Multiomics Analysis of Interleukin-21 as a Potential Immunologic and Biomarker in Hepatocellular Carcinoma.

Interleukin-21 (IL-21) is an important antitumor cytokine that contributes to the proliferation and differentiation of CD8+ T cells. It has been proven to enhance the response to immune checkpoint inhibitors (ICIs) in various solid tumors. However, its role in hepatocellular carcinoma (HCC) has not yet been clarified. In this research, we aimed to investigate the antitumor effect of IL-21 in HCC and its effect on ICI treatment. Through transcriptome sequencing analysis and immunohistochemistry validation, we found that patients with high IL-21 expression had a better prognosis. HCCs with high expression of IL-21 had higher infiltration of CD8+ T cells, increased expression of immune checkpoints, and an improved response to ICI treatment. In conclusion, IL-21 can enhance the efficacy of ICI treatment and improve the prognosis of patients by promoting the infiltration of CD8+ T cells and the expression of immune checkpoint-related genes.

Chemical Composition and Phytotoxic Activity of Mentha vagans Boriss. Essential Oil.

This study explored the composition of essential oil (EO) and the first phytotoxic screening of EO obtained from the stems and leaves of Mentha vagans Boriss (MVEO) via hydro-distillation technique. The EO ingredients were detected through Gas Chromatography-Mass Spectrometry (GC-MS). GC-MS analysis revealed that MVEO contained 49 constituents, constituting 93.95 % of the total oil. Among MVEO constituents, dihydrocarvone was observed as the dominant constituent (24.14%), followed by D-carvone (16.28%) and piperitone (18.14%). The phytotoxic effects of MVEO and its dominant compounds were examined against Amaranthus retroflexus, Lolium perenne, and Poa annua. Significant inhibition was observed by MVEO in comparison with the major constituents and their mixture, suppressing the seedling growth of tested species at the lowest dosage (0.01 mg/mL); in general, seedling growth of all tested species was markedly inhibited when applied concentration of the EO and its constituents reached 0.05 mg/mL. Our results also indicated that constituents other than the dominant compounds of MVEO possessed considerable phytotoxic effects because the EO's activity was stronger than its major constituents and their mixture. Thus, additional studies are required to investigate MVEO and its constituents and commercialize them as environment-friendly bio-herbicides.

Machine Learning Model Based on the Neutrophil-to-Eosinophil Ratio Predicts the Recurrence of Hepatocellular Carcinoma After Surgery.

Background: Circulating eosinophils are associated with tumor development. An eosinophil-related index, the neutrophil to eosinophil ratio (NER), can be used to predict the prognosis of patients with tumors. However, there is still a lack of efficient prognostic biomarkers for HCC. In this study, we aimed to investigate the predictive value of the NER and develop an optimal machine learning model for the recurrence of HCC patients. Patients and methods: A retrospective collection of 562 patients who underwent hepatectomy with a pathologic diagnosis of HCC was performed. The relationship between NER and progression-free survival (PFS) was investigated. We developed a new machine learning framework with 10 machine learning algorithms and their 101 combinations to select the best model for predicting recurrence after hepatectomy. The performance of the model was assessed by the area under the curve (AUC) of characteristics and calibration curves, and clinical utility was evaluated by decision curve analysis (DCA). Results: Kaplan‒Meier curves showed that the PFS in the low NER group was significantly better than that in the high NER group. Multivariate Cox regression analysis showed that NER was an independent risk factor for recurrence after surgery. The random survival forests (RSF) model was selected as the best model that had good predictive efficacy and outperformed the TNM, BCLC, and CNLC staging systems. Conclusion: The NER has good predictive value for postoperative recurrence in patients with hepatocellular carcinoma. Machine learning model based on NER can be used for accurate predictions.

Preoperative prediction model for non-neoplastic and benign neoplastic polyps of the gallbladder.

