Tumor cell-intrinsic epigenetic dysregulation shapes cancer-associated fibroblasts heterogeneity to metabolically support pancreatic cancer.

The tumor microenvironment (TME) in pancreatic ductal adenocarcinoma (PDAC) involves a significant accumulation of cancer-associated fibroblasts (CAFs) as part of the host response to tumor cells. The origins and functions of transcriptionally diverse CAF populations in PDAC remain poorly understood. Tumor cell-intrinsic genetic mutations and epigenetic dysregulation may reshape the TME; however, their impacts on CAF heterogeneity remain elusive. SETD2, a histone H3K36 trimethyl-transferase, functions as a tumor suppressor. Through single-cell RNA sequencing, we identify a lipid-laden CAF subpopulation marked by ABCA8a in Setd2-deficient pancreatic tumors. Our findings reveal that tumor-intrinsic SETD2 loss unleashes BMP2 signaling via ectopic gain of H3K27Ac, leading to CAFs differentiation toward lipid-rich phenotype. Lipid-laden CAFs then enhance tumor progression by providing lipids for mitochondrial oxidative phosphorylation via ABCA8a transporter. Together, our study links CAF heterogeneity to epigenetic dysregulation in tumor cells, highlighting a previously unappreciated metabolic interaction between CAFs and pancreatic tumor cells.

Is percutaneous tibial nerve stimulation (PTNS) effective for fecal incontinence (FI) in adults compared with sham electrical stimulation? A meta-analysis.

BACKGROUND: Sacral nerve neuromodulation (SNM) has been considered the optimal second-line treatment for fecal incontinence (FI). However, SNM involves high cost and requires highly skilled operators. Percutaneous tibial nerve stimulation (PTNS) has emerged as an alternative treatment modality for FI, yielding varying clinical outcomes. We conducted this meta-analysis to evaluate the effectiveness and safety of PTNS compared to sham electrical stimulation for FI. METHODS: PubMed, Embase, Web of Science, and the Cochrane Library were searched for studies from May 12, 2012 to May 12, 2022. RESULTS: Four randomized controlled studies were included in this review, involving a total of 439 adult patients with FI (300 in the PTNS group and 194 in the sham electrical stimulation group). Our meta-analysis revealed that PTNS demonstrated superior efficacy in reducing weekly episodes of FI compared to the control groups (MD - 1.6, 95% CI - 2.94 to - 0.26, p = 0.02, I2 = 30%). Furthermore, a greater proportion of patients in the PTNS group reported more than a 50% reduction in FI episodes per week (RR 0.73, 95% CI 0.57-0.94, p = 0.02, I2 = 6%). However, no significant differences were observed in any domains of the FI Quality of Life (QoL) and St Mark's incontinence scores (MD - 2.41, 95% CI - 5.1 to 0.27, p = 0.08, I2 = 67%). Importantly, no severe adverse events related to PTNS were reported in any of the participants. CONCLUSIONS: Our meta-analysis revealed that PTNS was more effective than sham stimulation in reducing FI episodes and led to a higher proportion of patients reporting more than a 50% reduction in weekly FI episodes.

Size-dependent toxicity of polystyrene microplastics on the gastrointestinal tract: Oxidative stress related-DNA damage and potential carcinogenicity.

