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Hang Zhou,1 Fang Ma,2 Yi Zhang,2 Youqin Tan,2 Yangjuan Bai,3 Qiulan Hu,4 Wei Wei,5 Yanjiao Wang1 1Department of Psychiatry, The First Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China; 2Department of Nursing, The First Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China; 3Cardiology Department, The First Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China; 4ICU in Geriatric Department, The First Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China; 5Neurosurgery Department, The First Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of ChinaCorrespondence: Yanjiao Wang, Department of Psychiatry, The First Affiliated Hospital of Kunming Medical University, 295#, Xichang Road, Kunming, People’s Republic of China, Tel +86-138-889-29699, Email mayuwyj1974@126.com Correspondence: Fang Ma, Department of Nursing, The First Affiliated Hospital of Kunming Medical University, 295#, Xichang Road, Kunming, People’s Republic of China, Tel +86-159-251-89957, Email rebeccamalei@126.comPurpose: To explore perceptions of antipsychotics associated side-effects among family caregivers of patients with schizophrenia.Patients and Methods: A descriptive qualitative study was applied in a tertiary referral hospital in China. Purposeful sampling of 18 family caregivers of patients with schizophrenia were interviewed about their perceptions towards antipsychotics related side effects.Results: According to content analysis, three themes emerged from the data: (a) nightmare in the treatment with the categories of sleep disturbances; physical impairment; appearance impairment; (b) opposite attitudes toward side-effect with the categories of being vigilant; do not care; (c) diverse ways of coping side-effects with the categories of asking for help from professionals; self-determined; try any quack’s prescription.Conclusion: The side effects of antipsychotics not only damage the health of patients, but also increase the burden and stress of caregivers. However, caregivers have different attitudes and coping styles about the side effects of antipsychotics. Health professionals should be aware of the influence of individual background and cultural factors on caregivers’ attitudes towards drug side effects. Furthermore, health professionals should also provide caregivers with knowledge about drug side effects, coping skills, and appropriate management strategies to promote health outcomes for people with schizophrenia.Keywords: schizophrenia, family caregivers, antipsychotics, drug side effects, content analysis

BACKGROUND Chronic allograft dysfunction (CAD) is the leading cause of graft loss among kidney transplant recipients (KTRs). Bile acids (BAs) play an important role in regulating inflammatory process, which is the major contributor to the development of CAD. The aim of this study was to evaluate the association between BAs metabolic dysregulation and CAD in KTRs. MATERIAL AND METHODS Fifteen serum BA species were determined in 43 healthy controls (HCs) and 131 KTRs by UPLC-MS/MS. KTRs were grouped into stable renal function (STA) and CAD1 and CAD2 groups based on eGFR levels. Circulating CYP7A1, CYP7B1, CYP27A1, and SLCO2B1 mRNA levels were determined by RT-PCR. RESULTS Total BA concentrations were comparable among the 4 groups. However, KTRs showed significantly different BAs profiling compared to HCs. KTRs with severe CAD (CAD2) had significantly lower unconjugated BAs and secondary BAs (SBAs) compared to the other 3 groups. KTRs had significantly lower SBAs/primary BAs (PBAs) ratios than HCs, which were comparable among the 3 KTR groups. Conjugated/unconjugated BAs ratios increased significantly with the deterioration of allograft function, which was further confirmed by correlation analysis. Differential correlation network analysis revealed that perturbations in intraclass and interclass BA coregulation existed during CAD progression. Moreover, relative gene expressions of CYP7B1 and CYP27A1 were positively correlated with eGFR. CONCLUSIONS BA species profiling, but not total BA concentrations, was significantly altered in KTRs with CAD. The shifts from unconjugated BAs toward conjugated BAs, SBAs toward PBAs, and distinct pairwise BAs coregulation patterns were the main characteristics of KTRs with CAD.

Background To develop and validate predictive nomograms for 5-year graft survival in kidney transplant recipients (KTRs) with easily-available laboratory data derived markers and clinical variables within the first year post-transplant. Methods The clinical and routine laboratory data from within the first year post-transplant of 1289 KTRs was collected to generate candidate predictors. Univariate and multivariate Cox analyses and LASSO were conducted to select final predictors. X-tile analysis was applied to identify optimal cutoff values to transform potential continuous factors into category variables and stratify patients. C-index, calibration curve, dynamic time-dependent AUC, decision curve analysis, and Kaplan-Meier curves were used to evaluate models' predictive accuracy and clinical utility. Results Two predictive nomograms were constructed by using 0-6- and 0-12- month laboratory data, and showed good predictive performance with C-indexes of 0.78 and 0.85, respectively, in the training cohort. Calibration curves showed that the prediction probabilities of 5-year graft survival were in concordance with actual observations. Additionally, KTRs could be successfully stratified into three risk groups by nomograms. Conclusions These predictive nomograms combining demographic and 0-6- or 0-12- month markers derived from post-transplant laboratory data could serve as useful tools for early identification of 5-year graft survival probability in individual KTRs.