BACKGROUND: Gallbladder adenoma represents a precancerous lesion of gallbladder cancer. However, distinguishing it from cholesteryl polyps of the gallbladder before surgery is challenging. Thus, we aimed to comprehensively explore various risk factors contributing to the formation of gallbladder adenoma to facilitate an informed diagnosis and treatment by clinicians. METHODS: We conducted a retrospective analysis of patients who had undergone cholecystectomy at the Affiliated Hospital of Qingdao University between January 2015 and December 2022. Following postoperative pathological examination, patients were categorized into cholesterol polyp and adenoma groups. We analyzed their baseline characteristics, ultrasound imaging variables, and biochemical data using logistic, lasso, and stepwise regression. Subsequently, we constructed a preoperative prediction model based on the independent risk factors. RESULTS: Regression analysis of 520 gallbladder polyps and 288 gallbladder adenomas in the model group revealed that age, gallbladder wall thickness, polyp size, echogenicity, pedunculation, and adenosine deaminase (ADA) levels were independent predictors of gallbladder adenoma, all with P < 0.05. Using these indicators, we established a regression equation: Logistic (P) = -5.615 + 0.018 ∗ age - 4.64 ∗ gallbladder wall thickness + 1.811 ∗ polyp size + 2.855 ∗ polyp echo + 0.97∗ pedunculation + 0.092 ∗ ADA. The resulting area under the curve (AUC) value was 0.894 (95 % CI: 0.872-0.917, P < 0.01), with a sensitivity of 89.20 %, specificity of 79.40 %, and overall accuracy of 84.41 % for adenoma detection. CONCLUSION: Age, polyp size, gallbladder wall thickness, polyp echogenicity, pedunculation, and ADA levels emerge as independent risk factors for gallbladder adenoma.

Circulating the HLA-DR+ T Cell Ratio Is a Prognostic Factor for Recurrence of Patients with Hepatocellular Carcinoma after Curative Surgery.

Background: HLA-DR+ T cell, accounting for 1.2%-5.8% of peripheral lymphocyte, is a type of activated T lymphocyte. This retrospective study aimed to evaluate the prognostic value of HLA-DR+ T cell for progression-free survival (PFS) and overall survival (OS) in hepatocellular carcinoma (HCC) patients after curative surgery. Patients and Methods. Clinicopathological data of 192 patients who underwent curative resection for hepatocellular carcinoma in the affiliated hospital of Qingdao University between January 2013 and December 2021 were collected and analyzed. Statistical tests used in this study were the chi-square test and Fisher's exact test. The prognostic value of the HLA-DR+ T cell ratio was analyzed using univariate and multivariate Cox regression analyses. The Kaplan-Meier curves were drawn by the R programming language. Results: HCC patients were divided into high (≥5.8%) and low (<5.8%) HLADR+ T cell ratio groups. Cox regression analysis indicated that a high HLA-DR+ T cell ratio was positively related to the PFS in HCC patients (P=0.003) and AFP-positive (≥20 ng/ml) HCC patients (P=0.020). HCC patients and AFP-positive HCC patients in the high HLA-DR+ T cell ratio group were prone to have a higher T cell ratio, a higher CD8+T cell ratio, and a lower B cell ratio than the low HLA-DR+ T cell ratio group. However, the HLA-DR+ T cell ratio was not a statistically significant predictor for OS in HCC patients (P=0.57) as well as PFS (P=0.088) and OS (P=0.63) in AFP-negative HCC patients. Conclusions: This study confirmed that the HLA-DR+ T cell ratio was a significant predictor of PFS in HCC patients and AFP-positive HCC patients after curative surgery. This association may have guiding significance for the follow-up work of HCC patients after surgery.

Polyester materials for mRNA delivery.

Messenger RNA (mRNA) has recently made important progress in clinical implementation, offering a promising therapeutic option for infectious disease and cancer. However, the nature of mRNA molecules rendered them poorly bioavailable and unstable in vivo, impeding their further clinical application. Therefore, safe and efficient delivery of mRNA therapeutics to the target site is crucial for their successful translation into the clinical setting. Various vectors have been explored for mRNA delivery. Among them, polyesters and their analogs, a family of biodegradable polymers, have exhibited great potential for mRNA delivery. In this short review, the authors briefly introduce mRNA therapeutics, their therapeutic applications and delivery challenges. The authors then presented the typical examples of polyester materials for mRNA delivery to highlight the current progress and discuss the challenges for the rational design of polyester based mRNA delivery vectors. The authors hope to provide a new insight for the design of biodegradable vectors for nucleic acids delivery, thereby promoting their further clinic translation.

Hyperacmosin R, a New Decarbonyl Prenylphloroglucinol with Unusual Spiroketal Subunit from Hypericum acmosepalum.

Two previously undescribed polycyclic polyprenylated acylphloroglucinols, hyperacmosins R-S (1-2), were obtained from the aerial parts of Hypericum acmosepalum. Their structures were elucidated by extensive spectroscopic analysis and electronic circular dichroism calculation (ECD). Compound 1 featured an unprecedented 5,8-spiroketal subunit as well as the loss of C-2' carbonyl in the phloroglucinol ring. In addition, compounds 1 and 4 showed weak hepatoprotective activity against paracetamol-induced HepG2 cell damage at 10 µm. The plausible biosynthetic pathway of 1 was proposed via a retro-Clasisen reaction and decarboxylation.