Microplastics (MPs) and nanoplastics (NPs) have been generally regarded as emerging pollutants and received worldwide attention in recent years. Water and food consumption are the primary pathways for human exposure to MPs/NPs, thus gastrointestinal tracts may be susceptible to their toxicity. Although the recent report has indicated the presence of MPs/NPs in multiple human organs, little is known about their gastric effects. Therefore, this study focused on the adverse effects of polystyrene microplastics (PS-MPs) on gastric epithelium in vivo and in vitro. Surface-enhanced Raman spectroscopy (SERS) revealed the distribution of PS-MPs was associated with their particle sizes, and predominantly concentrated in gastric tissues. Gastric barrier injury and mitochondrial damage were observed in rats after exposure to PS-MPs. Compared with the larger ones, polystyrene nanoplastics (PS-NPs) more significantly reduced the activity of antioxidant enzymes while enhancing the level of MDA, 8-OhdG and γ-H2AX. Meanwhile, PS-MPs caused upregulation of ß-catenin/YAP through redox-dependent regulation of nucleoredoxin (NXN) and dishevelled (Dvl). These findings supported the size-dependent effects of PS-MPs on oxidative stress and DNA damage. Moreover, the redox-dependent activation of the ß-catenin/YAP cascade suggested a novel toxic mechanism for PS-MPs and implied the potential carcinogenic effects.

A large sample-based case-control study of related risk factors of two types of lichenoid vulvar disease (LVD).

PURPOSE: The purpose of this study is to identify the associated factors of two types of lichenoid vulvar disease (LVD) and to compare the differences in related factors between the different pathological types of lichenoid vulvar disease (LVD). METHODS: The study conducted at the West China second Hospital of Sichuan University included a total of 1770 patients with biopsy-confirmed vulvar lichen simplex chronicus (VLSC)and vulvar lichen sclerosus(VLS), along with 1209 patients with normal vulvovagina as control. Further pathological subtype analysis was carried out on 163 cases of vulvar lichen simplex chronicus and 51 cases of vulvar lichen sclerosus. In addition, Univariate chi-square test and multivariate logistic regression were used to analyze the lichenoid vulvar disease group and vulvovaginal normal control group. RESULTS: Univariate analysis revealed that there were statistically significant differences (P < 0.05) in factors between the LVD group and the control group, except for living type, sleep habit, history of drinking, and allergic diseases. There was no significant difference in late sleep, spicy diet, and coffee intake in the factors of life and eating habits and the concomitant disease factors. Furthermore, univariate analysis showed that except for eating seafood, humid living environment, residence, caffeinated drinks, hypertension, and vaginitis, there were statistical differences in the related factors of LVSC. CONCLUSION: The incidence about lichenoid vulvar disease is influenced by various factors such as dietary habits, living environment, mental stress, concomitant diseases, hormone levels and so on, and there were no significant differences in these factors between VLS and VLSC except for income, work stress, systemic immune diseases, and menopause.

Generation and periodic evolution of third harmonics carrying transverse orbital angular momentum in air-plasma filaments.

Spatiotemporal optical vortex (STOV) pulses, possessing inherent transverse orbital angular momentum (OAM) and exhibiting phase singularity and intensity null in the spatiotemporal (ST) domain, have received increasing attention in recent years. Here, we investigate theoretically the third harmonic generation and evolution properties of STOV pulses via the interaction of 800-nm-STOV pulses with air-plasma filaments. We show that beautiful third harmonic STOV pulses are generated at a propagation distance of several millimeters. During further propagation, the ST intensity profiles of the third harmonics undergo variations in a periodic way, leading to the distortion and subsequent restoration to the initial ring pattern. The periodic evolution is a result of the interference effects between the third harmonics generated with different phases. Consequently, the evolution period is roughly twice the dephasing length of the third harmonics. Meanwhile, additional singularities emerge in the intensity patterns due to destructive interference occurring at specific dephasing lengths for the specific frequency components. The high-frequency components experience destructive interference earlier than the low-frequency components during each evolution period because the dephasing length decreases with frequency. This results in the sequentially appearance of the additional singularities from top to bottom in the ST intensity patterns. The proposed scheme demonstrates a way for higher-order STOV generation and manipulation in air-plasma filaments, which can be of interest for experiments related to vortex light science.

Review of Noninvasive Continuous Glucose Monitoring in Diabetics.