Objectives To explore the perceptions of patients undergoing percutaneous coronary intervention (PCI) regarding their pre‐operative health education. Methods A qualitative study using semi‐structured, in‐depth interviews was conducted in one cardiology unit in China from July 2019 to December 2019. Purposeful sampling of 17 patients undergoing PCI was interviewed about their perceptions of pre‐operative health education. Thematic analysis of the transcribed data was then used to identify the themes. Results Four themes emerged from the data:(a) triple roles of pre‐operative education with the categories of relief (reliving fear); burden (leading to stress); and meaningless (changing nothing); (b) family member involvement with the categories of shared responsibility and family members’ duty; (c) facilitators in the process of pre‐operative health education with the categories of emotional support, plain language and individualized pre‐operative education; (d) inhibitors in the process of pre‐operative health education with the categories of contradiction and threatening words. Conclusions Pre‐operative health education for patients undergoing PCI should be aligned with the individual patients’ information‐seeking styles and personal differences, emphasizing individualized patient education. Traditional Chinese philosophy should be considered in the practice of pre‐operative education for patients undergoing PCI, which emphasizes family member involvement; at the same time, patient empowerment and self‐care should also be stressed. In addition, emotional support and plain language from health professionals are important in pre‐operative health education for patients undergoing PCI; contradiction should be avoided, and threatening words should be used with caution and with consideration for cultural variations during pre‐operative education for patients undergoing PCI.

CD35, an important molecule implicated in inflammation and immunity, is reportedly associated with several cancers. However, very few studies have investigated the relationship between CD35 polymorphisms and hepatocellular carcinoma (HCC). The current study was conducted to investigate the association between tag SNPs in CD35 and HCC susceptibility and postoperative recurrence, in an attempt to elucidate the gene-environment interactions in HCC. A total of 1233 Chinese Han people, including 647 healthy controls and 586 HCC cases, were sampled in this study. Six Tag SNPs (rs10494885, rs2296160, rs3737002, rs3849266, rs669117, and rs7525160) of CD35 were selected using the HaploView 4.2 program and genotyped by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Overall, the mutation genotypes CC/CG of CD35 rs7525160 significantly increased the risk of HCC. Stratification analysis indicated that CD35 rs7525160 CC/CG genotypes increased HCC risk in patients younger than 65 years and were closely related to the pathological type of poor prognosis of HCC. Cox proportional hazard ratio model analysis revealed that the rs7525160 CC/CG genotype remains a significant independent risk factor for postoperative recurrence of HCC. In conclusion, CD35 rs7525160 polymorphism may contribute to the susceptibility and prognosis of HCC in the Chinese Han population.

BACKGROUND Tacrolimus is a widely used immunosuppressant in renal transplant recipients. It was demonstrated in rats and healthy volunteers that Wuzhi capsules could inhibit metabolism and maintain blood concentration of tacrolimus. However, there are no clinical studies of Wuzhi capsules in renal transplant recipients. This research aimed to assess the effect of Wuzhi capsules on the blood concentration of tacrolimus in renal transplant recipients. MATERIAL AND METHODS A total of 158 Chinese renal transplant recipients receiving tacrolimus with or without Wuzhi capsules were included in this retrospective study. The cohort study included 126 recipients, with 86 recipients receiving Wuzhi capsules (WZCs) and the other 40 recipients not receiving WZCs. Another 32 recipients were involved in a self-control study. RESULTS Dose- and body weight-adjusted trough concentrations (C0/D/W) of tacrolimus in the WZC group were found to be significantly higher than that in the non-WZC group (P

