Objective To investigate the intervention of Amlodipine combined with alanine aminotransferase(ALT)-711 on blood pressure and preventing of target organ remodels of Spontaneously Hypertensive Rats(SHR),and to explore an optimized treatment design.Methods A total of 24 SHRs at 12-Week-old male were randomly divided into 4 groups,with 6 SHRs in each group.In the control group(Group A)the SHR were given normal saline 1 ml/(kg · d)via intragastric administration; the SHRs in Group B were treated with Amlodipine 1 mg/(kg · d) via ntragastric administration; the SHRs in Group C were treated with ALT-711 10 mg/(kg · d)via ntragastric administration;the SHRs were treated with Amlodipine 1 mg/(kg · d)combined with ALT-711 10 mg/(kg · d)via ntragastric administration in Group D.All groups were treated for 8 weeks,and the blood pressure in mouse tail were monitored.After 8 weeks,all SHRs were executed in the condition of anaesthedia.Right cervical artery,heart and kidney were measured through immunohistochemistry,histological stain and imagine analysis.The remodeling of vascular,heart,kidney were compared,and collagen volume fraction,advanced glycation end products (AGEs) and fibronectin (FN) expression were measured.Results (1) After treatment for 8 weeks,blood pressure of SHRs in the 4 groups were (184.72 + 15.14),(108.00 ±10.19),(155.64±10.03)and (99.83 ± 12.27) nun Hg in Group A,B,C and D,respectively.The blood pressure in Group D was the lowest in the 4 groups (F =14.6702,P ＜ 0.05),whereas it is not significantly different from Group B (P ＞ 0.05).(2) The mean thickness of carotid arteries were (0.450 ± 0.023),(0.380 ±0.021),(0.420 ±0.019) and (0.320 ±0.020) mm in Group A,B,C and D,respectively.The mean thickness of carotid arteries in Group D was the lowest in the 4 groups(F =4.1463,P ＜0.05).(3).The mean intimal area of carotid arteries were (19.0 + 1.3) × 105,(25.0 ± 1.4) × 105,(29.8 + 1.5) × 105 and (21.3 ±1.3) × l05 μm2 in Group A,B,C and D,respectively.The mean intimal area of carotid arteries in Group D was significantly smallest than the other 3 groups(F =4.4305,P ＜0.05).(4) The collagen content in different organs in the 4 groups after treatment 8 weeks:in carotid arteries,they were (6.25 ± 0.19)％,(3.56 ± 0.03) ％,(4.25 ± 0.12) ％ and (1.32 ± 0.05) ％ in Group A,B,C and D,respectively.The collagen content in Group D were significantly lower than the other 3 groups (F =4.9316,P ＜ 0.01).In myocardia:collagen content in Group A,B,C and D were (6.02 ± 0.21)％,(4.08 ± 0.14)％,(4.44 ± 0.11)％ and (1.13 ± 0.08) ％ respectively,and it was the lowest in Group D (F =4.2469,P ＜ 0.01).In kidney,the collagen content in Group A,B,C and D were (13.23 ±0.51)％,(7.28 ±0.35)％,(8.33 ±0.22)％ and (5.66 ±0.13)％ respectively,and it was the lowest in Group D(F=8.1038,P ＜0.01).(5).Express rate of AGEs in carotid arteries in Group A,B,C and D were (31.48 ±7.30)％,(20.55 ±5.91)％,(10.48 ±0.98)％ and (7.56 ± 0.68) ％ respectively,with the lowest expression in Group D (F =11.4537,P ＜ 0.01).Express rate of FN in carotid arteries in Group A,B,C and D group were (28.18 ±5.66)％,(17.26 ±5.83)％,(18.20 ±1.44) ％ and (15.12 ± 1.03) ％ respectively,with the lowest expression in Group D (F =9.0036,P ＜ 0.01).Conclusion Amlodipine combined with ALT-711 decreased blood pressure more effectively and prevented the remodel of target organ in SHRs than Amlodipine or ALT-711 alone.

