This article analyzes the concept,the formation process,the main content of the United States food defense plan,the duties of stakeholders and the key points of the implementation.This article also summarizes the characteristics,similarities and differences between China and the United States in terms of food defense system,discusses the difficulties and put forward some suggestions for the food defense plan in China.

Objective To evaluate the effect of CYP3A5 genetic polymorphisms on tacrolimus (Tac) concentration/dosing and other clinical outcomes in a pilot cohort of 113 Chinese HTx recipients.Methods Association between CYP3A5 genetic variants and blood dose-adjusted trough concentrations (C0/D) of Tac at 1st month at the beginning of the immunosuppressive therapy was evaluated in cohorts of 113 patients,then at 1st,3rd,6th,and 12th months after transplantation in 41 patients who received Tac-based immunosuppressive therapy and never changed within one year after transplantation,respectively.In addition,we also evaluated the association between CYP3A5 genetic variants and other clinical outcomes,such as the classifications of endomyocardial biopsy and longterm prognosis.Results The CYP3A5 wild homozygote (* 1/* 1),mutant homozygote (* 3/* 3),and mutant heterozygote (* 1/* 3) occurred in 5,34 and 74 recipients respectively.The gene mutation rate of CYP3A5 in this cohort of Chinese HTx recipients was 80.5 ％ and the homozygous proportion was 65.5％.Compared with CYP3A5 expressors (* 1/* 1 or * 1/* 3),CYP3A5 nonexpressors (* 3/* 3) had a higher Tac C0/D at 1st month (47.34 ± 11.40 vs.116.11 ± 42.40 vs.293.70 ± 171.20,P =0.000),as well as other studied time points (3rd month:98.32 ± 39.43 vs.292.07 ± 141.08,P=0.003;6th month:90.00 ± 21.31 vs.341.68 ± 165.02,P =0.002;and 12th month:96.02 ± 29.33 vs.339.23 ± 162.30,P =0.018);and might have a lower classification of endomyocardial biopsy at 1st month (1.43 ± 0.73 vs.1.50 ± 0.58,P =0.867),3rd month (1.55 ±1.00 vs.2.00 ± 1.73,P =0.512),and 6th month (1.36 ± 0.84 vs.2.33 ± 1.53,P =0.132);as well as a higher mortality due to acute organ rejection (10％ vs.0,P =0.244) and all-cause mortality (20％ vs.9.7％,P =0.580).Conclusion In Chinese HTx recipients,the frequency of this * 3 allele is lower than that has been reported in the white population.The determinations of CYP3A5 genetypes in heart transplant recipients are helpful to guide the individualized Tac regimens.

Objective To study the effect of treadmill exercise on spatial learning and memory of autism rats and its possible mechanism.Methods Ten normal wistar rats were chosen as control group,and autism-like animal models were induced in other 20 rats by intraperitoneal injection of 600 mg/kg valproate acid (VPA);the autism models were randomly divided into vehicle group and training group (n=10).The rats in the training group were forced to run on a treadmill for 30 min once a d for 28 consecutive d,while rats in vehicle group and control group were housed on static treadmill only.Then,learning and memory capabilities of all rats were tested by Morris water maze test.Superoxide dismutase (SOD) and catalase (CAT) activities and methylene dioxyamphetamine (MDA) content of the hippocampus tissues were subsequently detected by ELISA Kits.Brain-derived neurotrophic factor (BDNF),phosphorylate (p)-protein kinase (Akt),B-cell lymphoma-2 (Bcl-2),and Bcl-2 associated X protein (Bax) expressions in the hippocampus CA1 were detected by Western blotting.Nissl staining and NeuN immunohistochemistry were utilized to observe the number of normal and mature neurons.Results (1) As compared with rats in the vehicle group,the rats in the training group had significantly shortened escape latency and increased times of passing through the platform (P＜0.05).(2) Nissl staining indicated that as compared with the rats in the vehicle group,the rats in the training group had significantly smaller number of apoptotic neurons in CA1 area of the hippocampus (P＜0.05).(3) NeuN immunohistochemistry showed that number of NeuN positive cells of the vehicle control group was significantly smaller than that of the control group,while that of the training group was significantly larger than that of the vehicle group (P＜0.05).(4) Western blotting showed that MDA content significantly decreased,glutathione content significantly increased,and SOD and glutathion peroxidase activities significantly enhanced in the training group as compared with those in the vehicle group (P＜0.05);The expressions of Bcl-2,BDNF,p-Akt/Akt,p-calmodulin-dependent kinase Ⅱa (CaMKⅡ)/CaMKⅡ and pcAMP-response element binding protein(CREB)/CREB were significant up-regulated,and caspase-3 and Bax expressions were significant down-regulated in the training group as compared with those in th evehicle group (P＜0.05).Conclusion The treadmill exercise may improve the spatial learning and memory abilities of autism rats;treadmill exercise strengthens the brain antioxidant ability and plays a neuroprotective role in hippocampal neuronal cells.