Polycyclic polyprenylated acylphloroglucinols from Hypericum beanii and their hepatoprotective activity.

Twenty-seven polycyclic polyprenylated acylphloroglucinols (PPAPs) with diverse skeletons, including seven previously undescribed ones (hyperbeanins A-G), were isolated from the aerial parts of Hypericum beanii. Their structures were established by comprehensive analysis of NMR, HRESIMS, and experimental electronic circular dichroism (ECD) spectra. Hyperbeanin A was a monocyclic polyprenylated acylphloroglucinols (MPAPs) with an unusual spiro-fused cyclopropane ring. Four of the isolated compounds showed obvious hepatoprotective activity against paracetamol-induced HepG2 cell damage at 10 µM. The present results suggested that these compounds would be potential hepatoprotective agents. In addition, the plausible biogenetic pathways of hyperbeanins A-G were proposed, which gave an insight for future biomimetic synthesis of them.

A Review of the Current State of Hospice Care in China.

PURPOSE OF REVIEW: This review was undertaken to analyze the main reasons behind the limited development of hospice care in China, and to put forward some suggestions. RECENT FINDINGS: Although the Chinese government has increased its support for hospice care in recent years, however, owing to the lack of education around hospice care and the heavy influence of the traditional Chinese Confucian concept of "filial piety," many individuals resist hospice care. Moreover, due to impaired patient rights, inadequate composition of hospice care teams, unbalanced geographical distribution, and limited service range, the development of hospice care in China is hindered. Hospice care education and continued training should be popularized and the government should strengthen the legal structure of the medical system to protect the rights of patients, families, and medical staff to promoting social support for hospice care. Through graded diagnosis and referral systems in medical institutions to integrate medical resources and expand the range of hospice care services.

Design, Synthesis, and Anticancer Activity of Novel Trimethoxyphenyl-Derived Chalcone-Benzimidazolium Salts.

A series of novel trimethoxyphenyl-derived chalcone-benzimidazolium salts were synthesized. The biological properties of the compounds were screened in vitro against five different human tumor cell lines. The results suggest that the 5,6-dimethyl-benzimidazole or 2-methyl-benzimidazole ring as well as the 2-naphthylmethyl, 4-methylbenzyl, or 2-naphthylacyl substituent at position-3 of the benzimidazole ring was important to the cytotoxic activity. Notably, (E)-5,6-dimethyl-3-(naphthalen-2-ylmethyl)-1-(3-(4-(3-(3,4,5-trimethoxyphenyl)acryloyl)phenoxy)propyl)-1H-benzo[d]imidazol-3-ium bromide (7f) was more selective to HL-60, MCF-7, and SW-480 cell lines with IC50 values 8.0-, 11.1-, and 5.8-fold lower than DDP. Studies of the antitumor mechanism of action showed that compound 7f could induce cell-cycle G1 phase arrest and apoptosis in SMMC-7721 cells.

Analysis and correction of stray thermal radiation in infrared optical systems including an experimental case study.

In infrared systems, the stray radiation from optical elements and mechanical structures is an important factor affecting quantitative measurements because the irradiance on detectors due to stray radiation depends on the operating temperature of the optical system. Without correcting for this effect, the accuracy of quantitative measurements made with such systems is degraded. To better understand this phenomenon, we derive herein a mathematical model that describes stray radiation as a function of temperature and use the model to quantitatively analyze the stray radiation of an infrared system at different operating temperatures. To test the theory, we use it to calculate the stray radiation from an experimental infrared system comprising a Cassegrain reflector in the first stage and a transmission mirror in the second stage. The maximum relative error between theory and experiment was 8.72%. At the same time, a corrective measure of stray radiation is provided to account for the effect of stray radiation on quantitative measurements. The relative error of quantitative measurements decreases from 2.16% to 0.31%. The measurement accuracy of the infrared system has been improved effectively.

Risk Factors for Cardiovascular Disease and Their Clustering among Adults in Jilin (China).

