WITHDRAWN: Construction and evaluation of risk prediction model for kidney injury in patients treated with PD-1 inhibitors

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The Effects of Self-Aromatherapy Massage on Pain and Sleep Quality in Patients with Rheumatoid Arthritis: A Randomized Controlled Trial.

BACKGROUND: Rheumatoid arthritis is the most common form of inflammatory arthritis and can lead to pain, joint deformity, and disability, resulting in poor sleep quality and lower quality of life. The efficacy of aromatherapy massage on pain levels and sleep quality among rheumatoid arthritis patients remains unclear. AIMS: To investigate the effects of aromatherapy on pain and sleep quality among rheumatoid arthritis patients. METHODS: This randomized controlled trial enrolled 102 patients with rheumatoid arthritis from one regional hospital in Taoyuan, Taiwan. Patients were randomly assigned to the intervention (n = 32), placebo (n = 36), or control groups (n = 34). The intervention and placebo groups underwent self-aromatherapy hand massage guided by a self-aromatherapy hand massage manual and video for 10 minutes 3 times a week for 3 weeks. The intervention group used 5% compound essential oils, the placebo group used sweet almond oil, and the control group had no intervention. Pain, sleep quality and sleepiness were measured by using the numerical rating scale for pain, the Pittsburgh Sleep Quality Index and the Epworth Sleepiness Scale at baseline and at 1, 2, and 3 weeks after the intervention. RESULTS: The intervention and placebo groups had significantly decreased sleep quality and sleepiness scores from baseline to 3 weeks after aromatherapy massage. Compared with the control group, the intervention group showed statistically significant improvement in the sleep quality scores in the first weeks after aromatherapy massage (B = -1.19, 95% confidence interval [CI]: -2.35, -0.02, P =.046), but no statistically significant differences were found in the changes in pain levels from baseline to the three time points. CONCLUSIONS: Aromatherapy massage is effective in improving sleep quality in rheumatoid arthritis patients. More studies are needed to evaluate the effects of aromatherapy hand massage on the pain levels of rheumatoid arthritis patients.

The systemic inflammation indexes predict all-cause mortality in peritoneal dialysis patients.

BACKGROUND: Chronic inflammation is a common complication in peritoneal dialysis (PD) patients. The aim of this study is to investigate the capacity of aggregate index of systemic inflammation (AISI), systemic immune-inflammation index (SII), and systemic inflammation response index (SIRI) to predict all-cause mortality in PD patients. METHODS: This was a single-center retrospective study. The optimal cutoff values were identified by receiver operating characteristic (ROC) curve analysis. The area under the curve (AUC) was calculated to evaluate the predictive ability of these indexes. The Kaplan-Meier curves and log-rank test were performed to estimate cumulative survival rate. Cox proportional hazards regression analyses were conducted to determine the independent prognostic power of inflammation indexes. RESULTS: A total of 369 incident PD patients were involved. During a median follow-up period of 32.83 months, 65 patients (24.2%) died. The ROC analysis indicated the largest value of AUC was obtained for SII (AUC = 0.644, 95% CI = 0.573-0.715, p < .001), followed in order by AISI (AUC = 0.617, 95% CI = 0.541-0.693, p = .003), and SIRI (AUC = 0.612, 95% CI = 0.535-0.688, p = .004). The Kaplan-Meier survival curves revealed significantly lower survival rate with higher AISI (p = .001), higher SSI (p = .001), and higher SIRI (p = .003). Even after adjustment for the confounding factors, higher AISI [hazard ratio (HR)=2.508, 95% confidence intervals (CI)=1.505-4.179, p < .001), SII (HR = 3.477, 95% CI = 1.785-6.775, p < .001), and SIRI (HR = 1.711, 95% CI = 1.012-2.895, p = .045) remained as independent predictors of all-cause mortality. CONCLUSIONS: The higher AISI, SII, and SIRI were independent indicators of all-cause mortality in PD patients. Furthermore, they could provide comparable predictive value and assist clinicians to ameliorate PD management.

New prenylated indole-benzodiazepine-2,5-diones with α-glucosidase inhibitory activities from the mangrove-derived Aspergillus spinosus.

Mangrove-derived fungi have been demonstrated to be promising source of structurally diverse and widely active secondary metabolites. During our search for new bioactive compounds, eight new indole-benzodiazepine-2,5-dione derivatives asperdinones A-H (1-8) and two known congeners (9 and 10) were isolated from the culture extracts of the mangrove-derived fungus Aspergillus spinosus WHUF0344 guided by one strain many compounds (OSMAC) and the heteronuclear 1H, 13C single-quantum coherence (HSQC) based small molecule accurate recognition technology (SMART) strategies. The structures and absolute configurations of the new compounds were elucidated by detailed spectroscopic analyze and electronic circular dichroism (ECD) calculations. The putative biosynthetic pathway of these compounds was proposed. Compounds 1-10 were evaluated for their antibacterial and α-glucosidase inhibitory activities. None of compounds showed antibacterial activity. Compounds 2-6 and 8 exhibited moderate inhibitory effects against α-glucosidase with IC50 values in the range of 24.65-312.25 µM. Besides, both 3 and 4 inhibited α-glucosidase variedly. Furthermore, the molecular docking study showed that compounds 2-4 were perfectly docking into the active sites of α-glucosidase. This study not only enriched the chemical diversity of secondary metabolites from the mangrove-derived fungi, but also provided potential hit compounds for further development of α-glucosidase inhibitors.

