Retrospective analysis of preoperative application of triple-modal pre-rehabilitation on postoperative recovery of colorectal cancer patients.

PURPOSE: To retrospectively analyze the difference between triple-modal pre-rehabilitation and common treatment in patients with colorectal cancer (CRC). METHODS: A total of 145 patients with CRC diagnosed by pathology and admitted to our hospital for surgery between June 2020 and June 2022 were included in the study. All patients were divided into two groups: the triple-modal pre-rehabilitation group (pre-rehabilitation group) and the common treatment group. The triple-modal pre-rehabilitation strategy included exercise (3-5 times per week, with each session lasting more than 50 min), nutritional support, and psychological support. The study was designed to assess the potential of the pre-rehabilitation intervention to accelerate postoperative recovery by assessing the 6-min walk test, nutritional indicators, and HADS score before and after surgery. RESULTS: The pre-rehabilitation intervention did not reduce the duration of initial postoperative recovery or the incidence of postoperative complications, but it did increase the patients' exercise capacity (as determined by the 6-min walk test), with the pre-rehabilitation group performing significantly better than the common group (433.0 (105.0) vs. 389.0 (103.5), P < 0.001). The study also found that triple-modal pre-rehabilitation was beneficial for the early recovery of nutritional status in surgical patients and improved anxiety and depression in patients after surgery, especially in those who had not received neoadjuvant therapy. CONCLUSION: The triple-modal pre-rehabilitation strategy is of significant importance for reducing stress and improving the functional reserve of patients with colorectal cancer (CRC) during the perioperative period. The results of our study provide further support for the integration of the triple-modal pre-rehabilitation strategy into the treatment and care of CRC patients.

Network pharmacology-based analysis of the mechanism of Saposhnikovia divaricata for the treatment of type I allergy.

CONTEXT: Saposhnikovia divaricata (Turcz.) Schischk (Apiaceae) (SD) has various pharmacological activities, but its effects on type I allergy (TIA) have not been comprehensively studied. OBJECTIVE: This study evaluates the treatment and molecular mechanisms of SD against TIA. MATERIALS AND METHODS: The effective components and action targets of SD were screened using TCMSP database, and allergy-related targets of SD were predicted using GeneCards and OMIM database. The obtained target intersections were imported into David database for GO analysis, and used R software to perform KEGG analysis. The RBL-2H3 cells sensitised by DNP-IgE/DNP-BSA were treated with different concentrations of SD (root decoction, 0.5, 1, and 2 mg/mL), prim-O-glucosylcimifugin (POG, 10, 40, and 80 µg/mL) and the positive control drug-ketotifen fumarate (KF, 30 µM) for 12 h, then subjected to cell degranulation and qPCR analysis. RESULTS: Eighteen active compounds of SD and 38 intersection targets were obtained: TIA-related signal pathways mainly include calcium signal pathway, PI3K-Akt signal pathway and MAPK signal pathway. Taking the ß-Hex release rate of the model group as the base, the release rate of SD and POG in high dose groups were 43.79% and 57.01%, respectively, which were significantly lower than model group (p < 0.01), and significantly lower than KF group (63.83%, p < 0.01, p < 0.05). SD and POG could down-regulate the expression of related proteins in the Lyn/Syk, PI3K/AKT and MAPK signalling pathways. DISCUSSION AND CONCLUSION: Saposhnikovia divaricata could inhibit IgE-induced degranulation of mast cells, providing a scientific basis for further research and clinical applications of SD in TIA treatment.

Long noncoding RNA FOXD2-AS1 promotes glioma malignancy and tumorigenesis via targeting miR-185-5p/CCND2 axis.

