Nanosilica-Anchored Polycaprolactone/Chitosan Nanofibrous Bioscaffold to Boost Osteogenesis for Bone Tissue Engineering.

The strategy of incorporating bioactive inorganic nanomaterials without side effects as osteoinductive supplements is promising for bone regeneration. In this work, a novel biomass nanofibrous scaffold synthesized by electrospinning silica (SiO2) nanoparticles into polycaprolactone/chitosan (PCL/CS) nanofibers was reported for bone tissue engineering. The nanosilica-anchored PCL/CS nanofibrous bioscaffold (PCL/CS/SiO2) exhibited an interlinked continuous fibers framework with SiO2 nanoparticles embedded in the fibers. Compact bone-derived cells (CBDCs), the stem cells derived from the bone cortex of the mouse, were seeded to the nanofibrous bioscaffolds. Scanning electron microscopy and cell counting were used to observe the cell adhesion. The Counting Kit-8 (CCK-8) assay was used. Alkaline phosphatase (ALP), Alizarin red staining, real-time Polymerase Chain Reaction and Western blot tests were performed to confirm the osteogenesis of the CBDCs on the bioscaffolds. The research results demonstrated that the mechanical property of the PCL together with the antibacterial and hydrophilic properties of the CS are conducive to promoting cell adhesion, growth, migration, proliferation and differentiation. SiO2 nanoparticles, serving as bone induction factors, effectively promote the osteoblast differentiation and bone regeneration. This novel SiO2-anchored nanofibrous bioscaffold with superior bone induction activity provides a better way for bone tissue regeneration.

[A multicenter epidemiological investigation of brain injury in hospitalized preterm infants in Anhui, China].

OBJECTIVE: To investigate the risk factors for brain injury in preterm infants by a multicenter epidemiological investigation of brain injury in hospitalized preterm infants in Anhui, China. METHODS: Preterm infants who were hospitalized in the department of neonatology in 9 hospitals of Anhui Neonatal Collaboration Network between January 2016 and January 2017 were enrolled as subjects. The data of maternal pregnancy and clinical data of preterm infants were collected, and the logistic regression model was used to analyze the risk factors for brain injury in preterm infants. RESULTS: A total of 3 378 preterm infants were enrolled. Of the 3 378 preterm infants, 798 (23.56%) had periventricular-intraventricular hemorrhage (PVH-IVH), and 88 (2.60%) had periventricular leukomalacia (PVL). Intrauterine distress, anemia, hypoglycemia and necrotizing enterocolitis (NEC) were risk factors for PVH-IVH (OR=1.310, 1.591, 1.835, and 3.310 respectively; P<0.05), while a higher gestational age was a protective factor against PVH-IVH (OR=0.671, P<0.05). PVH-IVH, NEC and mechanical ventilation were risk factors for PVL (OR=4.017, 3.018, and 2.166 respectively; P<0.05), and female sex and use of pulmonary surfactant were protective factors against PVL (OR=0.514 and 0.418 respectively; P<0.05). CONCLUSIONS: Asphyxia/anoxia, infection/inflammation, mechanical ventilation, anemia and hypoglycemia may increase the risk of brain injury in preterm infants.

Mixing Assisted "Hot Spots" Occupying SERS Strategy for Highly Sensitive In Situ Study.

To solve the problem that analyte molecules cannot easily enter "hot spots" on a conventional solid SERS substrate, we developed a mixing-assisted "hot spots" occupying (MAHSO) SERS strategy to improve utilization of "hot spots". Compared with the conventional substrate, the MAHSO substrate enhances the sensitivity of SERS measurement by thousands of times. The MAHSO substrate possesses excellent properties of high enhancement, high uniformity, and long-term stability because the MAHSO substrate is integrated inside an ultrafast microfluidic mixer. The mixer makes analytes and metal colloid homogeneously mixed, and analytes are naturally located in "hot spots", the gaps between adjacent NPs, during the process that NPs deposit on the channel wall. As a multi-inlet device, the MAHSO chip offers a convenient in situ method to study environmental effects on analytes or molecular interactions by flexibly regulating fluid in microchannels and monitoring responses of analytes by SERS spectra. Because all experiments are conducted in aqueous environments, which is similar to the physiological conditions, the MAHSO chip is especially suitable to be applied to study biomolecules. Using this strategy, different conformational changes of the wild type and mutant G150D of protein PMP22-TM4 depending on environmental pH have been observed in situ and analyzed. As a lab-on-a-chip (LoC) device, the MAHSO SERS chip will benefit the field of molecular dynamics, as well as molecule-molecule or molecule-surface interactions in the future.