Objective To investigate the effects of disulfiram (DS) combined with Cu on the human Burkitt lymphoma cell xenografts in nude mice.Methods Burkitt lymphoma xenograft was established by subcutaneous injection of Raji cell into nude mice after 2 Gy whole body X-irradiation (1×107 Raji cells were resuspended in 200 μl saline).18 bearing tumor mice were randomly divided into control group,DS group and DS/Cu group.During the experiment,the effects of DS/Cu on the nude mice with tumors were examined,including the tumor volumes,weights and the growth curves of xenograft tumor.Histopathological examination of tumor tissue was observed with optical microscape.The protein expression levels of p-JNK and c-jun were also detected by Western blot.Results Subsequent tumor size and weight in DS or DS/Cu-treated animals were (67.71±2.15) mm3,(33.35±7.74) mm3 and (43.35±4.22) mg,(18.05±2.88) mg.One-way ANOVA analysis indicated that the tumor size and weight in DS or DS/Cu-treated animals were reduced significantly relative to tumors in vehicle-treated animals (F =27.579,P =0.000;F =16.369,P =0.000).Furthermore,multiple comparisons revealed that the DS or DS/Cu-treated animals had significantly reduced tumor size and weight compared with control animals (all P ＜ 0.05).There were significant differences in tumor size and weight between DS or DS/Cu-treated animals (both P ＜ 0.05).Tumor inhibition rates in DS or DS/Cu group were 63.48 ％ and 80.24 ％,respectively.An increase of apoptosis changes in the xenograft tumor cells in DS or DS/Cu treated mice were more significant.Westem blot showed that the p-JNK and c-jun protein expressions in the tumors were improved after the DS or DS/Cu treatment,more obvious in DS/Cu treatment.Conclusion DS/Cu can inhibit the growth of xenografts,and one possible mechanism may involve the regulation of JNK signal pathway.

Objective Glucose metabolism trend was dynamicly mornitored following liver transplantation, and its affecting factors were assessed. Methods The glucose metabolism status were assessed at four time points respectively after liver transplants, then they were divided into two groups:normal glucose metabolism (NGM) and abnormal glucose metabolism (AGM). The clinical data were univariate analyzed and multivariate analyzed to screen the risk factors. Results At 1 month, 3 months, 1 year and 3 years post-transplantation, the incidence of AGM were 74.0%, 43.9%, 29.4%, 24.1% respectively Between these two groups, age > 45 y had a significant difference at 1 month, 3 months, 1 year and 3years post-transplantation; the use of tacrolimus had a significant difference at 3 months, 1 year and 3years post-transplantation, but the dose of tacrolimus or tacrolimus blood concentration showed no significant difference; high dose of glucocorticoid had significant difference at 1 month , 3 months post-transplantation; high BMI and acute rejection had significant difference at 1 month post-transplantation. Conclusions There is a high incidence of abnormal glucose metabolism (AGM) in the early stage post-transplantation, and a considerable number of patients' glucose metabolism improved in the later period. Age>45 y and tacrolimus affect glucose metabolism for a longer period post-transplants. High BMI and acute rejection have an impact on glucose metabolism only in the early stage post-transplantation. Large dose of glucocorticoid affect glucose metabolism for at least 3 months post-transplantation , and there is no significant difference after 1 year.

Soil water is one of the most important components in hydrological cycle. The stable hydrogen and oxygen isotopes in soil water have been increasingly used in the ecological, environment and hydrological research. In view of different techniques for extracting soil water, there is significant difference in theδD andδ18 O composition. This paper presents a method for analyzing hydrogen and oxygen isotopes in soil water by using elemental analyzer and isotope ratio mass spectrometry with accelerated solvent extraction for sample pretreatment. The conditions are: extraction solvent: dichloromethane, temperature: 100 ℃, pressure of 10. 3 MPa, static time:10 min. The samples were extracted three times, and with cycle values of four, four and three, respectively. Comparing with the added water, the deuterium and oxygen isotope values in the extracted soil water enrich 2. 12‰-4. 58‰ and 0. 17‰-0. 93‰, respectively. The reproducibility of replicate extractions of soil water is around ±0. 89‰ for δD and ±0. 37‰ for δ18 O.

Objective:To provide a potential platform for transferring specific antigen against fish bacterial diseases based on attenuated Lm (EGDe-ΔactA/ΔinlB).Methods: Attenuated Lm (EGDe-ΔactA/ΔinlB) was used to express outer membrane protein K (Ompk),a conserved and effective vaccine candidate in vibrio.The identification of recombinant strains and detection of antigen genes were operated with PCR and RT-PCR,respectively.Results: The results of PCR showed that Lm-Ompk (L-O),Lm-Lmo0576-Ompk (L-L-O) and Lm-P-Ompk (L-P-O) were constructed successfully.The identity of foreign gene was 100％ compared with sequence of NCBI.The analysis of transcription showed that the expressions of Ompk in L-O,L-L-O and L-P-O were significant (P<0.001).Moreover,the expression of Ompk in the condition of antibiotic was higher than that in the BHI without antibiotic (P<0.05).Conclusion: Lm-Ompk (L-O),Lm-Lmo0576-Ompk (L-L-O) and Lm-P-Ompk (L-P-O) were constructed successfully.

