Oncology patients undergoing cancer treatment and experiencing episodes of fever are known to be at increased risk for invasive bacterial infection, including bloodstream infection. This study aimed to identify the incidence of bacteremia along with the bloodstream isolates for immunocompromised oncology patients referred to the emergency department (ED) due to fever.

Oncology patients with fever were referred to the ED according to a protocol previously reported. Virtually all children had central venous access devices (CVAD) that underwent sterile access according to Hematology-Oncology (Hem-Onc) and ED protocol. Antibiotics were administered to all patients once CVAD were accessed and laboratory studies, including blood culture, were obtained. Data collected included patient demographic features, complete blood count profiles, proportions receiving antibiotics within 60 minutes of ED arrival and subsequent blood culture results.

Of 1,088 consecutively referred Hem-Onc patients, 439 were eligible for inclusion. The overall blood culture positive rate was 5.7%. Fifty-six percent of patients with positive blood cultures had an absolute neutrophil count greater than 500 µL at the time of ED presentation. Gram-positive organisms comprised 64% of isolates while gram-negative organisms accounted for 36% of the total isolates.

Immunocompromised oncology patients presenting to the ED with fever are susceptible to bloodstream infection caused by an array of gram-positive and gram-negative organisms. Bloodstream infection during episodes of fever includes many patients without severe neutropenia at presentation and with bloodstream isolates not typically associated with catheter-related bloodstream infection alone, highlighting the diversity and variability within this patient population.

Coptis teeta Wall. (C. teeta) is a herb that goes by the name “Mishmi Tita”, and holds significant value as a medicinal plant for treating various health conditions. This endangered plant, listed in the Red Data Book, is commonly found in India, Nepal, Bhutan and China. The present review aims to comprehensively summarize the traditional, pharmaceutical, and phytochemical aspects of C. teeta, providing a foundation for researchers to explore this endangered plant, and take bold steps to conserve, cultivate, and promote awareness among local people. A thorough literature search was conducted on PubMed, Google Scholar, Research Gate, SciFinder, and the ISI Web of Knowledge, using the following terms: “Coptis teeta”, “Coptis teeta Wall.”, “Mishmi tita”, “Rhizoma coptidis”, “Chinese medicine from Coptis teeta”, and “Traditional uses of Coptis teeta”. A comprehensive examination of 69 articles published between 1982 and 2023 was conducted to explore the properties and traditional applications of C. teeta. It was found that this plant and its active compounds exhibit a range of effects, such as fighting against microbes, alleviating diarrhoea, lowering blood pressure, regulating heart rhythm, reducing inflammation, improving mood, treating trachoma, managing diabetes, providing pain relief, and countering reactions. A total of 27 compounds were identified in different parts of this plant, according to the surveyed literature. These have been traditionally utilized to address ailments, including conditions, eye disorders, skin issues, gastrointestinal troubles like constipation and jaundice, and urinary disorders. Furthermore, these have shown potential in cancer treatment and mitigating inflammation. C. teeta boasts diverse traditional uses and promising pharmacological activities due to its rich chemical composition. Berberine is the main constituent, and various communities utilize it for various ailments. While endangered, C. teeta offers exciting medicinal potential, warranting further research and sustainable conservation efforts. Cultivating the plant and raising public awareness are crucial steps towards its preservation.