Respiratory syncytial virus infection up-regulates TLR7 expression by inducing oxidative stress via the Nrf2/ARE pathway in A549 cells.

In order to better understand the early pathways of the pathogenesis of, and immune response to, RSV, herein, we explored the relationship between TLR7 expression and oxidative stress induction following RSV infection in A549 cells. We studied the intervening effects of the Nrf2/ARE pathway agonist butylated hydroxyanisole (BHA) and inhibitor trigonelline (TRI) on TLR7 modulation or oxidative stress induction. For comparison purposes, we set up seven treatment groups in this study, including RSV-treated cells, BHA + RSV-treated cells, TRI + RSV-treated cells, normal cell controls, inactivated RSV controls, BHA controls and TRI controls. We measured changes in TLR7, IL-6, TNF-α mRNA using RT-PCR and IL-6, TNF-α and IL-1ß protein using ELISA as well as TLR7, Nrf2 and HO-1 protein using Western blot in A549 cells from the different treatment groups. We also assessed changes in cell proliferation and measured changes in ·OH and NO in A549 cells from the different treatment groups. The results indicate that TLR7 up-regulation is related to RSV infection and the induction of oxidative stress and that TLR7 expression was mediated by the anti-inflammatory effects of Nrf2/ARE pathway inhibitors or agonists. Our experiments may help elucidate the underlying pathology of RSV infection and suggest potential therapeutic targets for drug development and the prevention of RSV-induced human diseases.

The role of Cyclin Dependent Kinase Inhibitor 3 (CDKN3) in promoting human tumors: Literature review and pan-cancer analysis.

Background: Although many experiments and clinical studies have proved the link between the expression of CDKN3 and human tumors, we have not been able to identify any bioinformatics study in which the extensive tumor-promoting effect of CDKN3 was systematically analyzed. Objective: Explore the extensive tumor-promoting effects of CDKN3 and review the research progress of CDKN3 in cancer. Methods: We systematically reviewed the literature on CDKN3 and tumors. We explored the potential tumor-promoting effects of CDKN3 on different tumors in the TCGA database and the GTEx database using multiple platforms and websites. We studied the expression level of CDKN3, survival, prognosis, diagnosis, genetic variation, immune infiltration, and enrichment analysis using databases such as TIMER 2.0, GEPIA2, cBioPortal, and STRING. Results: We found that CDKN3 is highly expressed in most tumors. The expression of CDKN3 is closely related to the prognosis of some tumors. And CDKN3 may have diagnostic value. The conclusion of our literature review is roughly the same, but there are differences, which are worthy of further study. Moreover, CDKN3 may be related to immune cell infiltration in tumor tissues. The genetic alteration of LUAD, STAD, SARC, PCPG, and ESCA with "Amplification" as the main type. In addition, through enrichment analysis, we found that CDKN3 affects tumors mainly through the control of the cell cycle and mitosis. Conclusion: CDKN3 is highly expressed in most tumor tissues and has a statistical correlation with survival prognosis. It has extensive tumor-promoting effects that may be related to mechanisms such as immune infiltration.

Understanding, diagnosing, and treating pancreatic cancer from the perspective of telomeres and telomerase.

Telomerase is associated with cellular aging, and its presence limits cellular lifespan. Telomerase by preventing telomere shortening can extend the number of cell divisions for cancer cells. In adult pancreatic cells, telomeres gradually shorten, while in precancerous lesions of cancer, telomeres in cells are usually significantly shortened. At this time, telomerase is still in an inactive state, and it is not until before and after the onset of cancer that telomerase is reactivated, causing cancer cells to proliferate. Methylation of the telomerase reverse transcriptase (TERT) promoter and regulation of telomerase by lactate dehydrogenase B (LDHB) is the mechanism of telomerase reactivation in pancreatic cancer. Understanding the role of telomeres and telomerase in pancreatic cancer will help to diagnose and initiate targeted therapy as early as possible. This article reviews the role of telomeres and telomerase as biomarkers in the development of pancreatic cancer and the progress of research on telomeres and telomerase as targets for therapeutic intervention.