Glioma is the most aggressive malignant tumor in the adult central nervous system. Abnormal long noncoding RNA (lncRNA) FOXD2-AS1 expression was associated with tumor development. However, the possible role of FOXD2-AS1 in the progression of glioma is not known. In the present study, we used in vitro and in vivo assays to investigate the effect of abnormal expression of FOXD2-AS1 on glioma progression and to explore the mechanisms. FOXD2-AS1 was upregulated in glioma tissue, cells, and sphere subpopulation. Upregulation of FOXD2-AS1 was correlated with poor prognosis of glioma. Downregulation of FOXD2-AS1 decreased cell proliferation, migration, invasion, stemness, and epithelial-mesenchymal transition (EMT) in glioma cells and inhibited tumor growth in transplanted tumor. We also revealed that FOXD2-AS1 was mainly located in cytoplasm and microRNA (miR)-185-5p both targeted FOXD2-AS1 and CCND2 messenger RNA (mRNA) 3'-untranslated region (3'-UTR). miR-185-5p was downregulated in glioma tissue, cells, and sphere subpopulation. Downregulation of miR-185-5p was closely correlated with poor prognosis of glioma patients. In addition, miR-185-5p mimics decreased cell proliferation, migration, invasion, stemness, and EMT in glioma cells. CCND2 was upregulated in glioma tissue, cells, and sphere subpopulation. Upregulation of CCND2 was closely correlated with poor prognosis of glioma patients. CCND2 knockdown decreased cell proliferation, migration, invasion, and EMT in glioma cells. In glioma tissues, CCND2 expression was negatively associated with miR-185-5p, but positively correlated with FOXD2-AS1. FOXD2-AS1 knockdown and miR-185-5p mimics decreased CCND2 expression. Inhibition of miR-185-5p suppressed FOXD2-AS1 knockdown-induced decrease of CCND2 expression. Overexpression of CCND2 suppressed FOXD2-AS1 knockdown-induced inhibition of glioma malignancy. Taken together, our findings highlight the FOXD2-AS1/miR-185-5p/CCND2 axis in the glioma development.

Intravoxel Incoherent Motion Combined With Dynamic Contrast-Enhanced Perfusion MRI of Early Cervical Carcinoma: Correlations Between Multimodal Parameters and HIF-1α Expression.

BACKGROUND: The identification of hypoxia inducible factor (HIF-1α) expression is helpful for the quantitative assessment of tumor hypoxia. The application of multimodal imaging techniques may play a part in the assessment of HIF-1α expression of cervical carcinoma. PURPOSE: To investigate the correlations between multiple imaging parameters and HIF-1α expression of early cervical carcinoma and to determine whether tumor hypoxia can be predicted using multisequence imaging parameters. STUDY TYPE: Prospective observational. POPULATION: One hundred patients with early cervical carcinoma. FIELD STRENGTH/SEQUENCES: 3.0 T MRI including intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) and dynamic contrast-enhanced (DCE) perfusion MRI sequences. ASSESSMENT: DCE-MRI and IVIM DWI were performed for all patients. The imaging parameters included volume transfer constant (Ktrans ), rate constant (Kep ), extravascular extracellular volume fraction (Ve ), D, D*, and f. STATISTICAL TESTS: The comparisons of imaging parameters between two independent groups were performed using the Mann-Whitney U-test. Multiple linear regression analysis was performed to determine the correlation between multiple imaging parameters and HIF-1α expression. The diagnostic ability of DCE-MRI, IVIM DWI, and the combination of two techniques for discriminating high-expression and low-expression groups were analyzed. RESULTS: The high-expression group had a lower Ktrans or Kep value than the low-expression group (P = 0.03; 0.02), while the high-expression group had a higher Ve value than the low-expression group (P = 0.03). The high-expression group had a higher D or f value than the low-expression group (P = 0.02; 0.02). Ktrans , Kep , D, Ve , and f values were independently correlated with HIF-1α expression. The sensitivity or accuracy of a combined method was higher than that of DCE-MRI or IVIM DWI individually (P = 0.03, 0.02; 0.04, 0.03). DATA CONCLUSION: The combination of DCE-MRI and IVIM DWI can improve the diagnostic ability of discriminating different HIF-1α expression levels for early cervical tumors. LEVEL OF EVIDENCE: 1 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2019;50:918-929.

Knockdown on aPKC-ι inhibits epithelial-mesenchymal transition, migration and invasion of colorectal cancer cells through Rac1-JNK pathway.