The prognostic value of monocyte-to-lymphocyte ratio in peritoneal dialysis patients.

BACKGROUND: The monocyte-to-lymphocyte ratio (MLR) is considered as a new inflammation marker. This study was aimed to investigate the prognostic value of MLR for all-cause mortality and new-onset cardiovascular disease (CVD) events in peritoneal dialysis (PD) patients. METHODS: This study enrolled patients receiving PD treatment for ≥ 3 months. Baseline characteristics were obtained within 1 week before PD catheterization. The receiver operating characteristic curve analysis was conducted to determine the optimal cut-off value of MLR. The Kaplan-Meier curve estimated the cumulative survival rate and new CVD free survival rate. Univariate and multivariate Cox regression models were preformed to investigate the association between MLR and clinical outcomes. RESULTS: A total of 369 PD patients participated in this study. During a median follow-up period of 32.83 months, 65 patients (24.2%) died, and 141 patients (52.4%) occurred new-onset CVD events. The Kaplan-Meier curve revealed that survival rate in high MLR group (MLR > 0.2168) was significantly lower than in low MLR group (P = 0.008). Patients in high MLR group were more likely to experience CVD events (P = 0.002). Even after adjustment of traditional risk factors, including age, diabetes mellitus, CVD history, smoking, hyperlipidemia, high MLR remained an independent predictor of all-cause mortality [hazard ration (HR) = 2.518, 95% confidence intervals (CI) = 1.020-6.214, P = 0.045] and new-onset CVD events (HR = 1.815, 95% CI = 1.157-2.849, P = 0.010). CONCLUSIONS: This study suggested that high MLR was significantly and independently associated with all-cause mortality and CVD events in PD patients. The MLR is an inexpensive and straightforward indicator to reflect systemic inflammation status and help clinicians improve PD management.

(R,S)-2-chlorophenoxyl pyrazolides as novel substrates for improving lipase-catalyzed hydrolytic resolution.

The best reaction condition of Candida antartica lipase B as biocatalyst, 3-(2-pyridyl)pyrazole as leaving azole, and water-saturated methyl t-butyl ether as reaction medium at 45°C were first selected for performing the hydrolytic resolution of (R,S)-2-(4-chlorophenoxyl) azolides (1-4). In comparison with the kinetic resolution of (R,S)-2-phenylpropionyl 3-(2-pyridyl)pyrazolide or (R,S)-α-methoxyphenylacetyl 3-(2-pyridyl)pyrazolide at the same reaction condition, excellent enantioselectivity with more than two order-of-magnitudes higher activity for each enantiomer was obtained. The resolution was then extended to other (R,S)-3-(2-pyridyl)pyrazolides (5-7) containing 2-chloro, 3-chloro, or 2,4-dichloro substituent, giving good (E > 48) to excellent (E > 100) enantioselectivity. The thermodynamic analysis for 1, 2, and 4-7 demonstrates profound effects of the acyl or leaving moiety on varying enthalpic and entropic contributions to the difference of Gibbs free energies. A thorough kinetic analysis further indicates that on the basis of 6, the excellent enantiomeric ratio for 4 and 7 is due to the higher reactivity of (S)-4 and lower reactivity of (R)-7, respectively.

Lipase-mediated direct in situ ring-opening polymerization of ε-caprolactone formed by a chemo-enzymatic method.

A novel method to synthesize poly(ε-caprolactone) (PCL) through a three-step, lipase-mediated chemo-enzymatic reaction from cyclohexanone using an immobilized lipase from Trichosporon laibacchii (T. laibacchii) CBS5791 was developed. The immobilized preparation with 1280 U· g-1 used here was obtained by a method of purification and in situ immobilization where the crude intracellular lipase (cell homogenate) was subjected to partial purification by an aqueous two-phase system (ATPS) consisting of 12% (w/w) polyethylene glycol (PEG) 4000 and 13% (w/w) potassium phosphate (K2HPO4) and then in situ immobilization directly on diatomite from the top PEG-rich phase of ATPS. In this multi-step process, the ε-caprolactone (ε-CL) produced by lipase-mediated one-pot two-step chemo-enzymatic oxidation of cyclohexanone was directly subjected to in situ ring-opening polymerization (ROP) started by adding highly hydrophobic solvents. It is necessary to note that ε-CL synthesis and its subsequent ROP were catalyzed by the same lipase. The impact of various reaction parameters, e.g., solvent, cyclohexanone: hydrogen peroxide molar ratio, hydrogen peroxide forms and reaction temperature were investigated. Toluene was selected as a preferred solvent due to supporting the highest molecular weight (Mn = 2168) and moderate ε-CL conversion (65.42%). Through the optimization of reaction conditions, PCL was produced with a Mn of 2283 at 50 °C for 24 h. These results reveal that this lipase-mediated direct ring-opening polymerization of in situ formed ε-CL is an alternative route to the conventional synthesis of PCL.

