The protective effects of ruscogenin against lipopolysaccharide-induced myocardial injury in septic mice.

ABSTRACT: Sepsis-induced myocardial dysfunction (SIMD) commonly occurs in individuals with sepsis and is a severe complication with high morbidity and mortality rates. The current study aimed to investigate the effects and potential mechanisms of the natural steroidal sapogenin ruscogenin (RUS) against lipopolysaccharide (LPS)-induced myocardial injury in septic mice. We found that RUS effectively alleviated myocardial pathological damage, normalized cardiac function, and increased survival in septic mice. RNA sequencing (RNA-seq) demonstrated that RUS administration significantly inhibited the activation of the NOD-like receptor signaling pathway in the myocardial tissues of septic mice. Subsequent experiments further confirmed that RUS suppressed myocardial inflammation and pyroptosis during sepsis. Additionally, cultured HL-1 cardiomyocytes were challenged with LPS, and we observed that RUS could protect these cells against LPS-induced cytotoxicity by suppressing inflammation and pyroptosis. Notably, both the in vivo and in vitro findings indicated that RUS inhibited NLRP3 upregulation in cardiomyocytes stimulated with LPS. As expected, knockdown of NLRP3 blocked the LPS-induced activation of inflammation and pyroptosis in HL-1 cells. Furthermore, the cardioprotective effects of RUS on HL-1 cells under LPS stimulation were abolished by the novel NLRP3 agonist BMS-986299. Taken together, our results suggest that RUS can alleviate myocardial injury during sepsis, at least in part by suppressing NLRP3-mediated inflammation and pyroptosis, highlighting the potential of this molecule as a promising candidate for SIMD therapy.

Association between a single nucleotide polymorphism of the ALOX5 gene and susceptibility to multisystem tuberculosis in a Chinese Han population.

BACKGROUND: Host genetic single nucleotide polymorphisms can exert an influence susceptibility to tuberculosis infection. Previous investigations have demonstrated an association between the polymorphism in the ALOX5 gene and a range of diseases, encompassing not only noninfectious conditions like asthma, acute myocardial infarction, and cerebral infarction but also infections caused by various pathogens. However, the relationship between ALOX5 gene polymorphism and susceptibility to tuberculosis has received limited research attention. The ALOX5 gene encodes arachidonic acid 5-lipoxygenase(5-LO), which serves as the initiating catalyst in the generation of the inflammatory mediator leukotriene. Leukotrienes, products derived from the 5-LO pathway, are potent proinflammatory lipid mediators that assume a pivotal role in tuberculosis infections.Consequently, ALOX5 gene variants may be intricately associated with the pathogenesis of tuberculosis. In instances where the host exhibits immunocompromisation, infection with Mycobacterium tuberculosis can impact multiple systems. The involvement of multiple systems significantly augments the complexity of treatment and escalates patient mortality rates. Regrettably, the underlying mechanisms driving multisystem tuberculosis pathogenesis remain enigmatic, with clinicians paying scant attention to this aspect. Although the protein encoded by the ALOX5 gene represents a pivotal enzyme that catalyzes the metabolism of arachidonic acid into LXA4, and thereby plays a significant role in the inflammatory response during tuberculosis infection, studies investigating ALOX5 gene polymorphism and its association with susceptibility to multisystem tuberculosis in the Chinese Han population are exceptionally scarce. Therefore, the primary objective of this study is to comprehensively examine the correlation between ALOX5 gene polymorphisms and susceptibility to tuberculosis within the Chinese Han population, with particular emphasis on multisystemic tuberculosis. METHODS: A case‒control study design was employed, encompassing 382 individuals with pulmonary tuberculosis and 367 individuals with multisystemic tuberculosis as the case groups, along with 577 healthy controls.Whole blood DNA was extracted from all patients and healthy controls. Subsequently, three tag polymorphisms (rs2029253, rs7896431, rs2115819) within the ALOX5 gene were selectively identified and genotyped. RESULTS: After adjusting for age and sex, the presence of allele A at rs2029253 exhibited a pronounced association with an elevated risk of TB susceptibility when compared to the tuberculosis group and healthy control group. (ORa: 2.174, 95% CI: 1.827-2.587; Pa<0.001, respectively). Notably, the rs2029253 AG genotype and AA genotype displayed a significantly increased susceptibility to tuberculosis (ORa: 2.236, 95% CI: 1.769-2.825; Pa <0.001 and ORa: 4.577, 95% CI: 2.950-7.100; Pa <0.001, respectively) compared to the GG genotype. Moreover, in the analysis utilizing genetic models, rs2029253 also exhibited a markedly heightened susceptibility to tuberculosis in additive models, dominant models, and recessive models (Pa <0.001). Conversely, no significant association was observed between rs7896431, rs2115819, and tuberculosis. In the subgroup analysis, when comparing the pulmonary tuberculosis group with the healthy control group, we observed no significant disparities in the distribution frequencies of alleles, genotypes, and gene models (additive model, dominant model, and recessive model) for the three tag SNPs, with P-values were >0.05 after adjusting for age and sex. Additionally, we noted that the presence of allele A at rs2029253 was linked to an increased susceptibility to tuberculosis in the multisystemic tuberculosis group relative to the healthy control group (ORa: 2.292, 95% CI: 1.870-2.810; Pa<0.001). Similarly, the rs2029253 AG genotype, AA genotype, and gene models, including the additive model, dominant model, and recessive model, demonstrated a significantly elevated risk of tuberculosis susceptibility. CONCLUSIONS: The polymorphism in the ALOX5 gene is associated with susceptibility to multisystemic tuberculosis in the Chinese Han population.