BACKGROUND: Atypical protein kinase C-ι (aPKC-ι) is an oncogenic factor, and required for the epithelial-mesenchymal transition (EMT) of different types of cancer. Our study aimed to investigate the role of aPKC-ι in the EMT, migration and invasion of colorectal cancer (CRC) cells. METHODS: Expression of aPKC-ι was evaluated in CRC cell lines treated with TGF-ß1 using qPCR and western blot. After aPKC-ι was knocked down using shRNA, migration and invasion abilities of CRC cell lines were evaluated by wound healing assay and transwell assay, respectively. Activation status of downstream signaling factors of aPKC-ι, including Rac1, JNK, STAT3 and ß-catenin, was measured using western blot. Furthermore, auranofin, an aPKC-ι inhibitor, was used to treat CRC cell lines to investigate its possible inhibition on the EMT of CRC cell lines, as well as on the expression of aPKC-ι and its downstream signaling factors. RESULTS: TGF-ß1 induced the expression of aPKC-ι in CRC cells, and knockdown on aPKC-ι inhibited the TGF-ß1-induced EMT, migration and invasion of CRC cells. Interestingly, Rac1 GTPase level was decreased when aPKC-ι was knocked down, and overexpression of Rac1G12V rescued the cell EMT, migration and invasion in CRC cells as inhibited by sh-aPKC-ι. Moreover, knockdown on aPKC-ι suppressed the phosphorylation of JNK and STAT3, and nuclear translocation of ß-catenin. The aPKC- ι inhibitor, Auranofin, showed similar inhibitory effects as aPKC-ι knockdown. CONCLUSION: Knockdown on aPKC-ι inhibited the EMT, migration and invasion of CRC cells through suppressing of Rac1-JNK pathway. Those findings indicate that aPKC-ι may serve as a novel therapeutic target for CRC.

PI3K-AKT-mTOR signaling pathway: the intersection of allergic asthma and cataract.

Allergic asthma is a chronic inflammatory disease and involves many cells and cellular components. Cataract is a condition that affects the transparency of the lens, which the opacity of the lens caused by any innate or acquired factor degrades its transparency or changes in color. During the establishment of asthma model of rats with chicken ovalbumin nebulization, it was found that asthmatic rats were more likely to have monocular or binocular cataract symptoms than normal rats. Considering that they are all induced by immune imbalance, inflammation, etc., there may be some correlation in the mechanism, and many clues showed that both diseases are associated with activation of the PI3K-AKT-mTOR signaling pathway. Therefore, we hypothesized that the PI3K-AKT-mTOR signaling pathway produces inflammatory or immune imbalance based on allergy leading to cataract.

Intravoxel incoherent motion MR imaging of early cervical carcinoma: correlation between imaging parameters and tumor-stroma ratio.

OBJECTIVES: To investigate if intravoxel incoherent motion (IVIM) MR imaging can predict the tumour-stroma ratio (TSR) in patients with early cervical carcinoma. METHODS: Fifty-four patients with early cervical carcinoma were prospectively enrolled into this study. All patients underwent IVIM imaging and parameters including D, D* and f value were measured. The tumours were classified into stroma-rich and stroma-poor group according to TSR, and comparisons of IVIM parameters between two groups were performed. The relationships between IVIM parameters and TSR were analysed by using a multivariate multi-regression analysis. RESULTS: D and f values were significantly lower in stroma-poor tumours than in stroma-rich tumours (p=0.02, 0.04), while the difference in D* value between two groups didn't achieve statistical significance (p=0.09). The areas under ROC curves of D and f values in discriminating stroma-rich and stroma-poor tumours were 0.835 (95%CI=0.616~0.905) and 0.686 (95%CI=0.575~0.798). In multiple linear regression analysis, D value, pathologic type, histologic grade, tumour size and f value were independently correlated with TSR of cervical carcinoma. CONCLUSIONS: D and f values are independently correlated with TSR of cervical carcinoma and have the potential for quantitative measurement of TSR. KEY POINTS: • TSR is a recognized independent prognostic factor in many solid tumours. • D and f values measured by IVIM MRI are independently correlated with TSR while D* is not. • IVIM offers the potential to predict TSR.

Short-term therapeutic effects of low-dose cytarabine plus surgical resection on elderly patients with trigeminal nerve tumor and safety observation.