For diabetics, taking regular blood glucose measurements is crucial. However, traditional blood glucose monitoring methods are invasive and unfriendly to diabetics. Recent studies have proposed a biofluid-based glucose sensing technique that creatively combines wearable devices with noninvasive glucose monitoring technology to enhance diabetes management. This is a revolutionary advance in the diagnosis and management of diabetes, reflects the thoughtful modernization of medicine, and promotes the development of digital medicine. This paper reviews the research progress of noninvasive continuous blood glucose monitoring (CGM), with a focus on the biological liquids that replace blood in monitoring systems, the technical principles of continuous noninvasive glucose detection, and the output and calibration of sensor signals. In addition, the existing limits of noninvasive CGM systems and prospects for the future are discussed. This work serves as a resource for further promoting the development of noninvasive CGM systems.

Clustering-Triggered Emission Liquid Crystalline Polymer Bearing Cholesterol: Tunable Circularly Polarized Luminescence and Room-Temperature Phosphorescence.

Circularly polarized luminescence (CPL) materials with clustering-triggered emission (CTE) characteristic have gradually attracted attention for their unique photophysical properties. However, the majority of reported clusteroluminogens lack chirality and exhibit heterogeneity, making it challenging to achieve a well-defined helical structure necessary for efficient CPL with high dissymmetry factor (glum ). In this paper, chiral liquid crystals are constructed to obtain CTE-based CPL materials with high glum values. Side chain liquid crystal polymer PM6Chol bearing cholesterol clusteroluminogens are designed and synthesized. PM6Chol-coated film and PM6Chol thermal-treated film are also successfully prepared by different film-forming methods. Both the films inherit the CTE characteristic of cholesterol and show excitation wavelength-dependent luminescent behavior. However, the two polymer films exhibit different liquid crystal phase structures, with PM6Chol-coated film being a chiral bilayer smectic C phase and PM6Chol thermal-treated film being an achiral bilayer smectic A phase. Attributed to helical arrangement of cholesterol, PM6Chol-coated film emits efficient CPL with glum values up to 1.0 × 10-1 . For PM6Chol thermal-treated film, no CPL signal is detected due to the absence of helical structure. However, it shows obvious room-temperature phosphorescence with 2.0 s afterglow and 23.9 ms lifetime.

Clinical significance of the expression levels of serum transforming growth factor-ß and CXC type chemokine ligand 13 in primary Sjogren's syndrome patients.

OBJECTIVE: The aim of this study was to investigate the expression levels of the serum transforming growth factor-ß1 (TGF-ß1) CXC type chemokine ligand 13 (CXCL13) in primary Sjogren's syndrome (pSS) patients and its correlation with disease severity. METHOD: Thirty patients with pSS admitted to Nanjing Traditional Chinese Medicine Affiliated Hospital of Nanjing University of Traditional Chinese Medicine from January 2021 to December 2022 were included as the pSS group, while 30 patients who underwent physical examination during the same period were included as the control group. The levels of TGF-ß1 and CXCL13 were detected. The diagnostic value of TGF-ß1 and CXCL13 for pSS was analyzed. Detection of serum TGF-ß1 and CXCL13 levels in pSS patients with different disease activities and lip gland pathological grading of pSS was done. We compared the correlation between TGF-ß1 and CXCL13 levels and disease activity and labial gland pathological grading in pSS patients. RESULT: The TGF-ß1 and CXCL13 levels in the pSS group were higher than those in the control group. The area under the receiver operating characteristic (ROC) curve (AUC) for TGF-ß1 and CXCL13 diagnosis of pSS was 0.790 (95% confidence interval (CI): 0.720~0.861) and 0.838 (95% CI: 0.778~0.898), respectively. The serum TGF-ß1 and CXCL13 levels of pSS patients significantly increase with the increase of disease activity and lip gland pathological grading. The TGF-ß1 and CXCL13 levels in pSS patients were positively correlated with disease activity and lip gland pathological grading. CONCLUSION: The levels of TGF-ß1 and CXCL13 in pSS patients were increased, and it was closely related to disease activity and lip gland pathological grading, which can be used as an effective indicator for the diagnosis of pSS. Key Points • The TGF-ß1 and CXCL13 levels in the pSS group were higher than those in the control group. • The TGF-ß1 and CXCL13 levels in pSS patients were positively correlated with disease activity and lip gland pathological grading. • TGF-ß1 and CXCL13 can be used as an effective indicator for the diagnosis of pSS.

