Objective:To investigate whether intratumoral Gemella haemolysans(G.haemolysans)enhances the efficacy of neoadjuvant chemoimmunotherapy(NACI)in esophageal squamous cell carcinoma(ESCC)-bearing mice and the underlying mechanism.Methods:Twenty-five 4-week-old female C57BL/6 mice were randomized into five groups(n=5 per group):negative control(NC)group,chemo-therapy group,G.haemolysans+chemotherapy group,NACI group,and G.haemolysans+NACI group.A germ-free mouse model was established in each group by administering antibiotic cocktail for 2 weeks.On day 0,ESCC-bearing mouse models were built through subcutaneous inoculation of either murine esophageal cancer cell line AKR or G.haemolysans-AKR cells.On day 7 when tumors formed under the skin,drugs were injected into the abdomen thrice weekly.On day 28 when the treatments were finished,the mice were sacrificed to harvest their tumors,and then the tumors were fixed in 4%paraformaldehyde.We located and quantified G.haemolysans within the tumors through fluorescence in situ hybridization,and characterized immune cell composition in the tumor immune microen-vironment(TIME)of the mice treated with NACI through multiplex immunohistochemistry and flow cytometry.Results:G.haemolysans significantly strengthened the efficacy of NACI in ESCC(P<0.05),whereas no chemosensitizing effects were observed on chemo-therapy in ESCC-bearing mice.G.haemolysans significantly en-hanced natural killer(NK)cell infiltration within the TIME(P<0.01).Conclusion:G.haemolysans improves NACI efficacy in ESCC-bearing mice by increasing NK cell recruitment in the TIME.

Objective:To automatically synthesize Al 18F-1, 4, 7-triazacyclononane-1, 4, 7-triacetic acid (NOTA)-fibroblast activation protein inhibitor (FAPI)-04, perform PET/CT imaging in vivo, and evaluate its diagnostic efficacy on tumors. Methods:Al 18F-NOTA-FAPI-04 was produced in All-in-one automatic synthesis module and its quality control was conducted by high performance liquid chromatography (HPLC) equipped with a radioactive detector. Al 18F-NOTA-FAPI-04 PET/CT imaging was performed in normal BALB/c mice ( n=3) and 4T1 breast cancer models ( n=3) to determine its biodistribution. Then Al 18F-NOTA-FAPI-04 and 18F-FDG PET/CT imaging were performed in a hepatocellular carcinoma patient (male, 51 years old). Results:The synthesis time of Al 18F-NOTA-FAPI-04 was about 35 min, and the radiochemical yield was (25.2±1.9)% (attenuation correction, n=3). The product was colorless transparent solution with pH value of 7.0-7.5, and the specific activity was (46.11±3.07) GBq/μmol (attenuation correction, n=3). The radiochemical purity was above 99.0% and was still above 98.0% at room temperature after 6 h. PET/CT imaging in mice showed that physiological uptake of Al 18F-NOTA-FAPI-04 was mainly in biliary system and bladder, and Al 18F-NOTA-FAPI-04 highly concentrated in tumor xenografts. PET/CT imaging in the patient showed that Al 18F-NOTA-FAPI-04 obtained high tumor background ratio (TBR) values of 4.1, 8.9, 5.4, 4.8, 2.2 in parasternal lymph nodes, anterior diaphragmatic lymph nodes, hilar lymph nodes, pancreaticoduodenal ligament lymph nodes, abdominal aortic lymph nodes, respectively, while TBR values were 1.0, 2.8, 5.0, 2.1, 1.1 by 18F-FDG. Conclusions:Al 18F-NOTA-FAPI-04 can be synthesized with short time, high radiochemical yield and good stability using All-in-one module. Al 18F-NOTA-FAPI-04 PET/CT imaging has high contrast and excellent diagnostic efficacy on tumors.

Objective: To synthesize and analyze ¹⁸F-prostate specific membrane antigen (PSMA)-1007, followed by its imaging in prostate cancer. Methods: Based on one-step method, ¹⁸F-PSMA-1007 was produced by the CFN-MPS-200 automatic synthesis module and its quality analysis was conducted. ¹⁸F-PSMA-1007 PET/CT imaging was performed in a prostate cancer patient (66 years old). Results: The synthesis time of ¹⁸F-PSMA-1007 was about 50 min, and the radiochemical yield was (25.0±5.0) % (attenuation correction, n=3). The radiochemical purity was above 99.0% and was above 98.0% after 6 h. The product was colorless transparent solution with pH value of 7.0-7.5, and the specific activity was (410.0±11.0) MBq/ml and the radioactive nuclear purity was above 99.0%. PET/CT imaging in the patient showed that ¹⁸F-PSMA-1007 was highly concentrated in prostate cancer with maximum standardized uptake value (SUV_max) of 40.9. Conclusion Based on CFN-MPS-200 multifunction synthesis module, ¹⁸F-PSMA-1007 can be stably synthesized with high radiochemical yield and can be concentrated in prostate cancer.

