Volume 91  ·   Issue 08  ·  2011

dendritic cells (DCs) are the most powerful full-time antigen-presenting cells in the body.The traditional view is that DCs present antigens in non-inflammatory environment,integrate the surrounding signals and initiate a corresponding secondary immune response according to the information received, and induce specific immune response against the invading antigen.

：Objective To summarizethe histopathological features of posttransplant complications for renal allografts andevaluate the biopsy values. Methods Between January 1997 and May 2010, a total of 1712percutaneous renal allograft biopsies were performed in 1500 kidney transplants anddiagnostic procedures for staining, classification and staging had been performedaccording to the Banff 1997 and 2005 Schema. Results There were 213 ( 14.2% ) cases ofacute T cell-mediated rejection post transplantation in 1500 kidney transplants. Meanwhilethere were 36 ( 2.4%) cases of acute antibody-mediated rejection.Chronic T cell-mediatedrejection and chronic antibody-mediated rejection were 251 ( 16.7% ) cases and 45 (3.0%)cases, respectively. Acute CNI-nephrotoxicity and chronic CNI-nephrotoxicity were 106(7.1%)cases and 251 ( 16.7% ) cases, respectively. Relapsed or new nephropathy were 6 (0.4% ) cases. Chronic CNI-nephrotoxicity is the most common cause of allograft dysfunctionin the long survival recipients.Conclusion Percutaneous renal allograft biopsy is valuablefor the diagnosis of various posttransplantation complications.

Objective To evaluate short-term and long-term safety of using single-dose escalation of recombinant humanized anti-CD3 monoclonal antibody (OKT3) in kidney transplantation recipients.Methods A total of 29 recipients of cadaveric kidney transplant from June 2008 to December 2008 were sequently assigned to receive single-dose intravenous injection of OKT3 with different doses of 2. 5 mg( n =9) , 5.0 mg (n = 10) and 10. 0 mg (n = 10) at Days 7 - 14 post-operation. Meanwhile, a control group was established by selecting kidney transplant recipients, who did not participate in the trial in the same period.All patients were followed up for at least 2 years. During this period, liver function, kidney function,hemoglobin and other biochemical indicators were monitored and adverse events recorded over time. Results No obvious first dose effect was observed,except low heat (7/29), chills (4/29) , mild liver damage (2/29) , upper respiratory tract infection and headache (1/29) across all doses. Other adverse reactions were mild, unrelated with doses. The 2-year patients/ grafts survival rates of treatment goup and control group were 100% / 100%, and 100% / 97%, respectively. The incidence of acute rejection confirmed by renal biopsy was 6. 9% (2/29) and 10. 0% (3/30) in treatment group and control group, respectively. The incidence of lung infection was 10. 3% ( 3/29 ) and 13.3% ( 4/30 ), respectively. The values of serum creatinine at 1 week and 3, 6, 12, 24 months showed no statistically significance in two groups ( all P ＞0. 05). Conclusion It is safe to use single-shot OKT3 intravenously in kidney transplant recipients. The recombinant humanized OKT3 may be an effective immunosuppressive agent with milder toxicity for solid organ transplantation.