Supramolecular immunotherapy on diversiform immune cells.

Supramolecular immunotherapy employs supramolecular materials to stimulate the immune system for inhibiting tumor cell growth and metastasis, reducing the cancer recurrence rate, and improving the quality of the patient's life. Additionally, it can lessen patient suffering and the deterioration of their illness, as well as increase their survival rate. This paper will outline the fundamentals of tumor immunotherapy based on supramolecular materials as well as its current state of development and potential applications. To be more specific, we will first introduce the basic principles of supramolecular immunotherapy, including the processes, advantages and limitations of immunotherapy, the construction of supramolecular material structures, and its benefits in treatment. Second, considering the targeting of supramolecular drugs to immune cells, we comprehensively discuss the unique advantages of applying supramolecular drugs with different types of immune cells in tumor immunotherapy. The current research advances in supramolecular immunotherapy, including laboratory research and clinical applications, are also described in detail. Finally, we reveal the tremendous promise of supramolecular materials in tumor immunotherapy, as well as discuss the opportunities and challenges that may be faced in future development.

Novel receptor, mutation, vaccine, and establishment of coping mode for SARS-CoV-2: current status and future.

Since the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its resultant pneumonia in December 2019, the cumulative number of infected people worldwide has exceeded 670 million, with over 6.8 million deaths. Despite the marketing of multiple series of vaccines and the implementation of strict prevention and control measures in many countries, the spread and prevalence of SARS-CoV-2 have not been completely and effectively controlled. The latest research shows that in addition to angiotensin converting enzyme II (ACE2), dozens of protein molecules, including AXL, can act as host receptors for SARS-CoV-2 infecting human cells, and virus mutation and immune evasion never seem to stop. To sum up, this review summarizes and organizes the latest relevant literature, comprehensively reviews the genome characteristics of SARS-CoV-2 as well as receptor-based pathogenesis (including ACE2 and other new receptors), mutation and immune evasion, vaccine development and other aspects, and proposes a series of prevention and treatment opinions. It is expected to provide a theoretical basis for an in-depth understanding of the pathogenic mechanism of SARS-CoV-2 along with a research basis and new ideas for the diagnosis and classification, of COVID-19-related disease and for drug and vaccine research and development.

Whole-transcriptome sequencing with ceRNA regulation network construction and verification in glioblastoma.

OBJECTIVES: To explore the key genes involved in the occurrence and development of glioblastoma (GBM) by analyzing whole-transcriptome sequencing and biologic data from GBM and normal cerebral cortex tissues and to search for important noncoding RNA (ncRNA) molecular markers based on the competitive endogenous RNA (ceRNA) network. METHODS: Ten GBM and normal cerebral cortex tissues were collected for full transcriptome sequencing, screened for differentially expressed (DE) mRNAs, miRNAs, lncRNAs, and circRNAs, and subjected to bioinformatic analysis. We constructed a Protein-Protein Interaction (PPI) network and a circRNA/lncRNA-miRNA-mRNA regulatory network and identified them using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Finally, The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases were used to validate and conduct a survival analysis of the target genes. RESULTS: A total of 5341 DEmRNAs, 259 DEmiRNAs, 3122 DElncRNAs, and 2135 DEcircRNAs were identified. Enrichment analysis showed that target genes regulated by DEmiRNA, DElncRNA, and DEcircRNA were closely related to chemical synaptic transmission and ion transmembrane transport. A PPI network analysis screened 10 hub genes that directly participate in tumor cell mitosis regulation. In addition, the ceRNA composite network showed that hsa-miR-296-5p and hsa-miR-874-5p were the central nodes of the network, and the reliability of relevant key molecules was successfully verified through RT-qPCR identification and the TCGA database. The CGGA database survival analysis produced 8 DEmRNAs closely related to GBM patient survival prognosis. CONCLUSIONS: This study revealed the important regulatory functions and molecular mechanisms of ncRNA molecules and identified hsa-miR-296-5p and hsa-miR-874-5p as key molecules in the ceRNA network. They may play an important role in GBM pathogenesis, treatment, and prognosis.

