Increased Expression of INHBA Is Correlated With Poor Prognosis and High Immune Infiltrating Level in Breast Cancer.

Background: Inhibin, beta A (INHBA) is a member of the transforming growth factor-ß superfamily and is associated with carcinogenesis and cancer progression in several types of human cancers. However, its significance in breast cancer has not been evaluated. Here, we investigated the prognostic value of INHBA and its correlation with tumor-infiltration immune cells in the microenvironment of breast cancer. Methods: In this study, we analyzed the INHBA expression profile in the Oncomine database and Tumor Immune Estimation Resource 2.0 (TIMER2.0) site. Using Breast Cancer Gene-Expression Miner (bc-GenExMiner v4.7) tool and the UALCAN cancer database, we further evaluated the correlation of INHBA expression with clinicopathological factors in breast cancer. Then, we assessed the clinical prognostic value of INHBA using Kaplan-Meier Plotter and the PrognoScan databases. The correlations between INHBA and tumor-infiltrating immune cells were investigated via TIMER2.0. In addition, correlations between INHBA expression and gene markers of immune infiltrates were analyzed by TIMER2.0 and Gene Expression Profiling Interactive Analysis 2. Results: Compared with the level in normal tissues, the INHBA mRNA expression was upregulated in different subtypes of breast cancer, and its expression was positively correlated with progesterone receptor, human epidermal growth factor receptor-2 status, and PAM50 subtypes but negatively related to age and basal-like status. The INHBA protein was also highly expressed in primary breast cancer and closely related to the pathological stage. Patients with high INHBA expression levels showed worse overall survival, relapse-free survival, and distant metastasis-free survival. Also, high INHBA expression was significantly associated with worse overall survival and relapse-free survival in positive lymph nodes. Of interest, INHBA expression was negatively correlated with infiltrating levels of activated NK cells, NKT, and CD4+ T cells but was positively correlated with tumor infiltration of CD8+ T cells, neutrophils, especially macrophages and cancer-associated fibroblasts. Moreover, INHBA expression showed strong correlations with various markers of monocytes/macrophages and cancer-associated fibroblasts. Conclusion: High INHBA expression is correlated with poor prognosis and the infiltration of immune cells in the tumor microenvironment. These findings suggest that INHBA may be involved in immune escape and can serve as a potential biomarker of prognosis and tumor-infiltrating immune cells.

Application and Effect Evaluation of Needle Tract Nursing after External Fixation with 2% Chlorhexanol Gluconate Gauze.

In the medical domain, needle-track nursing especially after 2 percent chlorhexidine gluconate gauze pressure bandaging is a challenging issue and needs a timely response from the research community. In this research paper, a total of 213 patients who met the inclusion and exclusion criteria after external fixation with 2% chlorhexidine gluconate gauze pressure bandaging in the second orthopaedic ward from March 2018 to December 2017 were selected and randomly divided into three groups, each with 71 cases. For needle tract care, various intervention strategies are used. Gauze pressure bandage with 2% chlorhexidine gluconate is in Group A. In group B, BID was cleaned with a sterile cotton swab containing 2 percent chlorohexanol gluconate. BID uses a 75 percent alcohol sterile cotton swab wipe for basic needle maintenance. The intervention measures suggested by each group were provided to the three groups. Finally, the effects and differences of the intervention measures used by the three groups on the infection rate of the needle tract after external fixation and patient pain scores were examined. It is worth noting that chlorhexidine disinfectant has not only evident and quick germicidal effects but also long-term bacteriostatic efficiency against germs that are difficult to develop drug resistance to. The nursing technique of chlorhexidine pressure bandaging the needle tract minimises the risk of infection, particularly severe needle tract infection. The compression bandage group had a considerably lower rate of needle tract infection than the other two groups (P0.05), according to the statistics. The pain score in the pressure bandaging group was significantly lower than the other two groups after intervention (P0.05), notably in the typical alcohol disinfection group. The use of 2 percent chlorhexidine gluconate alcohol gauze pressure dressing nursing measures can minimise the rate of needle tract infection following external fixator surgery, as well as the pain and satisfaction of patients. The needle tract nursing technique offers clinical and promotional value.

Validation of the Chinese Version of the Modified Gait Efficacy Scale for Patients Removing Ilizarov External Fixation Device for Over One Year.

