Evaluating the effect of body mass index and 25-hydroxy-vitamin D level on basal cell carcinoma using Mendelian randomization.

Basal cell carcinoma (BCC) is the most common cancer with a rising incidence among white-skinned individuals. A number of epidemiological studies have suggested that obesity and serum 25-hydroxy-vitamin D (25(OH)D) levels may affect the arising of BCC. To address this, we selected 443 and 96 single nucleotide polymorphisms (SNPs) associated with body mass index (BMI) and serum level of 25(OH)D from large-scale genome-wide association studies (GWAS), respectively. The univariable and multivariable two-sample Mendelian randomization (MR) analyses were conducted with a series of sensitivity analyses to ensure the results were reliable and reproducible. The results of univariable two-sample MR analysis showed that higher BMI was related to lower risk for BCC (Odds ratio(OR) = 0.90; 95% confidence interval (CI),[0.81,0.99]; p = 0.02). In addition, this causal effect of BMI on BCC still remained (OR = 0.88; 95%CI,[- 0.22, - 0.03], p-value = 0.008) after adjusting for 25(OH)D level in the multivariable MR analysis. However, the results suggested that 25(OH)D level was not associated with BCC(OR = 1.02; 95%CI, [0.94,1.09], p-value = 0.67). In conclusion, similar to the conclusions of retrospective observational studies, the MR results indicate that high BMI is an independent protective factor for BCC. Meanwhile, vitamin D levels may not be causally associated with the risk of basal cell carcinoma and increasing vitamin D supplementation is unlikely to reduce the risk.

Effects of Melatonin Treatment on Perioperative Sleep Quality: A Systematic Review and Meta-Analysis with Trial Sequential Analysis of Randomized Controlled Trials.

Purpose: Perioperative sleep disorders have attracted much attention due to their high prevalence and severe harm, and the current treatment methods are insufficient. Some randomized controlled trials (RCTs) have produced controversial results on whether melatonin can improve perioperative sleep quality. This review aimed to evaluate the effects of melatonin treatment on perioperative sleep quality. Patients and Methods: A systematic search of six databases was performed to identify RCTs investigating melatonin and perioperative sleep. The outcomes analyzed were subjective sleep quality, sleep latency (SL), total sleep time (TST), sleep efficiency (SE), the behavior of awakenings and daily naps, and the incidence of poor sleep quality. RevMan 5.4 and Stata 16 software was used for the meta-analysis and sensitivity analysis, and trial sequential analysis was conducted using TSA 0.9.5.10 Beta software. This study was registered in PROSPERO (registration number: CRD42022311378). Results: 10 studies containing 725 participants were included. Melatonin improved postoperative subjective sleep quality (SMD: -0.30; 95% CI: [-0.47, -0.14]; P = 0.0004) but not preoperative sleep quality (MD: -2.76; 95% CI: [-10.44, 4.91]; P = 0.48). In the postoperative period, 6mg dose had the best efficacy (SMD: -0.31; 95% CI: [-0.57, -0.04]; P = 0.02). Melatonin increased postoperative TST (P = 0.02) and SE (P = 0.002) and decreased the incidence of postoperative poor sleep quality (P = 0.002) but had no effect on SL (P = 0.11), the number and duration of awakenings (P = 0.28; P=0.55), and the number and duration of daily naps (P = 0.26; P = 0.38). The trial sequential analysis showed that the accumulated Z value crossed both the traditional boundary value and the TSA boundary value, further confirming the stability of the result of the meta-analysis. Conclusion: Melatonin treatment can improve postoperative sleep quality. A 6mg daily dose of melatonin may have a better beneficial effect, which needs further exploration. This study supports the application of melatonin for improving postoperative sleep quality.

A two-step strategy for quality control of Xin-Yu-Tie-Pian, an ointment patch.

Xin-Yu-Tie-Pian, an ointment patch which is composed of Tetradium ruticarpum and Asarum sieboldii Miquel, can be used for curing recurrent oral ulcers owing to its good bioactivities. Currently, the lack of a method for its quality evaluation hinders the development and clinical application of Xin-Yu-Tie-Pian. Thus, it is necessary to perform research on quality control. The chromatographic fingerprint, as an identification method, and the simultaneous determination method for two bioactive constituents, evodiamine and rutecarpine, can be used to evaluate the quality of traditional medicine. In this study, a two-step strategy including fingerprint analysis for identification and a simultaneous determination method for two bioactive constituents was performed for Xin-Yu-Tie-Pian quality control. The fingerprint analysis was validated by stability, precision and repeatability tests and a similarity evaluation was performed with 10 selected characteristic fingerprint peaks of 10 batches of Xin-Yu-Tie-Pian patch. Meanwhile, the simultaneous determination method was evaluated by methodological experiments, including linearity, accuracy, repeatability, stability and feasibility. Finally, the results indicate that this two-step strategy, including HPLC fingerprint analysis and simultaneous determination method, can be successfully applied for the assessment of the quality and quantity of Xin-Yu-Tie-Pian.

Investigation of phytochemical composition and metabolite profiling in vivo of Beta vulgaris L.