Association between C-reactive protein-albumin ratio and overall survival in Parkinson's disease using publicly available data: A retrospective cohort study.

Background: At present, many studies have confirmed that inflammation plays a central role in Parkinson's disease (PD). The inflammatory index is related to the prognosis of the disease, but a single inflammatory index has some limitations. The C-reactive protein-albumin ratio (CAR) is a better marker of inflammation or nutritional status than C-reactive protein (CRP) or albumin (Alb), but there is limited study on the association between CAR and the overall survival (OS) of PD. Object: To study the association between CAR and OS in PD patients. Methods: All of these data were obtained from the Dryad Digital Repository, based on which we conducted a secondary analysis. The study was conducted by the Department of Neurology, the National Regional Center for Neurological Disorders, and the National Hospital of Utano study between March 2004 to November 2007. The final analytic sample included 235 PD patients with the outcome of survival or all-cause death from the study registration to the endpoint. In this study, univariate and multivariate COX regression analyses were used to calculate the adjusted hazard ratio (HR), with a 95% confidence interval (CI). In addition, the association between CAR and OS in PD patients was explored by Kaplan-Meier curve and subgroup analysis. Results: This study included 235 PD patients with an average age of 62.25 years, including 135 females and 100 males, and 45 died during the follow-up period. CAR was associated with gender, modified Hoehn-Yahr stages (mH-Y), and Mini-Mental State Examination (MMSE) of PD patients. In the COX multivariate regression model, after adjusting the age, gender, PD duration, mH-Y, MMSE, and the non-steroidal anti-inflammatory drugs, CAR was found to be associated with the OS in PD (HR = 1.54, 95% CI = 1.01-2.34, p = 0.044). Subgroup analysis showed that the subgroup did not play an interactive role in the association between the prognosis of patients with CAR and PD (p for interaction >0.05), and the results remained stable. Conclusions: The all-cause mortality of PD patients with a high level of CAR is higher, which indicates that the poor overall survival of PD patients is associated with the increase of CAR. The CAR may be a reliable prognostic biomarker for PD patients.

Coicis Semen for the treatment of malignant tumors of the female reproductive system: A review of traditional Chinese medicinal uses, phytochemistry, pharmacokinetics, and pharmacodynamics.

Coicis Semen is an important food product and traditional Chinese medicine (TCM) derived from the dried and mature seeds of Coix lacryma-jobi L.var.ma-yuen (Roman.) Stapf. An increasing number of studies have investigated its use, either alone or in combination with other botanical drugs, to treat female reproductive system malignancies, and its pharmacological effects have been confirmed clinically. This review aims to provide an overview of Coicis Semen's historical role in treating female reproductive system malignancies based on TCM theory, to summarize clinical trials results, and to analyze information pertaining to the main phytochemical components, pharmacokinetics, related anti-cancer pharmacological effects, and toxicology of Coicis Semen. Information on Coicis Semen was collected from internationally accepted scientific databases. Seventy-four clinical trials were identified that used Coicis Semen in combination with other Chinese medicine to treat female reproductive system malignancies, most of which demonstrated good anti-tumor efficacy and few adverse reactions. To date, more than 80 individual compounds have been isolated from this botanical drug. In terms of anti-tumor effects, Coix seed oil has been studied the most. Pharmacokinetic data suggest that the active ingredients in Coicis Semen are widely distributed after administration, and Coicis Semen and its active compounds play a beneficial role in treating female reproductive system malignancies. Mechanistically, the anti-cancer effects may be related to inhibition of tumor cell proliferation and promotion of apoptosis, inhibition of tumor angiogenesis, suppression of the chronic inflammatory microenvironment of tumors, modulation of immune function, and regulation of the female reproductive system. Most acute toxicity and genotoxicity studies have shown that Coicis Semen is non-toxic. However, the existing studies have many limitations, and the future research direction should emphasize 1) the relationship between drug concentration and pharmacological action as well as toxicity; 2) the structural modification or the synthesis of analogues led by the active ingredients of Coicis Semen to enhance pharmacological activities and bioavailability; 3) accurately revealing the anti-cancer pharmacological effects of Coicis Semen and its compounds through multi-omics technology. We hope that this review can determine future directions and inform novel drug development for treating female reproductive malignancies.

