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@#Modulating drug release from liposomes at tumor sites are important for eliciting therapeutic effects of platinum drugs considering their low permeability through liposomal membranes, here a novel secretory phospholipase A2 (sPLA2) responsive-liposome system was constructed for oxaliplatin (L-OHP).Lipid ingredients dipalmitoyl phosphatidylcholine and distearoyl phosphoethanolamine-PEG2k, together with facial amphiphiles (FAs) including lithocholic acid (LCA) or 3-keto lithocholic acid (kLCA) were used to prepare sPLA2 responsive-liposome (LCA-Lip or kLCA-Lip) by thin-film hydration method.The physicochemical properties, sPLA2-responsive drug release and anti-tumor activity were evaluated in vitro.The results indicated L-OHP loaded liposomes modified with FAs had similar particle sizes of approximately 100 nm and narrow size distributions (PDI < 0.11).Compared with non-FAs-containing liposomes (C-Lip), LCA-Lip or kLCA-Lip has a comparable entrapment efficiency and loading efficiency.LCA-Lip or kLCA-Lip didn't show significant higher drug leakage at the presence of 10% or 50% fetal bovine serum (FBS) in media than that in media without FBS.Treated with secretory phospholipase A2 from Colo205 cells culture conditioned medium (CCM sPLA2) for 24 h, FAs modified liposomes released about 70% of carboxyfluorescein (CF), while C-Lip only released 20% of CF.Compared to L-OHP loaded C-Lip, L-OHP-loaded FAs-included formulations had much greater anti-proliferative activity against sPLA2-secreting Colo205 cells.In summary, our results shows that LCA or kLCA promotes responsiveness of liposomes to tumor-related sPLA2 and points to a new way to develop platium drugs-loaded liposomal delivery systems with better release mechanisms.
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Objective:To investigate the safety and effectiveness of cytoreductive nephrectomy and tumor thrombectomy in patients with metastatic renal cancer with renal vein or inferior vena cava tumor thrombus.Methods:From February 2015 to May 2019, 56 cases of metastatic renal cell carcinoma with venous tumor thrombus were analyzed retrospectively, including 44 male (78.6%) and 12 female (21.4%)cases, and the average age was (59.2±10.7)(22-82). The clinical presentations covered local symptoms in 26 cases (46.4%), systemic symptoms in 8 cases (14.3%), both local symptoms and systemic symptoms in 12 cases (21.4%), and asymptomatic in 10 cases (17.9%). Among them, renal tumors were located in 35 cases (62.5%) on the right and 21 cases (37.5%) on the left. The average tumor diameter was (10.1±3.8)(1.5-21.1) cm. Forty-five cases (80.4%) scored 2 points and 11 cases (19.6%) scored 3 points by the American Society of anesthesiologists(ASA). Preoperative hemoglobin was (118.2±23.1)(72-178) g/L, and albumin was (37.9±5.6)(23-50) g/L, total protein was (67.7±6.7)(43-81) g/L, serum creatinine was (111.3±119.6)(32-958) μmol/L. There were 16 cases of Mayo 0 (28.6%), 14 cases of Mayo Ⅰ(25.0%), 17 cases of Mayo Ⅱ(30.4%), 4 cases of Mayo Ⅲ(7.1%), and 5 cases of Mayo Ⅳ(8.9%). Fourteen cases (25.0%) were in the stage of cN 0 and 42 cases (75.0%) in the stage of cN 1. Five cases (8.9%) had simple bone metastasis, 16 cases (28.6%) had simple lung metastasis, 2 cases (3.6%) had simple adrenal metastasis, 6 cases (10.7%) had simple liver metastasis, and 27 cases (48.2%) had 2 or more multiple system metastasis. According to the location of the organ system, 91 metastatic lesions were found in 56 patients. Among them, 37 cases (40.7%) had lung metastasis, 18 cases (19.8%) had liver metastasis, 21 cases (23.1%) had bone metastasis and 15 cases (16.5%) had adrenal metastasis. All 56 patients belonged to IMDC prognosis score model medium risk group. The surgical treatment of Mayo grade 0 tumor thrombus was the same as that of routine radical nephrectomy. The tumor thrombus of Mayo grade Ⅰ was removed after IVC was partially blocked by Satinsky′s forceps. The Mayo Ⅱ tumor thrombus was removed, after blocking the distal vena cava, the contralateral renal vein and the proximal vena cava. Mayo grade Ⅲ tumor thrombus needed pringer's method to block the first porta hepatis. For grade Ⅳ tumor thrombus the diaphragm could be cut directly, or the thrombus could be removed by cardiopulmonary bypass. Laparoscopic surgery was performed in 22 cases (39.3%) and open surgery in 30 cases (53.6%). Six cases (10.7%) underwent IVC wall resection because of tumor invasion. 