Association between a single nucleotide polymorphism of the IL23R gene and tuberculosis in a Chinese Han population: a case‒control study.

BACKGROUND: Severe tuberculosis constitutes a significant menace to human safety and well-being, with a considerable mortality rate. The severity of tuberculosis can be impacted by genetic variations in host genes, particularly single nucleotide polymorphisms (SNPs). METHODS: A case‒control study was undertaken, encompassing a cohort of 1137 tuberculosis patients (558 with severe tuberculosis and 579 with mild tuberculosis), alongside 581 healthy controls within the age range of fifteen to forty-five years. Whole blood DNA was extracted from all participants, and three tag polymorphisms (rs1884444, rs7518660, rs7539625) of the IL23R gene were selectively identified and genotyped. RESULTS: No significant correlation was observed between the IL23R gene polymorphisms (rs1884444, rs7518660, and rs7539625) and tuberculosis. Upon comparing the tuberculosis group with the healthy control group, the mild tuberculosis group with the healthy control group, and the severe tuberculosis group with the healthy control group, the obtained P-values were> 0.05. However, in the comparison between severe tuberculosis and mild tuberculosis, the presence of rs1884444 G alleles exhibited a significantly increased risk of severe tuberculosis after adjusting for age and sex (ORa: 1.199, 95% CI: 1.009-1.424; Pa=0.039, respectively). In subgroup analysis, after accounting for confounding factors, including age and sex, rs1884444 G alleles continued to demonstrate a significantly heightened risk of severe tuberculosis. Nonetheless, the comparison between the multisystemic tuberculosis group and the mild tuberculosis group was no significant difference. Notably, rs1884444 of the IL23R gene exhibited a noteworthy association with the risk of severe tuberculosis in the comparison between severe tuberculosis and mild tuberculosis before and after adjusting for age and sex (ORa: 1.301, 95% CI: 1.030-1.643; Pa=0.027, respectively). Furthermore, the presence of the rs1884444 G allele exhibited a significantly increased risk of severe tuberculosis after adjusting for age and sex in the comparison between tuberculous meningitis and mild tuberculosis (ORa: 1.646, 95% CI: 1.100-2.461; Pa=0.015, respectively). CONCLUSIONS: The present study suggests that there is no significant association between IL23R gene polymorphism and tuberculosis susceptibility in the Chinese Han population. However, it does indicate a potential link between IL23R polymorphism and an increased risk of developing severe tuberculosis.

Preoperative Quality of Life and Mental Health Can Predict Postoperative Outcomes and Quality of Life after Colorectal Cancer Surgery.