Application of natural polysaccharides and their novel dosage forms in gynecological cancers: therapeutic implications from the diversity potential of natural compounds.

Cancer is one of the most lethal diseases. Globally, the number of cancers is nearly 10 million per year. Gynecological cancers (for instance, ovarian, cervical, and endometrial), relying on hidden diseases, misdiagnoses, and high recurrence rates, have seriously affected women's health. Traditional chemotherapy, hormone therapy, targeted therapy, and immunotherapy effectively improve the prognosis of gynecological cancer patients. However, with the emergence of adverse reactions and drug resistance, leading to the occurrence of complications and poor compliance of patients, we have to focus on the new treatment direction of gynecological cancers. Because of the potential effects of natural drugs in regulating immune function, protecting against oxidative damage, and improving the energy metabolism of the body, natural compounds represented by polysaccharides have also attracted extensive attention in recent years. More and more studies have shown that polysaccharides are effective in the treatment of various tumors and in reducing the burden of metastasis. In this review, we focus on the positive role of natural polysaccharides in the treatment of gynecologic cancer, the molecular mechanisms, and the available evidence, and discuss the potential use of new dosage forms derived from polysaccharides in gynecologic cancer. This study covers the most comprehensive discussion on applying natural polysaccharides and their novel preparations in gynecological cancers. By providing complete and valuable sources of information, we hope to promote more effective treatment solutions for clinical diagnosis and treatment of gynecological cancers.

Lysosomes, curcumin, and anti-tumor effects: how are they linked?

Curcumin is a natural active ingredient from traditional Chinese medicine (TCM) that has multi-target characteristics to exert extensive pharmacological activities and thus has been applied in the treatment of various diseases such as cancer, cardiovascular diseases, nervous system, and autoimmune disorders. As an important class of membranous organelles in the intracellular membrane system, lysosomes are involved in biological processes such as programmed cell death, cell metabolism, and immune regulation, thus affecting tumor initiation and progression. It has been shown that curcumin can modulate lysosomal function through the aforementioned pathways, thereby affecting tumor proliferation, invasion, metastasis, drug resistance, and immune function. This review briefly elaborated the regulatory mechanisms of lysosome biogenesis and summarized curcumin-related studies with its anti-tumor effect, providing a reference for the clinical application of curcumin and anti-tumor research targeting lysosomes.

Independent predictive value of blood inflammatory composite markers in ovarian cancer: recent clinical evidence and perspective focusing on NLR and PLR.

Ovarian cancer (OC) is one of the deadliest malignant tumors affecting women worldwide. The predictive value of some blood inflammatory composite markers in OC has been extensively reported. They can be used for early detection and differential diagnosis of OC and can be used for predicting survival, treatment response, and recurrence in the affected patients. Here, we reviewed the predictive values of composite inflammatory markers based on complete blood count, namely neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio, and systemic inflammation index and markers based on blood protein, namely C-reactive protein-to-albumin ratio and prognostic nutritional index in OC, with a focus on NLR and PLR. We referred to the clinical studies on these six markers, reviewed the patient population, and summarized the marker cut-off values, significance, and limitations of these studies. All these studies were retrospective and most of them were single-center clinical studies with small sample sizes. We found that the cut-off values of these markers have not been unified, and methods used to determine these values varied among studies. The predictive value of these markers on survival was mainly reflected in the postoperative patients of multiple subtypes of ovarian cancer including epithelial OC, high-grade serous ovarian carcinoma, and ovarian clear cell carcinoma. We focused on NLR and PLR and calculated their pooled hazard ratios. NLR and PLR were reliable in predicting overall and progression-free survivals in patients with OC. Therefore, it is necessary to adjust important confounding factors and conduct a long-term follow-up prospective cohort study to further clarify the cut-off values of NLR and PLR and their clinical applications.