This study aimed to investigate the influence of TPMT*3C, ITPA, NUDT15, and 6-thioguanine nucleotides (6-TGN) on azathioprine (AZA)-induced myelosuppression in Southwest China patients with autoimmune hepatitis (AIH). A total of 113 Chinese patients with AIH receiving AZA maintenance treatment were evaluated. The relevant clinical data of the patients were collected from the hospital information system. Genotyping of TPMT*3C(rs1142345), ITPA (rs1127354) and NUDT15(rs116855232) was conducted using a TaqMan double fluorescent probe. The concentration of 6-TGN was determined using UPLC-MS/MS. Among AIH patients treated with AZA, 40 (35.4%) exhibited different degrees of myelosuppression. The NUDT15 variant was associated with leukopenia (P = 8.26 × 10–7; OR = 7.5; 95% CI 3.08–18.3) and neutropenia (P = 3.54 × 10–6; OR = 8.05; 95% CI 2.96–21.9); however, no significant association with myelosuppression was observed for TPMT*3C and ITPA variants (P > 0.05). There was no significant difference in 6-TGN concentration between AIH patients with or without myelosuppression (P = 0.556), nor was there a significant difference between patients with variant alleles of TPMT*3C, ITPA, or NUDT15 and wild-type patients (P > 0.05). Interestingly, it was found that patients with a lower BMI had higher adjusted 6-TGN levels and a higher incidence of myelosuppression (P = 0.026 and 0.003). This study confirmed that NUDT15 variants are a potential independent risk predictor for AZA-induced leukopenia and neutropenia. BMI may be a crucial non-genetic factor that affects the concentration of AZA metabolites and myelosuppression. In addition, the 6-TGN concentration in red blood cells does not reflect the toxicity of AZA treatment, and new biomarkers for AZA therapeutic drug monitoring need further research.

Aims: To investigate the influence of TPMT*3C, ITPA, NUDT15, and 6-thioguanine nucleotides (6-TGN) on AZA-induced myelosuppression in Southwest China AIH patients. Methods: A total of 113 Chinese AIH patients with AZA maintenance treatment were evaluated. Collect the relevant clinical data of patients from the hospital information system. TPMT*3C(rs1142345), ITPA(rs1127354) and NUDT15(rs116855232) genotyping was detected by TaqMan double fluorescent probe. The concentration of 6-TGN was determined using UPLC-MS/MS method. Results: 40 (35.4%) patients had different degrees of myelosuppression. The NUDT15 variant was associated with leukopenia (P=8.26X10-7; OR=7.5; 95% CI, 3.08–18.3) and neutropenia (P=3.54X10-6; OR=8.05; 95% CI, 2.96–21.9). However, no significant association was observed for TPMT*3C and ITPA variants (P>0.05). There was no significant difference of 6-TGN concentration between patients with or without myelosuppression (P= 0.556), and no association was found in patients with TPMT*3C, ITPA, NUDT15 variants alleles (P>0.05). However, we found that the body mass index may affect the corrected 6-TGN level (P=0.026). Conclusion: Our study once again confirmed that NUDT15 variants are a potential independent risk predictor for AZA-induced leukopenia and neutropenia. Also, we found that the detection of 6-TGN concentration in red blood cells does not reflect AZA treatment's efficacy and toxicity. New biomarkers for AZA therapeutic drug monitoring need further research to explore.

Objectives: To test the psychometric properties of the Chinese version of Miller Behavioral Style Scale(C-MBSS).Methods: The forward-back-translation procedure was adopted in the translation of the Miller Behavioral Style Scale. Content validity was assessed in a panel of experts. In a sample of 1343 individuals, reliability and construct validity were assessed using Cronbach’s alpha coefficient and factor analysis. For exploratory factor analysis, parallel analysis was used to decide number of factors, principal axis factoring and direct oblimin rotation method were used to select factor. For confirmatory factor analysis, structural equation modelling was established to verify the extracted factor structure.Results: The C-MBSS achieved conceptual and semantic equivalence with the original scale. The item content validity index(I-CVI) of each item ranged from 0.78 to 1, and the averaging scale content validity index(S-CVI/ Ave) was 0.95. The cronbach`s alpha coefficient for the scale and sub-scales were over 0.6. The exploratory factor analysis resulted in 2-factor assumption for each hypothetical threat-evoking scenario. Confirmatory factor analysis provided confirmatory evidence for the second-order factor structure of 2-factor solution (Monitoring and Blunting) and demonstrated a good fit between theoretical model and data. Conclusions: This study verified the psychometric properties of the C-MBSS and indicated that the C-MBSS can be used to identify individual`s information-seeking style in Chinese population. With the use of the C-MBSS, health care professionals in China can deliver health education based on patients’ information-seeking behavior, which can improve the effect of health education and patients’ health outcomes.