Background and Objectives: It remains unclear which domains of preoperative health-related quality of life (HRQOL) and mental health are predictive of postoperative clinical and patient-reported outcomes in colorectal cancer (CRC) patients. Materials and Methods: A prospective cohort of 78 CRC patients undergoing elective curative surgery was recruited. The EORTC QLQ-C30 and HADS questionnaires were administered preoperatively and one month after surgery. Results: Preoperative cognitive functioning scores (95% CI 0.131-1.158, p = 0.015) and low anterior resection (95% CI 14.861-63.260, p = 0.002) independently predicted poorer 1-month postoperative global QOL. When postoperative complications were represented using the comprehensive complication index (CCI), poorer preoperative physical function scores were associated with higher CCI scores (B = -0.277, p = 0.014). Preoperative social function score (OR = 0.925, 95% CI 0.87 to 0.99; p = 0.019) was an independent predictor for 30-day readmission, while physical functioning score (OR = -0.620, 95% CI -1.073--0.167, p = 0.008) was inversely related to the length of hospitalization. The overall regressions for 1-month postoperative global QOL (R2: 0.546, F: 1.961, p = 0.023) and 30-day readmission (R2: 0.322, χ2: 13.129, p < 0.001) were statistically significant. Conclusions: Various QLQ-C30 domains were found to be predictive of postoperative outcomes, including complications, readmission, and length of hospitalization. Preoperative cognitive dysfunction and low AR were independent predictors of poorer postoperative global QOL. Future research should seek to examine the efficacy of targeting specific baseline QOL domains in improving clinical as well as patient-reported outcomes after CRC surgery.

Psychological resilience among palliative patients with advanced cancer: A systematic review of definitions and associated factors.

OBJECTIVE: The palliative journey can be emotionally stressful for both patients with advanced cancer and their families. Psychological resilience is crucial in aiding with patients' adaptation and post-traumatic growth. The aim of this systematic review was to critically examine the definitions of psychological resilience and its associated factors in palliative patients with advanced cancer. METHODS: Four databases were systematically searched from inception to August 2020. Both qualitative and quantitative studies that examined factors associated with psychological resilience in a sample of patients with advanced cancer undergoing palliative care were included. RESULTS: A total of 15 studies met the criteria, of which 10 were qualitative and five were quantitative. Nine studies included a definition of psychological resilience, from which five common themes of buffering, adaptation, resources, recovery, and growth were derived. The quantitative studies found association between resilience and hope, independence, social support, fatigue, emotional distress, and coping strategies. The qualitative studies reported additional sources of resilience such as spirituality, social support, prior experience dealing with illness and life adversity, meaning-making, reconciling with life's finiteness, acceptance of illness, control, determination, positive attitude, dignity, engagement with palliative care and quality of life being supported by palliative care. CONCLUSIONS: More research is needed for developing an overarching definition of psychological resilience in palliative advanced cancer patients that acknowledges and appreciates the contextual sensitivity of this concept among different cultural groups. Further studies are also needed to examine a holistic range of bio-psycho-socio-spiritual factors associated with psychological resilience among these patients and their families.

Genetic association of TOLLIP gene polymorphisms and HIV infection: a case-control study.

BACKGROUND: Previous studies have indicated that host genetic factors play an essential role in immunity to human immunodeficiency virus (HIV) infection. We aimed to investigate the association between the toll-interacting protein (TOLLIP) and mannose-binding lectin 2 (MBL2) genes and HIV infection susceptibility among Chinese Han patients. METHODS: This is a case-control study. A total of 435 HIV-infected patients and 1013 seronegative healthy individuals were recruited. DNA was extracted from whole blood. Two SNPs in the MBL2 gene (rs7096206 and rs1800450) and three SNPs in the TOLLIP gene (rs5743899, rs3750920, and rs5743867) were selected and genotyped using a SNPscan Kit (Cat#: G0104, Genesky Biotechnologies Inc., Shanghai, China). Odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated using unconditional binary logistic regression. RESULTS: A significant association between the minor alleles rs5743899 (C allele) and rs5743867 (G allele) in the TOLLIP gene and susceptibility to HIV infection was found in this study after adjusting for age and sex (Pa = 0.011 and < 0.001, respectively). The rs5743867 in the TOLLIP gene was significantly associated with the risk of HIV infection in dominant, recessive, and additive models when adjusted for age and sex (Pa < 0.05). No significant association was found between MBL2 gene polymorphisms and HIV infection. CONCLUSION: Our study found a statistically significant association between the two SNPs (rs5743867 and rs5743899) in the TOLLIP gene and susceptibility to HIV infection in a Chinese Han population.