NRIP enhances HPV gene expression via interaction with either GR or E2.

We previously identified a gene, nuclear receptor-interaction protein (NRIP), which functions as a transcription cofactor in glucocorticoid receptor (GR) and human papillomavirus E2 (HPV E2)-driven gene expression. Here, we comprehensively evaluated the role of NRIP in HPV-16 gene expression. NRIP acts as a transcription cofactor to enhance GR-regulated HPV-16 gene expression in the presence of hormone. NRIP also can form complex with E2 that caused NRIP-induced HPV gene expression via E2-binding sites in a hormone-independent manner. Furthermore, NRIP can associate with GR and E2 to form tri-protein complex to activate HPV gene expression via GRE, not the E2-binding site, in a hormone-dependent manner. These results indicate that NRIP and GR are viral E2-binding proteins and that NRIP regulates HPV gene expression via GRE and/or E2 binding site in the HPV promoter in a hormone-dependent or independent manner, respectively.

Alendronate and raloxifene use related to cardiovascular diseases: differentiation by different dosing regimens of alendronate.

BACKGROUND: Bisphosphonates are the class of medication used most widely to treat osteoporosis. Since an article reported that patients who used zoledronic acid, a bisphosphonate, had a higher proportion of atrial fibrillation (AF) in 2007, the issue of bisphosphonates and AF has become a growing concern. Due to the widespread use of bisphosphonates, it is necessary to explore the relationship between bisphosphonates and AF and other cardiovascular diseases. OBJECTIVE: We aimed to investigate the risk of AF, stroke, or acute myocardial infarction (AMI) associated with the use of the bisphosphonates alendronate and raloxifene in patients with osteoporosis. We also focused our analysis on the impact of different dosing regimens of alendronate. METHODS: The National Health Insurance Research Database was used to conduct an 8-year, population-based, retrospective cohort study. The study population comprised women who first took alendronate or raloxifene between 2002 and 2006 and who had a history of osteoporosis and vertebral or spinal fracture. Follow-up was conducted for every patient until the first diagnosis of AF, stroke, or AMI or until the end of the 1-year follow-up period. The Cox proportional hazards model was used to evaluate the association between the risk of cardiovascular disease and the prescription of alendronate or raloxifene. RESULTS: We identified 9609 women who had been prescribed either alendronate (n = 6949) or raloxifene (n = 2660). The patients treated with alendronate were at a lower risk of AF, stroke, or AMI compared with the raloxifene group (AF: hazard ratio [HR] = 0.60 [95% CI, 0.42-0.85]; stroke: HR = 0.47 [95% CI, 0.39-0.57]; AMI: HR = 0.51 [95% CI, 0.36-0.72]). However, when analyzing the groups by different alendronate dosing regimens, those patients who received alendronate 10 mg had a significantly higher risk of AF and stroke compared with patients who received raloxifene (AF: HR = 1.66 [95% CI, 1.12-2.46]; stroke: HR = 1.56 [95% CI, 1.23-1.98]). The alendronate 70-mg group demonstrated a lower risk of cardiovascular disease, be it AF, stroke, or AMI (AF: HR = 0.28 [95% CI, 0.18-0.43]; stroke: HR = 0.23 [95% CI, 0.18-0.30]; AMI: HR = 0.28 [95% CI, 0.18-0.41]). When we assigned alendronate 10 mg as the reference group, the alendronate 70 mg group had a lower risk of 3 cardiovascular diseases (AF: HR = 0.17 [95% CI, 0.10-0.27]; stroke: HR = 0.16 [95% CI, 0.12-0.22]; AMI: HR = 0.21 [95% CI, 0.13-0.35]). CONCLUSIONS: Alendronate 10 mg was associated with a higher risk of cardiovascular disease than alendronate 70 mg. Further studies are required to investigate this relationship.

Predicting melting temperature directly from protein sequences.

Proteins of both hyperthermophilic and mesophilic microorganisms generally constitute from the same 20 amino acids; however, the extent of thermal tolerance of any given protein is an inherent property of its amino acid sequence. The present study is the first to report a rapid method for predicting Tm (melting temperature), the temperature at which 50% of the protein is unfolded, directly from protein sequences (the Tm Index program is available at http://tm.life.nthu.edu.tw/). We examined 75 complete microbial genomes using the Tm Index, and the analysis clearly differentiated hyperthermophilic from mesophilic microorganisms on this global genomic basis. These results are consistent with the previous hypothesis that hyperthermophiles express a greater number of high Tm proteins compared with mesophiles. The Tm Index will be valuable for modifying existing proteins (enzymes, protein drugs and vaccines) or designing novel proteins having a desired melting temperature.