OBJECTIVE: To evaluate the short-term therapeutic effects of low-dose cytarabine plus surgical resection on elderly patients with trigeminal nerve tumor and to observe the safety. METHODS: A total of 120 elderly patients with trigeminal nerve tumor were divided into a treatment group and a control group by random draw (n=60), and both groups were subjected to resection by stereotactic image-guided endoscopic nasal surgery. Afterwards, the control group was administered with high-dose cytarabine while the treatment group was given low-dose cytarabine for 14 days. RESULTS: Both groups completed treatment, but the effective rate of the treatment group (96.7%) was significantly higher than that of the control group (83.3%) (P < 0.05). The pain scores of the two groups were similar at T0, T1 and T2, but the score of the treatment group at T2 was significantly different from those at T0 and T1 (P < 0.05). During treatment, the treatment group was significantly less prone to complications such as headache, vomiting, vision impairment, nausea and local swelling than the control group (P < 0.05). During three months of follow-up, the appetite, sleep and daily living scores were significantly higher than those of the control group (P < 0.05). CONCLUSION: Stereotactic image-guided surgery was able to treat trigeminal nerve tumor well, and the effect was enhanced by low-dose cytarabine that improved postoperative outcomes and quality of life by dramatically decreasing complications.

Association of single-nucleotide polymorphisms in ERCC1 and ERCC2 with glioma risk.

We conducted a case-control study to assess the role of three single-nucleotide polymorphisms (SNPs) in excision repair cross-complementation group 1 (ERCC1) and two SNPs in excision repair cross-complementation group 2 (ERCC2) on the glioma risk in a Chinese population, and investigate the gene-environmental interaction for the cancer risk. A 1:2 matched case-control study was conducted. Logistic regression analysis revealed that individuals carrying ERCC1 rs2298881 CC genotype were associated with risk of glioma when compared with AA genotype carriers. The significant associations of ERCC1 rs2298881 polymorphism with glioma susceptibility were observed in both the dominant and the recessive models. In a stratification analysis, we found that ERCC1 rs2298881 variants showed an increased association with the risk of glioma in males, ever smokers, and high-grade glioma cases. In conclusion, our study suggests that ERCC1 rs2298881 polymorphism is associated with risk of glioma in codominant, dominant, and recessive models, especially in males, smokers, and high-grade glioma cases. This finding could be useful in revealing the genetic characteristics of glioma and suggests more effective strategies for prevention and treatment.

Involvement of miR-20a in promoting gastric cancer progression by targeting early growth response 2 (EGR2).

Gastric cancer (GC) is one of the most common cancers, with high incidences in East Asia. microRNAs (miRNAs) play essential roles in the carcinogenesis of GC. miR-20a was elevated in GC, while the potential function of miR-20a was poorly understood. miR-20a expression was examined in GC tissues and cell lines. The effects of miR-20a on the growth, migration, invasion, and chemoresistance of GC cells were examined. Luciferase reporter assay and Western blot were used to screen the target of miR-20a. miR-20a was increased in GC tissues and cell lines. miR-20a promoted the growth, migration and invasion of GC cells, enhanced the chemoresistance of GC cells to cisplatin and docetaxel. Luciferase activity and Western blot confirmed that miR-20a negatively regulated EGR2 expression. Overexpression of EGR2 significantly attenuated the oncogenic effect of miR-20a. miR-20a was involved in the carcinogenesis of GC through modulation of the EGR2 signaling pathway.

Cellular specificity of lactate metabolism and a novel lactate-related gene pair index for frontline treatment in clear cell renal cell carcinoma.