With the development of gene editing technology, its application in tumor diagnosis is becoming increasingly widespread. The CRISPR/Cas system is an important gene editing tool that can significantly improve the early detection rate and precision diagnosis level, enabling high-throughput and high-sensitivity detection of tumors. This article focuses on CRISPR/Cas system for detecting various tumor-related targets and elaborates on its applications in tumor diagnosis from five aspects: (1) detection of tumor-derived exosomes: by recognizing the surface proteins or nucleic acids of exosomes secreted by tumor cells into blood or other samples through adaptors, the CRISPR system is activated, achieving non-invasive liquid biopsy of tumors; (2) detection of circulating tumor DNA tumor cells disseminate DNA into the circulatory system to trigger nucleic acid reactions involving gene editing enzymes, enabling the monitoring of tumor dynamic states; (3) detection of circulating tumor cells (CTCs): by using aptamers to recognize surface proteins of tumor cells or directly detecting tumor-related nucleic acids, the integrated CRISPR system allows for the detection of circulating tumor cells even in trace amounts, achieving precise diagnosis; (4) detection of tumor markers: high sensitivity is achieved through the coupling of various tumor marker aptamers and gene editing systems; (5) detection and identification of tumor microenvironments: by activating gene editing enzyme activity through differential factors in the tumor tissue microenvironment and triggering nucleic acid reactions, the diagnosis and dynamic monitoring of tumors can be achieved. The progress and bottlenecks of the CRISPR/Cas system in tumor diagnosis in the future are also discussed.

The global burden of colorectal cancer (CRC) is a pressing concern, with a substantial impact on public health. Despite advancements in understanding the molecular mechanisms of CRC development, challenges remain in translating this knowledge into effective clinical interventions. Key genetic mutations, notably in the adenomatous polyposis coli (APC) and Kirsten rat sarcoma virus (KRAS) genes, are central to CRC initiation and progression. Current CRC treatments include surgery and chemotherapy, often combined with targeted agents. However, resistance and heterogeneity within CRC patients limit the effectiveness of these therapies. Promisingly, research has focused on targeting APC and KRAS mutations for therapy. Small molecules inhibiting the Wnt pathway and antibodies targeting specific components are under investigation. Targeting KRAS itself is challenging due to its conserved structure, but disrupting its membrane interactions and subcellular localization are potential therapeutic strategies. To address the limitations of single-drug therapy, combination approaches are gaining traction. Combination therapy not only minimizes off-target effects but also tackles drug resistance and diverse genetic alterations within tumors. The intricate interplay of mutations and pathways in CRC necessitates multifaceted therapeutic strategies. Although progress has been made in understanding CRC genetics and developing targeted therapies, there is still work to be done to translate these insights into effective clinical treatments for CRC patients. This review provides crucial information for novel combination treatments for CRC.

Prostate cancer (PC) is the second leading cause of death among American men, with most patients receiving androgen deprivation therapy and eventually developing resistance to treatment. The 5-year survival rate from 2015–2020 for men with distant disease was 33%, demonstrating the need for more optimal treatment regimens for patients with distant or metastatic PC. Pharmacogenomic (PGx) testing, a component of precision medicine, focuses on the way a patient’s genome affects drug metabolism. Combining PGx testing with current genetic testing provides an innovative and personalized approach to treating PC while both reducing adverse events and optimizing treatment dosages to fit the patient’s genetic make-up. This review paper describes how clinicians can use PGx testing in combination with genetic testing for PC patients.

High-grade endometrial stromal sarcoma (HGESS) is a rare sarcoma with aggressive biological behavior. Here we report a case of molecularly confirmed ZC3H7B-BCOR HGESS in extrauterine, with morphologic and immunohistochemical findings resembling a gastrointestinal stromal tumor. The patient, a 51-year-old woman, presented with extensive pelvic and abdominal masses. Histologically, the tumor displayed fascicles of spindle cells with myxoid stroma and abundant mitosis. Immunohistochemical staining revealed that the tumor cells were diffusely positive for cluster of differentiation 117 (CD117) and discovered on gastrointestinal stromal tumor 1 (DOG1). Gastrointestinal stromal tumor was initially diagnosed, and DNA sequencing was performed for targeted therapy. Unexpectedly, no mutations in KIT proto-oncogene, receptor tyrosine kinase (CKIT) or platelet-derived growth factor receptor, alpha polypeptide (PDGFRA) were identified, but amplification of murine double minute 2 (MDM2) and cyclin-dependent kinase 4 (CDK4) was found. Further, ZC3H7B-BCOR fusion was detected via RNA sequencing. Additional immunostaining showed that CD10 was diffusely positive, the estrogen receptor was negative, and the progesterone receptor was weakly positive. ZC3H7B-BCOR HGESS was definitively diagnosed. In conclusion, the coexpression of CD117 and DOG1 may present a potential diagnostic pitfall in the evaluation of pelvic/abdominal masses, which should be paid great attention.

