OBJECTIVE To explore the relationship between severe cardiotoxicity caused by oxaliplatin combined with capecitabine and genetic polymorphism， thereby providing references for safe clinical medication use. METHODS Clinical pharmacists conducted a correlation analysis on a case of severe cardiotoxicity in a rectal cancer patient at Qilu Hospital of Shandong University following first-time treatment with standard doses of oxaliplatin combined with capecitabine. Case reports of cardiotoxicity caused by oxaliplatin and capecitabine were retrieved from the Chinese and English databases such as CNKI and PubMed.Basic patient information， drug treatment plan， and cardiotoxic manifestations were extracted and summarized. Combined with the patient’s genetic polymorphism test results related to the metabolism and excretion of platinum-based and fluorouracil drugs， potential mechanisms and prevention strategies for cardiotoxicity induced by oxaliplatin and capecitabine were discussed. RESULTS The patient exhibited homozygous mutations in ABCB1 C3435T and G2677T/A， a heterozygous mutation in MTHFR A1298C， and a heterozygous mutation in GSTP1 A105G， indicating impaired metabolism and excretion of oxaliplatin and capecitabine. The pharmacists recommended discontinuing oxaliplatin and reducing capecitabine to 50% of the original dose for subsequent treatment. The physicians adopted this advice， and the patient experienced no further severe adverse reactions with stable disease progression. CONCLUSIONS Oxaliplatin and capecitabine may cause severe cardiotoxicity. Medical institutions with adequate resources should perform genetic polymorphism test related to drug metabolism and excretion in patients prescribed these agents. For patients with multiple gene mutations， close monitoring and appropriate dose reductions are recommended to ensure medication safety and efficacy.

Objective: To develop the matrix-matched calibration curve correction-inductively coupled plasma mass spectrometry (ICP-MS) for the determination of lead in blood. Methods: Whole blood samples and blank whole blood were pretreated by direct dilution with a solution of 0.5% nitric acid and 0.01% TritonX-100 to obtain whole blood sample solutions and matrix-matched solvents at a 10-fold dilution. The mass concentration of lead was determined by using an ICP-MS instrument in He mode. 175Lu was added online as an internal standard. The standard working curve was calibrated with the matrix-matched solvent, and the mass concentration of lead in the whole blood samples was calculated based on the standard working curve. Recovery tests were performed on whole blood blind samples by spiking, and the relative standard deviation and average recovery rate were calculated. The accuracy and precision of this method were assessed by comparing it with the method recommended in the national standard in detection of lead in three types of bovine blood lead standard materials. Results: Good linearity was shown for lead at 0.5 to 100.0 μg/L, with a correlation coefficient of 1.000. The detection limit of lead was 0.4 μg/L, and the quantitation limit was 1.3 μg/L. The relative standard deviations were 0.65% and 1.10%. The average recovery ranged from 96.89% to 99.73%. The lead determination results were all within the normal reference ranges specified by the three certified reference materials for bovine blood samples. Conclusion The matrix-matched calibration curve correction-ICP-MS is suitable for high-throughput determination of blood lead.

Objective : To establish a microwave-assisted digestion-inductively coupled plasma mass spectrometry (ICP-MS) with an octopole reaction system for simultaneous determination of six heavy metals in peanuts, including Cr, Ni, As, Cd, Pb, Hg. Methods : Peanut samples were shelled and crushed evenly, and 0.350 0 g was accurately weighed and digested with 5 mL nitric acid and 1 mL hydrogen peroxide in a digestion tank. Following microwave-assisted digestion, pure water was used to quantify the samples, and internal standards and an octopole reaction system were used to remove the interference. Then, the contents of six heavy metals were determined in peanuts by ICP-MS. The accuracy and precision of ICP-MS were evaluated using national criteria ( GBW 10013 and GBW 10044 ) and spike-and-recovery testing. Results : The six heavy metals showed good linearity at the selected linear range ( r≥0.999 8 ). The detection limits of ICP-MS ranged from 0.001 4 to 0.023 8 ng/mL, and the spike-and-recovery rates ranged from 94.7% to 98.8%, with the relative standard deviations ranging from 0.7% to 3.6%. In addition, the determination results of the standard reference materials were all within the normal reference range. The detection of six heavy metals was 100.0% in 60 peanut samples, and the contents of six heavy metals were all low. Conclusion The established ICP-MS assay is feasible for simultaneous determination of multiple heavy metals in peanuts.