Potential chemoprotective effects of active ingredients in Salvia miltiorrhiza on doxorubicin-induced cardiotoxicity: a systematic review of in vitro and in vivo studies.

Background: Recently, attention has been paid to the protective properties of active ingredients in Salvia miltiorrhiza (AISM) against organ toxicity induced by chemotherapy drugs. Purpose of the present systematic review is to evaluate the chemoprotective effects and mechanisms of AISM on in vitro and in vivo models of doxorubicin-induced cardiotoxicity (DIC). Methods: According to the PRISMA guideline, the current systematic review was conducted in the Web of Science, PubMed, Embase, and the Cochrane Library to collect all relevant in vitro and in vivo studies on "the role of AISM on DIC" published up until May 2023. The SYRCLE's tool was used to identify potential risk of bias. Results: Twenty-two eligible articles were included in this systematic review. Eleven types of active ingredients in Salvia miltiorrhiza were used for DIC, which have the following effects: improvement of physical signs and biochemical indicators, reduction of cardiac function damage caused by DIC, protection of heart tissue structure, enhancement of myocardial cell viability, prevention of cardiomyocyte apoptosis, increase of the chemosensitivity of cancer cells to Doxorubicin, etc. The cardioprotective mechanism of AISM involves inhibiting apoptosis, attenuating oxidative stress, suppressing endoplasmic reticulum (ER) stress, decreasing inflammation, improving mitochondrial structure and function, affecting cellular autophagy and calcium homeostasis. The quality scores of included studies ranged from 4 to 7 points (a total of 10 points), according to SYRCLE's risk of bias tool. Conclusion: This systematic review demonstrated that AISM have chemoprotective effects on DIC in vivo and in vitro models through several main mechanisms such as anti-apoptosis, antioxidant effects, anti-ER stress, and anti-inflammatory.

Pan-cancer analysis and experimental validation identify ndc1 as a potential immunological, prognostic and therapeutic biomarker in pancreatic cancer.

NDC1 is a transmembrane nucleoporin that participates in cell mitosis. In the field of oncology, NDC1 has shown its potential as a prognostic marker for multiple tumors. However, pan-cancer analysis of NDC1 to fully explore its role in tumors has not been performed and little is reported on its role in pancreatic cancers. In the present study, a pan-cancer analysis of NDC1 was performed using a bioinformatic approach. Survival analysis was performed by univariate Cox regression analysis and Kaplan-Meier survival analysis. Subsequently, the relationship between NDC1 and immune cell infiltration, TMB/MSI and drug sensitivity was analyzed. Moreover, the mechanism of NDC1 in pancreatic cancer were further analyzed by GSEA, GSVA. Finally, we conducted in vitro experiments including MTT, scratch, EdU, and apoptosis assays to explore the function of NDC1 in pancreatic cancer cells. High expression of NDC1 was demonstrated in 28 cancer types. Univariate Cox regression analysis revealed that NDC1 expression was closely associated with the survival outcome of 15 cancer types, and further Kaplan-Meier survival analysis showed negative associations with the progression-free survival in 14 cancers. In addition, a significant association between the NDC1 expression and immune cell infiltration in tumor microenvironment, immune-related genes, common tumor-regulatory and drug sensitivity was observed. Furthermore, NDC1 is abnormally expressed in pancreatic cancer, and is closely related to the prognosis of pancreatic cancer patients and chemosensitivity. The study reveals that NDC1 could be used as a potential immunological, prognostic and therapeutic target for pancreatic cancer.

Research progress and value of albumin-related inflammatory markers in the prognosis of non-small cell lung cancer: a review of clinical evidence.