Objective To summarize the clinical features,diagnosis and treatment and prognosis of trocar site hernia(TSH).Methods Clinical data of 12 patients with TSH receiving laparoscopic surgery from January 2019 to January 2023 were retrospectively analyzed.The clinical manifestations included intestinal obstruction in 8 cases,trocar incision prolongation with fluid seepage in 1 case,and no obvious symptoms in 3 cases.The patients were diagnosed by abdominal CT in 9 cases,by small intestine contrast imaging in 1 case,by abdominal MRI in 1 case,and by abdominal plain film combined with abdominal color ultrasound in 1 case.The hernia was located in the right lower abdomen in 5 cases,the left lower abdomen in 4 cases,and the right upper abdomen in 3 cases.The trocar diameter was 12 mm in 6 cases,10 mm in 5 cases,and 5 mm in 1 case.A drainage tube was placed at trocar site in 5 cases.Open operations were performed in 11 cases,including small intestine reduction and abdominal wall layer-by-layer suture in 4 cases,partial small intestine resection and anastomosis in 3 cases,Onlay repair in 3 cases,and partial omentectomy,transverse colon reduction and Onlay repair in 1 case.Another case developed trocar site refractoriness which did not heal,and the patient refused surgery,who was given dynamic observation.Results The operation was successful in the 11 cases.Postoperatively,1 case of inflammatory intestinal obstruction underwent intestinal decompression tube implantation,1 case of incision bleeding underwent emergency operation again to stop bleeding,and the rest recovered smoothly.All the 12 patients were followed up for 5-48 months,with a median of 13 months.The patient without surgery had persistent induration and intermittent exudation at the trocar site.One case died due to tumor metastasis,and none of the others had hernia recurrence.Conclusions The most common manifestation of TSH is intestinal obstruction,which mostly occurs at trocar with diameter≥10 mm.If there are symptoms,it should be treated by surgery as soon as possible.

Objective To construct a scientific and rational post competency model of human organ donation coordinators. Methods Based on the onion model, the index pool was initially constructed by literature research and behavioral event interview. The index system was screened, modified and improved using Delphi method. The weight of indexes at all levels was determined by analytic hierarchy process. Results The effective response rates of two rounds of Delphi expert inquiries were both 100%, indicating that the expert opinions were highly dependable. The experts' judgment coefficient (Ca), familiarity (Cs) and authoritative coefficient (Cr) were all above 0.7, indicating that the experts' opinions were highly reliable. The expert coordination coefficients (W) were 0.294 and 0.342 (both P<0.001), indicating that experts delivered coordinated opinions and yielded slight difference in understanding the importance of indexes. Finally, according to the "onion model" theory and experts' opinions, a set of coordinator's post competency model including 6 first-level and 55 second-level indexes was established, which comprised an index surface layer, a middle layer and a core layer. Among them, the core layer represented core professional values, the middle layer was personal quality and professional ethics and quality, and the surface layer was interpersonal communication capability, organizational cooperation capability and professional knowledge and lifelong learning capability. Conclusions The post competency model of organ donation coordinators established in this study consists of 6 first-level and 55 second-level indexes, which is highly effective and reliable.

Objective : To investigate the effect of high concentration of Caerulomycin A (Cae A) on HK2 in renal tubular epithelial cells and to explore the role of cytoplasmic nucleotide⁃binding oligomerization domain⁃like receptor protein 3 (NLRP3) in this process. Methods : The effect of different concentrations of Cae A on the viability of HK2 cells was determined by MTT; the expression of kidney injury molecule (KIM⁃1) and NLRP3 was detected by real⁃time quantitative PCR , Western blot and immunofluorescence , while the effect of Cae A on the mRNA expression of IL⁃1β , IL⁃18 , IL⁃33 , MCP⁃1 , TNF⁃α was also measured by real⁃time quantitative PCR. HK2 cells were divided into control group , high concentration of Cae A group and high concentration of Cae A plus NLRP3 inhibitor CY⁃09 group , and the expression of KIM⁃1 and NLRP3 protein was detected by Western blot. Results : The results of MTT showed that high concentration of Cae A could inhibit HK2 cell viability. Real⁃time quantitative PCR , Western blot and immunofluorescence assays showed that high concentration of Cae A upregulated the expression of KIM⁃1 and NLRP3 , as well as the mRNA levels of IL⁃1β , IL⁃18 , IL⁃33 , MCP⁃1 , TNF⁃α , while CY⁃09 could down⁃regulate the expression of NLRP3 and KIM⁃1. Conclusion High concentration of Cae A significantly inhibited the viability of HK2 cells and induced damage and inflammatory response to HK2 with some nephrotoxicity that might be achieved via NLRP3 pathway.

