The Role of Noncoding RNA Antisense Transcript of the B-Cell Translocation Gene 3 Regulation of BTG3 in Pancreatic Ductal Adenocarcinoma Tumor Progression.

Background: Antisense transcript of the B-cell translocation gene 3 (ASBEL) is a highly conserved antisense non-coding RNA (ncRNA) and participates in a variety of biological processes. However, the ASBEL expression status in pancreatic ductal adenocarcinoma (PDAC) and its correlation with BTG3 expression and tumor cell progression were not completely clear. Objective: We conducted cell experiments and animal experiments to confirm that ASBEL plays a crucial role in the tumorigenesis of PDAC by targeting BTG3. Methods: ASBEL regulation in PDAC tumorigenesis was evaluated using Western blotting, quantitative polymerase chain reaction, Cell Counting Kit-8 assay, flow cytometry, and cell transfection. We also evaluated the expression of ASBEL and BTG3 in tumor tissues and cells using Western blotting and quantitative real-time polymerase chain reaction. Finally, we explored the role of ASBEL in tumor development by silencing or overexpressing ASBEL gene in AsPC-1 or CFPAC-1 cells, respectively, and evaluated the antitumor activity in vivo using an ASBEL antagonist. Results: Our study revealed the expression of ASBEL in all pancreatic cell lines. The expression level of ASBEL in tumor tissues was found to be higher than that of paracarcinomatous tissues. ASBEL suppresses expression of BTG3, enhances proliferation and suppresses apoptosis, and promotes migration and invasion in pancreatic cancer cell. Antagonist regulates the expression of ASBEL in AsPC-1, and suppresses tumor growth in xenograft mouse model. Conclusions: Our results indicate that ASBEL may play a tumor-promoting factor in PDAC by targeting BTG3 and could be as an important biomarker for PDAC treatment. (Curr Ther Res Clin Exp. 2023; 84:XXX-XXX).

Surface-anchored microbial enzyme-responsive solid lipid nanoparticles enabling colonic budesonide release for ulcerative colitis treatment.

Colon-targeted oral drug delivery systems (CDDSs) are desirable for the treatment of ulcerative colitis (UC), which is a disease with high relapse and remission rates associated with immune system inflammation and dysregulation localized within the lining of the large bowel. However, the success of current available approaches used for colon-targeted therapy is limited. Budesonide (BUD) is a corticosteroid drug, and its rectal and oral formulations are used to treat UC, but the inconvenience of rectal administration and the systemic toxicity of oral administration restrict its long-term use. In this study, we designed and prepared colon-targeted solid lipid nanoparticles (SLNs) encapsulating BUD to treat UC by oral administration. A negatively charged surfactant (NaCS-C12) was synthesized to anchor cellulase-responsive layers consisting of polyelectrolyte complexes (PECs) formed by negatively charged NaCS and cationic chitosan onto the SLNs. The release rate and colon-specific release behavior of BUD could be easily modified by regulating the number of coated layers. We found that the two-layer BUD-loaded SLNs (SLN-BUD-2L) with a nanoscale particle size and negative zeta potential showed the designed colon-specific drug release profile in response to localized high cellulase activity. In addition, SLN-BUD-2L exhibited excellent anti-inflammatory activity in a dextran sulfate sodium (DSS)-induced colitis mouse model, suggesting its potential anti-UC applications.

Multi-Omics Analysis of the Prognostic and Immunological Role of Runt-Related Transcription Factor 3 in Pan-Cancer.

