Objective To study the antifungal activity of a new series of triazole compounds with n-propyl side chain and disubstituted benzyl structure. Methods Eleven target compounds were designed and synthesized. The structures were confirmed by ¹H NMR, and some compounds were confirmed by ¹³C NMR or HRMS. Three fungal strains were selected as experimental strains, and the antifungal activity was tested in vitro according to the standardized antifungal sensitivity test method recommended by National Committee for Clinical Laboratory Standards (NCCLS). Results Compound B11 showed better activity against candida albicans SC5314 than fluconazole and was comparable to posaconazole; Compounds B10, B11 and B4 showed better activity against cryptococcus neoformanis H99 than fluconazole, while compounds B2, B3, B5, B6 and B7 showed similar activity to fluconazole against cryptococcus neoformanis H99; while all compounds showed poor activity against aspergillus fumigatus. Conclusion Some of the target compounds with n-propyl side chain and disubstituted benzyl group structure had certain antifungal activity and could be identified as potential lead antifungal drugs.

Objective To investigate the pathogenesis of superficial mycosis among naval trainees, and observe the efficacy of a novel antifungal drug. Methods A questionnaire survey was conducted on the onset, medication and recurrence of superficial fungal infection among the trainees from January, 2020 to July, 2020. At the same time, the new antifungal drug sulconazole nitrate spray was provided for treatment and the drug efficacy was observed. Results The participants generally lacked understanding and attention to superficial fungal infections. The incidence rate of superficial fungal infection was 52%, of which 76.2% of patients had recurrence of superficial fungal infection. The sulconazole nitrate spray showed great effect against these infections. Conclusion The trainees should understand the causes of superficial fungal infection through health education and seek medical treatment and medication in time. The cure rate of superficial fungal infections could only be improved through the collaborative management of the school, hospital, and trainees to reduce the impact of these infections on naval trainees’ work and life.

Objective:To evaluate the effect of transfusion-free techniques on the prognosis of liver transplant patients.Methods:The recipients of adult liver transplantation at Tianjin First Central Hospital from August to December 2019 were included in the clinical observation. Liver transplantation without allogeneic blood transfusion was performed through anesthesia management techniques such as acute hemodilution or phlebotomy without volume replacement,maintaining decreased baseline central venous pressure and cell saver. According to the actual results,the patients were divided into two groups: transfusion-free group( n=21) and allogeneic transfusion group( n=28). There were 13 males and 8 females aged of (56.3±11.6) years in the transfusion-free group;and there were 16 males and 12 females aged (54.3±14.2)years in the allogeneic transfusion group. The transplant recipients who had not adopted transfusion management strategy from January to July 2019 were included as control group(27 males and 13 females,aged of (58.9±14.1)years). The clinical data of patients in perioperative period were collected to compare whether there were differences in the recovery of liver function and early complications among the three groups, one-way ANOVA test, rank-sum test, and χ 2 test were used for data analysis. Results:The amount of intraoperative blood loss in both the transfusion-free group and the transfusion group was less than that in the control group((454.2±271.3)ml vs.(673.6±333.4)ml vs.(890.3±346.7)ml; q=-6.342,-5.286,both P<0.05).The duration of stay in ICU of the transfusion-free group was less than that of the transfusion group and control group((36.4±9.1)hours vs.(44.3±14.9)hours vs.(58.2±21.1)hours; q=-4.432,-3.824,both P<0.05).The mean ALT level at 7 days after operation was significantly lower in the transfusion-free group than in the control group((56.8±32.1)U/L vs.(89.6±45.6)U/L; q=-3.358, P<0.05). Conclusions:The improvement of multi-disciplinary transfusion management technology aimed at transfusion-free liver transplantation can effectively reduce intraoperative hemorrhage and help to avoid surgical transfusion. Transfusion-free liver transplantation is beneficial to the early postoperative recovery,and its long-term clinical significance is worthy of further clinical research.