Prognostic value of preoperative circulating tumor cells for hepatocellular carcinoma with portal vein tumor thrombosis: A propensity score analysis.

PURPOSE: The role of circulating tumor cells (CTCs) in hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) is not fully understood. METHODS: In this retrospective analysis, we included 316 HCC patients who underwent hepatectomy and preoperative CTC detection. We selected 41 pairs of matched HCC patients with and without PVTT using propensity score matching (PSM) analysis. We compared the preoperative CTC counts in patients from both the full cohort and the PSM model. We also analyzed their associations with disease-free survival (DFS) and overall survival (OS). RESULTS: Before and after PSM analysis, the preoperative CTC counts in the HCC with PVTT group were substantially higher than in the HCC without PVTT group. In both the full cohort of patients and the PSM model, patients with CTC ≥ 2 had significantly shorter OS and DFS than patients with CTC < 2. The outcomes of HCC patients with PVTT could be well differentiated by preoperative CTC levels. HCC patients with CTC ≥ 2 had noticeably shorter OS (9.9 months vs. 24.6 months, P = 0.0003) and DFS (6.0 months vs. 12.3 months, P = 0.0041) than those with CTC < 2. Moreover, preoperative CTC ≥ 2 remained an independent predictor in all groups' multivariate analysis. CONCLUSION: We discovered a link between preoperative CTC counts and the occurrence of PVTT and confirmed the prognostic significance of preoperative CTC in HCC patients with PVTT. These findings suggest that preoperative CTC counts have the potential to assist in identifying patients with HCC and PVTT who may benefit from surgery.

The diverse pancreatic tumor cell-intrinsic response to IFNγ is determined by epigenetic heterogeneity.

IFNγ signaling is mainly mediated through the activation of the canonical JAK-STAT signaling pathway, transcription factors, and epigenetic modifications. The activation of IFNγ signaling pathway may provide a novel option for tumor immunotherapy, but the outcomes remain controversial. In fact, recent studies suggest that the resistance to IFNγ-dependent immunotherapies is commonly derived from the tumor cell-intrinsic heterogeneity, the molecular mechanism of which remains elusive. Therefore, elucidating the tumor cell-intrinsic heterogeneity in response to IFNγ would be beneficial to improve the efficacy of immunotherapy. Here, we first delineated the epigenetic redistribution and transcriptome alteration in response to IFNγ stimulation, and demonstrated that ectopic gain of H3K4me3 and H3K27Ac at the promoter region mainly contributed to the enhancement of IFNγ-mediated transcriptional activity of interferon-stimulated genes (ISGs). Furthermore, we found that the cellular heterogeneity of PD-L1 expression in response to IFNγ was mainly attributed to cell-intrinsic H3K27me3 levels. Enhancement of H3K27me3 by GSK-J4 limited PD-L1hi tumor growth by salvaging the intratumoral cytotoxicity of CD8+ T cells, which may provide therapeutic strategies to overcome immune escape and resistance to IFNγ-based immunotherapies in pancreatic cancer.

Periplocin inhibits hepatocellular carcinoma progression and reduces the recruitment of MDSCs through AKT/NF-κB pathway.