Efficacy of bedaquiline in the treatment of drug-resistant tuberculosis: a systematic review and meta-analysis.

BACKGROUND: Drug-resistant tuberculosis (DR-TB) remains a major public health concern worldwide. Bedaquiline, a novel diarylquinoline, was added to the WHO-recommended all-oral regimen for patients with multidrug-resistant tuberculosis. We performed a systematic review and meta-analysis to determine the effect of bedaquiline on tuberculosis treatment outcomes. METHODS: We searched the PubMed, Web of Science and EMBASE databases for relevant studies published up to March 12, 2021. We included studies in which some participants received bedaquiline and others did not. Stata version 16.0 (Stata Corp., College Station, Texas, USA) was used to analyze the results of the meta-analysis. Risk ratios (RRs) with 95% confidence intervals (95% CIs) were calculated to evaluate the effect of bedaquiline on drug-resistant tuberculosis. Between-study heterogeneity was examined by the I-squared test. Randomized controlled trials were assessed for quality using the Jadad scale, and cohort studies were assessed using the Newcastle-Ottawa scale. RESULTS: Eight studies, including 2 randomized controlled trials and 6 cohort studies involving a total of 21,836 subjects, were included. When compared with the control, bedaquiline treatment was associated with higher rates of culture conversion (risk ratio (RR):1.272 (1.165-1.389), P < 0.001). We found substantial evidence of a significant reduction in all-cause death (RR: 0.529 (0.454-0.616), P < 0.001)) in the bedaquiline treatment group. There was no significant reduction in treatment success (RR = 0.980 (0.948-1.013, P = 0.234)). CONCLUSIONS: This study demonstrated that compared with patients who do not receive bedaquiline, this drug has the potential to achieve a higher culture conversion rate and a lower mortality risk among drug-resistant tuberculosis cases.

Systematic review and meta-analysis of clinical outcomes comparison between different initial dialysis modalities in end-stage renal disease patients due to lupus nephritis prior to renal transplantation.

BACKGROUND: Regarding lupus disease activity, morbidity and survival, limited literature concluded conflicting results when comparing hemodialysis versus peritoneal dialysis as initial renal replacement therapies (RRT) prior to transplantation, in lupus nephritis end-stage renal disease (LN-ESRD) patients. This study was aimed to compare the risks of lupus flares, all-cause infections, all-cause cardiovascular events, and mortality, between hemodialysis versus peritoneal dialysis as initial RRT - modality before renal-transplant in LN-ESRD patients, by systematic review and meta-analysis. METHODS: PubMed, EMBASE, and SCOPUS were searched for observational-studies comparing LN-ESRD -patients undergoing hemodialysis (Group1) versus peritoneal-dialysis (Group 2) prior to renal-transplantation, by their risks of lupus flare, all-cause infections, all-cause cardiovascular events, and mortality as outcome measures. Relative-Risks of outcomes between the groups measured overall effects at a 95% significance level. RevMan 5.3 computer software was used for analysis. RESULTS: From search, 16 eligible studies reported 15,636 LN-ESRD -patients prior to renal transplantation with 4616 patients on hemodialysis, 2089 on peritoneal dialysis, 280 directly underwent kidney transplantation, 8319 were eliminated with reasons and 332 participants' details were not reported. Hemodialysis group had higher risk of all-cause cardiovascular events, Relative-Risk = 1.44 (Confidence Interval:1.02, 2.04), p-Value< 0.05. With regards to risks for mortality, flare and all-cause infections, there were trends that were not statistically significant (p-Value> 0.05). CONCLUSION: Except for all-cause cardiovascular events in which peritoneal dialysis is superior to hemodialysis offering better outcomes, both treatment modalities offer more or less similar clinical outcomes as effective initial choices of RRT in LN-ESRD patients prior to renal transplant. THE PROTOCOL REGISTRATION: PROSPERO 2019 CRD42019131600.

Heart rate and heart rate variability comparison between postural orthostatic tachycardia syndrome versus healthy participants; a systematic review and meta-analysis.

