OBJECTIVETo evaluate the safety and preliminary efficacy of dose-modified regimen of 5-fluorouracil plus oxaliplatin and irinotecan (mFOLFOXIRI) for patients with advanced colorectal cancer (CRC).

METHODSData of 312 CRC patients confirmed by pathology receiving triplet drug alone or combined with target therapy between October 2012 and December 2016 at the Sixth Affiliated Hospital of Sun Yat-sen University were retrospectively analyzed. CRC patients who had previously completed adjuvant therapy (or neoadjuvant therapy) within 6 months or palliative chemotherapy were excluded, meanwhile those with poor general condition (ECOG score > 2) or grade 2 neuropathy and allergy to oxaliplatin were excluded as well. Regimen of mFOLFOXIRI: oxaliplatin 85 mg/m² dissolved in 5% glucose solution 500 ml by intravenous infusion for 2 h; irinotecan 150 to 165 mg/m² dissolved in 0.9% sodium chloride 250 ml by intravenous infusion for 90 min; following intravenous infusion of leucovorin 400 mg/m² for 2 h, day 1; 5-FU 2800 mg/m², 48-h continuous intravenous infusion; once every 2 weeks. Therapy could be combined with a targeted drug, bevacizumab 5 mg/kg every two weeks; cetuximab 500 mg/m² every two weeks. Side effect was graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE 4.0.3). The objective response rate was evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) after administering at least four cycles of chemotherapy.

RESULTSThe median age was 52 years (range 16-73) in the whole group; 113 patients (36.2%) had locally advanced CRC, and 199 (63.8%) had metastatic CRC. Most patients (274/312, 87.8%) did not receive any treatment earlier. There were a total of 1651 chemotherapy cycles in the whole group, with a median of 6(1-19) cycles. Of these 1651 cycles, 124 cycles of chemotherapy(7.5%) were dose-adjusted; 176 cycles of chemotherapy(10.7%) were delayed for median 5(3-13) days; 124 cycles(7.5%) required dose decrease. The overall relative dose intensity was >90%; the specific drug dose intensity was 93.6%(2620 mg×m⁻²×d⁻¹) for fluorouracil, 97.8%(83 mg×m⁻²×d⁻¹) for oxaliplatin, and 94.2%(155 mg×m⁻²×d⁻¹) for irinotecan. Twenty-three patients (7 of intestinal perforation, 7 of intestinal obstruction, 1 of grade 4 hematologic toxicity, and 8 of grade 3 fatigue) refused subsequent chemotherapy due to intolerable toxicity. Main grade 3 or 4 adverse events in patients were neutropenia in 69 cases (22.1%), fatigue in 35 cases (11.2%), and anemia in 28 cases (8.9%). Twenty serious adverse events (6.4%) occurred, including 13 patients of febrile neutropenia (4.2%), 7 patients of intestinal perforation (2.2%, 4 patients in upper rectum, 2 in sigmoid colon, and 1 in transverse colon cancer), and 9 of them had subsequent sepsis (2.9%). All the patients with intestinal perforation underwent emergency operation. No treatment-related deaths occurred. In 199 patients with metastatic CRC, because 22 patients did not receive image evaluation, the preliminary efficacy of 177 patients was actually evaluated. A total of 113 objective response events were observed. The overall response rate was 63.8%(113/177), partial response rate was 61.6%(109/177), clinically complete response rate was 2.3%(4/177), stable disease was 29.9% (53/177), progressive disease was 6.2%(11/177), and the disease control rate was 93.8%(166/177). In 127 patients receiving triplet drug, objective response rate was 40.9% for those with less than four cycles and 81.1% for those with more than four cycles (P<0.001).

CONCLUSIONThe mFOLFOXIRI regimen with reduced dose can be safely used in advanced CRC and has achieved promising results in terms of short-term efficacy.