Runt-related transcription factor 3 (RUNX3) plays a pivotal role in tumor microenvironment and immune infiltration. However, the prognostic and immunological roles of RUNX3 in pancancer remain unclear. In the current study, we explored the expression profiles, prognostic landscape, and immune infiltration of RUNX3 in pancancer through a variety of online platforms, including HPA, ONCOMINE, UALCAN, GEPIA, PrognoScan, TCGA, TIMER, R2, and Reactome databases. In general, RUNX3 was widely expressed in tonsil, gallbladder, skin, spleen, lymph node, and bone marrow, and RUNX3 was frequently higher expression in tumor tissues compared to normal tissues. In prognostic analysis, the RUNX3 expression level was significantly correlated with the clinical outcomes of bladder cancer, blood cancer, brain cancer, breast cancer, colorectal cancer, lung cancer, and ovarian cancer. In mutation analysis, a total 72 mutation sites were located within amino acids 1 to 415 of RUNX3, including 65 missense sites and seven truncating sites, whereas the mutation frequency of skin cutaneous melanoma and uterine corpus endometrial carcinoma (UCEC) is relatively high (> 3%). In immune infiltration analysis, the RUNX3 expression level was significantly related to recognized markers and the immune infiltration levels of various types of immune cells in colon adenocarcinoma (COAD) and brain lower grade glioma (LGG). After that, 453 RUNX3 co-expressed genes were recognized in COAD, lymphoid neoplasm diffuse large B-cell lymphoma, LGG, and ovarian serous cystadenocarcinoma (OV). Pathway enrichment analysis revealed that RUNX3 co-expressed genes were remarkably enriched in immune system and tumor progression pathways. RUNX3 expression is associated with clinical prognosis, immune infiltration, and identified RUNX3 related pathways in a variety of tumors, which may serve as targets of promising prognostic markers and novel therapeutic targets for various human cancers.

Shaping Liquid Droplets on an Active Air-Ferrofluid Interface.

An air-liquid interface is important in many biological and industrial applications, where the manipulation of liquids on the air-liquid interface can have a significant impact. However, current manipulation techniques on the interface are mostly limited to transportation and trapping. Here, we report a magnetic liquid shaping method that can squeeze, rotate, and shape nonmagnetic liquids on an air-ferrofluid interface with programmable deformation. We can control the aspect ratio of the ellipse and generate repeatable quasi-static shapes of a hexadecane oil droplet. We can rotate droplets and stir liquids into spiral-like structures. We can also shape phase-changing liquids and fabricate shape-programmed thin films at the air-ferrofluid interface. The proposed method may potentially open up new possibilities for film fabrication, tissue engineering, and biological experiments that can be carried out at an air-liquid interface.

Carbonized human hair derived carbon dots for detection of clozapine.

Clozapine (CLZ) is known as the most effective antipsychotic medication for schizophrenia. However, low dosage or over dosage of CLZ is adverse to the treatment of Schizophrenia. Thus, it is necessary to develop effective detection method for CLZ. Recently, due to the advantages such as excellent optical properties, good photobleachability and sensitivity, carbon dots (CDs)-based fluorescent sensors for the detection of target analytes have drawn a great deal of attention. In this work, blue fluorescent CDs (Named as B-CDs) with quantum yield (QY) as high as 38% were obtained by using carbonized human hair as source material through one-step dialysis method for the first time. B-CDs showed obvious graphite-like structure with an average of 1.76 nm, containing abundant functional groups such as -C=O, amino N and C-N on the surface of carbon cores. Optical analysis showed that the B-CDs exhibited excitation-dependent emission property with maximum emission wavelength of 450 nm. Moreover, B-CDs were further applied as a fluorescence sensor to the detection of CLZ. The B-CDs based sensor exhibited a good quenching response by CLZ through the inner filter effect and static quenching mechanism with a limit of detection of 67 ng/mL, which was much lower than the minimal effective concentration in blood (0.35 µg/mL). Finally, to test the practical application value of the developed fluorescence method, the determination of the content of CLZ in tablets and the concentration in blood was carried out. Compared with the results of high-performance liquid chromatography (HPLC) method, it can be found that the constructed fluorescence detection method showed high accuracy and had great application potential in the detection of CLZ. Additionally, the results of cytotoxicity experiment showed that B-CDs had low cytotoxicity, which laid the foundation for the subsequent application of B-CDs in biological systems.

