Objective This study explores the efficacy and underlying mechanisms of combining rhCYGB with 5-FU to target hypoxia-induced treatment resistance in liver cancer.The aim is to develop a novel combinato-rial therapy strategy for improving outcomes in patients with refractory liver cancer.Methods The half-maximal inhibitory concentration(IC50)of drugs on liver cancer cells under normoxia and hypoxia was determined,and dose-response curves were generated to assess sensitivity to 5-FU.The combined effects of rhCYGB and 5-FU were analyzed withCompuSyn and SynergyFinder 3.0.Tumor stem cell sphere formation assays and flow cytometry for CD133-positive cells were conducted to evaluate the impact on cancer stemness.Wound healing assays assessed the effects on migration.Results The IC50 values under hypoxia exhibited a significant fold change compared to normoxia(P<0.05),specifically a 15.27-fold,4.25-fold,and 2.34-fold increase for Hep3B,Huh7,and HepG2 cells respectively.Assessment of drug combination effects demonstrated a synergistic interaction between 5-FU and rhCYGB.Compared to the 5-FU monotherapy group,the combination of 5-FU and rhCYGB exerted an inhibitory effect on the formation of liver cancer stem cell spheres(P<0.05)and significantly downregulated the proportion of CD133-positive subpopulations in Hep3B cells(P<0.05).Wound healing assay results revealed a synergistic inhibitory effect on the migration of Hep3B cells after 48 hours of treatment with rhCYGB combined with 5-FU undernormoxia(P<0.05).Conclusions The combination of rhCYGB and 5-FU demonstrates syner-gistic effects in liver cancer.The underlying mechanism may involve the modulation of stemness and cell migration capacity.

Objective:To explore the classification performance of combined model constructed from CT signs combined with radiomics for discriminating COVID-19 pneumonia and other viral pneumonia.Methods:The clinical and CT imaging data of 181 patients with viral pneumonia confirmed by reverse transcription-polymerase chain reaction in 15 hospitals of Yunnan Province from March 2015 to March 2020 were analyzed retrospectively. The 181 patients were divided into COVID-19 group (89 cases) and non-COVID-19 group (92 cases), which were further divided into training cohort (126 cases) and test cohort (55 cases) at a ratio of 7∶3 using random stratified sampling. The CT signs of pneumonia were determined and the radiomics features were extracted from the initial unenhanced chest CT images to build independent and combined models for predicting COVID-19 pneumonia. The diagnostic performance of the models were evaluated using receiver operating characteristic (ROC) analysis, continuous net reclassification index (NRI) calibration curve and decision curve analysis.Results:The combined models consisted of 3 significant CT signs and 14 selected radiomics features. For the radiomics model alone, the area under the ROC curve (AUC) were 0.904 (sensitivity was 85.5%, specificity was 84.4%, accuracy was 84.9%) in the training cohort and 0.866 (sensitivity was 77.8%, specificity was 78.6%, accuracy 78.2%) in the test cohort. After combining CT signs and radiomics features, AUC of the combined model for the training cohort was 0.956 (sensitivity was 91.9%, specificity was 85.9%, accuracy was 88.9%), while that for the test cohort was 0.943 (sensitivity was 88.9%, specificity was 85.7%, accuracy was 87.3%). The AUC values of the combined model and the radiomics model in the differentiation of COVID-19 group and the non-COVID-19 group were significantly different in the training cohort ( Z=-2.43, P=0.015), but difference had no statistical significance in the test cohort ( Z=-1.73, P=0.083), and further analysis using the NRI showed that the combined model in both the training cohort and the test cohort had a positive improvement ability compared with radiomics model alone (training cohort: continuous NRI 1.077, 95 %CI 0.783-1.370; test cohort: continuous NRI 1.421, 95 %CI 1.051-1.790). The calibration curve showed that the prediction probability of COVID-19 predicted by the combined model was in good agreement with the observed value in the training and test cohorts; the decision curve showed that a net benefit greater than 0.6 could be obtained when the threshold probability of the combined model was 0-0.75. Conclusion:The combination of CT signs and radiomics might be a potential method for distinguishing COVID-19 and other viral pneumonia with good performance.