32 cases (57.1%) underwent ipsilateral adrenalectomy because of tumor invasion or adrenal metastasis, and 23 cases (41.1%) underwent ipsilateral lymphadenectomy. In this study, there were 11 cases of solitary metastasis, 8 cases of which were operated on and 3 cases of which were not operated on. Forty-three patients were treated with sunitinib after palliative nephrectomy, 9 patients were treated with pazopanib, 3 patients were treated with acitinib, and 1 patient was treated with sorafenib. Results:The operations were successfully completed in 56 patients. Four cases (7.1%) changed from laparoscopic surgery to open surgery. The operation time was (326.8±114.9)(108-589) min. Intraoperative hemorrhage was (1 435.2±1 513.4)(20-6 000) ml, intraoperative red blood cells transfusion was (1 456.7±832.8)(400-3 600) ml in 30 cases, and intraoperative plasma transfusion was (700.0±473.6)(200-1 800) ml in 15 cases. The postoperative hospital stay was (10.6±4.6)(5-26) days. The serum creatinine one week after operation was (109.5±98.7) (47-772) μmol/L. There were 46 cases (82.1%) of renal clear cell carcinoma, 7 cases (12.5%) of papillary renal cell carcinoma and 3 cases (5.4%) of unclassified renal cell carcinoma. One case was WHO/ISUP 2016 nuclear grade 1 (1.8%), 20 cases(36.4%) was grade 2, 18 cases(32.7%)was grade 3, and 16 cases(29.1%)was grade 4. Early postoperative complications occurred in 22 cases (39.3%). Among them, 1 case of Clavien gradeⅠ was wound infection. There were 16 cases with Clavien gradeⅡ, including 5 cases who received blood transfusion due to anemia, 3 cases with chylous fistula, 4 cases with postoperative pulmonary infection, 2 cases with postoperative lower extremity venous thrombosis, 1 case with atrial fibrillation and 1 case with epididymitis. Clavien gradeⅢ a was found in 1 case with pneumothorax. Clavien gradeⅣ was found in 2 cases, including 1 case of acute cerebral infarction and 1 case of renal insufficiency.There were 2 cases with Clavien gradeⅤ with perioperative death. Among the 56 patients, 5 lost the follow-up, 2 died during the perioperative period, and the other 49 patients were followed up for 1-39 months, with a median follow-up of 14 months. The mean survival time was (25.6±2.5) months, and the median survival time was 25 months.Conclusions:It was relatively safe and effective to perform cytoreductive nephrectomy and tumor thrombectomy in patients with metastatic renal cancer with tumor thrombus. For the patients with clinical symptoms, IMDC prognosis score model medium risk group, and strong desire for surgery, the combination of cytoreductive nephrectomy with tumor thrombectomy and postoperative targeted medical therapy was recommended.
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Objective To investigate the diagnosis of colon cancer patients and the prediction of postoperative recurrence and metastasis in patients with colon cancer by serum angiopoietin-2 (Ang-2) , vascular endothelial growth factor (VEGF) , carbohydrate antigen 199 and carcinoembryonic antigen CEA. Methods 100 patients with colon cancer, 100 patients with benign colonic lesions and 100 healthy subjects were examined. The levels of Ang-2, VEGF, CA19-9 and CEA in serum were detected, and the diagnosis and postoperative recurrence and metastasis of colon cancer were investigated. Results The levels of serum Ang-2, VEGF, CA19-9 and CEA in colon cancer group were higher than those in benign lesions and healthy controls (P < 0.05). The levels of Ang-2, VEGF, CA19-9 and CEA were detected. The sensitivity and specificity of each index were significantly higher in the diagnosis of colon cancer. The preoperative recurrence and metastasis rates of patients with positive Ang-2, VEGF, CA19-9 and CEA were higher than those of the negative patients respectively. Survival analysis showed a statistically significant difference in the time of distant metastasis between different expression states (P < 0.05). Conclusion The detection of serum levels of Ang-2, VEGF, CA19-9 and CEA has clinical significance for the diagnosis of colon cancer. Combined detection can improve the diagnostic efficiency; the levels of Ang-2, VEGF, CA19-9 and CEA in serum before surgery colon cancer is associated with recurrence and metastasis, and combined testing can help to assess tumor metastasis.