BACKGROUND: A number of published literature has reported that, physiologically, heart rate variability (HRV) in patients with postural orthostatic tachycardia syndrome (POTS) to be greatly confounded by age, sex, race, physical fitness, and circadian rhythm. The purpose of this study was to compare between POTS patients versus healthy participants, in terms of heart rate (HR) and HRV after Head-Up tilt test (HUTT), by systematic review and meta-analysis of available published literature. METHODS: MEDLINE (using PubMed interphase), EMBASE and SCOPUS were systematically searched for observational studies comparing POTS patients versus healthy patients, in terms of HR and HRV. HRV was grouped into Time and frequency domain outcome measurements. The time domain was measured as mean RR- interval and mean the square root of the mean of squares of successive R-R waves (rMSSD) in milliseconds. The frequency domain was measured as mean values of Low frequency power (LF), High frequency power (HF), LF/HF-ratio, LF-normalized units (LF(n.u)) and HF-normalized units (HF(n.u)). Demographic data, comorbidities, and mean values of HR, RR- interval, rMSSD, LF, HF, LF/HF-ratio, LF-(n.u) and H.F-n.u were extracted from each group and compared, by their mean differences as an overall outcome measure. Computer software, RevMan 5.3 was utilized, at a 95% significance level. RESULTS: Twenty (20) eligible studies were found to report 717 POTS and 641 healthy participants. POTS group had a higher mean HR (p < 0.05), lower mean RR-Interval (p < 0.05), lower rMSSD (p < 0.05) than healthy participants. Furthermore, POTS group had lower mean HF(p > 0.05), lower mean LF(p > 0.05), and lower mean HF(n.u) (p > 0.05), higher LF/HF-Ratio (p > 0.05) and higher LF(n.u) (p > 0.05) as compared to healthy participants. CONCLUSION: POTS patients have a higher HR than healthy patients after HUTT and lower HRV in terms of time domain measure but not in terms of frequency domain measure. HR and time domain analyses of HRV are more reliable than frequency domain analysis in differentiating POTS patients from the healthy participants. We call upon sensitivity and specificity studies.

Treatment outcomes of tuberculous meningitis in adults: a systematic review and meta-analysis.

BACKGROUND: Tuberculous meningitis is the most devastating presentation of disease with Mycobacterium tuberculosis. We sought to evaluate treatment outcomes for adult patients with this disease. METHODS: The Ovid MEDLINE, EMBASE, Cochrane Library and Web of Science databases were searched to identify all relevant studies. We pooled appropriate data to estimate treatment outcomes at the end of treatment and follow-up. RESULTS: Among the articles identified, 22 met our inclusion criteria, with 2437 patients. In a pooled analysis, the risk of death was 24.7% (95%CI: 18.7-31.9). The risk of neurological sequelae among survivors was 50.9% (95%CI: 40.2-61.5). Patients diagnosed in stage III or human immunodeficiency virus (HIV) positive were significantly more likely to die (64.8, 53.4% respectively) during treatment. The frequency of cerebrospinal fluid (CSF) acid-fast-bacilli smear positivity was 10.0% (95% CI 5.5-17.6), 23.8% (15.2-35.3) for CSF culture positivity, and 22.3% (17.8-27.5) for CSF polymerase chain reaction positivity. We found that the headache, fever, vomiting, and abnormal chest radiograph were the most common symptoms and diagnostic findings among tuberculous meningitis patients. CONCLUSIONS: Despite anti-tuberculosis treatment, adult tuberculous meningitis has very poor outcomes. The mortality rate of patients diagnosed in stage III or HIV co-infection increased significantly during treatment.

Biofilm formation in erythromycin-resistant Staphylococcus aureus and the relationship with antimicrobial susceptibility and molecular characteristics.