Objective:To investigate the efficacy of liposomal doxorubicin intensive preconditioning regimen and allogeneic hematopoietic stem cell transplantation (allo-HSCT) in treatment of leukemia.Methods:The data of 20 patients with intensive preconditioning regimen allo-HSCT who were admitted to Shenzhen Second People's Hospital from January 2016 to June 2017 were retrospectively analyzed. The transplantation effect, occurrence of complications and prognosis of patients were analyzed.Results:The median time of granulocyte engraftment was 17 d (13-23 d); the median time of platelet engraftment was 22.5 d (minimum 13 d, maximum >90 d). The acute graft-versus-host disease (GVHD) and chronic GVHD occurred in 2 cases and 1 case, respectively. Eight cases occurred hemorrhagic cystitis, 15 cases occurred Epstein-Barr viremia, 8 cases occurred cytomegaloviremia, 1 case occurred sepsis, 1 case occurred acute liver injury, and 2 cases occurred fungal pneumonia. The median follow-up time was 31.7 months (0.8-53.8 months). One patient died of intracranial infection on the 25th day after transplantation; 3 patients relapsed during the follow-up period, and 2 of them died; the other 16 patients carried 100% donor genes during the follow-up period.Conclusions:The liposomal doxorubicin intensive preconditioning regimen and allo-HSCT have a good effect on leukemia. Increasing the intensity of pretreatment does not increase the treatment-related adverse reactions. The incidence rates of Epstein-Barr viremia and cytomegaloviremia are high, but they are improved after active treatment.

OBJECTIVE：To study the m edical insurance budget impact analysis （BIA）guidelines or nomative documents of some European countries ，and to provide the suggestions for the formulation and implementation of medical insurance BIA guidelines in China. METHODS ：Medical insurance BIA guidelines or related documents in European countries such as Ireland ， France，Poland，Belgium and UK were retrieved to summarize and comparatively analyze the general analysis framework and special specification. The formulation of medical insurance BIA guideline in China and the suggestions were put forward. RESULTS & CONCLUSIONS ：The above-mentioned medical insurance BIA guidelines or documents of the five European countries generally study the impact of the cost of health technology on resources within 3-5 years from the perspective of budget holders. The analysis framework of the guidelines or documents is basically the same ，but the guidelines or documents are adjusted according to the characteristics of national health system in terms of the positioning of medical insurance BIA ，the scope of cost data inclusion ， model design ，population subgroup analysis and so on. For example ，Ireland had special requirements on cost data inclusion ， sensitivity analysis and data source ，while France had detailed regulations on medical insurance BIA model ，sensitivity analysis and presentation of medical insurance BIA results. Our country should pay attention to the role of medical insurance BIA in medical and health decision-making ，formulate China ’s medical insurance BIA guidelines to standardize empirical research ，and combine the characteristics of China ’s health system when formulate the guideline. It is suggested that China ’s medical insurance BIA guidelines should at least include research perspective ，research time limit and discount ，reference situation ，target population ， cost，market share ，data source ，uncertainty analysis and other overall framework or basic elements to ensure the smooth operation of medical and health funds.

OBJECTIVE：To construc t the evaluation system of the research quality of medical insurance budget impact analysis （BIA），and to provide feasible evaluation tool for related departments as medical insurance department. METHODS ：Based on BIA guidance documents and relevant empirical literatures of ISPOR ，Canada，Poland，the United States and other countries ， combined with expert interview ，the relevant elements of medical insurance negotiation BIA material were confirmed （including key elements and adjuctive elements ）. The scale and system was established to calculate total score of BIA research quality evaluation. RESULTS ：Key elements included three data blocks as target population ，market situation and treatment cost ，involving 14 key elements such as total population ，new drug scenario market share ，treatment cost ，etc.. According to the degree of compliance，0-3 points were assigned and the lowest score after normalization was taken as the basic score of BIA research quality. The adjunctive elements included five data blocks as title & abstract ，research background ，analysis framework ，result presentation and other ，including 23 adjunctive elements such as title ，abstract，research angle ，research time limit ，etc.. According to whether there is quality grade difference ，the elements were divided into type A and type B ；the grade score （0-4 points）and 0/1 score（1 point for yes and 0 point for no ）were used respectively ，and the additional score of BIA research quality was obtained after calculation and addition. According to the addition of different weights （0.67 and 0.33）of basic score and additional score ，the total score system of BIA research quality evaluation could be calculated. CONCLUSIONS ：This study successfully constructed a new BIA quality evaluation system ，which can be used for the quality evaluation of BIA research submitted by medical insurance drug negotiation.