Olaparib is a selective poly (ADP-ribose) polymerase inhibitor. However, its clinical application is hindered by low solubility and undesired pharmacokinetic profiles (e.g., relatively short circulation). Therefore, the present study aims to exploit polymeric micelles as a safe solubilizer and nanocarrier of olaparib, in order to improve its solubility and pharmacokinetics.

Poly (ε-caprolactone)-co-poly (benzyl 5-methyl-2-oxo-1,3-dioxane-5-carboxylate), i.e., benzyl-functionalized trimethylene carbonate)-b-poly (ethylene glycol) (P(CL-co-TMC-Bz)-PEG), was synthesized by ring-opening polymerization, and used to prepare the π-π-stacked polymeric micelles for olaparib encapsulation. A series of olaparib-loaded micelles with different polymer concentrations and wt% loadings were prepared using different methods to investigate the effect of formulation variables on the size of polymeric micelles and drug loadings. In addition, the in vitro release of olaparib from the micelles, and the cytotoxicity of micellar olaparib formulations on the SKOV3 tumor cell line were evaluated by UV spectrophotometry and CCK-8 assay, respectively. Finally, the blood circulation kinetics and side effects of the incorporated olaparib in the micelles and free olaparib were investigated in SD rats using ultra-high performance liquid chromatography analysis and H&E staining, respectively.

It was found that P(CL11-co-TMC-Bz5)-PEG micelles served as a safe and excellent solubilizer for olaparib, and that the solubilization capacity was easily tailored by adjusting the polymer concentration. In addition, when loaded in micelles, olaparib exhibited a sustained release behavior in vitro, and obvious cytotoxicity on SKOV3 cells. The in vivo studies revealed that olaparib incorporated in P(CL11-co-TMC-Bz5)-PEG polymeric micelles exhibited prolonged circulation (t1/2 = 2.00 hours), when compared to free olaparib (t1/2 ≤ 0.25 hours), and excellent safety. However, in terms of taking advantage of the EPR effect of the micelle delivery system to achieve the targeted olaparib delivery, the circulation time of olaparib in the micelles remained rather short.

Improvements, such as chemical crosslinking and drug conjugation, are required to improve the retention of olaparib-loaded polymeric micelles in blood circulation, and benefit from the use of micelles as a targeted delivery system.

Eurotium cristatum (E. cristatum), commonly known as “golden flower”, is the dominant strain in the microbial fermentation process of Fu brick tea. E. cristatum has favorable biological characteristics, including enzyme production, antimicrobial properties, immune regulation, antitumor properties, fat reduction capabilities, and weight loss benefits. With its probiotic characteristics, E. cristatum can be combined with different varieties of tea substrates to make a variety of fermented teas. More importantly, in the process of tea fermentation, E. cristatum can secrete a variety of extracellular enzymes, including some hydrolytic enzymes and oxidoreductases. They metabolize and transform various chemical components in tea through a series of reactions such as oxidation, degradation, and condensation, which significantly affect the quality of tea. In this review, by summarizing its basic functional characteristics as well as its application in fermented tea, an in-depth analysis of the key problems existing in the fermentation application of E. cristatum is described and some beneficial suggestions are presented in order to provide a rich theoretical basis for the development and utilization of E. cristatum to a greater extent.

China accounts for nearly half of liver cancer deaths globally. A better understanding of the current liver cancer mortality will be helpful to establishing priorities for intervention and to decreasing the disease burden of liver cancer. The study aimed to explore and predict the mortality burden of liver cancer in China.