Objective To find whether the up-regulation of soluble human lecocyte antigen-G5 (sHLA-G5) levels is a new function mechanism of anti-interleukin-2 receptors (anti-IL-2R) monoclonal antibody treatment in kidney transplantation. Methods A total of 215 recipients at our centre from January 2006 to December 2007 were divided into antibody use group ( n = 141 ) and antibody non-use group ( n =74) and another healthy group (n =69). The sHLA-G5 level in peripheral blood was detected by enzymelinked immunosorbent assay (ELISA). And the expression of HLA-G5 was confirmed by Western blot and Real-time polymerase chain reaction (PCR). Results sHLA-G5 levels was (56 ± 30)μg/L in using antiIL-2 receptor monoclonal antibody before transplantation, It was higher than that before use antibody [(34 ±20) μg/L], also higher than healthy group [(35 ± 17) μg/L] and antibody non-use group [(36 ± 19)μg/L, P ＜0. 05, respectively]. At Day 1, Day 4, Week 1, Week 2 post-transplantation, the level of sHLA-G5 of recipients with antibody use was significantly higher than that of those with antibody non-use. The values were as follows: (95 ±35) μg/L vs (54 ± 16) μg/L , (131 ±24) μg/L vs (75 ±22) μg/L ,(167±44) μg/L vs (62 ± 17) μg/L, (172 ±35) μg/L vs (45 ±16) μg/L(all P＜0.01). And the results of Western blot and RT-PCR corresponded to those of ELISA. Conclusion The preoperative use of first dose of anti-IL-2R monoclonal antibodies results in the up-regulated level of sHLA-G5. Thus it is beneficial for protecting the kidney survival and reducing the risks of acute rejection.

Objective To compare the microchimeric and rejection rates in living donor kidney transplant recipients in mother and child relations and other relations. Methods This retrospective singlecenter study enrolled 130 recipients to receive allografts from living related donors from 2004 to 2008 at our hospital. They were followed up for 1 - 5 years. The demographic data of the study population were analyzed by basic statistical methods. A total of 43 recipient blood samples were collected for the detection of microchimerism by the assays of short tandem repeat (STR) and sex-determining region-y gene (SRY)polymerase chain reaction (PCR). Results The 1-year patient/graft survival rates were 93.8% and 92.3% respectively. And there was no significant differences between mother and child group and other relative group. Forty-six biopsy samples were collected from 46 recipients. Twenty-six (20.0% ) cases had the occurrences of acute rejection episodes in different Banff degrees as proven by biopsy. 53. 8% ( 14/26)cases were mother and child renal transplantation, higher than other relative (46. 2%, 12/26) . The mother donor kidney transplant recipients had about a twice higher rejection rate ( 30.4% vs 14. 3%, P = 0.028 ) and a twice higher microchimeric rate(25. 0% vs 14. 8% )than other relative. Conclusion Compared with other relations, the mother donor kidney recipients tend to have higher rates of microchimerism and acute rejection. And the special immune effect in mothers and children renal transplantation may influence its outcomes.

Objective To compare the different impacts of right ventricular apex, right ventricular outflow tract septum and left ventricular outflow tract septum region on interventricular electro-mechanical synchronization and assess the ideal pacing sites for maintaining the interventricular electro-mechanical synchronization. Methods A total of 30 patients without organic heart disease were operated with radiofrequency ablation at our hospital. The mapping electrodes were implanted post-operatively on the left ventricular posterior wall (LVPLW) and right ventricular anterior lateral wall (RVALW) respectively. And the ablation electrodes were placed subsequently in right ventricular apex, right ventricular outflow tract septum region and left ventricular outflow tract septum. The difference values were measured between transmission time from pacemaker to LVPLW, from pacemaker to RVALW and between aortic pre-ejection interval (APEI) and pulmonary artery pre-ejection interval (PPEI). Then their correlations were compared. Results When pacing at right ventricular apex, the difference value between transmission time from pacemaker to LNPLW and from pacemaker to RVALW was (34±7)ms. And it was (18 ±4)ms while pacing at right ventricular outflow tract septum region and ( 12 ± 4)ms at left ventricular outflow tract septum region. There was significant difference (P＜0.01). The absolute value of APEI-PPEI was (25 ±5) ms at right ventricular apex, (13±4) ms at right ventricular outflow tract septum region and (11±3) ms at left ventricular outflow tract septum region. And there was significant difference (P ＜0. 01 ). The absolute value of APEI-PPEI was positively correlated with the change of LNPLW-RVALW (r= 0. 993, P ＜ 0. 01 ). Left ventricular outflow tract septum pacing showed ABp and left ventricle end-systolic pressure significantly increased [(127±23) mm Hg, (142±22) mm Hg,P ＜0.05], left ventricular end-diastolic pressure was significantly lower [(9±3) mm Hg, P ＜ 0. 05]. Conclusion Compared with right ventricular apical pacing and right ventricular outflow tract ventricular septal pacing, left ventricular outflow tract septum has a smaller impact on the electro-mechanical synchronization. It conforms more closely to the physiological pacing so that there is a higher synchronization of electrical and mechanical ventricular contractions.