PURPOSE: In this study, we aimed to investigate biofilm formation characteristics in clinical Staphylococcus aureus (S. aureus) isolates with erythromycin (ERY) resistance from China and further analyze their correlations with antimicrobial susceptibility and molecular characteristics. METHODOLOGY: A total of 276 clinical isolates of ERY-resistant S. aureus, including 142 methicillin-resistant S. aureus (MRSA) strains and 134 methicillin-susceptible S. aureus (MSSA) strains, were retrospectively collected in China. Biofilms were determined by crystal violet staining and ERY resistance genes (ermA, ermB and ermC) were detected by polymerase chain reaction. Inducible clindamycin resistance was examined by D test and multilocus sequence typing, and clonal complexes (CCs) based on housekeeping genes were further determined. RESULTS: The frequency of biofilm formation among ERY-resistant S. aureus was 40.9% (113/276) in total and no significant difference was found for the frequency of biofilm formation between ERY-resistant MRSA and ERY-resistant MSSA (44.4% vs 37.3%, P > 0.05). In ERY-resistant MRSA isolates, the frequency of biofilm formation in ermA-positive, gentamicin-resistant and ciprofloxacin-resistant isolates was higher than that in ermA-negative, gentamicin-sensitive and ciprofloxacin-sensitive isolates, respectively (63.9% vs 23.6%, P < 0.01; 60.3% vs 27.5%, P < 0.01; 65.2% vs 26.3%, P < 0.01). In addition, tetracycline resistance facilitated biofilm formation in both ERY-resistant MRSA and MSSA and the frequency of biofilm formation in CC239- or CC7S. aureus isolates with ERY resistance was significantly higher compared with that in CC59S. aureus (both P < 0.01). CONCLUSION: The ermA gene, and gentamicin, ciprofloxacin and tetracycline resistance facilitate biofilm formation in ERY-resistant MRSA isolates and, moreover, ERY-resistant S. aureus isolates with positive biofilm formation exhibited clonality clustering regarding CC239 and CC7.

Association of TLR8 and TLR9 polymorphisms with tuberculosis in a Chinese Han population: a case-control study.

BACKGROUND: Toll-like receptor (TLR) single nucleotide polymorphisms (SNPs) have been associated with regulation of TLR expression and development of active tuberculosis (TB). The objectives of this study were to determine whether TLR8 and TLR9 SNPs were associated with the development of latent TB infection (LTBI) and the subsequent pulmonary TB (PTB) in a Chinese Han population. METHODS: Two independent samples were enrolled. The first sample contained 584 TB cases and 608 controls; the second sample included 204 healthy controls, 201 LTBI subjects and 209 bacteria-confirmed active PTB patients. Three SNPs (rs3764880, rs187084 and rs5743836) were genotyped. The associations between the SNPs and risk of LTBI or PTB were investigated using unconditional logistic regression analysis. RESULTS: The A-allele of TLR8 rs3764880 SNP was protective against the development of TB in males (A vs G, OR = 0.58, 95%CI = 0.37-0.91). The AA genotype of rs3764880 SNP was found to increase the risk of PTB among females with an OR of 4.81 (1.11-20.85). The G allele of TLR9 SNP rs187084 was found to increase the risk of PTB (G vs A, P = 0.01, OR = 1.48, 95% CI = 1.10-2.00), the significance was also observed under dominant genetic models. The GA-genotype of TLR9 rs187084 SNP was found to increase the risk of PTB with an OR of 1.68 (1.07-2.65), but was found to decrease the risk of MTB infection with an OR = 0.64 (0.41-0.98). TLR9_rs5743836 SNP was excluded from the data analyses, because the minimum allele frequency was< 1%. CONCLUSIONS: Our findings in two independent samples indicated that SNPs in TLR8 and TLR9 were associated with the development of TB, and highlight that SNPs may have different effects on disease pathogenesis and progression.

[Association of rs1495741 Single Nucleotide Polymorphism with Susceptibility of Anti-tuberculosis Drug-induced Hepatotoxicity].

OBJECTIVE: To investigate the potential association between the polymorphism of N- acetyltransferase 2 (NAT2) gene and anti-tuberculosis drug-induced hepatotoxicity (ATDH) in Han population. METHODS: The SNP rs1495741 was genotyped by using multiplex ligation detection reaction (MLDR) technique, and logistic regression analysis was used to analyze the association between this SNP and the susceptibility of ATDH. RESULTS: There were 247 PTB patients enrolled in this study, including 24 ATDH, and 223 controls (PTB without ATDH). No significant difference in genotype and allele distribution was observed for rs1495741 in NAT2 between the controls and ATDH group. After adjusting age, sex, body mass index (BMI) and smoking history, the SNP of rs1495741 showed a significant association with ATDH 〔odds ratio (OR)=2.728 (95% confidence interval: 1.022-7.281)〕 under recessive model (AA vs. GA+GG). CONCLUSIONS: The rs1495741 in NAT2 seems related to the development of ATDH among PTB patients, AA genotype of rs1495741 may be a causative factor for increased susceptibility to ATDH.