Background: Although lactate metabolism-related genes (LMRGs) have attracted attention for their effects on cancer immunity, little is known about their function in clear cell renal cell carcinoma (ccRCC). The aim of this study was to examine the cellular specificity of lactate metabolism and how it affected the first-line treatment outcomes in ccRCC. Methods: GSE159115 was used to examine the features of lactate metabolism at the single-cell level. Utilizing the transcriptome, methylation profile, and genomic data from TCGA-KIRC, a multi-omics study of LMRG expression characteristics was performed. A prognostic index based on a gene-pair algorithm was created to assess how LMRGs affected patients' clinical outcomes. To simulate the relationship between the prognostic index and the frontline treatment, pRRophetic and Subclass Mapping were used. E-MTAB-1980, E-MTAB-3267, Checkmate, and Javelin-101 were used for external validation. Results: The variable expression of some LMRGs in ccRCC can be linked to variations in DNA copy number or promoter methylation levels. Lactate metabolism was active in tumor cells and vSMCs, and LDHA, MCT1, and MCT4 were substantially expressed in tumor cells, according to single-cell analysis. The high-risk patients would benefit from immune checkpoint blockade monotherapy (ICB) and ICB plus tyrosine kinase inhibitors (TKI) therapy, whereas the low-risk individuals responded to mTOR-targeted therapy. Conclusions: At the single-cell level, our investigation demonstrated the cellular specificity of lactate metabolism in ccRCC. We proposed that the lactate-related gene pair index might be utilized to identify frontline therapy responders in ccRCC patients as well as predict prognosis.

[Simultaneous determination of 83 glucocorticoids in cosmetics by ultra performance liquid chromatography-tandem mass spectrometry].

Glucocorticoids, which are a class of steroidal hormones secreted by the adrenal cortex, have significant anti-inflammatory, immunosuppressive, and anti-allergic effects. Thus, these compounds are widely used in clinical practice. However, the long-term use of cosmetics containing glucocorticoids can lead to serious consequences, such as hormone-dependent dermatitis, hypertension, and other serious injuries. The Safety and Technical Specification for Cosmetics (2015 edition) and Regulation (EC) No. 1223/2009 of the European Parliament and Council on cosmetic products list glucocorticoids as prohibited raw materials. According to the National Medical Products Administration, reports on the illegal addition of glucocorticoids to cosmetics by manufacturers have increased in recent years. Therefore, establishing high-throughput screening methods to ensure the quality and safety of cosmetics is imperative. In this study, a comprehensive analytical method based on ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was developed for the rapid screening of 83 glucocorticoids in cosmetics. A series of conditions were optimized using three matrices that are commonly used in cosmetics: water, lotion, and cream (o/w-type). Four mobile-phase systems and three chromatographic columns were then optimized to achieve the best separation effects. Various MS parameters, such as the capillary voltages, cone voltages, desolvation gas flow rates, and collision energies of the ion pairs of the target compounds, were also optimized. Furthermore, pretreatment was essential for glucocorticoid determination owing to the complex matrix effects of cosmetics. The analytes were divided into two groups, with lg Kow=4 as the limit, to compare the effects of the extraction solvent on recoveries. The extraction recoveries of target analytes with six extraction methods, namely, extraction with acetonitrile, extraction with acetone, extraction with ethyl acetate, dispersion in saturated sodium chloride solution followed by extraction with acetonitrile, dispersion in saturated sodium chloride solution followed by extraction with acetone, and dispersion in saturated sodium chloride solution followed by extraction with ethyl acetate, were compared. The recoveries from QuEChERS and solid-phase extraction (SPE) purification were also compared. Based on the experimental results, the final sample pretreatment method included acetonitrile vortex dispersion, ultrasonic extraction, and sample loading after filtration. The 83 target compounds were separated on a Thermo Accucore PFP column (100 mm×2.1 mm, 2.6 µm) with 0.1% (v/v) acetic acid in acetonitrile and 0.1% (v/v) acetic acid in water as the mobile phases. The analytes were determined by dynamic multiple-reaction monitoring (MRM) in electrospray positive ionization mode (ESI+) and quantified using the external standard method. Matrix standard curves were used to reduce matrix effects. The calibration curves of the 83 target compounds were linear in the mass concentration range of 2-200 µg/L (r>0.995). At three levels of addition, the recoveries were 74.5%-112.4%, and the relative standard deviations (RSDs, n=6) were 0.8%-9.9%. The limits of detection (LODs, S/N≥3) were 0.001-0.023 µg/g, and the limits of quantification (LOQs, S/N≥10) were 0.002-0.076 µg/g. The developed method was used to detect glucocorticoids in 41 cosmetic samples. Fluocinolone acetonide, beclomethasone dipropionate, desonide 21-acetate, and desonide were detected in four samples. The content range of glucocorticoids in the positive samples was 0.53-634.27 µg/g. Notably, desonide 21-acetate, which is not included in the scope of the statutory detection method, was detected in two batches of samples. In conclusion, the proposed method is simple, sensitive, reliable, and suitable for the high-throughput analysis of the 83 glucocorticoids in cosmetics with different matrices. This method could provide reliable technical support for the daily supervision of cosmetics and serve as a supplement to current glucocorticoid standards.