OBJECTIVE:To investigate the compatibility stability of Ulinastatin for injection with 2 commonly used solvents in the infusion pump.METHODS:After Ulinastatin for injection 500 000 U was respectively added into 0.9％ Sodium chloride injection and 5％ Glucose injection 50 mL,the appearance of the mixture at 25 ℃,37 ℃ were observed at 0,1,2,4,8,12,24 h,re spctively,pH value and the number of insoluble particles were measured.The relative percentage of ulinastatin in the mixture was determined by HPGFC.RESULTS:Under this condition,the appearance and pH value of the mixture had no significant change within 24 h;the number of particles ≥10 μm was lower than 25 particle/mL,and that ≥25 μm was lower than 3 particle/mL,which was in line with the pharmacopeia standard.The relative percentage of ulinastatin within 24 h ranged 99.45％-102.55％.CONCLUSIONS:After mixed with 0.9％ Sodium chloride injection and 5％ Glucose injection,Ulinastatin for injection keep stable within 24 h at 25 ℃,37 ℃ and can be used for continuous administration in the infusion pump.

Objective To investigate the regularity of abdominal pain and its influence factors in patients with primary hepatic carcinoma (PHC) after receiving transcatheter arterial chemoembolization (TACE).Methods A total of 121 patients with PHC were enrolled in this study.All patients were admitted to the Department of Interventional Radiology of Zhejiang Provincial Cancer Hospital from December 2012 to June 2013,and all patients were suffered from PHC.The occurrence,duration and severity of the abdominal pain as well as the used dosage of morphine within 48 hours after TACE were documented.The results were statistically analyzed.Results A total of 96 patients (96/121,78.5％) complained of different degrees of abdominal pain after interventional therapy,and 72 patients (72/121,59.5％) showed moderate to severe pain,with the VAS score being more than 4 points.The average dosage of morphine used each time for one patient was 19.7 mg.Statistical analysis indicated that these patients were more prone to develop abdominal pain after TACE if they carried more than one of the following risk factors:age ≥60 years (when compared with patients ＜60 years,OR:0.307,P=0.008),preoperative ECOG score ＞2 (when compared with a ECOG score of 0-1,OR:0.195,P=0.006),the distance between tumor and liver capsule ＞1 cm (when compared with the distance ≤ 1 cm,OR:0.296,P=0.007),the use of THP in performing chemoembolization (when compared with other chemotherapeutic drugs,OR:0.232,P＜0.003 4).Conclusion After TACE abdominal pain is a high-frequency event.The independent factors affecting the occurrence of abdominal pain are age＜60 years,preoperative ECOG score ＞2,tumor located close to liver capsule,and the use of THP-lipiodol mixture as embolic agent.Therefore,for patients carrying moderate-high risk of abdominal pain,routine use of analgesics before TACE as well as within 12 hours after TACE to prevent the occurrence of abdominal pain is quite necessary.

AIM To establish an HPLC method for the simultaneous content determination of swertiamarin,gentiopicrin,swertianolin,taxifolin,silychristin,silydianin and silybin in Dangfei Liganning Capsules (Silybi Fructus and Swertiae Herba).METHODS The analysis of 75％ methanol extract of this drug was performed on a 30 ℃ thermostatic Kromasil C18 column (4.6 mm × 250 mm,5.0 μm),with the mobile phase comprising of methanol-0.1％ formic acid flowing at 0.9 mL/min in a gradient elution manner,and the detection wavelengths were set at 254 nm and 288 nm.RESULTS Seven constituents showed good linear relationships within their own ranges (r ＞ 0.999 0),whose average recoveries were 96.78％-100.45％ with the RSDs of less than 2.0％.CONCLUSION This accurate and reproducible method can be used for the rapid quality control of Dangfei Liganning Capsules.

BACKGROUND/AIMS: The motility change after peroral endoscopic myotomy (POEM) in achalasia is currently focused on lower esophageal sphincter (LES). This study aims to investigate the correlation of motility response between distal and proximal esophagus after POEM. METHODS: A total of 32 achalasia patients who received POEM and high-resolution manometry (HRM) were included for analysis. Eckardt score was used to assess symptom improvement. HRM was applied for studying motility. Main parameters analyzed were (1) LES: resting pressure (restP), 4-second integrated relaxation pressure; (2) esophageal body (EB): contractile integral of distal segment with myotomy (CI-DM) and proximal segment without myotomy (CI-PNM); and (3) upper esophageal sphincter (UES): relaxation pressure (UES-RP). RESULTS: There were 6 type I, 17 type II, and 9 type III achalasia patients included for analysis. (1) Eckardt score, LES tone, CI-DM, CI-PNM and UES-RP were reduced remarkably after POEM (P < 0.001). (2) no significant correlation was noted between LES tone and contractile intergral of EB. (3) a positive linear correlation of CI-DM and CI-PNM changes was detected (P < 0.001). (4) the change of UES-RP was positively correlated with the change of contractile integral of EB (P < 0.001). CONCLUSIONS: Myotomy of the distal esophagus would attenuate proximal EB contraction and assist UES relaxation in achalasia patients after POEM.
Esophageal Achalasia* ; Esophageal Sphincter, Lower ; Esophageal Sphincter, Upper* ; Esophagus* ; Humans ; Manometry ; Relaxation*