Background and Aims Chemokines are deeply involved in the process of inflammatory and immune responses. Interferon-γ-inducible chemokines C-X-C motif chemokine 9 and 10 (CXCL9 and CXCL10) are significantly associated with Th1 cells and monocytes and rise rapidly during early episode of renal allograft rejection and various infectious diseases. CXCL13 is one of the most potent B cells and T follicular helper (Tfh) cells chemoattractants when acts through its cognate receptor CXCR5. Recent work of CXCL13 indicated a critical immune regulatory role in both multiple infectious diseases and kidney transplantation. Additionally, C-C motif chemokine 2 (CCL2) is shown to be is critical for chronic kidney diseases. The aim of this study was to identify the predictive role of serum CXCL9, CXCL10, CXCL13 or CCL2 on kidney posttransplant infection. Method 95 kidney transplant recipients (KTRs) were enrolled in this study. 31 recipients experienced at least once infection episodes within the first posttransplant 12 months and 64 KTRs did not experience any infection episode during the follow-up period. Serum CXCL9, CXCL10, CXCL13 and CCL2 at the time points of pre-transplantation and post-transplant 30 days (POD 30) were analyzed with Bio-Plex® suspension array system. Results It was found that serum level of POD 30 CXCL9 and POD 30 CXCL13 was associated with infection within one year after transplantation (P=0.021, P=0.002, respectively, shown in Figure 1). The serum level of CXCL9 and CXCL13 before surgery, the serum level of CCL2 and CXCL10 before and after surgery were not associated with infection within posttransplant one year (P>0.05, shown in Figure 1). The combination of POD 30 CXCL9 plus POD 30 CXCL13 provided the best results with AUC of 0.721 (95%CI, 0.591-0.852), sensitivity of 71.4% and specificity of 68.5% at the optimal cut-off value of 52.72 pg/ml (shown in Figure 2). Conclusion Chemokines CXCL9 and CXCL13 as important chemokines could be used to predict the occurrence of infection within posttransplant one year in kidney transplant recipients.

Background and Aims Desensitization therapy has enabled successful transplantation of renal allografts across the ABO blood group barrier, which significantly expands the living donor pool. Whether the B cell depletion induced by rituximab would affect the proportions of peripheral blood (PB) and lymph nodes (LN) T follicular helper (Tfh) and T follicular regulatory (Tfr) cells, whose survival depends on B cells, in ABO-incompatible kidney transplant recipients (ABOi-KTRs) is unknown. Method PB and LN samples were simultaneously collected on the day of transplantation from 14 ABOi-KTRs and 12 ABO-compatible KTRs (ABOc-KTRs) between January to October 2019. Additional PB from ABOi-KTRs was obtained before desensitization treatment (Rituximab+plasmapheresis+ immunosuppression). All recipients were undergone living donor transplantation. The frequency of B, Tfh (CD4+CXCR5+Foxp3-) and Tfr (CD4+CXCR5+Foxp3+) cells and the expression the PD-1, ICOS on Tfh and Tfr cells were quantified by flow cytometry. Results After desensitization treatment, significantly lower proportions of PB and LN B cells were observed in ABOi-KTRs (ABOi-a) when compared to ABOc and ABOi-b (ABOi-KTRs before desensitization) groups (Fig. A). Circulating Tfr cells decreased significantly after desensitization therapy, while no difference was found in LN Tfr cells (Fig. F). In addition, ABOi-a group showed higher expression of PD-1 on Tfr cell within PB, but lower within LN when compared to ABOi-b and ABOc groups, respectively (Fig. G). For Tfh proportion and its expression of PD-1 and ICOS within PB and LN, no significant difference was observed among groups (Fig. B-D). Significantly lower ratio of Tfr to Tfh was observed after ABO desensitization (Fig. E). Conclusion Our results indicated that ABO desensitization had significant suppression effects on B cells both within the PB and LN of ABOi-KTRs. In addition, the desensitization treatment mainly affected circulating Tfr cells, instead of Tfh cells, which shifted the balance between Tfr and Tfh cells towards Tfr cells in PB. Whereas, this treatment showed no influence on Tfh and Tfr populations within LN in ABOi-KTRs.