Objective There is no consensus on the treatment of renal colic, a hazardous condition for both pregnant women and their fetus during pregnancy. The present study was to evaluate the therapeutic safety and efficacy of double-J stent. Methods Twenty-five pregnant women were admitted into our hospital for renal colic between January 2008 and June 2009. The mean age was (28.3±4.9) years old. And the mean gestational week was (20.1±6.9) weeks. The diagnostic and therapeutic procedures were as follows:(1) Upon admission, routine urine and blood tests, chemistry panel and ultrasonography were performed.(2) Analgesics or antispasticity drugs were dispended to the patients, such as progesterone. (3)Magnesium sulfate was used for anti-inflammation. (4)If renal colic was not relieved, a double-J stent was inserted into the ureter via cystoscopy. At pre-, intra- and post-operation, an obstetrician monitored the fetal heart and uterine contraction. ( 5 ) Ultrasonography was conducted to check the location of double-J stent. (6) After delivery, the women underwent ESWL (extracorporeal shock wave lithotripsy) and then the double-J stent was extracted. Results Five (20%, 5/25 ) patients had a positive previous history: three for renal calculus ( n = 3), solitary kidney (n=1) and reimplantation of ureter ( n = 1 ). Only one patient run a high fever of 40 ℃. Most patients (84%) had a positive percussion over renal regions. Only 6 patients (24%,6/25 ) were found to have a great quantity of red blood cells in urine. Half of the patients showed 10 - 20white blood cells (WBC) per high power field in urine. Fifteen patients (60%, 15/25) had an elevated count of WBC in routine blood test. Only one patient was with elevated serum creatinine because of her solitary kidney. The calcium level decreased in 8 patients (32%, 8/25 ). All patients suffered hydronephrosis while 18 patients (72% , 18/25) were not found with calculus in ureters or kidneys. Pain of six patients (24%, 6/25 ) was relieved after the dosing of analgesics. Eighteen patients (72%, 18/25)underwent double-J stent insertion and 1 patient (4%, 1/25 ) received percutaneous renal puncture. Then pain was relieved and hydronephrosis vanished. After delivery, calculi were treated properly and then the double-J stent were extracted. Iconography showed no residual calculi. Conclusion For pregnant women with renal colic, retrograde intra-ureteral cannula of double-J stent is both safe and effective. It should be recommended for all renal colic women during pregnancy with or without calculus after the ineffective dosing of analgesics.

Objective To summarize the clinical experiences of laparoendoscopic single-site splenectomy. Methods From January 2010 to June 2010, laparoendoscopic single-site splenectomy was performed in 4 patients, including traumatic rupture (n=1), hypersplenism ( n = 1 ), splenic aneurysm ( n = 1) and cardia cancer with invasiveness to spleen (n =1). Results All operations were successful with an operative duration 180- 360 min, a volume of intraoperative blood loss 100 -400 ml and a hospital stay 7 -9 days. All patients stayed free of such postoperative complications as hemorrhage, pancreatic leakage,venous thrombosis and fever. The umbilical incision healed well with satisfactory cosmetics. Conclusion Laparoendoscopic single-site splenectomy is both safe and feasible for experienced laparoscope surgeons.