Data were extracted from the Disease Surveillance Point system of the Chinese Center for Disease Control and Prevention from 2008 to 2020. Crude and age-standardized liver cancer mortality rates were reported by sex, urban or rural residence, and region. Trends in liver cancer mortality rates from 2008 to 2020 were estimated as average annual percentage change (AAPC). The changing trend of live cancer mortality in the future is also predicted.

In 2020, the crude mortality of liver cancer was 25.57/100,000, and males and people lived in rural areas had higher age-standardized liver cancer mortality rates than females and people lived in people in urban areas. Crude mortality and age-standardized mortality rates in southwest provinces (Guangxi, Sichuan, Tibet) and in a northeast province (Heilongjiang) were higher than that in other provinces, and age-specific mortality rates increased with age. From 2008 to 2020, liver cancer mortality rates decreased, but people under 50 years of age had a higher AAPC than those over 50 years of age, possibly because of the adoption of hepatitis B virus vaccination in newborns and children. Furthermore, the mortality of liver cancer in 2021–2030 is predicted to have a downward trend.

Liver cancer mortality rates declined in China from 2008 to 2020. Future interventions to control liver cancer mortality need to focus on people of male sex, older age, and living in rural areas or less developed provinces.

Obesity is a global health burden and is closely associated with severe chronic co-morbidities, which remain the leading causes of death. Significant progress has been made in the treatment of hypertension, diabetes, and hyperlipidemia over the last half-century. However, advancements in the management of obesity have been slow, with some medications exhibiting inadequate efficacy and dangerous side effects. Improved understanding of the gut-brain axis has inspired the pursuit of novel medications aiming to provide sustainable and safe weight loss. Current evidence-based practices for obesity management involve multi-modal approaches, including lifestyle modification, mechanical gastric restriction, modulation in the secretion of multiple gut hormones, alteration in the composition and secretion of bile acids, and alterations of the gut microbiome. Each physician is responsible for recognizing obesity as a disease and assisting patients in appropriate management based on strong evidence and a good safety profile, aligned with the patient’s goals. Through this review, we aim to inform the readers of recent approaches for managing obesity and comparing their beneficial effects and efficacy on obesity and its long-term co-morbidities.

The clinical introduction of hepcidin25 (Hep25) has led to a more detailed understanding of its relationship with ferroportin (FP) and divalent metal transporter1 in primary iron overload syndromes (PIOSs). In 2012, we proposed a classification of PIOSs based on the Hep25/FP system, which consists of prehepatic aceruloplasminemia, hepatic hemochromatosis (HC), and posthepatic FP disease (FP-D). However, in consideration of accumulated evidence on PIOSs, we aimed to renew the classification.

We reviewed the 2012 classification and retrospectively renewed it according to new information on PIOSs.

Iron-loading anemia was included in PIOSs as a prehepatic form because of the newly discovered erythroferrone-induced suppression of Hep25, and the state of traditional FP-D was remodeled as the BIOIRON proposal. The key molecules responsible for prehepatic PIOSs are low transferrin saturation in aceruloplasminemia and increased erythroferrone production by erythroblasts in iron-loading anemia. Hepatic PIOSs comprise four genotypes of HC, in each of which the synthesis of Hep25 is inappropriately reduced in the liver. Hepatic Hep25 synthesis is adequate in posthepatic PIOSs; however, two mutant FP molecules may resist Hep25 differently, resulting in SLC40A1-HC and FP-D, respectively. PIOS phenotypes are diagnosed using laboratory tests, including circulating Hep25, followed by suitable treatments. Direct sequencing of the candidate genes may be outsourced to gene centers when needed. Laboratory kits for the prevalent mutations, such as C282Y, may be the first choice for a genetic analysis of HC in Caucasians.

The revised classification may be useful worldwide.