Background and Aims With the application of B-cell-depleting agent rituximab, plasmapheresis and powerful immunosuppression, ABO-incompatible kidney transplant recipients (ABOi-KT) have successfully overcome the ABO antibody barrier. As an important immune cell population, B cells are not only involved in antibody-mediated rejection, but also have been reported to have different immunoregulatory effects due to the existence of distinct B cell subsets. Therefore, comprehensively understanding the reconstitution of B-cell subsets in ABOi-KTRs is crucial to know the immune status that may be related to the subsequent complications. Method Fresh whole blood were collected from 22 ABOi-KTRs and 22 ABO-compatible recipients (ABOc-KTRs) at 0, 1week, 2 weeks ,1month, 3months, and 6 months post-transplantation between October 2018 and May 2019. In addition, pre-desensitization samples were also collected from ABOi-KTRs. B cell subsets including total, naïve, memory, plasma, plasma blast and regulatory B cells were determined by flow cytometry. Results The percentages of B cells in ABOi group remained extremely low and significantly lower than ABOc group through the first 6 months after rituximab treatment (Fig. A). Similar trends were observed in total memory and switched memory B cells whose frequencies increased within first 2 weeks, then decreased thereafter. Meanwhile, the significant differences between ABOi and ABOc groups disappeared at 6 months (Fig. B-D). In addition, plasma and plasma blast B cells increased 2 weeks after transplantation and were significantly higher in ABOi group compared to ABOc group (Fig. E, G), while Naïve B cells started to elevate 1 month after transplantation in ABOi-KTRs and significantly higher proportions were found in ABOc group through the entire 6 months (Fig. F). No obvious difference was observed between ABOi and ABOc groups regarding unswitched memory and regulatory B cell percentages (Fig. C, H). Conclusion Our preliminary results indicated that B-cell depletion therapy applied in ABOi-KTRs not only significantly reduced the number of B cells, but also changed the composition of B cell subsets in the remaining B cell population. Whether such alteration would be clinical significance requires further follow-up.

Background and Aims T cell immunoglobulin and mucin domain (Tim-3) and its ligand, galectin-9 (Gal-9), play an important role in immune regulation. Serum soluble Tim-3 (sTim-3) and Gal-9 (sGal-9) were observed to be correlated with renal function after kidney transplantation in our previous study, but whether these two could predict the adverse outcomes after transplantation is unknown. Method 91 recipients receiving kidney transplantation were enrolled in this cohort study. 20 of all recipients suffered composite outcomes after kidney transplantation within two years. 71 recipients had stable renal function during this period. The expressions of sTim-3 and sGal-9 before and one month after transplantation were measured by ELISA. Results The level of sTim-3 before transplantation was significantly higher in recipients with stable renal function than composite outcomes (Median: range, 2275: 840-4236 pg/ml vs 1589: 353-3094 pg/ml, P=0.002, shown in Figure 1). The level of sGal-9 after transplantation was significantly lower in stable group than composite outcome group (Median: range, 4869: 1418-13080 pg/ml vs 6852: 4128-10760 pg/ml, P=0.003, shown in Figure 1). Area under curve (AUC) of sTim-3 before transplantation was 0.737 (P=0.002, shown in Figure 2) through the analysis of receiver operating characteristic curve (ROC curve). AUC of sGal-9 after transplantation was 0.751 (P=0.003, shown in Figure 2). After survival analysis, the percentage of recipients free from composite outcomes was significantly lower in patients with low level of sTim-3 than high sTim3 (P Conclusion Serum sTim-3 and sGal-9 could predict the adverse outcomes within two years after kidney transplantation.

Background There is a growing recognition that training is not translated into performance and the ‘transfer problem’ exists in organization training today. Although factors contributing to training transfer have been identified in business and industry, the factors influencing training transfer in nursing profession remain less clear. Methods A qualitative descriptive study was undertaken in two tertiary referral hospitals in China from February 2013 to September 2013. Purposeful sampling of 24 nursing staffs were interviewed about the factors influencing training transfer. Results Seven themes evolved from the analysis, categorized in 4 main domains, which described the factors influencing training transfer in nursing profession in trainee characteristics, training design, work environment and profession domain. The trainee characteristics domain included attitude and ability. The training design domain included training content and instruction method. The work environment domain included supports as facilitators and opposition as hindrance. The theme pertaining to the profession domain was professional development. Conclusions Health care managers need to understand the factors influencing training transfer for maximizing the benefits of training. The right beliefs and values about training, the rigorous employee selection for training, the relevance of training content, training instructions facilitating learning and transfer, supports from peer, supervisors and the organization, organizational culture such as change, sharing, learning and support, and professional development are key to successful training transfer. Furthermore, managers should be aware of the opposition from co-workers and find ways to prevent it. Electronic supplementary material The online version of this article (10.1186/s12909-018-1149-7) contains supplementary material, which is available to authorized users.