Objective:To investigate the effects of different lymph node dissection methods in radical resection of intrahepatic cholangiocarcinoma (ICC) on the number of harvested lymph nodes and prognosis of patients.Methods:The retrospective cohort study was conducted. The clinicopathological data of 57 patients with ICC who underwent radical resection in the Second Affiliated Hospital of Nanchang University from January 2011 to January 2016 were collected. There were 25 males and 32 females, aged from 45 to 72 years, with an average age of 59 years. Of the 57 patients, 36 undergoing en bloc fusion lymph node dissection and 21 undergoing conventional lymph node dissection were allocated into observation group and control group, respectively. Observation indicators: (1) intraoperative situations; (2) results of postoperative pathological examination; (3) postoperative complications; (4) follow-up. Follow-up using outpatient examination or telephone interview was performed once every six months after hospital discharge to detect survival of patients up to January 2019. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was done using the t test. Measurement data with skewed distribution were described as M (range), and comparison between groups was analyzed by the Mann-Whitney U test. Count data were described as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test or Fisher exact propability. Comparison of ordinal data between groups was analyzed using the Mann-Whitney U test. The survival curve and rate were drawn and calculated using the Kaplan-Meier method, and survival of patients was analyzed by the Log-rank test. Results:(1) Intraoperative situations: operation time, volume of intraoperative blood loss, hepatic portal occlusion time, cases with <3 segments of hepatectomy and ≥3 segments of hepatectomy for the observation group were (218±53)minutes, (266±24)mL, (21±9)minutes, 5, 31, respectively, versus (207±45)minutes, (270±23)mL, (19±8)minutes, 2, 19 for the control group, showing no significant difference in the above indicators between the two groups ( t=-0.530, 0.774, 0.590, χ2=0.004, P>0.05). (2) Results of postoperative pathological examination: the number of harvested lymph nodes and percentage of positive lymph nodes of the observation group were 11±3 and 16.58%(66/398), respectively, versus 5±2 and 6.80%(7/103) of the control group, showing significant differences in the above indicators between the two groups ( t=-9.454, 2.148, P<0.05). (3) Postoperative complications: cases with Clavien-Dindo grade Ⅰ-Ⅱ complications or Clavien-Dindo grade Ⅲ-Ⅳ complications, cases with bile leakage, cases with postoperative hemorrhage, cases with incision infection, cases with gastroparesis were respectively 35, 1, 6, 1, 8, 0 in the observation group and 19, 2, 3, 1, 1, 2 in the control group. There was no significant difference in the cases with complications of Clavien-Dindo classification, cases with bile leakage, cases with incision infection between the two groups ( χ2=0.236, 0.000, 1.870, P>0.05) and no significant difference in the cases with postoperative hemorrhage, cases with gastroparesis between the two groups ( P>0.05). (4) Follow-up: 57 patients were followed up for 5-42 months, with a median time of 36 months. The survival time and postoperative 3-year survival rate were respectively 36 months (range, 8-42 months) and 66.7% of the observation group, versus 23 months (range, 5-39 months) and 38.1% of the control group, showing significant differences in the above indicators between the two groups ( Z=-2.253, χ2=5.317, P<0.05). Conclusion:For radical resection of ICC, the en bloc fusion lymph node dissection is beneficial to increase the number of harvested lymph nodes and improve survival rate of patients.