Objective To investigate the surgical treatment of initially unresectable primary and secondary hepatic tumors. Methods For the patients with multiple and bilobar colonic hepatic metastases,a first-stage hepatectomy consisted in a radical resection of sigmoid colonic carcinoma and left lateral hepatic segment. Subsequently, under the guidance of ultrasonography and radiography, a right portal vein chemoembolization (PVCE) was performed via a percutaneous approach through left portal branch to induce the atrophy of right hemiliver and hypertrophy of left hemiliver. At Week 5 post-PVCE, a second-stage hepatectomy was planned to resect the right hemiliver. For patients with huge hepatocellular carcinoma (HCC), transcatheter arterial chemoembolization (TACE) were performed and it was followed by PVCE 1 week later. At Week 4 post-PVCE, a right trisegmentectomy was attempted to resect the right liver tumor.The volume of liver was evaluated with three-dimensional CT scan at Weeks 2 and 4 weeks post-PVCE.Results At Week 4 post-PVCE, the atrophy of right lobe was induced and the left lobe underwent compensatory hypertrophy. The remnant volumes of right lobe and right trisegment for HCC decreased from 1380. 0 cm3, 1685.4 cm3 at pre-PVCE to 740. 2 cm3 , 1228. 1 cm3 at Post-PVCE. The values increased from pre-PVCE 435.1 cm3, 151.5 cm3 to Post-PVCE 624.4 cm3, 560. 2 cm3 for left hepatic lobe remnant of colonic liver metastases and left lateral segment for HCC. The ratios of liver remnant to estimated total liver volume increased from 25.6%, 13.6% at pre-PVCE to 50.0%, 43. 1% post-PVCE respectively. The postoperative course was uneventful. The liver function, serum CEA and AFP decreased to the normal levels. Two patients were followed up for 18 and 8 months respectively. There was no tumor recurrence.Conclusion PVCE prevents the hepatic function failure after a major hepatectomy. And it may benefit more patients with previously unresectable liver tumors.

Objective To summarize the clinical characteristics of Bartter syndrome and investigate its pathogenesis. Methods The clinical data of 6 cases of Bartter syndrome at our hospital from November 2006 to May 2010 were analyzed retrospectively. Results The onset age of Bartter syndrome was 13-35years old. The main symptoms included weakness (6/6), paralysis ( 1/6 ), numbness ( 5/6 ) and tetany (4/6). All patients had normal blood pressure. The biochemical tests showed persistent hypokalemia, metabolic alkalosis (6/6) and hyperreninemia. The pathological examination of deltoid muscle biopsy showed the swelling, degeneration and necrosis of myocytes and the deposition of immunocomplex in myolemma. And the pathological examination of renal biopsy showed the hyperplasia of juxtaglomerular apparatus (5/6) and the deposition of immunocomplex.All symptoms were relieved after a therapy of potassium supplementation or a combination of indomethacin, spironolactone and immunosuppressant.Conclusion When such clinical features as weakness, paralysis, tetany, hypokalemic alkalosis and normotension are encountered, Bartter syndrome should be suspected. Serum electrolytes, blood gas analysis and activation of the renin-angiotensin-aldosterone system should be examined for a definite diagnosis. The treatment of choice includes potassium and magnesium supplementation or in combination with prostaglandin synthetase inhibitor, aldosterone antagonist and immunosuppressant. Immunologic mechanism may participate in the course of Bartter syndrome.

Objective To assess the application value of emergency colonoscopy in the diagnosis and treatment of acute colorectal obstruction. Methods A total of 459 patients with acute colorectal obstruction received emergent colonoscopy from July 2002 to July 2010. The safety and effective rates were analyzed. Results The diagnostic rate of successful emergency colonoscopy was 100% (459/459) without any complication. Colorectal cancer were found in 71.3% cases (327/459), volvulus of sigmoid in 11.3%(52/459), diaphragmatocele in 0.4%(2/459), megacolon congenitum in 0.6% ( 3/459 ), fecal obstruction in 2.7% (12/459) and none in 13.7% (63/459). The therapeutic rate of colonoscopy was 83.2% (385/459). There were colorectal cancer (n =327), volvulus of sigmoid (n =52) and megacolon congenitum (n = 3). The successful treatment rate was 95. 8% (369/385) and the complication rate 1.4%(5/385). Among all colorectal cancers, 93.9% (307/327) received endoscopic drainage ( mental stents or drainage tube) so as to avoid emergency operations and stoma. And 232 cases underwent phase Ⅰ operation and another 75 cases received chemotherapy or supportive treatment. Conclusion Emergency colonoscopy is an effective, safe, minimal invasive approach for diagnosing and managing acute colorectal obstruction.