Objective To evaluate the safety and clinical efficacy of CT-guided 125I seeds interstitial implantation in treating the refractory liver cancers that show poor response to commonly used therapies. Methods A total of 40 patients with refractory clinically or pathologically-proved liver cancer were enrolled in this study, the diseases included primary liver cancer (n = 27, with coexisting portal vein cancerous thrombus in 2) and metastatic liver cancer (n = 13). CT-guided 125I seeds interstitial implantation was performed in all patients. Preoperative plan of seeds implantation protocol was formulated by using the treatment plan system (TPS); the 125I seed activity was 0.6 -0.8 mCi and the peripheral matching dose (MPD) was 100 -140 Gy. The procedure of 125I seeds interstitial implantation was performed under local anesthesia in all patients. By using percutaneous trans-hepatic puncturing and single-or multiple-needle technique, the 125I seeds were implanted along a line parallel to the long axis of the tumor and/or tumorous thrombus with an interval of 0.5 -1.0 cm. The short-term efficacy was evaluated by modified response evaluation criteria in solid tumors (mRECIST), and the median time to tumor progression (mTTP) and the median overall survival time (mOS) were calculated by Kaplan and Meier method. Results The technical success rate was 100%. The diameter of the tumor was 1.5 -12.0 cm (mean 4.0 cm), and a total of 1 748 125I seeds were implanted in 40 patients (mean 44 seeds per patient). The short-term effective rate was 37.5%(n = 15), including complete remission in 8 cases and partial remission in 7 cases, the stable disease was seen in 15 cases (37.5%), and the disease control rate was 75%. The mTTP was 7.0 months (95%CI:4.524-9.476 months), while mOS was 10 months (95%CI: 6.901 -13.099 months). The procedure-related adverse reactions included small amount of subcapsular hemorrhage (n =2, 5%), intrahepatic migration of 125I seeds (n=2, 5%), pain at liver area (n=1, 2.5%); and no special treatment was needed in these patients. One patient developed high fever with chills 3 hours after the procedure, which was relieved after symptomatic and antipyretic treatment. Conclusion For the treatment of refractory liver cancers, CT-guided 125I seeds permanent interstitial implantation, used as a remedial therapy, is safe and effective. This technique is worth popularizing in clinical practice.

Objective To investigate the efficacy and safety of CT-guided radiofrequency ablation (RFA) in treating lung tumors. Methods A total of 33 patients with lung cancer (35 lesions in total), who were admitted to authors’ hospital during the period from May 2007 to August 2013 to receive treatment, were enrolled in this study. RFA was carried out in all patients. After RFA the patients were followed up regularly (once every 3 months) to evaluate the therapeutic efficacy and the adverse reaction. The deadline for the following-up was November 2013, or to the time when tumor progression occurred. Results Of the total 34 lesions in 32 patients who had received RFA and had complete follow-up data, the one-year local control rate was 85.3%. The average one-year progression-free survival rate was 75.0%, among them 15 cases with primary lung cancer had a mean one-year progression-free survival rate of 80.0% and 17 cases with metastatic lung cancer had a mean one-year progression-free survival rate of 70.6%. The overall median progression-free survival (PFS) was(18.0±1.3) months. No obvious correlation existed between PFS and age, sex, tumor size, pathological type, clinical stage (P<0.05). The main adverse reactions of RFA were pain, hydrothorax and pneumothorax; no serious life-threatening complications occurred. Conclusion RFA is a safe, effective and minimally-invasive treatment for lung cancer, regardless of early stage or late stage of the tumor.

Objective To explore the long-term survival of primary liver cancer of TACE combined with RFA. Methods A total of 100 cases were selected from June 2009 to June 2014 in our hospital treated with advanced hepatocellular carcinoma, according to a random number table method, they were randomly divided into treatment group radiofre-quency(RFA, 50 patients), and combined treatment group (TACE+RFA, 50 patients). Among them, the RF-treated patients were treated with RFA alone; the combined treatment group were taken RFA and TACE combined with combi-nation therapy. Follow-up for 12 to 50 months, the long-term efficacy and survival of the two groups of patients were compared. Results By analyzing and comparing two groups of patients after treatment, long-term survival of discovery, survival radiofrequency of treatment group was 1 to 60 months, the survival of patients combined treatment group was 2 to 89 months. 1-year survival rate of the combined treatment group was significantly higher than the radiofrequency treatment group(P<0.05); 3-year survival rate of the combined treatment group was significantly higher than radiofre-quency treatment group (P<0.05); 5-year survival rate of the combined treatment group was significantly higher than radiofrequency treatment group(P<0.05). The combined treatment group survival index statistics were better than the former, and the difference was statistically significant(P<0.05). Conclusion TACE and RFA combination therapy has a better therapeutic effect in improving long-term survival of patients on a more selective advantage for clinicians to use in the treatment of preference.