Expression of Acid-Sensing Ion Channels in Renal Tubular Epithelial Cells and Their Role in Patients with Henoch-Schönlein Purpura Nephritis.

BACKGROUND Acid-sensing ion channels (ASICs) are ligand-gated cation channels activated by extracellular protons. However, the role of ASICs in kidney diseases remains uncertain. This study investigated ASICs expression in kidney tissues and their role in the development of Henoch-Schönlein purpura nephritis (HSPN). MATERIAL AND METHODS The expression of ASIC subunits was examined by immunochemical techniques in the kidney tissue from HSPN patients. Acid-induced ASICs expression in cultured renal tubular epithelial cells was determined by quantitative RT-PCR analysis. The expression of K7 and K18 protein in renal tubular epithelial cells was used to evaluate acid-induced cell injury. In addition, we observed the effect of blocking ASICs on acid-induced cell injury to assess the role of ASICs in renal tubular epithelial cell injury. RESULTS The results showed that ASIC1, ASIC2, and ASIC3 proteins were obviously expressed in renal tubular cells from HSPN patients. ASIC1 expression and 24-h urine protein level were higher in the pathological grade ISKD III group than in the ISKD II group. ASIC1, ASIC2, and ASIC3 mRNA, and K7 and K18 protein expression in cultured renal tubular epithelial cells were increased when exposed to pH 6.5. K7 and K18 protein expression was closely related to ASIC1 expression, and ASICs blockers reduced K7 and K18 protein expression in tubular epithelial cells. CONCLUSIONS These findings suggest ASICs are most highly expressed in renal tubular cells of HSPN patients, which is closely related to renal tubular injury. ASICs might be involved in the development of HSPN.

Micrometer-resolution in-fiber OCT probe with tunable working distance.

Optical coherence tomography (OCT) is an attractive modality in biomedical imaging systems due to its non-invasive imaging character. Since the image quality of OCT may be limited by the decrease of transverse resolution away from the focus spot, working distance tunable probe can be a strategy to overcome such limitation and maintain high transverse resolution at different imaging depths. In this paper, a miniature, working distance-tunable in-fiber OCT probe is demonstrated. The influences of the graded index fiber (GIF) length as well as the air cavity length on the working distance and the transverse resolution are simulated and discussed. Experimental results prove that the working distance can be tuned freely from 337.31 µm to 22.28 µm, producing the transverse resolution from 13.86 µm to 3.6 µm, which are in good agreement with the simulated results. The application of the probe in an OCT system for imagining a standard USAF resolution target is investigated in detail. The best resolutions for the standard USAF resolution target imaging are 4.9 µm and 6.9 µm in horizontal and vertical direction, respectively.

[Correlation of high-risk HPV 16/18 infections with prostate cancer].

OBJECTIVE: To study the correlation of high-risk human papillomavirus 16 and 18 (HPV16/18) infections with the risk of prostate cancer (PCa) and their association with the clinicopathologic indexes of PCa. METHODS: We collected tissue samples from 75 cases of PCa and 73 cases of benign prostatic hyperplasia (BPH). We detected HPV16/18 infections in the samples by immunohistochemistry and PCR combined with reverse dot blot (RDB) assay. RESULTS: Immunohistochemistry revealed 16 cases of HPV16/18 positive in the PCa (21.3%) and 7 cases in the BPH samples (9.5%), with statistically significant difference between the two groups (P=0.049). PCR combined with RDB assay showed 17 cases of HPV16 infection (22.6%) and 13 cases of HPV18 infection (17.8%), including 4 cases of HPV16/18 positive, in the PCa group, remarkably higher than 6 cases of HPV16 infection (8.2%), 3 cases of HPV18 infection (4.1%) and no HPV16/18 positive in the BPH controls (P=0.001). No significant differences were observed between the result of immunohistochemistry and that of PCR combined with RDB assay (P=0.069). The risk of HPV16/18 infections was found to be correlated with the clinical T-stage and Gleason score of PCa (P<0.05 ) but not with the patient's age, PSA level or lymph node metastasis (P>0.05 ). CONCLUSIONS: High-risk HPV16/18 infections are correlated with the risk of prostate cancer.