OBJECTIVE: To establish a novel standardized magnetization transfer ratio (MTR) parameter which considers the element of the normal bowel wall and to compare the efficacy of the MTR, normalized MTR, and standardized MTR in evaluating intestinal fibrosis in Crohn's disease (CD).MATERIALS AND METHODS: Abdominal magnetization transfer imaging from 20 consecutive CD patients were analyzed before performing elective operations. MTR parameters were calculated by delineating regions of interest in specified segments on MTR maps. Specimens with pathologically confirmed bowel fibrosis were classified into one of four severity grades. The correlation between MTR parameters and fibrosis score was tested by Spearman's rank correlation. Differences in MTR, normalized MTR, and standardized MTR across diverse histologic fibrosis scores were analyzed using the independent sample t test or the Mann-Whitney U test. The area under the receiver operating characteristic curve (AUC) was computed to test the efficacies of the MTR parameters in differentiating severe intestinal fibrosis from mild-to-moderate fibrosis.RESULTS: Normalized (r = 0.700; p < 0.001) and standardized MTR (r = 0.695; p < 0.001) showed a strong correlation with bowel fibrosis scores, followed by MTR (r = 0.590; p < 0.001). Significant differences in MTR (t = −4.470; p < 0.001), normalized MTR (Z = −5.003; p < 0.001), and standardized MTR (Z = −5.133; p < 0.001) were found between mild-to-moderate and severe bowel fibrosis. Standardized MTR (AUC = 0.895; p < 0.001) had the highest accuracy in differentiating severe bowel fibrosis from mild-to-moderate bowel wall fibrosis, followed by normalized MTR (AUC = 0.885; p < 0.001) and MTR (AUC = 0.798; p < 0.001).CONCLUSION: Standardized MTR is slightly superior to MTR and normalized MTR and therefore may be an optimal parameter for evaluating the severity of intestinal fibrosis in CD.
Crohn Disease ; Fibrosis ; Humans ; Magnetic Resonance Imaging ; ROC Curve

OBJECTIVE： To study the relationships of polymorphism of MTRR gene rs1801394 locus and SLCO1B1 gene rs11045879 locus with drug concentration of methotrexate （MTX） and high-dose MTX （HD-MTX）-induced ADR in acute lymphoblastic leukemia （ALL） children. METHODS： From Oct. 2015 to Sept. 2018， 70 ALL hospitalized children of Han nationality in Sichuan area who received HD-MTX treatment and were in consolidation chemotherapy were selected retrospectively from Sichuan People’s Hospital. The blood concentration of MTX at 48 and 72 hours after administration was measured by EMIT. The genetic typing of MTRR gene rs1801394 locus and SLCO1B1 gene rs11045879 locus were detected with real-time PCR. The relationships of the polymorphism of MTRR gene and SLCO1B1 gene with MTX blood concentration [dose-corrected concentration （c48 h/D，48 h）， the proportion of children with different concentration of MTX （≤0.1， ＞0.1 μmol/L）] and ADR （such as myelosuppression， liver function damage， gastrointestinal response， mucosal damage， rash， etc.） were analyzed. Binary Logistic regression analysis for the correlation of ADR with different influencing factors （gene polymor- phism， blood concentration of MTX， immunophenotyping， body mass index， etc.） was carried out by Wald method. RESULTS： Totally 31， 32， 7 children with MTRR gene AA， AG and GG genotype， while 23， 37， 10 children with SLCO1B1 gene TT， TC and CC genotype were detected. The distribution of each genotype in 70 children conformed to Hardy-Weinberg equilibrium （P＞0.05）. There was no significant difference in c48 h/D（48 h） of children and the proportion of children with different concentration of MTX （72 h） among difterent genotypes of MTRR and SLCO1B1 gene （P＞0.05）. There was statistical significance in the incidence of liver function injury in children with different genotypes of MTRR gene （P＜0.05）， and the AA genotype was significantly higher than the AG+GG genotype （P＜0.05）. There was no correlation of MTRR gene polymorphism with the incidence of other ADR， neither SLCO1B1 gene polymorphism with the incidence of ADR （P＞0.05）. The results of Binary Logistic regression analysis showed that liver function damage in ALL children was related to the gene polymorphism of MTRR； gastrointestinal reaction was related to whether the plasma concentration was more than 0.1 μmol/L at 72 h； mucosal damage was related to the immune type and BMI of children； the occurrence of skin allergy was correlated with body weight of children（P＜0.05）. CONCLUSIONS： Gene polymorphism of MTRR rs1801394 locus may associated with the occurrence of HD-HTX-induced liver function injury in ALL children， but its polymorphism and gene polymorphism of SLCO1B1 rs11045879 locus are not related to MTX blood concentration in ALL children.

