Risk Factors and Outcomes in Critically Ill Patients with Hematological Malignancies Complicated by Hospital-Acquired Infections.

Background and objectives: Patients admitted to the intensive care unit (ICU) have an increased risk of hospital-acquired infection (HAI). A diagnosis of cancer alone increases the risk of sepsis three-five-fold, which further increases the risk of nosocomial infection, subsequently deteriorates results, and leads to high mortality. In this study, we aimed to assess the mortality rate among hematologic oncologic patients with suspected infection who were subsequently admitted to the ICU and the predictive factors that are associated with high ICU mortality. Materials and Methods: This retrospective cohort study was conducted in the hematological oncology critical care unit of a tertiary care hospital between November 2017 and February 2021. We analyzed anonymized medical records of hospitalized hematologic oncologic patients who were suspected or proven to have infection in the hematology-oncology department and were subsequently transferred to the ICU. Results: Both shorter hospitalization and shorter ICU stay length were observed in survivors [9.2 (7.7-10.4)] vs. non-survivors [10 (9.1-12.9), p = 0.004]. Sepsis had the highest hazard ratio (7.38) among all other factors, as patients with sepsis had higher mortality rates (98% among ICU non-survivors and 57% among ICU survivors) than those who had febrile neutropenia. Conclusions: The overall ICU mortality in patients with hematologic malignancies was 66%. Sepsis had the highest hazard ratio among all other predictive factors, as patients with sepsis had higher mortality rates than those who had febrile neutropenia. Chronic hepatitis (HBV and HCV) was significantly associated with higher ICU mortality.

Network Pharmacology with Experimental Investigation of the Mechanisms of Rhizoma Polygonati against Prostate Cancer with Additional Herbzymatic Activity.

A combination therapy of Rhizoma Polygonati (RP) with goji (Lycium chinense) has earned a long history in the prescriptions to promote male health. However, the mechanisms at both molecular and nanoscale quantum levels are unclear. Here, we found that processed RP extract induces apoptosis and cell cycle arrest in cancer cells, thereby inhibiting prostate cancer cell proliferation enhanced by processed goji extract associated with an augment of the nanoscale herbzyme of phosphatase. For network pharmacology analysis, RP-induced PI3K-AKT pathways are essential for both benign prostatic hyperplasia and prostate cancer, and the RP/goji combination induces potent pathways which include androgen and estrogen response, kinase regulation, apoptosis, and prostate cancer singling. In addition, the experimental investigation showed that the prostate cancer cells are sensitive to RP extract for inhibiting colony formation. Finally, the natural compound baicalein found in RP ingredients showed a linked activity of top-ranked signaling targets of kinases including MAPK, AKT, and EGFR by the database of cMAP and HERB. Thus, both the nanozyme and ingredients might contribute to the RP in anti-prostate cancer which can be enhanced by goji extract. The proposed nanoscale RP extract might be of significance in developing novel anti-prostate cancer agents by combining goji compositions and targeted therapy compounds.

Genetic factors associated with obesity risks in a Kazakhstani population.

OBJECTIVES: There is limited published literature on the genetic risks of chronic inflammatory related disease (eg, obesity and cardiovascular disease) among the Central Asia population. The aim is to determine potential genetic loci as risk factors for obesity for the Kazakhstani population. SETTING: Kazakhstan. PARTICIPANTS: One hundred and sixty-three Kazakhstani nationals (ethnic groups: both Russians and Kazakhs) were recruited for the cross-sectional study. Linear regression models, adjusted for confounding factors, were used to examine the genetic associations of single nucleotide polymorphisms (SNPs) in 19 genetic loci with obesity (73 obese/overweight individuals and 90 controls). RESULTS: Overall, logistic regression analyses revealed genotypes C/T in CRP (rs1205), A/C in AGTR1 (rs5186), A/G in CBS (rs234706), G/G in FUT2 (rs602662), A/G in PAI-1 (rs1799889), G/T (rs1801131) and A/G (rs1801133) in MTHFR genes significantly decrease risk of overweight/obesity. After stratification for ethnicity, rs234706 was significantly associated with overweight/obesity in both Russians and Kazakhs, while rs1800871 was significant in Kazakhs only. CONCLUSIONS: This study revealed that variations in SNPs known to be associated with cardiovascular health can also contribute to the risks of developing obesity in the population of Kazakhstan.

Generation of particle assemblies mimicking enzymatic activity by processing of herbal food: the case of rhizoma polygonati and other natural ingredients in traditional Chinese medicine.

Processed herbs have been widely used in eastern and western medicine; however, the mechanism of their medicinal effects has not yet been revealed. It is commonly believed that a central role is played by chemically active molecules produced by the herbs' metabolism. In this work, processed rhizoma polygonati (RP) and other herbal foods are shown to exhibit intrinsic phosphatase-like (PL) activity bounded with the formation of nano-size flower-shaped assembly. Via quantum mechanical calculations, an enzymatic mechanism is proposed. The enzymatic activity may be induced by the interaction between the sugar molecules distributed on the surface of the nanoassemblies and the phosphatase substrate via either a hydroxyl group or the deprotonated hydroxyl group. Meanwhile, the investigation was further extended by processing some fresh herbs and herbal food through a similar protocol, wherein other enzymatic activities (such as protease, and amylase) were observed. The PL activity exhibited by the processed natural herbs was found to be able to effectively inhibit cancer cell growth via phosphatase signaling, possibly by crosstalk with kinase signaling or DNA damage by either directly binding or unwinding of DNA, as evidenced by high-resolution atomic-force microscopy (HR-AFM). In this work, the neologism herbzyme (herb + enzyme) is proposed. This study represents the first case of scientific literature introducing this new term. Besides the well-known pharmacological properties of the natural molecules contained in herbs and herbal food, there exists an enzymatic/co-enzymatic activity attributed to the nanosized assemblies.