OBJECTIVE: To validate the Chinese version of the modified Gait Efficacy Scale (C-mGES) in people who have had an Ilizarov external fixation apparatus removed more than 1 year ago. METHODS: (1) Translating and cultural adapting the English version mGES into Chinese. (2) Validation of the C-mGES with the Perceived Efficacy Patient-Physician Interactions Scale (PEPPI-10), Self-Efficacy for Rehabilitation Outcome Scale (SER), Lower Extremities Function Assessment Scale (LEFS), and Pain Self-Efficacy Questionnaire (PSEQ). Instrument measurements included item generation, construct validity, reliability testing, test-retest reliability and correlation with other scales. Confirmatory factor analysis (CFA) was applied to determine internal consistency and construct validity. One hundred five persons who had Ilizarov external fixation devices removed more than 1 year ago were investigated. RESULTS: One hundred and two patients were included in this research. Our study showed that the C-mGES has high internal consistency (Cronbach's α-coefficient 0.928). CFA confirmed good fit indices for a unidimensional model of the C-mGES. In test-retest reliability, 97 patients were analyzed. The results showed that the substantial kappa coefficient is 0.680, and the ICC is 0.98 (95% CI). CONCLUSION: Our study showed that the Chinese version mGES has a good internal consistency, construct validity and satisfactory criterion-related validity. This scale can assist in the assessment of walking self-efficacy in patients who have had Ilizarov external fixation devices removed for over 1 year.

Regulation of intrinsic apoptosis in cycloheximide-treated macrophages by the Sichuan human strain of Chinese Leishmania isolates.

Leishmania spp. are able to survive and proliferate inside mammals' mononuclear phagocytes, causing Leishmaniasis. Previous studies have noted that the regulation of apoptosis in host cells by these parasites may contribute to their ability to evade the immune system. However, current results remain unclear about whether the parasites can promote or delay the apoptotic process in host cells, because the regulatory effect of Leishmania was assumed to be strain-, species- and even infection time-dependent. The aim of this study was to investigate whether the Sichuan isolates of Chinese Leishmania (SC10H2) can alter the process of intrinsic apoptosis induced by cycloheximide in different types of macrophage cell lines and to determine in which steps of the signaling pathway the parasites were involved. Human THP-1 and mouse RAW264.7 macrophages were infected by SC10H2 promastigotes followed by cycloheximide stimulation to assess the alteration of intrinsic apoptosis in these cells. The results indicated that SC10H2 infection of human THP-1 macrophages could promote the initiation of intrinsic apoptosis, but completely opposite results were found in mouse RAW264.7 macrophages. Nevertheless, the expression of Bcl-2 and the DNA fragmentation rates were not altered by SC10H2 infection in the cell lines used in the experiments. This study suggests that SC10H2 promastigote infection is able to promote and delay the transduction of early apoptotic signals induced by cycloheximide in THP-1 and RAW264.7 macrophages, revealing that the regulation of intrinsic apoptosis in host cells by SC10H2 in vitro occurs in a host cell-dependent manner. The data from this study might play a significant role in further understanding the relationship between Leishmania and different host cells.

Personality as a predictor of general health in captive golden snub-nosed monkeys (Rhinopithecus roxellana).

Increasing studies in human and animals have shown that personality is related to biological profile and affects health outcomes. Understanding the link between personality and health will contribute to preventing illness and promoting well-being in non-human primates. The present study examined whether personality predicted health outcomes in captive golden snub-nosed monkeys (Rhinopithecus roxellana). Personality was measured by rating on a list of traits and four factors (Aggressiveness, Sociability, Mellowness, and Excitability) were extracted. Morbidity was measured by occurrence, duration, and number of illnesses, as well as (mean and maximum) digestive dysfunction symptoms scores. Morbidity measurements were coded from illness history which was recorded during the 27 months since the personality assessment. The results showed that lower Aggressiveness predicted greater number of illness, longer illness duration, and more serious digestive dysfunction. In addition, Mellowness, Excitability, and age by Sociability interaction influenced digestive function significantly. Low mellow individuals, high excitable individuals, high sociable younger individuals and low sociable older individuals had poorer digestive function. The present study demonstrated that personality was associated with morbidity in captive R. roxellanae and stress might contribute to this association. Personality assessment provided useful information on individual vulnerability. Carefully looking for early signs of illness among vulnerable individuals is expected to reduce health risks, which would promote welfare in captive non-human primates.