Sequence based local-global information fusion framework for vertebrae detection under pathological and FOV variation challenges.

Automated vertebrae detection (identification and localization) aims to identify vertebrae and locate their centroids in medical images, which is a critical step of spinal computer-aided systems. However, due to unpredictable field-of-view and various pathology cases, the image content is diverse and the vertebral morphology can be abnormal in a variety of ways, which challenges the designed systems. In this paper, we propose an effective sequence-based framework robust to various tough cases for accurate vertebrae identification and localization. Our method consists of three sub-modules: (1) Local Feature Extraction (LFE) module designs a shape-compatible category-balanced sampler to collect patches to train a convolution neural network, which extracts representative local features and generates score maps. (2) Discriminative Sequential Image Description (DSID) module proposes a node screening strategy for reliable vertebral feature sequence construction based on feature maps and score maps. This effectively prevents false positives and false negatives in light-weighted dense prediction schemes and fuses local features into a hierarchical discriminative description of given images. (3) Spinal Pattern Exploitation (SPE) module designs an end-balanced relative position learning scheme to fuse hierarchical local-global information for comprehensively exploiting spinal patterns to overcome the FOV and pathological variation challenges in vertebrae detection. Extensive experiments on a challenging dataset consisting of 450 spinal MRIs show that the identification rate of FSDF reaches 0.974 ±0.025 and the localization error is only 4.742 ±2.928 pixels, which demonstrates the effectiveness of our method with pathological and field-of-view variations and its superiority over other state-of-the-art methods.

Crosstalk between autophagy and bladder transitional cell carcinoma by autophagy-related lncRNAs.

The aim of this study was to investigate the crosstalk between autophagy and bladder transitional cell carcinoma (TCC) by autophagy-related long noncoding RNAs (lncRNAs). A total of 400 TCC patients from The Cancer Genome Atlas were enrolled in this study. We identified the autophagy-related lncRNA expression profile of the TCC patients and then constructed a prognostic signature using the least absolute shrinkage and selection operation and Cox regression. Risk, survival, and independent prognostic analyses were carried out. Receiver operating characteristic curve, nomogram, and calibration curves were explored. Gene Set Enrichment Analysis was employed to verify the enhanced autophagy-related functions. Finally, we compared the signature with several other lncRNA-based signatures. A 9-autophagy-related lncRNA signature was established by least absolute shrinkage and selection operation-Cox regression that was significantly associated with overall survival in TCC. Among them, 8 of the 9 lncRNAs were protective factors while the remaining was a risk factor. The risk scores calculated by the signature showed significant prognostic value in survival analysis between the high- or low-risk groups. The 5-year survival rate for the high-risk group was 26.0% while the rate for the low-risk group was 56.0% (P < .05). Risk score was the only significant risk factor in the multivariate Cox regression survival analysis (P < .001). A nomogram connecting this signature with clinicopathologic characteristics was assembled. To assess the performance of the nomogram, a C-index (0.71) was calculated, which showed great convergence with an ideal model. The Gene Set Enrichment Analysis results demonstrated 2 major autophagy-related pathways were significantly enhanced in TCC. And this signature performed a similar predictive effect as other publications. The crosstalk between autophagy and TCC is significant, and this 9 autophagy-related lncRNA signature is a great predictor of TCC.

Pancreatic ductal cells acquire mesenchymal characteristics through cell fusion with bone marrow-derived mesenchymal stem cells and SIRT1 attenuates the apoptosis of hybrid cells.