Adolescent ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; therapeutic use ; Camptothecin ; administration & dosage ; analogs & derivatives ; Colorectal Neoplasms ; drug therapy ; Fluorouracil ; administration & dosage ; Humans ; Leucovorin ; administration & dosage ; Middle Aged ; Organoplatinum Compounds ; administration & dosage ; Retrospective Studies ; Treatment Outcome ; Young Adult

OBJECTIVETo compare the clinical efficacy differences between acupoint plaster therapy with midnight-noon ebb-flow hour-prescription method and traditional acupoint plaster therapy for senile osteoporosis (SOP).

METHODSWith randomized controlled blind design, 76 SOP patients with deficiency of liver and kidney syndrome were randomly divided into an observation group and a control group, 38 cases in each one. Based on oral administration of caltrate D, the patients in the observation group were treated with acupoint plaster therapy with midnight-noon ebb-flow hour-prescription method at Yingu (KI 10), Taixi (KI 3), Dazhong (KI 4), Fuliu (KI 7) and Zhiyin (BL 67), while the patients in the control group were treated with traditional acupoint plaster therapy. Each plaster therapy lasted for 6 h, once a day; there was an interval of 2 d after consecutive 5-day treatment; 4 weeks were taken as one course, and totally 2 courses were given. Visual analogue scale (VAS) and Oswestry Disability Index (ODI) were used to evaluate the pain and dysfunction before intervention, after 4 weeks and 8 weeks intervention. Osteoporosis symptom rating sale and quality of life questionnaire of the European foundation for Osteoporosis (QUALEFFO-41) were adopted to evaluate the TCM syndrome and quality of life before and after 8-week intervention.

RESULTSAll the outcomes were significantly improved after treatment in the two groups (<0.01,<0.05); after 4 weeks and 8 weeks of treatment, the VAS and ODI in the observation group were lower than those in the control group (all<0.05). Repeated ANOVA indicated the VAS and ODI were significant in group effect, time effect and interaction effect (all<0.01). Further comparison showed that VAS and ODI at later time points were lower than those in the early time points (all<0.01). After the treatment, the scores of TCM syndrome and QUALEFFO-41 in the observation group were lower than those in the control group (all<0.05). The effective rate was 85.7% (30/35) in the observation group, which was superior to the effective rate in the control group[74.3%(26/35),<0.05].

CONCLUSIONSThe acupoint plaster therapy with midnight-noon ebb-flow hour-prescription method is superior to traditional acupoint plaster therapy in improving pain, dysfunction, TCM syndrome and quality of life in SOP patients; in addition, its clinical efficacy is significant.

Objective To investigate the changes of erythrocyte parameters and the value of differential diagnosis in pregnant women with β-mediterranean anemia.Methods A total of 300 pregnancy women from July 2014 to December 2015 in Center Hospital of Longgang were recruited in this study,100 pregnant women with β-mediterranean anemia in β-mediterranean anemia pregnancy group,100 healthy pregnant women in normal pregnancy group,100 pregnant women with iron deficiency anemia in iron deficiency anemia pregnancy group.Mean red cell volume(MCV),mean erythrocyte hemoglobin(MCH),reticulocyte percentage(Ret%) were detected and compared in the three groups.Results Compared with the normal pregnancy group and iron deficiency anemia pregnancy group,the MCV,MCH significantly reduced,and Ret% significantly rised in the β-mediterranean anemia pregnant group,the differences were significant(P<0.05).The best cut-off value of Ret% was 1.7% in differential diagnosis of β-mediterranean anemia pregnancy and iron deficiency anemia pregnancy,the sensitivity was 63.00%,the specificity was 74.00%,the area under of receiver operating characteristic curve was 0.841.The sensitivity of joint detection including MCV,MCH and Ret% in differential diagnosis of β-mediterranean anemia pregnancy and iron deficiency anemia pregnancy was 84.00%,the specificity was 90.00%.Conclusion MCV,MCH and Ret% in pregnancy women with β-mediterranean anemia changes significant compared with normal pregnancy group and iron deficiency anemia pregnancy group,the joint detection including MCV,MCH and Ret% could significantly improve the differential diagnosis of β-mediterranean anemia and iron deficiency anemia in pregnancy women.