Background Most organizations invest in people for training to improve human capital and maximize profitability. Yet it is reported in industry and nursing as well that training effectiveness is constrained because of inadequate transfer of training and the underlying reasons for the transfer problem remain unknown. And there is lack of tool to measure transfer problem. Methods The purpose of this study was to develop and validate a questionnaire to evaluate the scores of factors influencing training transfer (FITT) among nursing professionals. The questionnaire was developed by item generation through interview with nurses and literature review. The FITT was validated in terms of content validity through expert reviews. Psychometric properties of the final instrument were assessed in a sample of 960 nurses with training experiences. Results The content validity of the instrument were as follows: the IR was 0.8095. 51 items on the 63-item scale had I-CVIs of 1.0 and the remaining 12 items had I-CVIs of 0.88. The S-CVI/UA was 0.976 and the S-CVI/Ave was 0.977. For the exploratory step, principal axis factoring (PAF) was selected for this study. Parallel analysis was used to decide the number of factors to extract and oblimin rotation method was used. Exploratory factor analysis identified a five-factor solution including 53 items, accounting for 68.23% of the total variance. The confirmatory factor analysis showed some support for this five-factor model. The findings demonstrate high internal consistency (Cronbach’s alpha = .965). Conclusions This study indicates that the FITT is a valid and reliable instrument for assessing the factors influencing training transfer among nursing professionals. The FITT can be used to assess individual perceptions of catalysts and barriers to the transfer of training among nursing professionals, which can help promote training transfer and training effectiveness in the workplace.

BACKGROUND We investigated whether a low fixed Tac starting dose regimen could lead to a better achievement of Tac target concentrations, as well as an effective immunosuppressive treatment, in Chinese kidney transplant recipients (KTRs). MATERIAL AND METHODS We collected whole-blood and serum samples from 189 KTRs and the Tac starting dose was 2, 2.5, or 3 mg/day. Information on Tac C0, dose, body weight, body mass index (BMI), Scr, eGFR, and CYP3A5 genotypes were collected from a routine therapeutic drug monitoring database. The correlation between Tac C0 and body weight (or BMI) was investigated by calculating the goodness of fit. Multivariable logistic regression was performed to estimate the independent associated factors. RESULTS The patients with 3 mg per day of Tac had higher C0 at day 7 compared to those with 2 or 2.5 mg. For patients receiving the same Tac starting dose, no significant difference was found in Tac C0 at day 7 among different body weight or BMI groups. There was no significant difference in Scr or eGFR at 1 year after transplant, nor was there a significant difference in the rates of DGF or AR at post-transplant day 30 among different Tac starting dose groups or among the 3 Tac C0 range groups. CYP3A5 genotype and Tac initial dose were independently associated with Tac C0. CONCLUSIONS CYP3A5 genotype and Tac initial dose were independently associated with Tac C0 in renal transplant recipients. Our results suggest that a low Tac target C0 range (5-8 ng/ml) with a low fixed starting dose (3 mg/day) would be safe and effective among Chinese KTRs.

Individualized therapy involves genetic test of drug metabolism, which provides information about the initial dose and therapeutic drug monitoring for adjusting the subsequent dose. Consequently, toxic side effects are expected to be minimized and therapeutic effects to be maximized. In this study, an ultra-performance liquid chromatography tandem mass spectrometry method that was specific, accurate and sensitive was developed to simultaneously determine azathioprine two metabolites, 6-thioguanine nucleotides (6-TGN) and 6-methyl-mercaptopurine riboside (6-MMPr) in the whole blood lysate. We precipitated the sample by trifluoroacetic acid under the protection of dithiothreitol, with 6-MMPr and 6-TGN being hydrolyzed to produce 6-methymercaptopurine and 6-thioguanine. In the chromatographic separation, Waters ACQUITY BEH C18 (2.1 × 100 mm, 1.7 μm) chromatographic column was applied and gradient elution was conducted with 0.02 mol/L ammonium acetate buffer (which contains 0.3% formic acid) and acetonitrile at a flow rate of 0.4 ml/min. Tandem mass spectrometry in multiple reaction monitoring mode was applied for detection via electrospray ionization source in positive ionization mode. The analyzing process lasted for no more than 2 min. The calibration curve for each metabolite fitted a least squares model (weighed 1/X) from 1.25 to 5000 ng/ml (r2 > 0.99). The ion pairs were detected as 6-MMP m/z 167.07 → 152.15, 6-TG m/z 168.06 → 134.13, and internal standard m/z 171.07 → 137.14. Under the guidance of FDA guidelines for bioanalytical method validation, we carried out validation and obtained satisfactory results. The method was successfully utilized for monitoring the concentrations of each metabolite from 65 affected patients who had received azathioprine maintenance therapy and achieved optimal results.