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Objective To analyze the clinical features,diagnosis and treatment of testicular torsion.Methods The clinical data of 95 patients with testicular torsion admitted from March 2001 to April 2017 were analyzed retrospectively.Results The age of patients ranged from 13 to 42 years (mean 19.6 years).Among 95 patients,91 cases had essential clinical symptoms of scrotal pain;1 case reported the right testicular enlargement without pain,and 3 cases presented with left inguinal mass.Color Doppler flow imaging (CDFI) was performed in 91 patients,reduction or loss of blood flow signals were detected in 88 cases,and normal blood flow signals were presented in 3 cases.The diagnosis of testicular torsion was confirmed by CDFI in 91 cases before surgery,and 4 cases were diagnosed by medical history and physical examination.The duration from onset to surgery was ＜ 5 h in 10 cases,5-10 h in 25 cases,and ＞ 10 h in 60 cases.All the patients received operation,92 cases were diagnosed as testicular torsion in scrotum and 3 cases as cryptorchidism torsion after surgery.Among 92 cases of testicular torsion in scrotum,twisted testicles were removed in 41 cases and the testicles were retained in 51 cases;while testicles were removed in 1 case of cryptorchidism torsion,and the testicles were fixed in the scrotum in other 2 cases of cryptorchidism.Sixty eight patients were postoperatively followed-up for 1 month to 15 years,the retained necrotic testis atrophy occurred in 1 case,and the testicular size was normal in other 67 cases.In the 68 cases,there was no testicular discomfort and no testicular torsion after operation.Conclusions CDFI is valuable in preoperative diagnosis of testicular tortion.Once the diagnosis is made,it should be operated as soon as possible to retain the testicular function,and the affected testicle should be retained with caution for cryptorchidism torsion.
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Objective To investigate the effect of miR-210 on angiogenesis of human renal clear cell carcinoma . Methods Detect the expression of miR-210 in 40 cases of renal clear cell carcinoma tissues , and analyze the rela-tionship between the expression of miR-210 and microvessel density ( MVD) .miR-210-ASO was lipotransfected in-to renal clear cell carcinoma cell line 786-O.RT-qPCR was used to verify the transfection effect .The effect of the supernatant of control group , negative control group and miR-210-ASO group tumor cells on the lumen formation of human umbilical vein endothelial cells ( HUVEC) was observed in a 3-D culturesystems .The transplantation tumor model of nude mice was established , and the effect of miR-210 on the formation of the transplanted tumor micro vessel was observed by endomucin and VEGF immunofluorescence staining under laser scanning confocal micro -scope.Results The expression of miR-210 was positively correlated with microvessel density in renal clear cell carcinoma ( P<0.05 ) .The expression of miR-210 was significantly decreased in 786-O cells transfected with miR-210-ASO( P<0.05 ) .The lumen formation of HUVEC cells co cultured with miR-210-ASO group cell supernatant was significantly less than that of control group and negative control group ( P<0.05 ) .The tumor volume of miR-210-ASO group was less than that of the control group , and the number of the micro vessel and the VEGF expres-sion were significantly less than that of the control group ( P<0.05 ) .Conclusions Inhibition of miR-210 can suppress blood vessel formation in renal clear cell carcinoma .
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Objective To investigate the relationship between circulating tumor cells(CTCs) in peripher-al blood and the prognosis of pancreatic cancer patients. Method From Mar 2010 to Mar 2015, patients with pancreatic cancer in guangzhou first people′s hospital were enrolled in this study. Immunomagetic negative en-richhment together with immunofluorescence were used to identify CTCs. The clinical data of all patients were analyzed. Result No CTCs were found in peripheral blood of healthy control cases. The detection date of CTCs was 60.0%. The positive rate of CTCs was closely correlated with cell differentiation and the clinical stage. Con clusion CTCs count in old patients with pancreatic cancer can reflect the status of the patients and is help-ful for the diagnosis of micrometastasis , re-determination of the clinical stage and the guidance of patients′s treatment. CTCs count can predict the survival time of elderly patients with pancreatic cancer.
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Objective To compare the effect and safety between lightwand and general-laryngo-scope application of trachea cannula in cervical spine fracture patients undergoing general anesthesia. Methods Forty cervical spine fracture patients with tracheal intubation anesthesia were selected,including twenty-eight males and twelve females,aged 18-65 years,ASA physical statusⅡor Ⅲ.These patients were randomly divided into two groups,twenty cases in each group.After anesthesia induction,group L was giv-en general laryngoscope intubation,whereas group C was taken lightwand guided tracheal intubation.The success case of intubation at first,intubation time,adverse reaction of intubation,changes of MAP and HR at intubation and 5 minutes after intubation were observed.Results Compared with group L,success rate of intubation at first was higher (90% vs.60%),intubation time was shorter [(31.3±11.1)s vs.(46.6 ±15.2)s]in group C (P <0.05).The changes of MAP and HR were more stable during intubation in group C compared with group L.Four cases of arrhythmia (20%)occurred in group C,while none in group L.Conclusion Compared with intubation by general laryngoscope,application of tracheal intubation led by lightwand in cervical fracture patients is more effective and safer.