AIMS: We aimed to evaluate the effect of periplocin on inhibiting hepatocellular carcinoma (HCC) and further determine its mechanisms. MAIN METHODS: Cytotoxic activity of periplocin against HCC cells was tested by CCK-8 and colony formation assays. The antitumor effects of periplocin were evaluated in human HCC SK-HEP-1 xenograft and murine HCC Hepa 1-6 allograft mouse models. Flow cytometry was used to measure cell cycle distribution, apopotosis, and the number of myeloid-derived suppressor cells (MDSCs). Hoechst 33258 dye was applied to observe the nuclear morphology. Network pharmacology was performed to predict possible signaling pathways. Drug affinity responsive target stability assay (DARTS) was used to evaluate AKT binding of periplocin. Western blotting, immunohistochemistry, and immunofluorescence were used to examine the protein expression levels. KEY FINDING: Periplocin inhibited cell viability with IC50 values from 50 nM to 300 nM in human HCC cells. Periplocin disrupted cell cycle distribution and promoted cell apoptosis. Moreover, AKT was predicted as the target of periplocin by network pharmacology, which was confirmed by that AKT/NF-κB signaling was inhibited in periplocin-treated HCC cells. Periplocin also inhibited the expression of CXCL1 and CXCL3, leading to decreased accumulation of MDSCs in HCC tumors. SIGNIFICANCE: These findings reveal the function of periplocin in inhibiting HCC progression by G2/M arrest, apoptosis and suppression of MDSCs accumulation through blockade of the AKT/NF-κB pathway. Our study further suggests that periplocin has the potential to be developed as an effective therapeutic agent for HCC.

Protective effect and mechanism research of Phyllanthus emblica Linn. fruit extract on UV-induced photodamage in keratinocytes.

Ultraviolet (UV) irradiation causes acute and chronic cutaneous effects that may result in photodamage and photoaging. Epidermis keratinocytes, as the closest surface of skin, are susceptible to damage from UV rays. Phyllanthus emblica Linn. fruit (PE) extract, as a medicine and food dual-use plant, contains high levels of polyphenols and possesses multiple pharmacological properties. The present study investigated common and different molecular mechanisms and signaling pathway activations of UVA and UVB stimulated cell damage and photoprotective effect of PE extract against UVA and UVB by Methyl Thiazolyl Tetrazolium (MTT) method, Elisa assay, flow cytometry, differentially expressed genes analysis and western blot analysis. The results showed that UVA exposure (10 J/cm2) reduced HaCaT cell viability significantly, increased the apoptosis rate, elevated intracellular reactive oxygen species level and reduced antioxidant enzyme activities. And UVA irradiation could inhibit the ERK/TGF-ß/Smad signaling pathway to downregulate collagen I, collagen III and elastin expressions, resulting in the photoaging of skin cells. We also found UVB exposure (30 mJ/cm2) caused HaCaT cell damage, promoted apoptosis, increased ROS production and induced the release of proinflammatory cytokines (IL-1α, IL-6 and PGE2). Further, in HaCaT cells, UVB ray was able to induce the activation of apoptosis markers (cleaved PARP1 and cleaved caspase3) through the MAPK/AP-1 signaling pathway using western blot analysis. Pre-treatment of PE extract prevented the UVA and UVB induced photoaging and injury in HaCaT cells through activation of ERK/TGF-ß/Smad pathway and inhibition of MAPK/AP-1 pathway, respectively. Therefore, PE extract has the potential to be used as an oral and topical preparation against skin aging and injury induced by UVA and UVB.

A retrospective comparative cohort study of ultra-pulse CO2 lattice laser and glucocorticoids in the treatment of vulvar epithelial nonneoplastic lesions.