BACKGROUND: Clustering of cardiovascular disease (CVD) risk factors constitutes a major public health challenge. Although a number of researchers have investigated the CVD risk factor clusters in China, little is known about the related prevalence and clustering associated with demographics in Jilin Province in China; this study aims to reveal that relationship. METHODS: A cross-sectional survey based on a sample of 16,834 adults aged 18 to 79 years was conducted in Jilin in 2012. The prevalence and clustering of CVD risk factors were analysed through complex weighted computation. Quantitative variables were compared by the t test, and categorical variables were compared by the Rao-Scott-χ² test. Finally, multivariable logistic regression analysis was used to evaluate the CVD risk factor clusters associated with demographics. RESULTS: The prevalences of hypertension, diabetes, dyslipidemia, overweight and smoking were 37.3%, 8.2%, 36.8%, 47.3%, and 31.0%, respectively, and these risk factors were associated with gender, education level, age, occupation and family income (p < 0.05). Overall, compared with females, the adjusted ORs of ≥1, ≥2 and ≥3 risk factors clusters in males were 3.70 (95%CI 3.26 to 4.20), 4.66 (95%CI 4.09 to 5.31), and 5.76 (95%CI 5.01 to 6.63), respectively. In particular, the adjusted ORs of ≥1, ≥2 and ≥3 risk factors increased with age. CONCLUSIONS: CVD risk factor clusters are common among adults in northeast China, and they constitute a major public health challenge. More effective attention and interventions should be directed toward the elderly and toward persons with lower incomes and low levels of education.

[Risk factors for cardiovascular disease and their clustering among middle aged and old people in Jilin province].

OBJECTIVE: To understand the risk factors for cardiovascular disease (CVD) and their clustering among middle aged and old people in Jilin province and provide evidence for the development of effective intervention measures. METHODS: A total of 13 914 people aged 35-79 years were selected from 32 counties (district) in 9 prefectures (municipality) of Jilin province through multi-stage stratified cluster sampling to conduct a face to face questionnaire survey and health examination. Complex weighted computation was conducted to analyze the survey results. RESULTS: The prevalence of hypertension, diabetes, dyslipidemia, smoking and overweight were 41.3%, 11.5%, 42.8%, 31.5% and 53.5%, respectively. Only 16.2% of the subjects surveyed were free of the 5 risk factors. ≥ 1 risk factor and ≥ 3 risk factors were found to clustering in 83.8% and 29.9% of the middle aged and old people. Compared with females, the odds ratios of ≥ 1, ≥ 2 and ≥ 3 risk factors clustering in males were 3.18, 4.28 and 5.58 times higher, respectively. Compared with urban residents, the odds ratios of ≥ 1, ≥ 2 risk factors clustering in rural residents were 1.22 and 1.20 times higher. In addition, the odds ratios of ≥ 1, ≥ 2 and ≥ 3 risk factors clustering increased with age (all P < 0.001). CONCLUSION: High prevalence of major cardiovascular disease risk factors and their clustering were found in middle aged and old people in Jilin province. More attention and intervention should be given to the old males in rural areas.

The role of Pygopus 2 in rat glioma cell growth.

Glioma is a common malignant tumor of the human neural system, and Wnt signaling activation is closely connected with glioma malignancy. Pygopus 2 (Pygo2) was recently discovered as a component of the Wnt signaling pathway regulating ß-catenin/Tcf dependent transcription. However, the role of Pygo2 in glioma cells has not yet been defined. In the current study, we investigated the role of Pygo2 in rat glioma C6 cells for the first time. Our results showed that over-expression of Pygo2 promoted cell proliferation as well as enhanced cell cycle progression from G1 to S phase associated with an increase in the expression of the Wnt target gene cyclin D1. In contrast, knockdown of Pygo2 suppressed cell proliferation with cell cycle block from G1 to S phase and down-regulation of cyclin D1. In addition, the expression of Pygo2 and cyclin D1 in 67 glioma tissue samples was quantified by real-time reverse transcription polymerase chain reaction (RT-PCR) and immunochemistry. The data indicated that tumor grade was significantly associated with over-expression of Pygo2 and cyclin D1. We conclude that Pygo2 is highly expressed in and promotes the growth of glioma cells by an increase in the expression of cyclin D1 to improve G1/S transition.

Plasma synthesis of carbon magnetic nanoparticles and immobilization of doxorubicin for targeted drug delivery.

Using dense medium plasma technology, carbon magnetic nanoparticles (CMNP) were synthesized at room temperature and atmospheric pressure. Based on results from X-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy and scanning electron microscopy, we conclude that these nanoparticles are composed of spherical particles, 40-50 nm in diameter, with iron/iron oxide particles dispersed in a carbon-based host-structure. Thermal gravimetry/differential thermal gravimetry analysis shows these nanoparticles are stable to temperatures as high as 600 degrees C. The synthesized CMNP were treated by argon-plasma, aminated with ethylene diamine and subsequently activated by generating aldehyde groups on them. Free doxorubicin (DOX) molecules were then immobilized onto the surfaces of activated CMNP particles to form CMNP-DOX conjugates. The corresponding loading efficiency was determined. The in vitro antiproliferative activity of immobilized doxorubicin in the conjugates was demonstrated in tumor cell cytotoxicity assays. It is suggested that this CMNP-DOX system can be used for targeted drug-delivery systems.