Objective To observe the relationship between Toll-like receptor 4 (TLR4) and the sensitivity of PANC1 cells to gemcitabine (GEM),and to analyze the potential mechanism.Methods PANC1 cells were divided into GEM group,lipopolysaccharide (LPS) + GEM group and TLR4-siRNA + GEM group.GEM group was treated by GEM alone.LPS + GEM group was pretreated with 1 mg/L LPS for 4 h and then treated by GEM.TLR4-siRNA + GEM group was transfected with 100 pmol/mL TLR4-siRNA for 4 h and then treated by GEM.The untreated cells were used as the control group.MTT method was used to detect the cell proliferation.Morphological changes and apoptosis rate of the cells were examined by Hoechst33258 staining and flow cytometry,respectively.The protein expression of TLR4,phosphorylated AKT (p-AKT) and activated Caspase-3 were detected by Western blot.Results The median inhibition concentration (ICs0) of GEM in the GEM group,LPS + GEM group and TLR4-siRNA + GEM group was (8.9 ± 0.32),(14.21 ±0.95),(3.96 ± 0.27) mg/L,respectively.The IC50 in LPS + GEM group was significantly higher than that in GEM group (P ＜ 0.01),and the IC50 of GEM in TLR4-siRNA + GEM group was significantly lower than that in GEM group (P ＜0.01).Compared with that in GEM group,the cells with typical apoptotic morphological changes were decreased in LPS + GEM group,which was increased in TLR4-siRNA + GEM group.The apoptotic rate in control group,GEM group,LPS + GEM group,TLR4-siRNA + GEM group was (2.1 ± 0.3) ％,(15.1 ± 2.3) ％,(9.8 ± 1.5) ％,(22.9 ± 3.1) ％,respectively.Compared with that in GEM group,the cells apoptotic rate was significantly reduced in LPS + GEM group (P ＜0.01),which was significantly increased in TLR4-siRNA + GEM group (P ＜0.01).TLR4 protein level in the 4 groups was 0.83 ±0.08,0.81 ±0.07,0.85 ±0.07 and 0.16 ±0.03;p-AKT protein level 0.61 ±0.05,0.36 ±0.03,0.73 ± 0.07 and 0.21 ± 0.02;activated Caspase-3 protein level was 0.66 ± 0.05,0.73 ± 0.07,0.45 ± 0.04 and 0.91 ± 0.07,respectively.The expression of TLR4 and p-AKT in TLR4-siRNA + GEM group was significantly lower than that in GEM group (P ＜0.01),while the expression of activated Caspase-3 protein was increased significantly (P ＜ 0.05).Compared with the GEM group,the expression of p-AKT protein in LPS + GEM group was significantly increased (P＜0.01),and the expression of activated Caspase-3 protein was significantly decreased (P＜0.01).Conclusions TLR4 can inhibit the sensitivity of pancreatic cancer PNAC1 cells to GEM,and the mechanism is related to the activation of PI3K/AKT pathway and downregulation of activated Caspase-3.