Objective:To evaluate the effect of transfusion-free techniques on the prognosis of liver transplant patients.Methods:The recipients of adult liver transplantation at Tianjin First Central Hospital from August to December 2019 were included in the clinical observation. Liver transplantation without allogeneic blood transfusion was performed through anesthesia management techniques such as acute hemodilution or phlebotomy without volume replacement,maintaining decreased baseline central venous pressure and cell saver. According to the actual results,the patients were divided into two groups: transfusion-free group( n=21) and allogeneic transfusion group( n=28). There were 13 males and 8 females aged of (56.3±11.6) years in the transfusion-free group;and there were 16 males and 12 females aged (54.3±14.2)years in the allogeneic transfusion group. The transplant recipients who had not adopted transfusion management strategy from January to July 2019 were included as control group(27 males and 13 females,aged of (58.9±14.1)years). The clinical data of patients in perioperative period were collected to compare whether there were differences in the recovery of liver function and early complications among the three groups, one-way ANOVA test, rank-sum test, and χ 2 test were used for data analysis. Results:The amount of intraoperative blood loss in both the transfusion-free group and the transfusion group was less than that in the control group((454.2±271.3)ml vs.(673.6±333.4)ml vs.(890.3±346.7)ml; q=-6.342,-5.286,both P<0.05).The duration of stay in ICU of the transfusion-free group was less than that of the transfusion group and control group((36.4±9.1)hours vs.(44.3±14.9)hours vs.(58.2±21.1)hours; q=-4.432,-3.824,both P<0.05).The mean ALT level at 7 days after operation was significantly lower in the transfusion-free group than in the control group((56.8±32.1)U/L vs.(89.6±45.6)U/L; q=-3.358, P<0.05). Conclusions:The improvement of multi-disciplinary transfusion management technology aimed at transfusion-free liver transplantation can effectively reduce intraoperative hemorrhage and help to avoid surgical transfusion. Transfusion-free liver transplantation is beneficial to the early postoperative recovery,and its long-term clinical significance is worthy of further clinical research.

Objective To explore the early prognosis and the risk factors of delayed graft function (DGF) of the recipients undergoing liver transplantation from donor liver with moderate-to-severe steatosis. Methods Clinical data of 475 donors and 475 recipients undergoing liver transplantation from donor liver of organ donation after citizen's death were retrospectively analyzed. According to the classification criteria of steatosis proposed by Australia National Liver Transplantation Unit (ANLTU), all recipients were divided into the S0 group (no steatosis, n=308), S1 group (mild steatosis, n=97), S2 group (moderate steatosis, n=52) and S3 group (severe steatosis, n=18), respectively. The early postoperative death and incidence of postoperative complications were statistically compared among each group. The risk factors from donors, recipients and operation leading to DGF were analyzed by univariate and multivariate logistic regression models. Results The incidence of postoperative DGF in the S2 and S3 groups was significantly higher than that in the S1 and S0 groups (all P < 0.05). The incidence of postoperative DGF in the S3 group was remarkably higher than that in the S2 group (P < 0.05). The early postoperative fatality, the incidence of primary nonfunction (PNF) of the transplant liver, postoperative bleeding, infection, biliary complications and vascular complications did not significantly differ among each group (all P > 0.05). Univariate regression analysis showed that severe steatosis of donor liver, long cold ischemia time, high model for end-stage liver disease (MELD) score and tumors of the recipients before operation were the risk factors of DGF (all P < 0.05). Multivariate logistic regression analysis demonstrated that moderate-to-severe steatosis of donor liver, cold ischemia time > 8 h and MELD score > 30 of the recipients were the independent risk factors for early postoperative DGF. Conclusions The early-stage incidence of DGF after adult liver transplantation from donor liver with moderate-to-severe steatosis is high, whereas it does not affect the early survival rate of the recipients. The selection of donor liver with moderate-to-severe steatosis should be considered in combination with cold ischemia time of the donors and MELD score of the recipients before operation, etc.