Although multiple intricate and drawn-out in vivo investigations and complex in vitro assays are carried out as a part of the routine safety screening of drugs, medication failures arising out of safety-related issues continue to be an area of concern for pharmaceutical operations. Some of these failures may be explained by a lack of mathematical models to translate animal data into human data. Moreover, there may be differences in the sensitivity and drug disposition between humans and animals. Microphysiological systems may offer a way to more accurately represent these target tissues and a chance to better evaluate certain facets of human safety. As such, the ability of organs-on-chips to provide information at various development phases in drug discovery has sparked interest in recent years. This cutting-edge technology may aid in shedding light on the functioning of human organs and the pathophysiology of diseases. Also, they can be used to accurately predict the efficacy and safety of experimental medications in humans. Organs-on-chips know-how has been employed to successfully imitate specific nephron components including but not limited to the glomeruli, proximal as well as distal tubules, and collecting duct, all of which can be used in the testing of drugs for genetic kidney disorders. This review includes an overview of this technology along with some of its applications, challenges, and recommendations for the future.

Malignant rhabdoid tumor (MRT) is an aggressive malignancy driven by pathogenic variants of SMARCB1/INI1 or, rarely, SMARCA4/BRG1. The heterogeneity of MRT suggests that other genomic alterations might contribute to tumor behavior. This study aimed to evaluate somatic copy number alterations (SCNAs) and mutation landscapes in MRT before and after treatment.

With IRB approval, five patients underwent normal-tumor paired whole exome sequencing. Subsequently, the results were further analyzed using MuTect v1.1 for variant DNA and cn.mops for SCNA.

Our study revealed recurrent SCNAs harboring genes known to be involved in tumorigenesis. These include 2q37.3 gain (4/5, 80%, programmed death 1, TWIST2), 7q32.1 gain (3/5, 60%), 11q12.2 gain (3/5, 60%), 14q32.3 gain (4/5, 80%), 19p13.2 loss (SMARCA4, 4/5, 80%), 21q22.3 gain (3/5, 60%), and 22q11.1 loss (2/5, 40%, involving SMARCB1). Alterations more common in posttreatment MRTs included 11p15.4 gain (3/3, 100%) and 11q12.2 gain (2/3, 67%). No actionable pathogenic variants were observed. PD-1 immunohistochemistry correlated with 2q37.3 gain.

Our study revealed recurrent SCNAs in MRT. Genes within these regions are known to be associated with the tumor immune response and metastasis. This preliminary study demonstrated the potential value of SCNAs in furthering the understanding of this highly malignant tumor.

Chronic myeloid leukemia with a BCR::ABL1 b2a3 transcript is difficult to detect by conventional polymerase chain reaction (PCR). This can result in an incorrect diagnosis. We report a man with typical features of chronic myeloid leukemia but with a negative conventional PCR test for BCR::ABL1 in whom we identified a BCR::ABL1 fusion gene by fluorescence in situ hybridization and PCR with custom BCR and ABL1 primers.

Hepatopulmonary syndrome (HPS) is characterized by arterial oxygenation defects due to pulmonary vascular dilation in liver disease. To date, liver transplantation remains the only effective treatment for HPS. This study aimed to explore the preventative role of baicalein in HPS development.

Sixty male rats were randomly assigned to three groups: sham, common bile duct ligation (CBDL), and baicalein, receiving intraperitoneal injections of baicalein (40 mg·kg−1·d−1, diluted in saline) for 21 days. Survival rate, liver and kidney function, and bile acid metabolism levels were evaluated. Liver and lung angiogenesis and hepatic glycogen staining were assessed, and the expression of relevant proteins was evaluated by immunohistochemistry.

Baicalein improved survival rates and hypoxemia in rats post-CBDL, reducing angiogenic protein levels and enhancing glucose homeostasis. Compared to the untreated group, baicalein suppressed the expression of vascular endothelial growth factor, placental growth factors, matrix metalloprotease 9 and C-X-C motif chemokine 2, and it increased the expression of glycemic regulatory proteins, including dipeptidyl peptidase-4, sirtuin 1, peroxisome proliferator-activated receptor gamma co-activator 1α, and 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3.

Baicalein significantly improves hepatic function and hypoxia in HPS rats by attenuating pathological angiogenesis in the liver and lungs, showing promise as a treatment for HPS.