Inflammatory markers have a wide range of predictive values in the prognosis of non-small lung cancer (NSCLC). Poor nutritional status usually means a poor prognosis in patients with NSCLC, which is widely recognized by oncologists and nutritionists. Serum albumin has a certain value in evaluating the prognosis of patients. Several inflammatory albumin-related markers have been proposed, but they have not been widely used in predicting the prognosis of NSCLC in clinical practice. We aim to systematically review the published clinical evidence of albumin-related inflammatory markers in predicting the prognosis of NSCLC and to describe their progress and value. The results showed that the markers included in the review could be prognostic indicators in patients with NSCLC. However, we found that the cut-off value of albumin-related inflammatory markers with quantitative nature was very chaotic and needed to be defined by recognized standards. We summarized and compared the advantages and disadvantages of these markers, but a prospective cohort study with long-term follow-up after adjustment for important confounders is still necessary. Whether the results and conclusions could be directly applied in clinical practice needs to be identified and evaluated. There is an urgent need to classify and standardize the albumin-related inflammatory markers that play an important role in the prognosis of NSCLC, which is the key to ensuring the transformation from clinical study to clinical application.

Albumin-related inflammatory markers could be prognostic indicators in non-small cell lung cancer.The classification and standardization of albumin-related inflammatory markers guarantee the transformation from clinical study to clinical application.Future prospective studies of albumin-related inflammatory markers excluding confounding factors are very necessary.

Ferritinophagy-mediated iron competition in RUTIs: Tug-of-war between UPEC and host.

Uropathogenic Escherichia coli (UPEC) is the main pathogen of recurrent urinary tract infections (RUTIs). Urinary tract infection is a complicated interaction between UPEC and the host. During infection, UPEC can evade the host's immune response and retain in bladder epithelial cells, which requires adequate nutritional support. Iron is the first necessary trace element in life and a key nutritional factor, making it an important part of the competition between UPEC and the host. On the one hand, UPEC grabs iron to satisfy its reproduction, on the other hand, the host relies on iron to build nutritional immunity defenses against UPEC. Ferritinophagy is a selective autophagy of ferritin mediated by nuclear receptor coactivator 4, which is not only a way for the host to regulate iron metabolism to maintain iron homeostasis, but also a key point of competition between the host and UPEC. Although recent studies have confirmed the role of ferritinophagy in the progression of many diseases, the mechanism of potential interactions between ferritinophagy in UPEC and the host is poorly understood. In this paper, we reviewed the potential mechanisms of ferritinophagy-mediated iron competition in the UPEC-host interactions. This competitive relationship, like a tug-of-war, is a confrontation between the capability of UPEC to capture iron and the host's nutritional immunity defense, which could be the trigger for RUTIs. Therefore, understanding ferritinophagy-mediated iron competition may provide new strategies for exploring effective antibiotic alternative therapies to prevent and treat RUTIs.

SDC1 and ITGA2 as novel prognostic biomarkers for PDAC related to IPMN.

The existing biomarkers are insufficient for predicting the prognosis of pancreatic ductal adenocarcinoma (PDAC). Intraductal papillary mucinous neoplasm (IPMN) is a precursor to PDAC; therefore, identifying biomarkers from differentially expressed genes (DEGs) of PDAC and IPMN is a new and reliable strategy for predicting the prognosis of PDAC. In this study, four datasets were downloaded from the Gene Expression Omnibus database and standardized using the R package 'limma.' A total of 51 IPMN and 81 PDAC samples were analyzed, and 341 DEGs in PDAC and IPMN were identified; DEGs were involved in the extracellular matrix and tumor microenvironment. An acceptable survival prognosis was demonstrated by SDC1 and ITGA2, which were highly expressed during in vitro PDAC cell proliferation, apoptosis, and migration. SDC1high was enriched in interferon alpha (IFN-α) response and ITGA2high was primarily detected in epithelial-mesenchymal transition (EMT), which was verified using western blotting. We concluded that SDC1 and ITGA2 are potential prognostic biomarkers for PDAC associated with IPMN. Downregulation of SDC1 and ITGA2 expression in PDAC occurs via a mechanism involving possible regulation of IFN-α response, EMT, and immunity, which may act as new targets for PDAC therapy.

Prognostic Value of Glasgow Prognostic Score in Non-small Cell Lung Cancer: A Systematic Review and Meta-Analysis.