Objective To investigate the effect of high-fat diet(HFD)on liver damage caused by autoimmune hepatitis(AIH)in mice.Methods Fifty C57BL/6 male mice were divided randomly into four groups:standard chow(SC)group,HFD group,AIH + SC group and AIH+ HFD group.AIH model was built after feeding for one week and all mice were sacrificed after four weeks.Liver and spleen tissues and serum were collected. Liver histopathology was detected by HE staining. Serum alanine aminotransperase(ALT)and aspartate aminotransferase(AST)levels were measured.Western blot analysis and real-time polymerase chain reaction(PCR)analysis were used to test the expressions of NLR pyrin domain containing 3(NLRP3)and cysteinyl aspartate specific proteinase 1(Caspase-1).The concentrations of interleukin(IL)-6,IL-1β and tumor necrosis factor(TNF)-α were analyzed using enzyme linked immunosorbent assay technology.The amount of Th17 cells in spleen was analyzed by FACS.Means among groups were analyzed with one-way ANOVA.SNK-q analysis was used for groups with homogeneity of variance, while nonparametric test was used for groups with variance nonhomogeneity.Results Histologically,the H&E staining of liver tissue from HFD group showed adipose degeneration,and there was inflammation around vessel in AIH+SC group.Moreover,in AIH+HFD group,the inflammation was more serious with mildly adipose degeneration.Compared with SC group,serum levels of ALT and AST increased in HFD group and AIH +SC group,and greatest increase was observed in AIH+ HFD group.The differences were statistically significant(F=57.12 and 37.58, both P<0.05).The proportions of Th17 cells in SC group,HFD group,AIH+ SC group and AIH+HFD group were(2.98 ± 0.90)%,(6.89 ± 0.99)%,(6.47 ± 1.08)% and(9.96 ± 0.83)%, respectively.The differences among all groups were statistically significant(F=54.05,P<0.05).The concentrations of IL-1β,IL-6 and TNF-α in each group were as follows:SC:IL-1β[(7.62 ± 2.81)ng/L],IL-6 [(106.54 ± 53.08)ng/L],T NF-α[(107.26 ± 36.20)ng/L];HFD:IL-1β[(25.06 ± 7.09)ng/L],IL-6 [(220.11 ± 47.41)ng/L],TNF-α[(273.77 ± 33.62)ng/L];AIH+SC:IL-1β[(17.49 ± 5.68)ng/L],IL-6 [(260.73 ± 50.29)ng/L],TNF-α[(250.49 ± 81.63)ng/L];AIH+ HFD:IL-1β[(52.04 ± 10.22)ng/L], IL-6[(785.93 ± 70.91)ng/L],TNF-α[(913.97 ± 64.57)ng/L].The differences were statistically significant(F=44.66,242.15 and 233.49,respectively,all P<0.05).The expressions of NLRP3 and Caspase-1 were significantly increased in AIH+ HFD group than the other three groups(all P<0.05). Conclusions High-fat diet potentiates liver damage induced by autoimmune hepatitis,which might relate to the secretion of pro-inflammatory cytokines,the activation of Th17 cells and the NLRP3 inflammasome as well as pyroptosis.