One novel susceptibility locus associate with systemic lupus erythematosus in Chinese Han population.

The aim of the study is to explore additional susceptibility factors for systemic lupus erythematosus (SLE) in Chinese Hans. Based on our previous GWAS of SLE, we performed a multistage replication study involving 3,152 cases and 7,050 controls from China to identify additional susceptibility loci for SLE by using the Sequenom MassArray system. All Chinese Han samples used in this study were obtained from doctors through collaboration with multiple hospitals in two geographic regions (central and southern China). Single-marker association analyses were performed using logistic regression with gender as a covariate in each case-control cohort. The joint analysis of all combined samples was performed using logistic regression with gender and sample cohorts as covariates. The significant association evidence for rs906868 (OR = 1.14, 95% CI 1.08-1.20, P combined = 7.71 × 10(-10)) and rs7579944 (OR = 1.13, 95% CI 1.07-1.19, P combined = 5.55 × 10(-9)) was observed, which located at 2p23.1. In this region, limb bud and heart development homolog (LBH) was the only gene indicated, suggesting LBH might be a susceptibility gene for SLE, although its function was still unknown. The results indicated that the SNP rs7579944, rs906868 at 2p23.1 showed significant association with SLE. The genes LBH which located in this loci might be the predisposing genes of SLE.

Follow-up study identifies two novel susceptibility loci PRKCB and 8p11.21 for systemic lupus erythematosus.

OBJECTIVE: We have performed a large-scale replication study based on our previous genome-wide association study (GWAS) of SLE in the Chinese Han population to further explore additional genetic variants affecting susceptibility to SLE. METHODS: Thirty-eight single nucleotide polymorphisms from our GWAS were genotyped in two additional Chinese Han cohorts (total 3152 cases and 7050 controls) using the Sequenom Massarray system. Association analyses were performed using logistic regression with gender or sample cohorts as a covariate. RESULTS: Association evidence for rs16972959 (PRKCB at 16p11.2) and rs12676482 (8p11.21) with SLE was replicated independently in both replication cohorts (P < 0.05), showing high significance for SLE in combined all 4199 cases and 8255 controls of Chinese Han [rs16972959: odds ratio (OR) = 0.81; 95% CI 0.76, 0.87; P(combined) = 1.35 × 10(-9); rs12676482: OR = 1.26; 95% CI 1.15, 1.38; P(combined) = 6.68 × 10(-7)). PRKCB is related to the established SLE immune-related pathway (NF-κB) and 8p11.21 contains important candidate genes such as IKBKB and DKK4. IKBKB is a critical component of NF-κB and DKK4 is an inhibitor of canonical Wnt signalling pathway. Interestingly, PRKCB is required for recruiting IKBKB into lipid rafts, up-regulating NF-κB-dependent survival signal. CONCLUSIONS: Our findings provided novel insights into the genetic architecture of SLE and emphasized the contribution of multiple variants of modest effect. Further study focused on PRKCB, 8p11.21, should advance our understanding on the pathogenesis of SLE.

Down-regulated expression of IKZF1 mRNA in peripheral blood mononuclear cells from patients with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a multi-system autoimmune disease with complex genetic inheritance. IKZF1 was established as a new susceptibility gene for SLE in a recent genome-wide association study (GWAS) in Chinese Han population. In order to examine whether expression levels of IKZF1 contribute to the pathogenesis of SLE, we estimated IKZF1 mRNA expression levels in peripheral blood mononuclear cells (PBMCs) via fluorescent quantitative reverse transcription polymerase chain reaction (RT-PCR) in 60 patients with SLE and 60 controls. We also explored whether the IKZF1 mRNA expression levels are associated with the variant of the SNP rs4917014 and the SLE Disease Activity Index (SLEDAI). The expression levels of IKZF1 mRNA in patients with SLE were significantly decreased compared with those in healthy controls (P<0.001). No significant differences were found between IKZF1 mRNA expression levels and SLEDAI scores, SNP rs4917014. Our results suggest that decreased expression of IKZF1 mRNA may be correlated with the pathogenesis of SLE.