Objective To investigate a novel therapeutic regiment for gastrointestinal stromal tumor (GIST) based on c-kit RNA interference (RNAi) under the mediation of AdMax adenovirus. Methods c-kit shRNA, whose lateral sides were decorated with restriction endonuclease sequences, was designed. The joining of c-kit shRNA and PDC316-EGFP-U6 was catalyzed by T4 DNA ligase to construct PDC316-EGFP-U6-C-KIT. Homologous recombination of AdEGFP-U6-C-KIT was performed with AdMax system.Heterotopic transplantation of GIST in nude mice was established. AdEGFP-U6-C-KIT was intratumorally injected in experimental group while blank admax adenovirus AdEGFP-U6 in control group. The volume,inhibition ratio of tumor and CD117 expression of graft tumor were compared between test and control groups.Results The length of c-kit shRNA was around 50 bp in agarose electrophoresis. Gene sequencing revealed the designed c-kit RNAi sequence in PDC316-EGFP-U6-C-KIT. After transfection with AdEGFP-U6-C-KIT,293 cells presented green fluorescence. The physical and infective titer of AdEGFP-U6-C-KIT was 5 × 1011vp/ml and 5.67 × 107 pfu/ml respectively. At the end of test, the mean volume of graft tumor was significantly smaller in test group than in control group [(75 ±23) vs (989 ±31 ) mm3, P =0. 000]. The inhibition ratio of tumor was 59.6% in test group. Two cases(20% )in test group and 10( 100% )in control group had a positive expression of CD117 ( P = 0. 001 ). Conclusion c-kit RNAi mediated by Admax vector system can inhibit effectively the expression of c-kit gene and the growth of GIST in nude mice.

Objective To investigate the effect of inhibiting the expression of human suppressor of morphogenesis in genitalia-1 (hSMG-1) on chemosensitivity in human lung cancer H1299 cells. Methods Specialized small interference RNAs (siRNAs) of hSMG-1 were transfected into H1299 cells. The knockdown effect was evaluated by quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) and immunofluorescence. After the administration of anti-cancer drugs, the cell viable rate was determined by cell counting kit (CCK-8) and apoptotic rate was measured by Annexin V-FITC PI double staining on flow cytometry. The apoptotic related activated caspase 3 and caspase 9 were determined by colorimetric assay. Results The expression of hSMG-1 mRNA was significantly inhibited by hSMG-1 siRNA. And the inhibition rate of (73.8 ± 10. 3) % was obtained ( P ＜ 0. 01 ). The knockdown effect was further confirmed by immunofluorescence. The inhibition of hSMG-1 enhanced the sensitivity of H1299 cells to gemcitabine and cisplatin. The survival rates significantly decreased when the hSMG-1 siRNA transfected cells were treated with 10. 0 mg/L gemcitabine and 10. 0 mg/L cisplatin for 48 h respectively (0. 51 ±0. 02 vs 0. 69 ± 0. 01, P ＜ 0. 01 and 0. 34 ± 0. 03 vs 0. 48 ± 0. 01, P ＜ 0. 02; all compared with control siRNA group). Annexin V-FITC PI double staining showed that, under the treatment of anti-cancer drugs, the apoptotic rate of H1299 cells was significantly increased by hSMG-1 knockdown [gemcitabine, (20.9 ±3.4)% vs (12.0±2.7)%, P＜0.05; cisplatin, (10.2 ±1.8)% vs (4.5 ±2.0)%, P＜0.05; all compared with control siRNA group]. Further study showed the inhibition of hSMG-1 up-regulated the activated caspase 3 and caspase 9 in the treated H1299 cells (gemcitabine, 0. 1 mg/L, 48 h, caspase 3:14. 4 ± 3.8 vs 2. 3 ± 0. 4, P ＜ 0. 01; caspase 9: 15.5 ± 2.4 vs 4. 2 ± 0. 9, P ＜ 0. 01; cisplatin, 1. 0 mg/L,48 h, caspase 3:18.8±3.0 vs 6.5 ±1.5, P＜0. 01; caspase 9:20.3±4.2 vs 8. 1 ±2.0, P ＜0.05; all compared with control siRNA group). Conclusion The inhibition of hSMG-1 significantly enhances the sensitivity of human lung cancer H1299 cells to gemcitabine and cisplatin through an induction of more apoptotic cells. And the activation of mitochondrial apoptotic pathway is involved.