OBJECTIVE:To systematically evaluate the efficacy and safety of metronidazole combined with hydrogen peroxide for uterine cavity lavage in the treatment of puerperal infection. METHODS:Retrieved from PubMed,Cochrane library,Wanfang database,VIP,CBM and CNKI,Meta-analysis was performed by using Cochrane collaboration Rev Man 5.3 software after data extraction and quality evaluation with modified Jadad scale. RESULTS:A total of 16 RCTs were included,involving 1 280 patients. Meta-analysis showed that total response rate of observation group was significantly higher than that of control group [OR＝5.76,95%CI(3.21,10.35),P＜0.001],but febrile duration [MD＝－2.08,95%CI(－2.32,－1.84),P＜0.001],duration of clinical symptom [MD＝－2.71,95%CI(－2.89,－2.53),P＜0.001] and average hospital stay [MD＝－3.05,95%CI(－3.32,－2.79),P＜0.001] are significantly shorter than control group; the incidence of ADR [OR＝0.27,95%CI(0.08,0.89),P＝0.03] was significantly lower than control group,with statistical significance. CONCLUSIONS:Metronidazole combined with hydrogen peroxide for uterine cavity lavage show good therapeutic efficacy and safety in the treatment of puerperal infection.

Objective: To explore the characteristics of adverse drug reactions (ADRs) in a grade three class A hospital to provide reference for rational drug use and reduction of ADRs. Methods: The new and serious ADRs reported during 2014 and 2016 were sta-tistically analyzed in terms of the report type, age, gender, administration route, drug variety and involving system. Results: The new and serious ADR reports reached to 400 cases, which accounted for 64. 52% of the total reports. Of the 400 ADR reports,there were 34. 25% distributed in the 60-74-year old. The proportion of male and female in the ADRs was basically equal, while that of male (50. 25% ) was slightly higher than that of female (49. 75% ). There were 57. 00% of ADRs caused by intravenous administration, and 31. 25% caused by anti-infective drugs, in which cephalosporins accounted for the most (32. 00% ). The most common manifesta-tion of ADR was damage to skin and its appendages, which accounted for 33. 00% , followed by the damage to gastrointestinal system (15. 50% ) and hepatorenal function (14. 00% ). Conclusion: Great attention should be paid to monitoring and reporting ADRs in our hospital, and drugs should be rationally used so as to reduce the occurrence of ADRs.

[Objective] To analyze the image findings of MR enterography (MRE) and diffusion weighted imaging (DWI) in Crohn disease (CD) and to discuss the diagnostic value of MRI for evaluating the activity of CD.[Methods] 26 patients proved by clinical,imaging and pathological data were enrolled in this study.The intra-/extra-intestinal image features of CD were retrospectively analyzed,and the intestinal lesions were evaluated by MRE+DWI scoring system.The differences in image features of active and inactive CD were compared.[Results] 26 bowel segments were evaluated and included active (n =20) and inactive CD (n =6).The intestinal performance of CD included wall thickening,T2WI hyperintensity and hyperenhancement.The pathological changes of active CD were more serious when comparing with that of inactive CD.DWI showed hyperintensity in the affected bowel wall.ADC of active C D [(0.9 ± 0.2) × 10-3 mm2/s] was significantly lower than that of inactive CD [(1.5 ± 0.4)× 10-3 mm2/s] (P ＜ 0.001).Extra-enteric performance of active CD included comb sign,lymphadenectasis of mesentery,mesenteric exudation,fistula and abdominal abscess.[Conclusion] MRE combined with DWI can accurately assess CD activity and diagnose extra-enteric complications.