Background: Systemic inflammation is a key factor in tumor growth. The Glasgow Prognostic Score (GPS) has a certain value in predicting the prognosis of lung cancer. However, these results still do not have a unified direction. Methods: A systematic review and meta-analysis were performed to investigate the relationship between GPS and the prognosis of patients with non-small cell lung cancer (NSCLC). We set patients as follows: GPS = 0 vs. GPS = 1 or 2, GPS = 0 vs. GPS = 1, GPS = 0 vs. GPS = 2. We collected the hazard ratio (HR) and the 95% confidence interval (CI). Results: A total of 21 studies were included, involving 7333 patients. We observed a significant correlation with GPS and poor OS in NSCLC patients (HRGPS=0 vs. GPS=1 or 2 = 1.62, 95% CI: 1.27-2.07, p ≤ .001; HRGPS=0 vs GPS=1 = 2.14, 95% CI:1.31-3.49, p ≤ .001; HRGPS=0 vs. GPS=2 = 2.64, 95% CI: 1.45-4.82, p ≤ .001). Moreover, we made a subgroup analysis of surgery and stage. The results showed that when divided into GPS = 0 group and GPS = 1 or 2 group, the effect of high GPS on OS was more obvious in surgery (HR = 1.79, 95% CI: 1.08-2.97, p = .024). When GPS was divided into two groups (GPS = 0 and GPS = 1 or 2), the III-IV stage, higher GPS is associated with poor OS (HR = 1.73, 95% CI: 1.43-2.09, p ≤ .001). In the comparison of GPS = 0 and GPS = 1 group (HR = 1.56, 95% CI: 1.05-2.31, p = .026) and the grouping of GPS = 0 and GPS = 2(HR = 2.23, 95% CI: 1.17-4.26, p = .015), we came to the same conclusion. Conclusion: For patients with NSCLC, higher GPS is associated with poor prognosis, and GPS may be a reliable prognostic indicator. The decrease of GPS after pretreatment may be an effective way to improve the prognosis of NSCLC.

The Origin and Development of Piji Pills: An Ancient Prescription of Traditional Chinese Medicine.

Objective: Ancient prescriptions of traditional Chinese medicine (TCM) are an important source for innovative drug research and development, which has garnered increasing attention in recent years. Piji Pills, an ancient TCM prescription, has a long history and remarkable clinical efficacy in the treatment of digestive disorders. Thus, the purpose of this study was to explore the origin and development of Piji Pills and to discuss the potential future direction of an ancient TCM prescription. Method: We analyzed the origin and development of the Piji Pills by reviewing literature records and their evolution in ancient books. We used a full-text database covering 2,090 TCM ancient books and implemented the full-text retrieval function based on Ulysses software. A full-text search was conducted using the keyword "Piji Pills" ("" in Chinese). The results generated 128 pieces of literature from 35 ancient TCM books. In order to identify pertinent sections from the generated results, the results were proofread by two independent authors (Fudong Liu and Xiaochen Jiang) who had sufficient experience concerning ancient books. The developmental process of the Piji Pills was divided into early, late, and modern times. With the approach of statistical methods and chronological description, we manually searched, indexed, and transformed 2,090 ancient TCM books. Result: From the time Piji Pills were first proposed, the records in ancient books became increasingly detailed, providing an in-depth discussion of their composition, dosage, and action mechanisms. In modern times, the research on key drugs found in Piji Pills has made a great contribution to clinical practice. However, the compound research on Piji Pills is still relatively superficial and requires further in-depth study. Conclusions: In this study, statistical methods were used to chronologically clarify the developmental process of Piji Pills. We found that the Piji Pills were widely used and had a significant advantage in the treatment of digestive system diseases. In-depth knowledge mining of ancient books could potentially promote the theoretical innovation of TCM and the research of new drugs.

Analysis of the correlation between Zeste enhancer homolog 2 (EZH2) mRNA expression and the prognosis of mesothelioma patients and immune infiltration.