Objective To investigate the transcriptioncal regulation of osmotic response element binding protein (OREBP) to heat shock proteins (HSP)70 and its effect on mucus secretion under hypertonic conditions. Methods Human bronchial epithelial HBE16 cells were cultured in vitro in hypertonic medium for different times. Western blot was used to analyze the levels of OREBP and HSP70-2 protein. The mucin (MUC)5AC protein content in supernatant were detected by enzyme linked immunosorbent assay (ELISA). Different deletions and mutants of HSP70-2 promoter in upstream region were cloned in the reporter pGL3-Basic plasmid. These reporter plasmids were co-transfected with OREBP siRNA and the promoter activities detected with dual luciferase assay to study the ORE site in the HSP70-2 promoter and its impact on MUC5AC. Results Compared with control group (0. 21 ±0. 05, 0. 15 ±0. 06,0. 13 ±0. 04), the levels of OREBP, HSP70-2 and MUC5AC in supernatant significantly increased (0. 54 ±0. 07, 0. 20 ±0. 08, 0. 17 ±0. 04) after HBE16 cells were exposed to 600 mOsm/L hypertonic mediums for 3 h (2. 57, 1.33 and 1. 31 fold in protein respectively ) ( all P ＜ 0. 05 ), and their expression contents increased in a time-dependent manner, for 6 h (2. 81, 3.07 and 3. 77 fold) ( all P ＜ 0. 01 ), for 9 h (3.57, 5. 13 and 4.00 fold) (all P＜0.01), for 12 h (4.24, 5.33 and 4.54 fold) (all P＜0.01). After a knock-down of OREBP by RNAi for 48 h, the levels of OREBP, HSP70-2 and MUC5AC significantly decreased (0. 36 ±0. 08;0. 33 ±0. 08; 0. 24 ±0. 05) versus the control group (0. 95 ±0. 27, 0. 75 ±0. 22,0. 58 ± 0. 22) ( protein inhibition ratio at 62%, 56% and 59% respectively) ( P ＜ 0. 05, P ＜ 0. 01, P ＜0. 05). Luciferase assay indicated that an important ORE site in HSP70-2 promoter was in the region from -353 to -66. The inactivation of ORE site at -93 by site-directed mutagenesis led to a complete loss of HSP70-2 promoter activity (P ＜ 0. 01 ). Conclusion One ORE site at - 93 in the HSP70-2 promoter and OREBP were found to play essential roles in inducing the HSP70-2 transcription and MUC5AC hypersecretion in human bronchial epithelial cells in response to hypertonicity.