Objective To explore the protective effect and mechanism of swimming rehabilitation training on learning and memory impairment of cerebral ischemia reperfusion gerbil. Methods Forty adult healthy male gerbils were randomly divided into sham group,sham+swimming group (Sham+S group),cere-bral ischemia / reperfusion group ( I/R group), cerebral ischemia/reperfusion+swimming group ( I/R+S group),with 10 rats in each group. The gerbil models of cerebral ischemia/reperfusion in I/R group and I/R+S group were established by blocking bilateral common carotid artery,while for gerbils in Sham group and Sham+S group, only bilateral common carotid arteries of gerbils were exposed, but no arteries were clamped. Morris water maze was used to detect the changes of learning and memory function in rats. Oxida- tive stress injury in hippocampal neurons was detected by detection kit analysis. And the expression of Bax, Bcl-2 and CaMK Ⅱ protein in hippocampal tissue was detected by Western blot. Results Compared with Sham group,the gerbils in I/R group had longer positioning cruise time and less shuttle times ( both P<0. 01). Compared with I/R group,the positioning cruise time and shuttle times in I/R+S group were signifi-cantly shortened and increased respectively (both P<0. 01). Compared with sham group( SOD:(123. 13± 7. 50)U/mg,GSH:(42. 10±2. 17) μg/g,GSH-Px:(61. 37±2. 51) μg/g,MDA:( 2. 91± 0. 23) nmol/mg), the activities of SOD,GSH,GSH-Px in I/R group decreased significantly,while the content of MDA increased significantly(SOD:(75. 50±6. 96)U/mg,GSH:(22. 50±1. 64) μg/g,GSH-Px:(33. 15±2. 04)μg/g,MDA:(5. 96±0. 32)nmol/mg;all P<0. 01). Furthermore,compared with I/R group,the above indexes in I/R+S group were significantly reversed(SOD:(110. 30±5. 90)U/mg,GSH:(34. 31±1. 73)μg/g,GSH-Px:(50. 13 ±2. 31)μg/g,MDA:(3. 57±0. 29) nmol/mg;all P<0. 01). Compared with Sham group,the expression of Bax protein in hippocampus of gerbils in I/R group was increased,while the expression of Bcl-2 protein and p-CaMK Ⅱ protein was decreased (all P<0. 05). Compared with I/R group,the expression of Bax protein in hippocampus of gerbils in I/R+S group was decreased,while the expression of Bcl-2 protein and p-CaMK Ⅱprotein was increased (all P<0. 05). Conclusion Swimming rehabilitation training can improve learning and memory impairment of gerbils after ischemia-reperfusion through anti-oxidative stress and anti-apoptosis, which may be related to CaMK Ⅱ signaling system.

Sertoli cell (SC) is intrinsic to the testis and provides an appropriate growth environment for the germ cells. It was separated from rat's testis and identified by hematoxylin and eosin staining(HE) and immunocytochemical reaction, then cultivated in vitro. Culture conditions such as pH, osmotic pressure and metabolic parameters that include consumption rates of glucose, glutamine, amino acids and formation rates of lactic acid, ammonium ion were investigated. It was showed that adhesion process of SCs was accomplished within 2-4 hours after inoculation. It was also observed that the SCs entered into the decline phase when the concentration of ammonium ion and lactic acid were above 2.3 mmol/L and 14 mmol/L, respectively, which caused osmotic pressure above 326 mosm/kg and pH below 6.8 in the medium. As the changes of amino acids during culture were concerned, Glu and Ala accumulated rapidly, while Val, Leu, Ile reduced slightly and at the same time Ser, Arg, and Gly were stable. The restrict factors for SCs grown in static culture might be high osmotic pressure and low pH, which were generated when glutamine and glucose were metabolized into lactic acid. The findings could be fundamental in the process optimization of large scale Sertoli cells in vitro culture.
Amino Acids ; metabolism ; Animals ; Animals, Newborn ; Cell Culture Techniques ; Cells, Cultured ; Culture Media ; Male ; Rats ; Sertoli Cells ; cytology ; metabolism ; Testis ; cytology

