG ; Cheng-Hui ZHANG ; Wei-Zhang ZHANG ; Pei-Hong WU ; Li-Xia LU ; Jia-Yao LI ; Yao-Pan WU ; Hao-Gao LIN
Chinese Journal of Cancer 2001;20(1):84-88
Objective: The current study was designed to assess the clinical value of heteromorphic enhanced vessel sign in the thin section CT images in diagnosis and distinguished diagnosis for small lung cancer. Methods: A total of 37 distinguished small peripheral lung cancer with less than 3 cm diameter were compared between enhanced thin section CT and conventional enhanced CT. At the same time,18 pulmonary inflammatory pseudotumors and pulmonary tuberculomas required distinguished have been studied as control. The enhanced thin section CT images of the three kinds of diseases were investigated. Results: 1.The enhanced thin section CT scan apparently showed the special signs (heteromorphic enhanced vessel signs) of the tumor vessel in small lung cancer, which was rarely displayed on conventional CT images. 2.The heteromorphic enhanced vessel sign was rarely found in pulmonary inflammatory pseudotumor and pulmonary tuberculoma. Conclusion: The heteromorphic enhanced vessel sign is a valuable CT characteristic for diagnosis and distinguishing diagnosis for small lung carcinoma.
9.Characteristics of Blood Pressure in Elderly Patients with Hypertensive Cerebral Small Vessel Disease and Their Correlation with Traditional Chinese Medicine Syndrome Types
Shi-Xing HAO ; Hui-Pei AO ; Hui-Cong LI ; Wei-Sen ZHONG ; Jia-Cheng HUANG ; Xiao-Lu MIAO
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(8):1962-1970
Objective To explore the characteristics of blood pressure in the elderly patients with hypertensive cerebral small vessel disease(CSVD)and their correlation with traditional Chinese medicine(TCM)syndrome types.Methods A retrospective analysis was conducted in 189 elderly patients with essential hypertension.With reference to the presence or absence of CSVD,the patients were divided into CSVD group(87 cases)and non-CSVD group(102 cases).The blood pressure related parameters and clinical data obtained by four diagnostic methods of TCM in the two groups were collected,and then the characteristics of blood pressure and their correlation with TCM syndromes were analyzed with statistical methods.Results(1)CSVD group had higher values than non-CSVD group in the ambulatory blood pressure parameters of 24-hour systolic blood pressure(24hSBP),24-hour diastolic blood pressure(24hDBP),daytime systolic blood pressure(DSBP),daytime diastolic blood pressure(DDBP),nighttime systolic blood pressure(NSBP),nighttime diastolic blood pressure(NDBP),24-hour pulse pressure(24hPP),daytime pulse pressure(DPP),nighttime pulse pressure(NPP),maximum SBP,morning SBP,daytime SBP load and nighttime SBP load(P<0.01).(2)The analysis of blood pressure variability showed that the mean value of nighttime SBP standard deviation(NSSD)in CSVD group was higher than that in the non-CSVD group(P<0.01).(3)The analysis of circadian rhythm of blood pressure showed that there was significant difference in the comparison of circadian rhythm of ambulatory blood pressure between the two groups(P<0.05):non-CSVD group was predominated by non-dipper type blood pressure(50 cases,49.02%)and dipper type blood pressure(31 cases,30.39%),and CSVD group was predominated by non-dipper type blood pressure(38 cases,43.68%)and super-dipper type blood pressure(31 cases,35.63%).(4)Logistic regression analysis showed that 24hSBP(OR=1.296,95%CI:1.112-1.511),maximum SBP(OR=1.074,95%CI:1.006-1.146),morning SBP(OR=1.064,95%CI:1.013-1.118),abnormal circadian rhythm of blood pressure(OR=3.736,95%CI:1.663-8.390)were the influence factors of CSVD(P<0.05 or P<0.01).(5)The analysis of the distribution of TCM syndrome types showed that non-CSVD group was dominated by accumulation of excess phlegm-damp syndrome(58.82%)and yin deficiency and yang hyperactivity syndrome(21.57%),and CSVD group was dominated by yin deficiency and yang hyperactivity syndrome(51.72%)and accumulation of excess phlegm-damp syndrome(21.84%).(6)The analysis of blood pressure in patients with various syndrome types showed that the DPP of patients with accumulation of excess phlegm-damp syndrome in the CSVD group was significantly higher than that in the non-CSVD group(P<0.01),and the 24hDBP and NDBP of patients with yin deficiency and yang hyperactivity syndrome in the CSVD group were significantly higher than those in the non-CSVD group(P<0.01).Conclusion It is indicated that 24hSBP,maximum SBP,elevated morning SBP,and abnormal blood pressure circadian rhythms may be the important risk factors for the hypertensive CSVD in the elderly.Elderly hypertensive patients with accumulation of excess phlegm-damp syndrome should pay more attention to the mean daytime pulse pressure,and elderly hypertensive patients with yin deficiency and yang hyperactivity syndrome should pay more attention to monitoring DBP.The dynamic observation and early control of the blood pressure is helpful for the prevention and treatment of CSVD in the elderly patients with hypertension.
10.The clinic research of the modified laparoscopic splenectomy for massive splenomegaly in the treatment of children with hematologic diseases.
Xiao-Geng DENG ; Jing TANG ; Yao-Hao WU ; Maharjan AUMIR ; Jie ZHANG ; Jia-Jia ZHOU ; Le-Xiang ZENG ; Rong-Lin QIU
Chinese Journal of Surgery 2013;51(9):788-791
OBJECTIVETo summarize the experience and characteristics of the modified laparoscopic splenectomy for massive splenomegaly in the treatment of children with hematologic disease.
METHODSThe clinical data of 30 cases of laparoscopic splenectomy for massive splenomegaly of children with hematologic disease from March 2007 to December 2011 was analyzed retrospectively. There were 18 male and 12 female patients, aging from 2 to 14 years. Primary disease included mediterranean anemia (17 cases), hereditary spherocytosis (4 cases) and idiopathic thrombocytopenic purpura (ITP, 9 cases). Dissection started with cutting off the gastrosplenic ligaments and lesser sac to fully reveal the splenic hilum, the splenic artery was clamped twice with 10 mm tiatanum clamp. When most of blood stored in the spleen back to heart through the veins and the splenic volume had already decreased, the splenic vein was ligated with 10 mm titanium clip and cut with ligsure and splenic pedicle separated. The Surgery and complication were recorded. For 1 week after surgery, the hemoglobin and platelet counts were reviewed.
RESULTSTwenty-six cases were performed successfully, and 4 cases were converted to open procedure. Of the 4 cases, 2 cases was obesity because of idiopathic thrombocytopenic purpura, 1 case was β thalassaemia combined severe liver enlargement, and 1 case was after partial splenic embolization. In cases of laparoscopic splenectomy, operation time was 110 to 130 minutes, with an average of 120 minutes, and blood loss during operation was 35 to 180 ml, with an average of 45 ml. Compared with pre-operation, the hemoglobin of mediterranean anemia and hereditary spherocytosis patients were (92 ± 8) g/L, and blood platelet count of ITP patients was (127 ± 20)×10(9)/L, and they increased obviously at 1 week after operation (t = 4.175 and 8.253, both P = 0.000).
CONCLUSIONThe modified surgical method make the laparoscopic splenectomy for massive splenomegaly in many children with hematologic diseases possible, which was thought to be impossible in the past.
Child ; Hematologic Diseases ; Humans ; Laparoscopy ; Splenectomy ; Splenomegaly ; Treatment Outcome