Objective·To explore the immune-related characteristics of non-small cell lung cancer(NSCLC),discover potential tumor markers in V-J genes,and lay the foundation for establishing a TCR-antigen recognition prediction model.Methods·A total of 704 NSCLC samples were collected to establish a comprehensive T-cell receptor(TCR)repertoire analysis workflow.The upstream analysis included steps such as raw data processing,quality control,filtering,TCR sequence identification,and extraction.The downstream analysis included repertoire clone distribution,clone typing,V-J gene sharing,CDR3 distribution characteristics,and clone tracking.The sample clone distribution was analyzed by using indices such as Shannon-Weiner index and Chaol index.Clone typing was performed based on the number of clone amplifications to explore differences among different types.The degree of V-J gene segment sharing was analyzed,and the sharing of low-frequency clone types was determined through clone amplification weight analysis of V-J genes by using two samples of papillary thyroid carcinoma.Finally,analysis of the distribution characteristics of V genes and high-frequency clone type CDR3,and clone tracking analysis were conducted to monitor changes in tumor immune clone frequencies before and after analysis,aiming to identify potential tumor markers.Results·① Significant differences were observed in clone distribution and clone typing among different NSCLC tissues,as well as among different ages and genders.② Specific highly-shared V-J genes were identified in the analysis of V-J gene sharing,and non-normal distribution of high-clone V genes and amino acid high-frequency clone types were found in the CDR3 distribution analysis.③ In the analysis of high-frequency clone type clone tracking,highly expressed or newly expressed high-frequency clone types were observed in NSCLC,suggesting that these clone types could serve as potential tumor-associated antigens or bind with CDR3 reference sequences of new antigens.④ It was found that the expression frequency of TRBJ2-5 gene,originally low-expressed,significantly increased,indicating its potential role as a key low-frequency gene in tumor immune response.Conclusion·The TRAV21 and TRBV6.5 genes show high clone amplification in NSCLC and could serve as potential tumor biomarkers.

Objective: To study the correlation between the level of serum Chitinase-3-like protein 1 (CHI3L1) and the significant liver fibrosis and liver cirrhosis in patients with chronic liver disease, and to evaluate its diagnostic value. Methods: 165 patients with chronic liver disease were selected, liver histopathological examination was performed to detect serum CHI3L1 concentration. Four indexes of hepatic fibrosis (type III procollagen, collagen IV, laminin, hyaluronic acid), aspartate aminotransferase/platelet ratio index (APRI) and FIB-4 (fibrosis- 4) scores were based on the pathological findings of liver biopsy and compared the advantages and disadvantages of serum CHI3L1 with other methods for the diagnosis of hepatic fibrosis and liver cirrhosis. A multivariate regression analysis model was created, and receiver operating characteristic curve was analyzed. Results: The level of serum CHI3L1 increased with increase of fibrosis stage and was highest in liver cirrhosis stage. In the period of S0 to 1, the levels of S2 to 3 and S4 were 62.82 (41.40 ~ 87.20), 70.94 (48.47 to 122.60) and 141.06 (78.18 ~ 197.40), and there were statistically significant differences between the groups (P < 0.001). The area under the curve for the diagnosis of significant liver fibrosis was 0.68 (0.60 to 0.77), and 0.74 (0.65 to 0.83) for cirrhosis in CHI3L1. Multivariate regression analysis showed that CHI3L1 was an independent predictor of significant fibrosis and cirrhosis. The combined diagnostic model based on CHI3L1, collagen IV and FIB-4 scores further improved the diagnostic value. The area under the curve for the diagnosis of significant fibrosis and cirrhosis was 0.79 (0.72 to 0.86) and 0.80 (0.73 to 0.87), respectively. Conclusion CHI3L1 has a good diagnostic value in patients with chronic liver disease with significant fibrosis and liver cirrhosis. The diagnostic model in combination with other markers like Collagen IV and FIB-4 scores could further improve the diagnostic value and is worthy of further study.