Objective To study the immunoregulatory effect of sodium butyrate(NaB)on T helper cell 17(Th17)and the effect on toll-like receptor 4(TLR4)signal pathway in autoimmune hepatitis (AIH).Methods Fifty male C57BL/6 mice(6 weeks of age)according to the random number table method divided into control group(n=10),AIH group(n=10),NaB group(n=10)and high roughage diet(HRD)group(n=10),and the other ten mice were used to extract hepatic sytosolic S-100.After the establishment of AIH model,mice in NaB group were given sodium butyrate 500 mg/(kg·d)by gavage and those in HRD group were fed with high-fiber stuff.After 3 weeks of treatment,all the mice were sacrificed.The pathological change was observed.The serum levels of alanine aminotransferase(ALT), aspartate transaminase(AST),IL-17A and TNF-α,the proportion of Th17 in spleen,the expression levels of TLR4 and myeloid differentiation factor 88(MyD88)in liver were observed in each group.The tests of normality and homogeneity of variance were used to compare the means of each group.One-way analysis of variance and multiple comparative analyses were used in the statistical analysis.Results HE staining showed that inflammatory cell infiltration and hepatocyte necrosis were significantly reduced in mice treated with NaB and HRD compared to AIH group.Serum ALT levels in control group,AIH group,NaB group and HRD group were(24.833 ± 2.229),(88.333 ± 9.543),(27.167 ± 3.189)and (29.833 ± 6.113)U/L,respectively,while AST levels in each group were(97.00 ± 14.953),(285.000 ± 35.434),(139.500 ± 38.976)and(127.167 ± 28.687)U/L,respectively.The differences among groups were all statistically significant(F=156.49 and 44.118,respectively,both P<0.01).The proportion of Th17 in spleen and the expressions of the transcription factors retinoid-related orphan receptor gamma t in the spleen of the NaB group and HRD group were significantly lower than those of AIH group.The differences were statistically significantly(F=21.780 and 68.283,respectively,both P<0.05).The expressions of TLR4 and MyD88 in liver of AIH group were significantly higher than control group,but those were inhibited in NaB group and HRD group.The differences were statistically significantly(F= 26.235 and 28.293,respectively,both P<0.01).The expressions of IL-17 and TNF-α in liver and serum decreased in NaB group and HRD group.Conclusion NaB exerts an immunoregulatory effect in AIH and improves inflammatory reaction in liver.

Objective To investigate the relationship between disrupted corticospinal tract (CST) and motor recovery after stroke by using diffusion tensor tracking (DTT). Methods From March, 2012 to June, 2013, 15 chronic stroke patients with left subcortical lesions and 15 age- and sex- matched healthy subjects were performed diffusion tensor imaging (DTI) examination. The CST was tracked by DTT technique, and the damaged values of the CST caused by the stroke lesions were quantified using a CST template generated from healthy controls. Furthermore, the correlations of the damaged values of the CST with Fugl-Meyer Assessment (FMA) were performed. Results The range of the damaged values of CST in stroke patients was 0.00% to 29.6%. There were very strong negative correlation between the damaged values of the CST and FMA scores (the wrist, r = -0.660; hand, r = -0.813; wrist plus hand, r = -0.795, respectively, P < 0.01). It also showed strong negative correlation between the damaged values of the CST and FMA scores (upper limb, r = -0.614; upper limb plus lower limb, r = -0.563, respectively, P < 0.05). Whereas, there was no correlation between the damaged values of the CST and FMA scores of lower limb (r = -0.270, P = 0.331). In addition, the lesion volumes of stroke and FMA scores were not significantly correlated (P > 0.05). Conclusion The severity of motor deficit after stroke was closely related to the overlap of lesions with CST. The damaged values of the CST based on DTT may be used as a potential biomarker to assess motor impairments of upper limbs, especially hand and wrist in stroke patients.