Honey is a viscous, hygroscopic liquid in nature. It has the ability to treat wounds, wrinkles, aging, and inflammation. This study’s objective was to create and characterize a nanoemulsion containing honey and evaluate its stability.

A pseudo-ternary phase diagram was retraced with several concentrations of the Smix, water, and liquid paraffin oil to formulate nanoemulsions containing honey. From the results of pre-formulation stability studies, formulation HNE-19, with a hydrophilic lipophilic balance value of 10, and a surfactant and oil ratio of 1:1, was selected as the most stable formulation. HNE-19 and base (B-19) were further subjected to thermodynamic studies of heating and cooling cycles and centrifugation. HNE-19 and its respective base B-19 were characterized for physical changes, droplet size analysis, pH measurements, turbidity, viscosity, and rheological parameters for a period of 90 days.

Results showed that the nanoemulsion containing honey was clear and milky white. There was no evidence of phase separation in HNE-19 and B-19 after the thermodynamic study. The droplet size of fresh HNE-19 was 91.07 nm with a zeta potential of −38.5 mV. After three months, the droplet size and zeta potential were 197.06 nm and −32.5 mV respectively. The observed pH was between 5.8 and 6.7, which corresponds with the pH of the skin. HNE-19 showed non-Newtonian flow and pseudo-plastic behaviour.

Stability and characterization showed that the nanoemulsion containing honey is a remarkable topical delivery formulation and could be evaluated comparatively with conventional topical applications against skin-related diseases like wounds, wrinkles, aging, and inflammations.

The global prevalence of nonalcoholic fatty liver disease (NAFLD) is 25%. This study aimed to explore differences in the gut microbial community and blood lipids between normal livers and those affected by NAFLD using 16S ribosomal deoxyribonucleic acid sequencing.

Gut microbiome profiles of 40 NAFLD and 20 non-NAFLD controls were analyzed. Information about four blood lipids and 13 other clinical features was collected. Patients were divided into three groups by ultrasound and FibroScan, those with a normal liver, mild FL (FL1), and moderate-to-severe FL (FL2). FL1 and FL2 patients were divided into two groups, those with either hyperlipidemia or non-hyperlipidemia based on their blood lipids. Potential keystone species within the groups were identified using univariate analysis and a specificity–occupancy plot. Significant difference in biochemical parameters ion NAFLD patients and healthy individuals were identified by detrended correspondence analysis and canonical correspondence analysis.

Decreased gut bacterial diversity was found in patients with NAFLD. Firmicutes/Bacteroidetes decreased as NAFLD progressed. Faecalibacterium and Ruminococcus 2 were the most representative fatty-related bacteria. Glutamate pyruvic transaminase, aspartate aminotransferase, and white blood cell count were selected as the most significant biochemical indexes. Calculation of areas under the curve identified two microbiomes combined with the three biochemical indexes that identified normal liver and FL2 very well but performed poorly in diagnosing FL1.

Faecalibacterium and Ruminococcus 2, combined with glutamate pyruvic transaminase, aspartate aminotransferase, and white blood cell count distinguished NAFLD. We speculate that regulating the health of gut microbiota may release NAFLD, in addition to providing new targets for clinicians to treat NAFLD.

Subnormal levels of liver enzymes, below the lower limit of normal on local laboratory reports, can be useful diagnostically. For instance, subnormal levels of aminotransferases can be observed in vitamin B6 deficiency and chronic kidney disease. Subnormal alkaline phosphatase levels may indicate the presence of hypophosphatasia, Wilson’s disease, deficiencies of divalent ions, or malnutrition. Subnormal levels of gamma glutamyl transferase may be seen in cases of acute intrahepatic cholestasis, the use of certain medications, and in bone disease. Finally, subnormal levels of 5′-nucleotidase have been reported in lead poisoning and nonspherocytic hemolytic anemia. The aim of this review is to bring attention to the fact that subnormal levels of these enzymes should not be ignored as they may indicate pathological conditions and provide a means of early diagnosis.