Generation of transgenic rats through induced pluripotent stem cells.

The rat is an important animal model for human disease research. Using inhibitors of glycogen synthase kinase 3 and MAPK signaling pathways, rat embryonic stem cells and rat induced pluripotent stem cells (riPSCs) have been derived. However, unlike rat embryonic stem cells, germ line competent riPSCs have only been derived from Wistar rats at low efficiency. Here, we found that an optimized induction medium containing knock-out serum replacement and vitamin C improved the rate and efficiency of riPSCs generation from Dark Agouti rat fibroblasts and Sertoli cells. riPSCs maintained an undifferentiated status for >30 passages and could differentiate into various cells types including germ cells when injected into rat blastocysts. Moreover, transgenic riPSCs could be generated through the PiggyBac transposon, which could be used to generate transgenic rats through germ line transmission. riPSCs can be used as a novel tool in genetic and genomic studies of the rat.

Apoptosis of human umbilical vein endothelial cells (HUVEC) induced by IgA1 isolated from Henoch-Schonlein purpura children.

OBJECTIVE: It had been shown that apoptosis of vascular endothelial cells played an important role in the pathogenesis of HSP. The present study was designed to investigate the apoptosis of vascular endothelial cells induced by isolated IgA1 from sera of HSP patients. METHODS: HUVEC were cultured in 3 different types of media with IgA1 from HSP patients, normal healthy children and simply medium (blank control). Serum IgA1 was purified by jacalin affinity chromatography. The rates of apoptosis in HUVEC incubated with IgA1 were determined by the TUNEL method and flow cytometry, respectively. The expression of bax/bcl-2 and p53 was detected with the methods of Real-time PCR and Westernblot, respectively. RESULT: The results showed that the apoptosis rate of HUVEC by IgA1 isolated from HSP patients was higher than that the normal controls (14.77±2.23% vs 9.97±1.48%) and blank controls (14.77±2.23% vs 2.25±0.77%) (P <0.01). Moreover the rate of HUVEC by IgA1 from normal healthy children was higher than the blank controls (9.97±1.48% vs 2.25±0.77%) (P <0.01). In addition, the bax and P53 expression were up-regulated and the Bcl-2 expression was down-regulated in HUVEC co-cultured with IgA1 isolated from HSP patients for 24 hours. CONCLUSIONS: These findings suggested that IgA1 from HSP patients could induce the apoptosis of HUVEC, which might be related to the vascular endothelial injury of HSP.

Health-related quality of life thresholds of clinical importance at diagnosis can predict longitudinal post-operative health functioning in colorectal cancer patients: A prospective multicentre observational study.

BACKGROUND: Health-related quality of life (HRQOL) is an increasingly important outcome in colorectal cancer (CRC) treatment. Established thresholds for clinical importance (TCI) permit an absolute interpretation of HRQOL scores but less emphasis has been placed on whether these can be used in a predictive manner. This study aimed to examine if patients' baseline HRQOL functioning scores, subgrouped based on TCI, would significantly predict HRQOL over time. METHODS: 211 CRC patients were prospectively followed up from diagnosis to 18 months after surgery. Patients were administered the EORTC Core Quality of Life Questionnaire (EORTC QLQ-C30) at each timepoint. Baseline demographic and clinical data were extracted from electronic medical records. RESULTS: Only the physical and emotional functioning scales of the EORTC QLQ-C30 were utilised with their respective TCIs (score of ≤83 for physical; ≤71 for emotional). Physical functioning was below-threshold for most patients at pre-discharge (81.77 %) and 1-month (56.48 %) before stabilising to baseline proportions by 6-month. For emotional functioning, 22.04 %-30.98 % of patients were below-threshold between baseline to 3-month, stabilising to approximately 14.00 % after 6-month. Baseline TCI subgrouping was significantly associated with change in HRQOL scores over time for both the physical (ß = 14.09, 95 % CI: 8.22, 19.97) and emotional (ß = 25.66, 95 % CI: 18.79, 32.53) functioning scales (p < 0.01). CONCLUSION: EORTC QLQ-C30 TCIs can be utilised not just to concretely identify clinically significant impairments in presenting CRC patients, but also as potential predictive tools towards more value-driven delivery of pre- and post-surgical supportive and allied healthcare.