Background: A comparison of topical glucocorticoids with CO2 fractional laser treatment was conducted to investigate the differences in the efficacy of non-neoplastic vulvar epithelial lesion treatments in different pathological types and to provide a scientific basis for the management of these disorders. This paper was to study the difference of curative effect of different pathological types of non-tumor vulvar epithelial lesions and provide scientific basis for the treatment of these diseases. Methods: From November 2016 to July 2018, 178 cases of vulvar lichen simplex chronicus (LSC) or lichen sclerosus were confirmed with vulvar biopsy at our institute. Finally, 160 patients were enrolled in this trial. The patients were divided into 2 groups: a group treated with topical hormone and a group treated with CO2 lattice laser therapies. There were 80 cases in each group, including 40 with LSC and 40 with lichen sclerosus. Patients applied 1 gram of progesterone cream and betamethasone cream to the affected area in the morning and evening, respectively, once a day for 3 months. The efficacy was evaluated with the Patient Global Impression of Change (PGI-C) subjective symptom improvement scale and clinical efficacy evaluation scale. The formula was applied to calculate the curative effect index. Results: The PGI-C scores at 1, 3, and 6 months of treatment showed that the laser treatment group had remarkably superior outcomes to the glucocorticoid treatment group. The clinical efficacy score scale at 3- and 6-month treatments indicated a significantly greater curative effect in the laser than in the glucocorticoid treatment (P=0.006 and P=0.002 respectively). In the glucocorticoid group, the clinical effects of different pathological subtypes were significantly different following the 1- and 3-month treatments. The efficacy of treatment for LSC was better than that for lichen sclerosus. Following the 3- and 6-month treatments, the clinical effect for LSC was better than that of lichen sclerosus (3 months: 95% vs. 75%; 6 months: and 95% vs. 70%). Conclusions: Ultrapulse CO2 lattice laser was more effective than was glucocorticoid therapy in the treatment of vulvar epithelial non-tumor-like lesions.

Silica nanoparticles promoted pro-inflammatory macrophage and foam cell transformation via ROS/PPARγ/NF-κB signaling.

Experimental evidence has pointed out silica nanoparticles (SiNPs) possessing a proatherogenic capability. However, the interplay between SiNPs and macrophages in the pathogenesis of atherosclerosis was poorly understood. Here, we demonstrated SiNPs could promote macrophage adhesion to endothelial cells, accompanied by elevated Vcam1 and Mcp1. Upon SiNPs stimuli, macrophages manifested enhanced phagocytic activity and a pro-inflammatory phenotype, as reflected by the transcriptional determination of M1/M2-related biomarkers. In particular, our data certified the increased macrophage M1 subset facilitated more lipid accumulation and resultant foam cell transformation in comparison to the M2 phenotype. More importantly, the mechanistic investigations revealed ROS-mediated PPARγ/NF-κB signaling was a key contributor to the above phenomena. That was, SiNPs caused ROS accumulation in macrophages, resulting in the deactivation of PPARγ, nuclear translocation of NF-κB, ultimately contributing to macrophage phenotype shift toward M1 and foam cell transformation. Collectively, we first revealed SiNPs facilitated pro-inflammatory macrophage and foam cell transformation via ROS/PPARγ/NF-κB signaling. These data would provide new insight into the atherogenic property of SiNPs in a macrophage model.

Comparison of electrophysiology therapy and glucocorticoid therapy in the treatment of 2 subtypes of vulvar epithelial non-neoplastic lesions: a prospective cohort study.