Bone marrow-derived mesenchymal stem cells (bMSCs) contribute to tissue repair and regeneration. Cell fusion between somatic cells and bMSCs to form hybrid cells may have an important role in tissue repair through the subsequent reprogramming of the somatic cell nucleus. Few studies have assessed the mesenchymal characteristics of fusion-induced hybrid cells and their survival mechanisms. In this study, we investigated the effect of cell fusion on the biological characteristics of pancreatic ductal cells (PDCs) and on the survival mechanism of hybrid cells. To this end, we generated mouse-mouse hybrid cells in vitro by polyethylene glycol-mediated fusion of primary mouse bMSCs with primary mouse PDCs. Hybrid cells showed an enhanced capacity for proliferation and self-renewal compared with PDCs. No PDC had the capacity for anchorage-independent growth or invasion into Matrigel, but some hybrid cells were able to form colonies in soft agar and invade Matrigel. Expression of the tumor suppressor protein p53, which initiates apoptosis, was detected in hybrid cells but not in PDCs or bMSCs. However, the p53 deacetylase, sirtuin 1 (SIRT1), was also detected in hybrid cells, and the level of acetylated p53, the active form, was low. The addition of nicotinamide (Nam) inhibited the deacetylation activity of SIRT1 on p53 and induced cell apoptosis in hybrid cells. This study demonstrated that PDCs could obtain high proliferation rates, self-renewal capabilities, and mesenchymal characteristics by fusion with bMSCs. SIRT1 expression in the hybrid cells attenuated their apoptosis.

Photoacid-Enabled Synthesis of Indanes via Formal [3 + 2] Cycloaddition of Benzyl Alcohols with Olefins.

An environmentally friendly and highly diastereoselective method for synthesizing indanes has been developed via a metastable-state photoacid system containing catalytic protonated merocyanine (MEH). Under visible-light irradiation, MEH yields a metastable spiro structure and liberated protons, which facilitates the formation of carbocations from benzyl alcohols, thus delivering diverse molecules in the presence of various nucleophiles. Mainly, a variety of indanes could be easily obtained from benzyl alcohols and olefins, and water is the only byproduct.

Tenecteplase vs. alteplase for the treatment of patients with acute ischemic stroke: a systematic review and meta-analysis.

BACKGROUND: At present, studies regarding the efficacy and safety of tenecteplase for the treatment of patients with acute ischemic stroke (AIS) are still limited and inconsistent. The purpose of this systematic review and meta-analysis is to compare the efficacy and safety of tenecteplase with alteplase for the treatment of AIS patients. METHODS: Literature search was conducted in PubMed, Embase, and Cochrane Library up to May 10, 2022. Primary outcomes of this study included 90-day good outcome (defined as an mRS score of 0-2) and 90-day excellent outcome (defined as an mRS score of 0-1). Risk ratios (RRs) with 95% confidence intervals (95% CIs) were calculated using a random-effect model for each outcome. RESULTS: Fourteen studies with a total of 3537 patients were finally included in this meta-analysis. There was no statistical difference between patients receiving tenecteplase and those receiving alteplase in the rates of 90-day good outcome (RR 1.01; 95% CI 0.91-1.13; P = 0.79) and 90-day excellent outcome (RR 1.04; 95% CI 0.92-1.19; P = 0.50). Patients receiving tenecteplase might associated with higher incidence of early neurologic improvement compared with those receiving alteplase (RR 1.29; 95% CI 1.04-1.61; P = 0.02). In addition, no statistical difference was observed between the two groups in other outcomes. CONCLUSION: This meta-analysis indicated that tenecteplase in AIS patients is as safe and effective as alteplase and might provide more benefit than alteplase. However, due to several inherent limitations of this study, more prospective studies should be conducted to confirm the above results.

Network pharmacology-based analysis and experimental in vitro validation on the mechanism of Paeonia lactiflora Pall. in the treatment for type I allergy.