Objective To investigate the effect of Iodine 125 seeds short time low dose rate irradiation on perineural invasion (PNI) in pancreatic cancer Capan-2 cells,and explore its molecular mechanism.Methods The co-culture model was established by co-culturing the dorsal root ganglion (DRG) of SD rat and Capzn-2 cells line,while Capan-2 culture model and DRG culture model was also established.Iodine 125 seeds short time low dose rate irradiation tablet was used for the 3 models,and the model without irradiation was used as control.Cancer cell and DRG growth was observed under inverted microscopy,surface of neurite and cell colony growth was determined by image analysis software.The concentration of nerve growth factor (NGF),transforming growth factor-α (TGF-α) in cell culture supernatant and matrigel solution was tested by ELISA,and the expression of neurotrophin-3 (NT-3) mRNA was detected by semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR).Results In the co-culture model,neurite of DRG showed a direction to cancer cells and had a concentrated growth towards cancer cells.And Capan-2 cells formed more colonies towards neurite.However,in irradiation groups,the symbiotic phenomenon was inhibited to some degree.Increased surface of neurite in co-culture model at 5th day was 290.15 ± 12.08,which was significantly higher than that in DRG group (124.83 ± 6.96,P ＜ 0.01),but the surface of neurite was decreased to 201.53 ± 12.20 after irradiation (P ＜0.01).Increased surface of Capan-2 cell was 300.47 ± 12.99,which was significantly higher than that in Capan-2 group (199.30 ± 8.60,P ＜ 0.01),but the surface of Capan-2 was decreased to 202.35 ± 7.97 after irradiation (P ＜ 0.01).NT-3 mRNA was seldom or not expressed in supernatant of co-culture model,but it was strongly expressed (0.68 ± 0.04) after irradiation (P ＜ 0.05).The concentration of NGF and TGF-α in supernatant of co-culture model were (27.56 ± 13.73),(40.86 ± 20.73) ng/ml,after irradiation they were increased to (94.98 ± 33.80),(157.54 ± 83.76) ng,/ml,and the difference between the two groups was statistically significant (P＜0.05 or ＜0.01).The concentration of NGF and TGF-α in matrigel lysate of co-culture model were (60.42 ± 33.03),(64.39 ± 21.52)ng/ml,after irradiation they were increased to (132.52 ±53.01),(138.38 ±83.58)ng/ml,and the difference of NGF concentration between the two groups was statistically significant (P ＜ 0.05).Conclusions Iodine-125 seeds short-time low-dose rate irradiation could inhibit interactions between nerve and Capan-2 cells,and the mechanism may be related to up-regulation of cancer cells perineural invasion promoter NGF,TGF-α and NT-3.

Objective To analyze the effects of individualized lifestyle intervention on compliance and metabolic status of patients with type 2 diabetes mellitus (T2DM).Methods Two hundred T2DM patients were selected and randomly divided into experimental and control groups of 100 patients respectively.The experimental group was given individualized lifestyle intervention for 6 months in addition to conventional oral medications.The intervention was to prescribe diet control and exercise therapy according to the patients' individual conditions.The control group was given conventional treatment and verbal lifestyle intervention for 6 months.Comparison was made in patients compliance and various metabolic markers between the two groups.Results The percentage of conduction of diet control and exercise therapy in experimental group was significantly higher than control group ( Diet control:80 vs.52,x2=7.08,P=0.029;Exercise therapy:78 vs.44,x2=11.207,P=0.004).After intervention,the fasting plasma glucose (FPG),2-hour postprandial blood glucose (2hPG),glycated hemoglobin ( HbA1c),body mass index ( BMI),triglyceride ( TG),total cholesterol (TC),low-density lipoprotein ( LDL-C ),and insulin resistance index ( HOMA-IR ) in experimental group decreased significantly,and high-density lipoprotein ( HDL-C ) increased significantly [FPG:( 8.45 ± 1.46 ) mmol/L vs.(6.66 ± 0.67) mmol/L,P=0.000;2hPG:( 12.76 ± 2.25 ) mmol/L vs.(8.22 ± 1.79) mmol/L,P=0.000;HbA1c:(7.68 ± 1.06 ) ％ vs.( 6.48 ± 0.69 ) ％,P=0.000;BMI:( 25.90 ± 1.72 ) kg/m2 vs.( 22.81 ±1.41 ) kg/m2,P=0.016;TG:(2.57 ±0.68) mmol/Lvs.( 1.88 ±0.35) mmol/L,P=0.006;TC:(5.72 ±0.13) mmol/L vs.(5.14 ± 1.38) mmol/L,P=0.043;LDL-C:(3.28 ±0.10)mmol/L vs.(2.81 ±0.57)mmol/L,P=0.009;HOMA-IR:7.58 ± 0.19 vs.4.58 ± 1.98,P=0.000;HDL-C:( 1.29 ± 0.04) mmol/L vs.( 1.62 ± 0.27 ) mmol/L,P=0.003].The levels of FPG,2hPG,HbA1c,BMI,TG,HOMA-IR also decreased in control group after intervention compared with before intervention [FPG:( 8.67 ± 2.71 ) mmol/L vs.( 7.26 ± 1.21 ) mmol/L,P=0.001;2hPG:( 12.82 ± 2.15 ) mmol/L vs.( 10.85 ± 1.98 ) mmol/L,P=0.000,HbA1c:( 7.75 ± 1.08 ) ％ vs.( 7.01 ± 0.87 ) ％,P=0.002;BMI:( 25.82 ± 1.74 ) kg/m2 vs.( 24.23 ± 1.36 ) kg/m2,P=0.024;TG:(2.47 ±0.75) mmol/L vs.(2.13 ± 0.43 ) mmol/L,P=0.018;HoMA-IR:7.88 ± 0.20 vs.6.15 ± 2.01,P=0.042].No significant difference was found on the values of TC,HDL-C and LDL-C before and after intervention in control group (P ＞ 0.05).The effect of intervention of experimental group was more obvious when compared with control group ( FPG:P=0.036;2hPG:P=0.000;HbA1c:P=0.045;BMI:P=0.037;TG:P=0.022;HoMA-IR:P=0.000).Conclusion Individualized lifestyle intervention can improve the compliance of T2DM patients,and was in favor of control metabolic status of T2DM patients to delay the occurrence and development of complications.