Objective To investigate the effect of trichostatin A(TSA),a histone deacetylase inhibitor, on s-100-induced autoimmune hepatitis in mice.Methods A total of 26 six-week-old male C57BL/6 mice were randomly divided into control group,model group and TSA group(six in each group),and the rest 8 mice were used to extract the s-100 protein from liver tissue.Mice of model group and TSA group were injected intraperitoneally with s-100 with complete Freund's adjuvant to induce autoimmune hepatitis model.At day 21, TSA group mice were injected intraperitoneally with TSA 2 mg/(kg·d)for 7 days,and 0.9% sodium chloride solution containing 1% dimethyl sulfoxide was injected into the control and model group mice.Alanine transaminase(ALT)and aspartate aminotransferase(AST)in serum were measured and liver histopathology was observed.The protein levels of nuclear factor(NF)-κB and acetylated histone H3 in liver tissue were detected by Western Blot.The hepatic mRNA levels of NF-κB,HDAC3,toll-like receptor 4(TLR4)and TNF-α were measured by real-time PCR.ELISA was used to determine the TNF-α in serum.The results were analyzed with t test.Results The serum levels of ALT in control group,model group and TSA group were(122.00 ± 45.29),(459.33 ± 167.58)and(217.33 ± 49.25)U/L,respectively.The differences between model group and control group or TSA group were significant(t=4.76 and 3.41,respectively,both P<0.05).The serum levels of AST in control group,model group and TSA group were(127.83 ± 18.55),(389.67 ± 87.14)and (249.50 ± 71.72)U/L,respectively.The differences between model group and control group or TSA group were also significant(t= 7.20 and 3.04,respectively,both P< 0.05).The inflammation of the liver histopathology induced by s100 was alleviated by TSA.The relative expressions of NF-κB protein,NF-κB mRNA,TNF-α mRNA,HDAC3 mRNA and TLR4 mRNA in the liver tissue of model group mice were 2.43 ± 0.42,9.51 ± 0.36,10.53 ± 0.74,2.90 ± 0.22,and 4.50 ± 0.73,respectively,which were significantly higher than those of the control group(1.28 ± 0.49,1.28 ± 0.49,1.06 ± 0.14,1.72 ± 0.73,and 1.01 ± 0.31, respectively)(t=4.68,37.14,30.69,4.33 and 10.85,respectively,all P <0.05).In TSA group,the relative expressions of NF-κB protein,NF-κB mRNA,TNF-α mRNA,HDAC3 mRNA and TLR4 mRNA were decreased(1.30 ± 0.36,1.30 ± 0.36,2.38 ± 0.36,2.13 ± 0.32 and 2.40 ± 0.51,respectively),which were statistically lower than those in model group(t=4.58,30.62,24.12,2.81 and 5.81,respectively,all P<0.05).The serum TNF-α levels in control group,model group and TSA group were(122.37 ± 68.12), (1361.44 207.13)and(691.64 ± 162.12)ng/L,respectively.Compared with model group,the differences were statistically significant(t=13.92 and 6.24,respectively,both P<0.05).The relative expression of ac-H3 protein in the model group was 1.10 ± 0.08,which was higher than that in the control group 0.96 ± 0.17(t=2.27,P<0.05).That in TSA group was 1.30 ± 0.04,which was higher than the model group(t=-0.30, P <0.05).Conclusion Histone deacetylase inhibitor TSA alleviates autoimmune hepatitis by enhancing histone acetylation and inhibiting NF-κB and inflammatory factors.

Objective To explore the cost-effectiveness and clinical effect of three platinum based chemotherapy regiments for advanced non small cell lung cancer (NSCLC).Methods 100 patients who were diagnosed as NSCLC,were randomly divided into four groups.The group Ⅰ received NP which was given NVB and DDP.The group Ⅱreceived GP which was given GEM and DDP.The group Ⅲ received TP which was given taxotere and DDP.The clinical effect,adverse reaction and cost effectiveness of the three groups were assessed.Results The clinical effective rates of the three groups were 31.43%,36.36%,37.50% from Ⅰ to Ⅲ group.The adverse events of the group Ⅰ and group Ⅱ were more than those of the group Ⅲ.In the adverse effects of treatment,the major cytotoxicity was digestive reaction and leukopenia in the two groups,but they were tolerable.The ratios of cost effectiveness in the four groups were 550.22yuan,556.48yuan,583.23yuan from Ⅰ to Ⅲ group.Conclusion The NP group is the best one in total cost.