Objective:To discuss the clinical effects of implantation of radioative 125I seeds by the way of percutaneous puncture and laparotomy under the guidance of ultrasound in the treatment of locally advanced pancreatic cancer, and to provide the basis for choosing surgical methods in treating advanced pancreatic cancer.Methods:The clinical materials of 73 patients with advanced pancreatic cancer were collected, including 42 patients who underwent implantation of radioactive 125I seeds by percutaneous puncture(group A) and 31 patients who underwent impantation of radioactive 125I seeds by laparotomy(group B).The pain relief, local control of tumor, postoperative survival time and complications of the patients were compared between two groups. Results:The rates of pain relief of the patients in group A and group B were 91.89% and 86.40%,and there was no significant difference(P=0.815).The local control rates of the patients in group A and group B were 71.43% and 77.42% ,and there was no significant difference(P=0.564).The medium survival time of the patients in group A and group B were 11 months and 12 months;the one-year survival rates were 36.9% and 35.8%, and there was no significant difference(P=0.664).Seven patients in group A got fever;in group B, six patients got fever, two got calf muscle venous thrombosis, one got gastric retention, one got bilioentric anastomosis, one got abdominal distension and one got intestinal obstruction in the early stage after operation.The incidence rates of complications of the patients in two groups were 16.67% and 38.71%, and there was significant difference(P=0.034).Conclusion:Percutaneous implantation of radioactive 125I particles guided by ultrasound causes less complications in the treatment of locally advanced pancreatic cancer.Moreover, the percutaneous way reaches the same effect as the intraoperative way does on the pain relief, local control of tumor and survival time prolonged.

Objective:To investigate the relationship of CYP2C19 gene polymorphisms and clopidogrel resistance in the patients with coronary atherosclerotic heart disease ( CAHD) accepted percutaneous coronary intervention ( PCI) in Chinese Han population from north Sichuan. Methods:The patients with CAHD undergoing PCI were recruited. The fluorescence in situ hybridization ( FISH) technology was used to detect the CYP2C19 gene polymorphisms in all the patients. According to the different genotypes, the patients were divided into different groups. The platelet maximum aggregation rate ( MAP) induced by ADP was detected before and after the administration of clopidogrel. Results:The 110 patients were divided into three groups:52(47. 3%) patients were divided into the fast metabolism group, 42(38. 1%) patients were in the moderate metabolism group and 16(14. 6%) patients were in the slow metab-olism group. Before the administration, there was no significant difference in the basic values of the platelet aggregation rate among the groups with various metabolism type (P=0. 873). In 24 hours after the administration of 300mg clopidogrel, there was notable differ-ence in the platelet aggregation rate (17. 74% ± 5. 87% vs 21. 44% ± 8. 71% vs 27. 05% ± 8. 83%, P=0. 044) and the decrease de-gree (20. 08% ± 5. 94% vs 18. 87% ± 4. 72% vs 11. 54% ± 2. 94%, P=0. 01) among the three groups. The moderate metabolism group and slow metabolism group had higher MAP with lower decrease degree than the fast metabolism group. Totally 21 patients (19. 1%)were with CR, and among them, 2 patients (3. 8%) were in the fast metabolism group,12 patients (28. 6%) in the moder-ate metabolism group and 7 ones (43. 8%) in the slow metabolism group, and the difference of CR distribution among the three groups was significant (P<0. 001). The moderate metabolism group and slow metabolism group were more likely to have clopidogrel resist-ance, especially the slow metabolism group. Conclusion: There is a certain relationship of CYP2C19 gene polymorphisms and clopi-dogrel resistance in the patients with CAHD accepted PCI in Chinese Han population from north Sichuan, and those with slow metabo-lism genotype are more likely to have clopidogrel resistance with reduced efficacy.

Objective:To establish the drug utilization evaluation(DUE)criteria for isophane protamine biosyntheti(30R)to provide reference for the rational drug use. Methods:Referred to the domestic and foreign literatures and the authorized guidelines for diabetes treatment,and combined with the Delphi expert consultation method,the drug utilization evaluation criteria was established,and after the evaluation,intervention and revaluation,the final criteria were determined. Results:The drug utilization evaluation criteria for isophane protamine biosyntheti(30R)contained three parts,including medication indications,medication process and medication results,which showed the clinical feasibility. Conclusion:The established DUE criteria for isophane protamine biosyntheti(30R)can not only be applied in the drug utilization evaluation,but also provide reference for the DUE in medical institutions.