Objective To investigate the effect of adjusting tube current time product (mAs) according to head circumference index on head CT image quality and organ-specific-dose level based on Monte Carlo analysis platform.Methods A total of 92 patients including children and adolescents with different clinical symptoms undergoing head CT scan were prospectively selected between September 2017 and June 2018 in the First Hospital of Jilin University.Without limiting the size of the head circumference,there were 22 patients were selected as conventional group by random number table,whose head circumference was 48.1-59.2 cm.Low dose group was divided into following three subgroups according to different head circumferences:A group 54.1-57.0 cm (n=22);B group 51.1-54.0 cm (n=26) and C group 48.1-51.0 cm (n=22).Tube current time product was 250 mAs for conventional group,200 mAs for A group,150 mAs for B group and 100 mAs for C group,respectively.The organ-specific-radiation doses (brain,eye lens and salivary gland) were recorded by Monte Carlo analysis platform and the subjective and objective image quality score was evaluated.Analyses of the differences between four groups were compared with image quality score as well as organ-specific-radiation dose by single factor variance.Results Radiation dose to brain was conventional group (34.37±3.62),A group (25.91±0.99),B group (23.18±6.11) and C group (17.38 ± 3.23) mSv,respectively.The difference was of statistical significance in the four groups (F=54.51,P＜0.05).Dose to eye lens was conventional group (41.54± 1.04),A group (33.03±0.35),B group (26.18±2.72) and C group (20.88±4.45) mSv,with statistical significance in difference between the four groups (F=189.75,P＜0.05).Dose to salivary gland was conventional group (35.04 ± 4.94),A group (25.92 ± 0.99),B group (22.93 ± 6.54) and C (14.96±2.67) mSv,respectively,with statistical significance in difference between the four groups (F=65.74,P＜0.05).Image quality scores were respectively conventional group (4.97±0.13),A group (4.77 ± 0.49),B group (4.60 ± 0.49) and C group (3.98 ± 0.61),respectively,with statistical significance between them (F=3.89,P＜0.05),but without statistical significance in difference between the four groups (P ＞ 0.05).The signal-to-noise ratios of gray matter in A,B and C groups were conventional group (18.69 ± 3.55),A group (16.76 ± 2.87),B group (15.05 ± 2.80) and C group (13.65±2.53),respectively,without statistical significance in difference between the four groups (P＞ 0.05);The signal-to-noise ratios of white matter in conventional group (17.46±3.72),A group (15.54± 2.81),B group (13.71±2.43) and C group (11.77±2.18),respectively,without statistical significance in difference between the four groups (P＞0.05).Conclusions Adjusting the tube current time product (mAs) according to head circumference index of children and adolescents can make scanning program more personalized and reduce organ-specific-radiation doses to sensitive organs without compromise of image quality.

Objective:The study aimed to study the efficacy and safety of combined dual therapy using anti-programmed death (PD)-1 and tyrosine kinase inhibitor (TKI) with combined triple therapy using anti-PD-1, TKI and locoregional intervention triple therapy in patients with postoperative refractory recurrent liver cancer.Methods:Patients with postoperative refractory recurrent liver cancer who had undergone either anti-PD-1 and TKI dual therapy or anti-PD-1, TKI and locoregional intervention triple therapy between July 2016 and March 2019 at the First Medical Center, Chinese PLA General Hospital were retrospectively studied. Tumor responses were assessed by the modified response evaluation criteria in solid tumors and overall survival and progression free survival were compared. Adverse events were evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events.Results:Of 63 patients who were included in this study, there were 25 patients in the dual therapy group (16 males and 9 females, aged 54.3±8.8 years) and 38 patients in the triple therapy group (31 males and 7 females, aged 55.5±8.4 years). The 1-year survival rate of the triple therapy group was significantly higher than the dual therapy group (94.5%vs 54.9%) ( P<0.01). The disease control rate was 64.0% (16/25) in the dual therapy group and 84.2% (32/38) in the triple therapy group, and the difference was not significant ( P>0.05). The incidence of treatment-related adverse events in the triple therapy group and the dual therapy group were 78.9% (30/38) and 80% (20/25), respectively. There was no treatment-related death in the 2 groups. Conclusions:Anti-PD-1 and TKI dual therapy and anti-PD-1, TKI and locoregional intervention triple therapy were effective and tolerable treatments for postoperative refractory recurrent liver cancer. The latter treatment had a significantly better clinical benefit on survival outcomes.

Laparoscopic ultrasound (LUS) has the advantage of high resolution,multi-angle exploration,and is widely used in minimally invasive surgery of biliary tract.LUS has a series of auxiliary function in difficult laparoscopic cholecystectomy (LC),common bile duct exploration,surgery of intrahepatic biliary calculi,and intraoperative staging of pancreato-biliary tumor.This paper summarizes the application of LUS in laparoscopic biliary surgeries and the related technical essentials.