BACKGROUND: The incidence of allergic reaction is increasing year by year, but the specific mechanism is still unclear. Paeonia lactiflora Pall.(PLP) is a traditional Chinese medicine with various pharmacological effects such as anti-tumor, anti-inflammatory, and immune regulation. Previous studies have shown that PLP has potential anti-allergic activity. However, there is still no comprehensive analysis of the targeted effects and exact molecular mechanisms of the anti-allergic components of PLP. This study aimed to reveal the mechanism of PLP. in the treatment of type I allergy by combining network pharmacological methods and experimental verification. METHODS: First, we used the traditional Chinese medicine systems pharmacology (TCMSP) database and analysis platform to screen the main components and targets of PLP, and then used databases such as GeneCards to retrieve target information related to 'allergy'. Protein-protein interaction (PPI) analysis obtained the core target genes in the intersection target, and then imported the intersection target into the David database for gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) analysis. Furthermore, the therapeutic effect of paeoniflorin, the main component of PLP, on IgE-induced type I allergy was evaluated in vitro. RESULTS: GO analysis obtained the main biological processes, cell components and molecular functions involved in the target genes. KEGG analysis screened out MAPK1, MAPK10, MAPK14 and TNF that have a strong correlation with PLP anti-type I allergy, and showed that PLP may pass through signal pathways such as IgE/FcεR I, PI3K/Akt and MAPK to regulate type I allergy. RT-qPCR and Western Blot results confirmed that paeoniflorin can inhibit the expression of key genes and down-regulate the phosphorylation level of proteins in these signal pathways. It further proved the reliability of the results of network pharmacology research. CONCLUSION: The results of this study will provide a basis for revealing the multi-dimensional regulatory mechanism of PLP for the treatment of type I allergy and the development of new drugs.

Intraductal oncocytic papillary neoplasm arising in Peutz-Jeghers Syndrome bile duct: a unique case report.

BACKGROUND: Peutz-Jeghers syndrome (PJS) is a rare, autosomal dominant disorder caused by germline mutations of STK11/LKB1, with an increased risk of tumors at multiple sites. Intraductal oncocytic papillary neoplasm (IOPN) is a unique subtype of intraductal papillary neoplasm of the bile duct (IPNB) defined by a premalignant neoplasm with intraductal papillary or villous growth of biliary-type epithelium. IOPN has a distinct mutation profile compared with both IPNB and intraductal papillary mucinous neoplasm (IPMN). CASE PRESENTATION: We herein describe the case of a 44-year-old woman who presented as polyps in the intestinal lumen of sigmoid colon and a 3.1 × 2.1 cm mass in the left lobe of liver. Gross feature revealed a cystic papillary mass and the neoplasm had a clear boundary with the surrounding liver tissue. Histology revealed complex papillary structures, a small amount of fine fibrovascular cores and immunohistochemistry showed extensive positive for MUC5AC, MUC6, CD117. Therefore, histological and immunohistochemical examination of the liver tumor suggested the diagnosis of IOPN. Next-generation sequencing (NGS) revealed other than STK11 germline mutation, the tumor also harbors GNAS somatic mutation at codon 478 and EGFR amplification. CONCLUSION: To our knowledge, this is the first report of IOPN arising in PJS. This case enlarges the spectrum of PJS related tumors and genetic rearrangements in IOPN.

Genome-Wide Association Studies Reveal Candidate Genes Related to Stem Diameter in Cucumber (Cucumis sativus L.).

The stem diameter, an important agronomic trait, affects cucumber growth and yield. However, no genes responsible for cucumber stem diameter have been identified yet. In this study, the stem diameter of 88 cucumber core germplasms were measured in spring 2020, autumn 2020 and autumn 2021, and a genome-wide association study (GWAS) was carried out based on the gene sequence and stem diameter of core germplasms. A total of eight loci (gSD1.1, gSD2.1, gSD3.1, gSD3.2, gSD4.1, gSD5.1, gSD5.2, and gSD6.1) significantly associated with cucumber stem diameter were detected. Of these, five loci (gSD1.1, gSD2.1, gSD3.1, gSD5.2, and gSD6.1) were repeatedly detected in two or more seasons and were considered as robust and reliable loci. Based on the linkage disequilibrium sequences of the associated SNP loci, 37 genes were selected. By further investigating the five loci via analyzing Arabidopsis homologous genes and gene haplotypes, five genes (CsaV3_1G028310, CsaV3_2G006960, CsaV3_3G009560, CsaV3_5G031320, and CsaV3_6G031260) showed variations in amino acid sequence between thick stem lines and thin stem lines. Expression pattern analyses of these genes also showed a significant difference between thick stem and thin stem lines. This study laid the foundation for gene cloning and molecular mechanism study of cucumber stem development.