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Objective To explore the impact of Th17 cells adoptive immunity on tumor growth of diffuse large B cell lymphoma (DLBCL)-bearing mice.Methods The CD4+ CD62L+ na(i)ve T cells purified by Mini MACS immunomagnetic beads were stimulated under the condition of TGF-β, IL-6, anti-IFN-γ, anti-IL-4, IL-23.IL-17 expression was detected by ELISA.SCID mice were inoculated with DLBCL cells line SUDHL-4 to estaldish the model of DLBCL-bearing mice, and then they received Th17 cells adoptive immunotherapy at the 0, 8 th or 18th day (3 groups in total, 5 mice pre-group).The tumor volume and the survival of tumor model were observed.Results Formation of tumor nodules in mice was observed at about the 8th day after the mice received the Th17 SUDHL-4 cells.The tumors volume of DLBCL-bearing mice that had received Th17 cells adoptive immunotherapy was obviously smaller than that of the mice had not (P ＜ 0.05).The survival time of the tumor-bearing mice that had received Th17 cells adoptive immunotherapy was also longer than that of the tumor-bearing mice had not (P ＜ 0.05).Conclusion Th17 cells adoptive immunotherapy displays an anti-tumor effect on DLBCL-bearing mice.
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Objective To determine vascular endothelial growth factor(VEGF)-460 gene polymorphism in Uyghurs and its relationship to urolithiasis in south Xinjiang. Methods Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP),gene sequencing and genetic analysis methods were used in 200 urolithiasis patients of Uyghurs, and 200 healthy Uyghurs. Results The distribution of genotype and allele had no significant difference between urolithiasis patients and normal controls (P＞0. 05). The frequencies for the CC,TT and CT genotypes in patients with urolithiasis and normal controls were 1.5 %, 29.0 %, 69.5 % and 0. 5 %, 27.5 %, 72.0 %, respectively. The frequencies for C and T allele were 36.2%,63.7% and 36.9% ,63.1%, respectively. Conclusions The results of VEGF-460 gene polymorphisms indicate no significant relationship between patients with turolithiasis and normal controls in Uyghurs in south Xinjiang,which may not be urolithiasis susceptibility genetic locus.
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Purpose To clarify the morphologic changes and significance of interstitial cells of Cajal-like cells in the bladder of diabetic guinea pig.Methods The experimental guinea pigs were induced by a single intraperitoneal injection of streptozotocin(STZ).The diabetic guinea pig model, who were made succesful for 4 weeks, were detected through the urodynamic evaluation.The distribution of ICCs-like cells in the detrusor, which were taken from these guinea pigs,were quantitatively analyzed after frozen section and indirect immunofluorescence methods and observed by electron microscopy.Results In the diabetic group, the maximum detrusor pressure was signifently lower than controls (P＜0.01), maximum bladder capacity, compliance, residual volume and leak point pressures was significently higer than controls (P＜0.05 or P＜0.01);In detrusor, compared with control, the ICCs-like cells of diabetes group showed significently decreased in quantity. In diabetic bladder, the quantity of gap junctions between ICCs-like cells and cells around,such as smoth muscle cells,terminal nerves and other ICCs-like cells,decreased significently.And more cavities and less organoids occurred in cytoplasm of diabetic ICCs-like cells. Mitochondria became swollen or even disapeared, accompanied with swollen endocytoplasmic reticulum.Conclusion The decrease and injures of ICCs-like cells in bladder may be one of the mechanisms resulting in urodynamic changes of diabetic cystopathy.
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Objective To discuss the feasibility and long-term effect of free latissimus dorsi muscle flap in repair of severe lower extremity injury in children. Methods From July 1999 to June 2004, nine child patients (at age of 6-13 years) with severe lower extremity injury involving soft tissue defects a-round the calf and the foot associated with complex open fractures, bare dislocation, and injury of the nerve, tendon and artery were repaired with free latissimus donsi flap, with flap area ranging from 30 cm ×12 cm to 10 cm × 5 cm. Results All the latissimus dorsi flaps survived, with success rate of 100%. A follow-up for 4-9 years showed that the flap had sound shape and function and normal blood supply, without significant influence on donor area. Conclusion Latissimus dorsi flap has advantages of constant anatomical site, abundant blood supply, massive area, strong anti-infection ability and less in-fluence on donor area and hence is an ideal method for repairing severe lower extremity injury in children.