Chemokines are majorly involved in inflammatory and immune responses. The interferon-γ-inducible chemokines C-X-C motif chemokines 9 and 10 (CXCL9 and CXCL10) are considerably associated with Th1 cells and monocytes, and their expression levels rapidly increase during the early episodes of renal allograft rejection and various infectious diseases. CXCL13 is one of the most potent B-cell and T follicular helper-cell chemoattractants. The expression of CXCL13 in the presence of infection indicates an important chemotactic activity in multiple infectious diseases. C-C motif chemokine ligand 2 (CCL2) can attract monocytes and macrophages during inflammatory responses. However, there are no studies on the role of these chemokines in posttransplant infection in kidney transplant recipients.In this study, CXCL9, CXCL10, CXCL13, and CCL2 were analyzed using the Bio-Plex suspension array system before transplant and 30 days after transplant.The serum levels of CXCL9 and CXCL13 30 days after kidney transplant were associated with infection within 1 year after transplant (P = .021 and P = .002, respectively). The serum levels of CXCL9 and CXCL13 before surgery and those of CCL2 and CXCL10 before and after surgery were not associated with infection within 1 year after transplant (P > .05). The combination of postoperative day (POD) 30 CXCL9 and postoperative day 30 CXCL13 provided the best results with an area under the curve of 0.721 (95% confidence interval, 0.591-0.852), with a sensitivity of 71.4% and specificity of 68.5% at the optimal cutoff value of 52.72 pg/mL.As important chemokines, CXCL9 and CXCL13 could be used to predict the occurrence of infection after kidney transplant.

Interview Guide. The interview guides developed for the study. (DOCX 15Â kb)

Background Currently, the pathogenesis of rheumatoid arthritis (RA) is not clearly understood. The LIGHT/HVEM/BTLA co-signaling pathway may be involved in the pathogenesis of RA, although reports on the expression levels of LIGHT, HVEM and BTLA in T lymphocytes from RA patients are limited. Method In this study, we recruited 30 healthy controls and 21 RA patients. Clinical characteristics were collected for RA patients. The levels of LIGHT, HVEM and BTLA expressed on the surface of circulating T cells of RA patients and healthy controls were measured by flow cytometry. Result The percentages of CD3+, CD4+ and CD8+ T lymphocytes that expressed BTLA from RA patients were all higher than those of the controls (all p < 0.05), while the percentages of CD3+, CD4+ and CD8+ T lymphocytes that expressed HVEM and LIGHT were all lower than those of the controls (all p < 0.05). The rheumatoid factor and the percentage of HVEM+CD4+ T lymphocytes showed a statistically significant negative correlation in RA patients (r = -0.453, p = 0.039), as did the swollen joint count and the percentage of BTLA+CD8+ T lymphocytes (r = -0.501, p = 0.021). Conclusion Here, we provide the first report on the increased expression of BTLA in T lymphocytes and on the decreased expression of HVEM and LIGHT in RA patients. BTLA, HVEM and LIGHT might be involved in the pathogenesis of RA and have the potential to be new clinically useful characteristics of RA.

Chronic hepatitis B (CHB) affects 400 million people and is the most common cause of liver cirrhosis (LC) and hepatocellular carcinoma (HCC) worldwide. Cellular immune regulation plays an important role in determining the infection outcome. Co-signal molecules and Th17/Treg were studied to explore their association with the progression of HBV infection.Ninety-four HBV-infected patients were categorized into three groups: 31 patients with LC caused by CHB, 30 with HCC caused by CHB and 33 with HCC caused by CHB. Co-signal molecules, Th17/Treg, and Stat3 and Stat5 were analyzed by flow cytometry.CHB patients who progressed to LC or HCC showed a significantly higher level of co-inhibitory molecules such as BTLA and PD-1, while there was no significant difference in co-stimulatory molecules among LC, HCC and CHB. Stat3 and Stat5 were significantly increased in LC and HCC compared to CHB patients.Co-inhibitory molecules play more important roles than co-stimulatory molecules. Increased PD-1 and BTLA/HVEM inhibited immune cells and the immune process. At the same time activated Stat3 and Stat5 stimulate the key factors in differentiation of Th17 and Treg, thus leading to imbalanced expansion of Th17 and Treg; immune tolerance was induced and HBV persistent. This resulted in hepatic inflammation that progressed to cirrhosis and carcinoma.