Objective To study the controllabe expression of soluble tumor necrosis factor-related apoptosis-iuducing ligand (TRAIL) in mesenchymal stem cells and evaluate its potential tumoricidal effects in cancer therapy. Methods The controllable TRAIL expression vector of Ad-Tet-TRE-TRAIL was established in an adenovirus vector for transfection into murine mesenchymal stem cells. The controllable expression and secretion of TRAIL were detected by Western blot and enzyme-linked immunosorbent assay.The viability of hepatocellular carcinoma cells was determined by MTT assay. The tumoricidal activity of TRAIL was determined by Annexin-V/PI staining and flow cytometry. Results The murine expression model of TRAIL was successfully established in the presence of doxycycline. The secreted TRAIL in cell culture medium could efficaciously suppress the growth of human hepatocellular carcinoma SMMC-7402 by induced apoptosis. The cell viability of SMMC-7402 was 66. 5% ± 4. 8% and 42.9% ± 6. 5% at post-treatment versus 97.3% ±2. 2% and 99. 4% ±4. 7% in the control group at 24 h and 48 h. Conclusion The controllable TRAIL expression mediated by mesenchymal stem cells kills human hepatocellular carcinoma cells effectively. And it may provide a novel therapeutic strategy for hepatocellular carcinoma.

The patient was a 25-year-old male who was admitted to the Department of Hematology of our hospital on December 13, 2009 due to "repeated fever for 2 months". At the beginning of October 2009, the patient developed fever without obvious trigger, with the highest body temperature of 39.2℃, which was obvious in the afternoon, accompanied by chills, no chills, occasional cough, no phlegm, night sweats, no epistaxis and gingival bleeding, no skin bleeding spots and ecchymosis, etc. Blood routine in other hospitals: white blood cells 0.81×109/L, neutrophils 0.63×109/L; Hemoglobin 59 g/L, platelets 45×109/L, blood lactate dehydrogenase (LDH) 389.6 U/L, abdominal B-ultrasound showed enlargement of liver and spleen, chest CT showed left hilar lesion with mediastinal lymphadenopathy.

Venous thromboembolism is a common disease, with an annual incidence of about 1‰ ~2‰. The standard treatment is intravenous heparin in the acute phase, and then vitamin K antagonist is maintained. However, vitamin K antagonist is affected by various foods and drugs, so it is necessary to monitor the coagulation function and adjust the dose, which is inconvenient for outpatients to use; And after one year of maintenance use, about 1% to 2% of patients will have severe hemorrhage complications related to vitamin K antagonists.

Epithelial mesenchymal cell transformation (EMT) is the basis of embryonic development and maturation of multicellular organisms, and promotes organ formation, regeneration and tissue fibrosis. Recently, it has been found that EMT is closely related to tumor invasion and metastasis in the pathological processes associated with EMT. Some studies have confirmed that tumor cells with EMT have cell motility, invasiveness, ability to inhibit apoptosis and some characteristics of stem cells. Related signaling pathways have also been shown to play an important role in inducing EMT, including transforming growth factor (TGF) -β signaling pathway, Wnt signaling pathway, Notch signaling pathway, etc. Therefore, a new breakthrough may be found in tumor therapy by studying the occurrence of EMT in tumor cells.

Wolfram syndrome was first proposed by Wolfram and Wagener [1] in 1938. It is a single gene diabetes mellitus caused by mutation of WFS1 gene [2]. It is autosomal recessive inheritance, and its clinical manifestations are mainly diabetes insipidus, diabetes mellitus, optic atrophy and deafness [3-4]. Besides special types of diabetes mellitus, single nucleotide polymorphism of WFS1 gene is also associated with the pathogenesis of type 2 [5-7] and type 1 diabetes mellitus [8].

Case 1: A 12-year-old male was admitted to the Department of Cardiology of Zhejiang Provincial People's Hospital in March 2008 due to congenital atrial septal defect, patent ductus arteriosus, and dyspnea for 15 days after repair of pulmonary arteriovenous fistula. After the aforementioned operation, the patient underwent tracheal intubation and mechanical ventilation in the intensive care unit (ICU) for about 10 days. Chest X-ray, CT and bronchoscopy found that dyspnea was caused by tracheal stenosis (Figure 1A, 1b), so he was transferred to the otolaryngology department for surgical treatment.