Objective To establish the orthotopic human pancreatic cancer model in mice and study the method to detect the tumor growth. Methods Human pancreatic cancer cell lines SW1990 in logarithmic phase was made into cell suspension and in situ injected into the envelope of pancreatic tail of BALB/c nude mice. High-frequency endoscopy ultrasound was used to observe the growth of tumor mass and its imaging characteristics were studied. Results 20 nude mice were successfully implanted, and 1 died 25 h after implantation. 14 days after implantation, the tumor of pancreatic cancer on EUS was (8.09 ± 2.61) mm3, the tumor appeared as homogeneous hypoechoic mass with clear boundary, and envelope as well as sound halo was present, and the shape was regular; there was low speed circular vasculature signal in around 30% of tumor.The tumor size increased to (12.40 ± 3.51)mm3, and the shape of 70% tumor was irregular, and some appeared as lobulated, and the tumor appeared as heterogeneous hypoechoic mass, no necrosis or liquefaction was found 28 days after implantation. There was low speed circular vasculature signal in around 70% tumors.Conclusions The orthotopic pancreatic cancer model in nude mouse can be established by in situ injection and this method is relatively ideal because it is simple and effective. The high frequency probe of endoscopic ultrasonograph is a reliable method for monitoring implanted pancreatic cancer.

Objective To study the effect of static magnetic field (SMF) on levels of lipid peroxidation in liver kidney and brain tissues in mice. MethodsThirty mice were randomly assigned to groups A,B,C and D, and exposed to static magnetic fields with four different intensities of(24.6?4.2)mT, (42.0?2.1)mT, (63.5?3.0)mT, (85.1?2.9)mT, respectively, for an average of 4 hours daily for 15 days. Then the mice were sacrificed and the amount of MDA in liver, kidney and brain tissues in mice were measured. ResultsThe amount of MDA were significantly decreased in the liver and kidney in rat exposed to (24.6?4.2)mT, (42.0?2.1)mT MSF as compared with that in the control group( P

AIM: To explore the effect of pyrrolidine dithiocarbamate (PDTC), the specific inhibitor of NF-?B, on anti-thymocyte serum nephritis (ATSN) in rats. METHODS: The rat model of ATSN was reproduced with rabbit anti-thymocyte serum (ATS). The rats were divided into ATSN group, ATSN+PDTC group and control group. The expression of NF-?B p65 and the apoptosis, lysis as well as proliferation of mesangial cells (MC) were examined by immunohistochemical staining, Tdt-mediated X-dUTP nick end labeling (TUNEL), light microscope and electron microscope at 40 minutes, 24 hours and 7 days after injection of ATS or normal serum. RESULTS: The expression of glomerular NF-?B p65 in the ATSN group was observed with significant difference compared to controls at 40 min (P