Objective:To intestigate the clinical efficacy between modified Overlap anastomosis and traditional auxiliary incision anastomosis in laparoscopic total gastrectomy.Methods:The retrospective cohort study was conducted. The clinicopathological data of 115 patients with gastric cancer who were admitted to the Second Affiliated Hospital of Fujian Medical University from January 2016 to December 2018 were collected. There were 62 males and 53 females, aged from 27 to 83 years, with a median age of 62 years. Of 115 patients, 51 patients undergoing totally laparoscopic total gastrectomy with modified Overlap anastomosis using linear stapler were divided into modified Overlap group and 64 patients undergoing laparoscopic assisted total gastrectomy with traditional auxiliary incision anastomosis using circular stapler were divided into traditional assisted group. Observation indicators: (1) surgical situations; (2) postoperative situations; (3) anastomotic complications; (4) follow-up. Follow-up using outpatient examination or telephone interview was conducted to detected tumor recurrence and survival of patients up to December 2019. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Count data were represented as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test or Fisher exact probability. Comparison of ranked data was analyzed using the rank sum test. Results:(1) Surgical situations: the operation time, time of esophagojejunostomy, volume of intraoperative blood loss, the number of lymph node dissected, length of proximal incisional margin and length of auxiliary incision of the modified Overlap group were (234.0±11.0)minutes, (29.4±2.1)minutes, (53±14)mL, 42±13, (2.0±0.3)cm and (5.1±0.4)cm, respectively. The above indicators of the traditional assisted group were (231.0±11.0)minutes, (29.2±2.2)minutes, (50±13)mL, 40±10, (2.2±0.4)cm and (8.2±0.4)cm, respectively. There was significant difference in the length of auxiliary incision between the two groups ( t=-43.098, P<0.05), and there was no significant difference in the operation time, time of esophagojejunostomy, volume of intraoperative blood loss, the number of lymph node dissected, length of proximal incisional margin between the two groups ( t=1.168, 0.460, 0.990, 1.127, -1.926, P>0.05). (2) Postoperative situations: cases with mild, moderate, severe pain (postoperative pain degree), time to first flatus, time to initial fluid diet intake, duration of postoperative hospital stay of the modified Overlap group were 40, 9, 2, (2.9±1.0)days, (4.8±2.2)days, (11.7±2.8)days, respectively. The above indicators of the traditional assisted group were 31, 27, 6, (3.9±1.4)days, (6.5±2.5)days, (13.0±3.1)days, respectively. There were significant differences in the above indicators between the two groups ( Z=-3.217, t= -4.344, -3.888, -2.261, P<0.05). (3) Anastomotic complications: cases with anastomotic leakage, cases with anastomotic bleeding, cases with anastomotic stenosis of the modified Overlap group were 1, 1, 0, respectively. The above indicators of the traditional assisted group were all 1. There was no significant difference in the above indicators between the two groups ( P>0.05). Cases with anastomotic leakage were cured after the treatment of enteral nutritional support through nasogastric catheterization, which were confirmed by gastroenterography. Cases with anastomotic bleeding were improved by active hemostatic therapy. Cases with anastomotic stenosis were improved after the symptomatic treatment of anti-inflammatory and anti-swelling. (4) Follow-up: 109 of the 115 patients were followed up. Forty-eight of 51 patients in the modified Overlap group were followed up for 15.0-45.0 months, with a median follow-up time of 33.5 months. Sixty-one of 64 patients in the traditional assisted group were followed up for 16.0-46.0 months, with a median follow-up time of 27.0 months. There was no tumor recurrence in the modified Overlap group. One patient in the traditional assisted group had tumor recurrence with liver metastasis and survived with tumor. There was no significant difference in tumor recurrence rate between the two groups ( P>0.05). There was no patient died during the follow-up. Conclusion:Compared with traditional auxiliary incision anastomosis, patients undergoing total laparoscopic total gastrectomy with modified Overlap anastomosis have small incision, good postoperative recovery.