Background The published data revealed conflicting results of the polymorphism of MDR1 exon 26 SNP C3435T on the pharmacokinetics of tacrolimus in different post transplant times; thus, the aim was to perform a meta-analysis of different post transplant times to investigate the influence of SNP C3435T on the tacrolimus pharmacokinetics. Methods A literature search was conducted to locate the relevant papers by using the PUBMED and EMBASE electronic source until 2011. The pharmacokinetic parameters, including dose administration, concentration and concentration to dose ratio were extracted and a meta-analysis was performed by using STATA10.0. Results A total of 13 papers concerning 1327 individuals were included in the meta-analysis. The overall results showed SNP C3435T could influence the pharmacokinetic parameters in different post transplant times, the subjects with CC genotype had lower concentration dose ratio and need higher tacrolimus dose than the CT and TT genotype. Conclusions Our meta-analysis of available studies has demonstrated a definite correlation between the SNP C3435T in MDR1 gene and pharmacokinetics of tacrolimus. However, additional studies with large sample size and better study designs are warranted to verify our finding.

A simple, sensitive, reliable and economical HPLC method for quantifying paraquat concentration in human plasma has been developed, using diethyl paraquat as an internal standard. The drugs were extracted from the sample and separated on Xtimate C18 column with a mobile phase of 15% acetonitrile in 0.1M orthophosphoric acid containing SDS (150 mg/l). The pH of the mobile phase was adjusted to 3 with triethylamine and the detection wavelength was 256 nm for both paraquat and the internal standard. The average extraction recoveries were 91.9%. Good linearity (R(2)=0.9984) was observed throughout the range of 0.02-10 μg/ml in 0.5 ml plasma. The overall accuracy of this method was 97.6-107.3% and the lower limit of detection was 0.01 μg/ml. The intra- and inter-day variations were lower than 3.65% and 2.64%, respectively. We used this method to examine the paraquat concentrations of 53 patients with acute paraquat intoxication of whom 26 (49.1%) survived. In conclusion, this method was suitable for quantification of paraquat plasma concentration in toxicological samples. It was helpful in both assessing the severity of intoxication and predicting the outcome of paraquat poisoning.

Supplemental Digital Content is available in the text, Previous study has identified that the genetic variants in the human leukocyte antigen (HLA)-DP/DQ region were strongly associated with hepatitis B virus (HBV) infection. But their roles in liver function recovery after hepatic transplantation were still obscure. This study aimed to investigate whether HLA-DP/DQ polymorphisms were associated with post-transplant etiologies and prognosis in Chinese liver transplant recipients. A total of 144 liver transplant recipients were enrolled, which were divided into 2 groups according to the transplant etiology: HBV-related disease and non-HBV-related disease. HBV-related disease includes 3 subgroups: liver cirrhosis, hepatocellular carcinoma, and progressive HBV hepatitis. Three single-nucleotide polymorphisms HLA-DP (rs3077 and rs9277535) and HLA-DQ (rs7453920) were studied in all recipients by high-resolution melting curve analysis. Liver function indices (albumin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyltranspeptidase, direct bilirubin, total bilirubin) and coagulation indices (prothrombin time, platelet, international normalized ratio, fibrinogen) were routinely tested. After transplant, 10 recipients who were positive for HBsAg or with elevation in HBV virus load were regarded as HBV recurrence. No significant association of HLA-DP/DQ polymorphisms with HBV recurrence or transplant etiology was observed (P

Background The need to provide humanistic care in the contemporary healthcare system is more imperative now and the importance of cultivating caring in nursing education is urgent. Caring as the primary work of nursing has been discussed extensively, such as the meaning of caring, and teaching and learning strategies to improve nursing students’ caring ability. Yet attempts to understand students’ perspectives on learning about caring and to know their learning needs are seldom presented. The aim of this qualitative descriptive study was to explore the baccalaureate nursing students’ perspectives on learning about caring in China. Methods A qualitative descriptive study using focus group interviews were undertaken in two colleges in Yunnan Province, China from February 2010 to April 2010. Purposeful sampling of 20 baccalaureate nursing students were recruited. Content analysis of the transcribed data was adopted to identify the themes. Results Four categories with some sub-categories related to students’ perspectives on learning about caring were identified from the data: 1) Learning caring by role model; 2) conducive learning environment as the incentive to the learning about caring; 3) lack of directive substantive way of learning as the hindrance to the learning about caring; 4) lack of cultural competency as the barrier to the learning about caring. Conclusions Both caring and uncaring experiences can promote the learning about caring in a way of reflective practice. The formal, informal and hidden curricula play an important role in the learning about caring. Cultural awareness, sensitivity and humility are important in the process of learning to care in a multicultural area.

Background Currently, the pathogenesis of rheumatoid arthritis (RA) is not clearly understood. The LIGHT/HVEM/BTLA co-signaling pathway may be involved in the pathogenesis of RA, although reports on the expression levels of LIGHT, HVEM and BTLA in T lymphocytes from RA patients are limited.