Mesothelioma lies one of the most malignant tumors, in which the identification of the corresponding biomarkers is extremely critical. This study aims to investigate the prognostic value of enhancer homolog 2 (EZH2) mRNA expression in mesothelioma patients accompanied with its immune infiltration analysis. Gene expression, clinical information and enrichment analysis were obtained based on the Cancer Genome Atlas (TCGA), the immune infiltration analysis and bioinformatics analysis were performed. Clinical information and gene expression were obtained from 86 patients with mesothelioma based on TCGA database. Survival analysis, GSEA enrichment analysis, and immune infiltration analysis of EZH2 expression were carried out using R (version 3.6.3) (statistical analysis and visualization). The correlation of EZH2 expression with immune cell infiltration in mesothelioma was analyzed according to the TIMER database (Fig. https://cistrome.shinyapps.io/timer/ ). A univariate and multivariate analysis of general data obtained from the TCGA database was performed, involving age, gender, stage, pathological type, and whether they had received radiotherapy, the results indicated the association of high expression of EZH2 with poor prognosis in mesothelioma patients, with the worse prognosis in the High group (HR = 2.75, 95% CI 1.68-4.52, P < 0.010). Moreover, ROC curves showed that EZH2 expression predicted 1-year survival with an AUC of 0.740, 2-year survival with an AUC of 0.756, and 3-year survival with an AUC of 0.692, suggesting a robust predictive effect of EZH2 expression on prognosis. KEGG pathway analysis indicated five pathways showing the strongest positive correlation with EZH2 expression: cell cycle, DNA replication, Cell adhesion molecules cams, Primary immuno deficiency, Tsate transduction, and five pathways showing the strongest negative correlation with EZH2 expression: Glycolysis gluconeogenesis, Drug metabolism, cytochrome P450, retinol metabolism, fatty acid metabolism ribosome. We investigated the correlation between EZH2 expression and the level of immune infiltration in mesothelioma tissues. The results indicated that EZH2 expression played a critical role in immune infiltration, of which the high expression was correlated with the reduced number of NK cells, Mast cells, and Th17 cells. Moreover, mesothelioma patients with high EZH2 expression differ from those with low EZH2 expression in their tumor immune microenvironment. EZH2, as a new prognostic biomarker for mesothelioma, contributes to elucidating how changes in the immune environment promote the development of mesothelioma. Further analysis, EZH2 may serve as a biological test to predict the prognosis of mesothelioma.

An immune-related microRNA signature prognostic model for pancreatic carcinoma and association with immune microenvironment.

To establish a prognostic model based on immune-related microRNA (miRNA) for pancreatic carcinoma. Weighted correlation network analysis (WGCNA) was performed using the "WGCNA" package to find the key module genes involved in pancreatic carcinoma. Spearman correlation analysis was conducted to screen immune-related miRNAs. Uni- and multi-variate COX regression analyses were carried out to identify miRNAs prognostic for overall survival (OS) of pancreatic carcinoma, which were then combined to generate a prognostic model. Kaplan-Meier survival analysis, receiver operating characteristic (ROC) analysis, distribution plot of survival status in patients and regression analysis were collectively performed to study the accuracy of the model in prognosis. Target genes of the miRNAs in the model were intersected with the key module genes, and a miRNA-mRNA network was generated and visualized by Cytoscape3.8.0. TIMER analysis was conducted to study the abundance of immune infiltrates in tumor microenvironment of pancreatic carcinoma. Expression levels of immune checkpoint genes in subgroups stratified by the model were compared by Wilcoxon test. Gene Set Enrichment Analysis (GSEA) was performed to analyze the enriched signaling pathways between subgroups. Differential analysis revealed 1826 genes differentially up-regulated in pancreatic carcinoma and 1276 genes differentially down-regulated. A total of 700 immune-related miRNAs were obtained, of which 7 miRNAs were significantly associated with OS of patients and used to establish a prognostic model with accurate predictive performance. There were 99 mRNAs overlapped from the 318 target genes of the 7 miRNAs and the key modules genes analyzed by WGCNA. Patient samples were categorized as high or low risk according to the prognostic model, which were significantly associated with dendritic cell infiltration and expression of immune checkpoint genes (TNFSF9, TNFRSF9, KIR3DL1, HAVCR2, CD276 and CD80). GSEA showed remarkably enriched signaling pathways in the two subgroups. This study identified an immune-related 7-miRNA based prognostic model for pancreatic carcinoma, which could be used as a reliable tool for prognosis.