RATIONALE: Beta vulgaris L. has attracted increasing attention because of its broad application. The root of B. vulgaris L. (beetroot) possesses many excellent biological properties such as antianemic, anti-inflammatory, antihypertensive, antioxidant, anticarcinogenic, antipyretic, antibacterial, detoxicant, and diuretic. The chemical constituents of beetroot play a major role in the research on beetroot application and development. At present, no systematic identification study that focuses on the chemical constituents of beetroot has been reported. METHODS: This study investigated a three-step strategy comprising phytochemical profiling, prototype profiling, and metabolism of its correlative metabolites in vivo using ultra-performance liquid chromatography tandem quadruple time-of-flight mass spectrometry (UPLC-QTOF-MS/MS). RESULTS: UPLC-QTOF-MS/MS technique proved to be a rapid, sensitive, and reliable method for monitoring the specific ingredients as well as the whole chemical constituents in beetroot. In sum, 95 phytochemical compounds, 51 prototype compounds, and 37 derived metabolites in vivo were found in beetroot. CONCLUSIONS: The main metabolic pathways were sulfonation, glucuronidation, methylation/sulfonation, and methylation. The present findings provided the phytochemical basis both in vitro and in vivo for future application.

New Determination Method of Two Bioactive Saponins in Lysimachia capillipes Hemsl. by Quantitative Analysis of Multi-Components by Single-Marker.

Capilliposide B (CPS-B) and Capilliposide C (CPS-C), as the key components in Lysimachia capillipes Hemsl., increasingly aroused the interest and research concern of many researchers due to the good bioactivities. Nowadays, the reference standards of CPS-B and CPS-C yield were very limited. Due to the deficit of reference standards, the determination could be difficult to carry out, and the quality control and evaluation would be restrained afterwards. To solve this urgent problem, a quantitative analysis of multi-components by single-marker (QAMS) method was proposed and established based on high-performance liquid-chromatography tandem evaporative light-scattering detector. In this QAMS method, the content of the two bioactive components could be calculated by buddlejasaponin IV, which is applied as an external standard and readily obtained. And the methodological experiments were evaluated and indicated accuracy, stability and feasibility of this QAMS method. Therefore, in this study, this built method would properly meet the requirement of determination of CPS-B, CPS-C and quality control of the L. capillipes Hemsl. plant.

Analysis of clinical prognosis in patients with non-hepatic hyperammonemia.

ABSTRACT: The aim of this study was to evaluate the association of non-hepatic hyperammonemia (NHH) with the prognosis of critically ill patients with NHH.According to the serum ammonia level, the patients with NHH (n = 498) were retrieved by us. The risk factors of the mortality with NHH patients were investigated by conducting univariate and multivariate logistic regression analyses. A nomogram to predict the risk of hospital mortality was constructed. Receiver operating characteristic curve (ROC) analysis was conducted to compare nomogram (ammonia into a prognostic model, P1) with the simplified acute physiology II (SAPSII) and quick sequential organ failure assessment (qSOFA).Five independent factors for the mortality in patients with NHH were identified, including age, platelets, bun, hemoglobin, and ammonia. Models P1 using ammonia showed good prediction power. The AUROC of P1 (AUROC, 0.755 [95% CI, 0.713-0.796]) was higher than that of qSOFA (AUROC, 0.500 [95% CI, 0.449-0.551]), and SAPS II (AUROC, 0.703[95% CI, 0.658-0.748]).Ammonia was an independent prognostic predictor of mortality for NHH patients. We developed a nomogram that can predict hospital mortality with patients. Nomogram had superior discriminative power to qSOFA and SAPS II, indicating that the nomogram may have clinical utility.

Molecular characterization and functional analysis of the hepcidin gene from roughskin sculpin (Trachidermus fasciatus).

Hepcidin is a kind of cysteine-rich antimicrobial peptide that plays a vital role in host innate immune activity and iron regulation. Here, we report the molecular characterization and functional analysis of a novel hamp1 hepcidin isoforms Tf-Hep from roughskin sculpin, Trachidermus fasciatus. A cDNA fragment of 988 bp with an ORF of 273 bp was obtained. The coding sequence encodes for a signal peptide of 24 amino acids coupled with a prodomain of 40 amino acids and a mature peptide of 26 amino acids. Tissue distribution analysis indicated that Tf-Hep was most abundant in the liver. It could be significantly induced post lipopolysaccharide (LPS) challenge and heavy metal exposure. The mature peptide was expressed as a 6.061 kDa fusion protein in Pichia pastoris GS115. The active purified recombinant protein (rTf-Hep) exhibited a wide spectrum of potent antimicrobial activity in vitro against 4 Gram-negative bacteria Escherichia coli, Vibrio Anguillarum, Klebsiella pneumoniae, and Pseudomonas aeruginosa and 4 Gram-positive bacteria Staphylococcus aureus, Bacillus subtilis, Bacillus thuringiensis, and Bacillus megaterium with minimum inhibitory concentrations (MICs) of 5-80 µg/ml (0.825-13.2 µM). It also displayed high affinity to polysaccharides on bacteria surface including LPS, lipoteichoic acid (LTA) and peptidoglycan (PGN). We further revealed that rTf-hep was capable of agglutinating 6 of the 8 bacteria. All these results suggest that rTf-hep may be both an antibacterial effector and a pattern recognition molecule in fish immune defense. The in vivo bacterial treatment results demonstrated that rTf-Hep could significantly improve the survival rate of fish infected with V. anguillarum. Taken together, these data indicate an important role for Tf-hep in the innate immunity of Trachidermus fasciatus and suggest its potential application in aquaculture for increasing fish resistance to disease.