Objective:To investigate the role of interleukin-13(IL-13), interleukin-13 receptor α2(IL-13Rα2) and 11 β -hydroxysteroid dehydrogenase 2(11βHSD2) signaling pathway in liver metastasis of colon cancer and its mechanism.Methods:A retrospective case-control study was conducted to analyze the clinical data of 80 patients with colorectal cancer who were operated in Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology from January 2015 to December 2018.All patients were followed up by clinic or telephone until August 30, 2019.According to the occurrence of liver metastasis, the patients were divided into metastasis group ( n=22) and non metastasis group ( n=58). Real-time fluorescence quantitative Polymerase Chain Reaction(PCR) and Western blotting were used to detect and compare the mRNA relative expression and protein expression of IL-13, IL-13Rα2, 11βHSD2, cyclooxygenase 2(COX 2) and protein kinase B in cancer tissues and cancer adjacent tissues. Glycyrrhetinic acid, an inhibitor of 11 β HSD2, was used to inhibit the activity of 11hsd2 in human colon cancer cell line HCT-8.The mRNA relative expression and protein expression of IL-13, IL-13Rα2, 11βHSD2, COX 2 and protein kinase B were detected by real-time fluorescence quantitative PCR and Western blotting before and 24 hours after glycyrrhetinic acid addition. Results:The mRNA relative expression of IL-13(0.79±0.11, 0.40±0.10), IL-13Rα2(0.72±0.13, 0.46±0.11), 11βHSD2(0.84±0.26, 0.60±0.08), COX 2(0.70±0.25, 0.37±0.04), protein kinase B (0.76±0.13, 0.42±0.06) in colon cancer tissues of metastatic and non metastatic groups were higher than those in cancer adjacent tissues(0.09±0.01, 0.10±0.06, 0.09±0.02, 0.09±0.03, 0.09±0.01, 0.09±0.02, 0.13±0.02, 0.12±0.07, 0.05±0.02, 0.05±0.03). The difference was statistically significant (t value was 28.36, 23.20, 22.07, 24.88, 16.47, 16.47, 47.86, 18.55, 24.55, 26.20, 44.40, all P<0.001). The protein expression of IL-13(0.48±0.11, 0.32±0.07), IL-13Rα2(0.52±0.11, 0.36±0.11), 11βHSD2(0.63±0.12, 0.48±0.11), COX2(0.45±0.15, 0.27±0.09), protein kinase B(0.50±0.12, 0.29±0.08) in colon cancer tissues of metastatic and non metastatic groups were higher than those in cancer adjacent tissues(0.12±0.02, 0.13±0.01, 0.10±0.02, 0.10±0.02, 0.14±0.06, 0.13±0.05, 0.10±0.03, 0.10±0.04, 0.10±0.03, 0.10±0.02). The difference was statistically significant ( t value were 15.63, 21.15, 17.71, 17.28, 11.01, 18.14, 10.55, 13.12, 15.76 and 18.90 respectively, all P<0.001). The relative expression of mRNA and protein in metastasis group was higher than that in non metastasis group ( t=15.15, 3.01, 8.97, 2.52, 6.34, 2.26, 9.82, 2.52, 16.02, 3.57, respectively, all P< 0.05). Compared with that those of before glycyrrhetinic acid addition, after 24 hours of glycyrrhetinic acid addition, the mRNA relative expression and protein expression of IL-13, IL-13Rα2 had no significant change (all P>0.05), while the mRNA relative expression and protein expression of COX 2 and protein kinase B(before adding: 0.725±0.159, 0.639±0.162, 0.741±0.178, 0.668±0.145, after adding: 0.108±0.085, 0.116±0.048, 0.122±0.063, 0.119±0.066) were decreased( t value were 18.744, 16.954, 17.956, 18.875 respectively , all P<0.01). Conclusion:The activation of IL-13/IL-13α2/11βHSD2 signaling pathway can promote liver metastasis of colon cancer.The mechanism may be that 11βHSD2 over expression promotes cancer cells invasion and migration-related COX2 expression and PI3K/protein kinase B pathway, and promotes liver metastasis of colon cancer.

Long non-coding RNAs (lncRNAs) regulate various biological processes ranging from gene expression to animal behavior. Although protein-coding genes, microRNAs, and neuropep-tides play important roles in the regulation of phenotypic plasticity in migratory locust, empirical studies on the function of lncRNAs in this process remain limited. Here, we applied high-throughput RNA-seq to compare the expression patterns of lncRNAs and mRNAs in the time course of locust phase change. We found that lncRNAs responded more rapidly at the early stages of phase transition. Functional annotations demonstrated that early changed lncRNAs employed different pathways in isolation and crowding phases to cope with changes in the population density. Two overlapping hub lncRNA loci in the crowding and isolation networks were screened for func-tional verification. One of them, LNC1010057, was validated as a potential regulator of locust phase change. This work offers insights into the molecular mechanism underlying locust phase change and expands the scope of lncRNA functions in animal behavior.