Objective:To study the safety and efficacy of a treatment protocol using immune checkpoint inhibitors (ICIs) and antiangiogenic targeted drugs (AATDs) in converting 41 patients with initially unresectable to resectable hepatocellular carcinoma (HCC).Methods:The data of 41 patients with initially unresectable HCC treated with immunotherapy combined with targeted therapy from December 2018 to April 2021 in Chinese PLA General Hospital were analysed. There were 34 males and 7 females, aged (51.8±10.7) years. The clinical characteristics, conversion to resectable HCC, adverse drug reactions, surgical data and postoperative complications were analysed. Patients were followed-up by outpatients clinics or telephone calls.Results:There were 5 patients with Chinese Liver Cancer Staging (CNLC)-Ⅰb, 4 with CNLC-Ⅱ, 28 with CNLC-Ⅲa and 4 with CNLC-Ⅲb before the treatment protocol. Among them, 28 patients had portal vein tumor thrombosis (PVTT) and 4 had retroperitoneal lymph node metastases. All patients had a mean tumor diameter of (9.16±4.43) cm before and (6.49±4.69) cm after the treatment protocol. The latter was based on the last assessment before hepatectomy. The efficacy of the treatment protocol in converting unresectable to resectable HCC was assessed by the modified Response Evaluation Criteria in Solid Tumors after 3-15 cycles (median dose cycles, 5) of protocal therapy: 15 patients achieved a complete response; 15 patients achieved a partial response; 6 patients had a stable disease, and 5 patients had a progressive disease. 21 patients (51.2%) experienced adverse reactions associated with drug treatment, which resolved with symptomatic treatment or brief discontinuation of the therapy. All patients underwent successful hepatectomy. Postoperative complications of grade Ⅱ or higher occurred in 9 patients (22.0%). The cumulative overall survival rates at 6 months, 1 year and 2 years from diagnosis were 100.0%, 92.6% and 64.7% respectively. The cumulative overall survival rates at 6 months, 1 year and 2 years after surgery were 95.1%, 74.7% and 60.8%, and the recurrence-free survival rates at 6 months, 1 year and 2 years after surgery were 87.8%, 56.7% and 48.6%, respectively.Conclusions:This study provided preliminary evidences that surgical resection after immunotherapy combined with targeted therapy in patients with initially unresectable HCC was safe and efficacious.

Objective:To assess the clinical efficacy of sequential radical surgery after immune and targeted therapy in downstaging patients with initially unresectable hepatocellular carcinoma.Methods:Data were prospectively collected from December 2018 to July 2022 on patients with initially unresectable hepatocellular carcinoma which were downstaged to undergo sequential surgery after treatment with immune and targeted therapy at the Faculty of Hepato-Pancreato-Biliary Surgery, Chinese PLA General Hospital. There were 79 patients, with 69 men and 10 women, aged (53.0±10.9) years, being enrolled into this study. The Kaplan-Meier method was used to calculate the survival rate, and the log-rank test was used for survival rate comparison. Univariate and multivariate Cox regression were used to analyze factors influencing patient prognosis.Results:There were 7 patients (8.9%) with China Liver Cancer Staging (CNLC) Ⅰb, Ⅱa, Ⅱb who had insufficient residual liver volume or tumor rupture before the downstaging therapy, and 38 patients (48.1%) with CNLC Ⅲa and 34 patients (43.0%) with CNLC Ⅲb. These 79 patients underwent R 0 resection after 3-20 cycles (median 5 cycles) of immune and targeted therapy. Based on the modified response evaluation criteria in solid tumor, the results of preoperative imaging assessment were: complete remission in 12 patients (15.2%), partial remission in 50 patients (63.3%), stable disease in 15 patients (19.0%), and disease progression in 2 patients (2.5%). The overall survival rates of patients at 1, 2, and 3 years after diagnosis were 96.1%, 83.5%, and 76.6%; and the recurrence-free survival rates at 1, 2, and 3 years after surgery were 62.1%, 52.9%, and 34.7%, respectively. On multivariate Cox regression analysis, patients with a preoperative alpha-fetoprotein >20 μg/L ( HR=2.816, 95% CI: 1.232-6.432, P=0.014) and a high proportion of pathological residual tumors ( HR=1.015, 95% CI: 1.004-1.026, P=0.006) had a higher risk of postoperative recurrence; and patients with a high proportion of pathological residual tumors ( HR=1.028, 95% CI: 1.007-1.049, P=0.007) and preoperative alpha-fetoprotein >400 μg/L ( HR=4.099, 95% CI: 1.193-14.076, P=0.025) had a higher risk of death. Conclusion:Immunotherapy combined with targeted therapy and sequential surgery for patients with initially unresectable hepatocellular carcinoma provided long-term survival benefits. Elevated preoperative alpha-fetoprotein and a high proportion of pathological residual tumor were independent risk factors for recurrence-free survival and overall survival in this group of patients.