Background: Lichen-like lesions with degeneration and pigmentation alterations can be divided into the following 2 types: (I) chronic simple lichen; and (II) sclerosing lichen. The etiology of the disease is unknown. This study sought to examine the therapeutic effects of electrophysiological smooth-muscle electrical stimulation in the treatment of lichen-like lesions of the vulva. Methods: A total of 80 outpatients, who had been confirmed to have vulvar lichen-like lesions by vulvar biopsy at our hospital from November 2016 to March 2018, were prospectively included in this study. The patients received electrophysiology or glucocorticoid therapy. After completing a treatment cycle according to the clinical treatment routine, the outpatients were monitored at 1-, 3- and 6-month intervals. Patients used an improvement scale (i.e., the patient global impression of change scale) to score their subjective perceptions and subjective symptoms. The clinical curative effect scale was used to calculate the curative effect index and grade the curative effect. Results: After 1 month of treatment, the active enhancement of simple lichen in the electrophysiological treatment group and glucocorticoid treatment group improved, while the active enhancement of simple lichen in the electrophysiological treatment group improved after 3 months of treatment. After 6 months of treatment, the subjective improvement score of the electrophysiological treatment group was better than that of lichen sclerosus. After 3 months of treatment, the effective rate of the electrophysiological therapy group was better than that of the glucocorticoid therapy group. After 6 months of treatment in the electrophysiological treatment group, the efficacy of simple lichen is also better than that of sclerotic lichen. Conclusions: Conventional hormone therapy is easier for patients to accept because of its convenience and low costs.

Investigation and Countermeasures Research of Hospital Information Construction of Tertiary Class-A Public Hospitals in China: Questionnaire Study.

BACKGROUND: Medical informatization has initially demonstrated its advantages in improving the medical service industry. Over the past decade, the Chinese government have made a lot of effort to complete infrastructural information construction in the medical and health domain, and smart hospitals will be the next priority according to policies released by Chinese government in recent years. OBJECTIVE: To provide strategic support for further development of medical information construction in China, this study aimed to investigate the current situation of medical information construction in tertiary class-A public hospitals and analyze the existing problems and countermeasures. METHODS: This study surveyed 23 tertiary class-A public hospitals in China who voluntarily responded to a self-designed questionnaire distributed in April 2020 to investigate the current medical information construction status. Descriptive statistics were used to summarize the current configurations of hospital information department, hospital information systems, hospital internet service and its application, and the satisfaction of hospital information construction. Interviews were also conducted with the respondents in this study for requirement analysis. RESULTS: The results show that hospital information construction has become one of the priorities of the hospitals' daily work, and the medical information infrastructural construction and internet service application of the hospitals are good; however, a remarkable gap among the different level of hospitals can be observed. Although most hospitals had built their own IT team to undertake information construction work, the actual utilization rate of big data collected and stored in the hospital information system was not satisfactory. CONCLUSIONS: Support for the construction of information technology in primary care institutions should be increased to balance the level of development of medical informatization in medical institutions at all levels. The training of complex talents with both IT and medical backgrounds should be emphasized, and specialized disease information standards should be developed to lay a solid data foundation for data utilization and improve the utilization of medical big data.

Hyperin up-regulates miR-7031-5P to promote osteogenic differentiation of MC3T3-E1 cells.

OBJECTIVE: To investigate the effects of Hyperin (Hyp) on osteogenic differentiation of MC3T3-E1 cells. METHODS: Differentially expressed miRNA was screened by miRNA Microarray. miR-7031-5P overexpression and knockdown MC3T3-E1 cell models were constructed by transfecting miR-7031-5P mimics and inhibitor. Alizarin red staining (ARS) assay was used to observe the formation of mineralized nodules in MC3T3-E1 cells. ALP activity was detected by using ALP detection kit. Western blot assay was used to examine the changes in osteogenic differentiation-related proteins. The relationship between miR-7031-5P and Wnt7a was revealed by dual luciferase report experiments. RESULTS: We found that miR-7031-5P was up-regulated in MC3T3-E1 cells after Hyp treatment. The results indicated that compared with the untreated group, Hyp promoted the formation of mineralized nodules and the alkaline phosphatase (ALP) activity of MC3T3-E1 cells via overexpressing miR-7031-5P. Besides, elevated miR-7031-5P increased OPN, COL1A1, and Runx2 mRNA expression. More importantly, Wnt7a was identified as the downstream target gene of miR-7031-5P promoting osteogenic differentiation of MC3T3-E1 cells. CONCLUSIONS: Hyp up-regulated miR-7031-5P to promote osteogenic differentiation of MC3T3-E1 cells by targeting Wnt7a.