Red Cell Distribution Width-to-Platelet Count Ratio: A Promising Predictor of In-Hospital All-Cause Mortality in Critically Ill Patients with Acute Ischemic Stroke.

INTRODUCTION: The red blood cell distribution width-to-platelet ratio (RPR), a novel inflammatory index, has already been proven as a prognostic factor in some other diseases, but its prognostic effect on critically ill patients with acute ischemic stroke (AIS) has been rarely investigated. This study aimed to investigate the association between RPR and in-hospital mortality in these patients. METHODS: We extracted clinical data from the Medical Information Mart for Intensive Care IV 1.0 database. The primary outcome was in-hospital all-cause mortality of patients with critical AIS. The main independent variable was RPR. To investigate the association between RPR and in-hospital all-cause mortality in patients with critical AIS, multivariable logistic analyses, smooth curve fitting, and stratified analyses were conducted. RESULTS: In total, 2,673 patients with AIS who were admitted to the intensive care unit were included in the study. In the multivariable analysis, in-hospital mortality was positively related to RPR (odds ratio [OR] 1.28, 95% confidence interval [CI] 1.02-1.59). According to the two-piecewise logistic regression model, we found that the inflection point of RPR was 1.89%. To the left of the inflection point (RPR ≤1.89%), we did not detect any relationship between RPR and in-hospital all-cause mortality (OR [95% CI]: 0.73 [0.41, 1.31], p = 0.2884). In contrast, to the right of the inflection point (RPR >1.89%), RPR was positively related to in-hospital all-cause mortality (OR [95% CI]: 1.61 [1.18, 2.19], p = 0.0027). CONCLUSIONS: RPR showed a nonlinear relationship with in-hospital all-cause mortality in patients with critical AIS.

Association of Long-term exposure to air pollution and residential greenness with lipid profile: Mediating role of inflammation.

Lipidemic effect of air pollutants are still inconsistent and their joint effects are neglected. Meanwhile, identified inflammation pathways in animal have not been applied in epidemiological studies, and beneficial effect of residential greenness remained unclear. Therefore, we used data from typically air-polluted Chinese cities to answer these questions. Particulate matter (PM) with a diameter of ≤ 1 µm (PM1), PM with a diameter of ≤ 2.5 µm (PM2.5), PM with a diameter of ≤ 10 µm (PM10), sulphur dioxide (SO2), nitrogen dioxide (NO2), and ozone (O3) were predicted by space-time extremely randomized trees model. Residential greenness was reflected by Normalized Difference Vegetation Index (NDVI). Total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were measured, and atherogenic coefficient (AC) and TG/HDL-C (TGH) ratio were calculated to indicate lipid metabolism. Generalized additive mixed model and quantile g-computation were respectively conducted to investigate individual and joint lipidemic effect of air pollutants. Covariates including demographical characteristics, living habits, meteorological factors, time trends, and disease information were considered to avoid confounding our results. Complement C3 and high-sensitivity C-reactive protein (hsCRP) were analyzed as potential mediators. Finally, association between NDVI and lipid markers were explored. We found that long-term air pollutants exposure were positively associated with lipid markers. Complement C3 mediated 54.72% (95% CI: 0.30, 63.10) and 72.53% (95% CI: 0.65, 77.61) of the association between PM1 and TC and LDL-C, respectively. We found some significant associations of lipid markers with NDVI1000 m rather than NDVI500 m. BMI, disease status, smoke/drink habits are important effect modifiers. Results are robust in sensitive analysis. Our study indicated that air pollutants exposure may detriment lipid metabolism and inflammation may be the potential triggering pathways, while greenness may exert beneficial effects. This study provided insights for the lipidemic effects of air pollution and greenness.

Development and validation of novel prognostic models for zinc finger proteins-related genes in soft tissue sarcoma.

As the most common transcriptional regulators, zinc finer proteins (ZNFs) play vital roles in occurrence and progression of malignant tumors. Whereas, information regarding the roles of ZNFs in soft tissue sarcomas (STS) remains scarce. In this study, a comprehensive bioinformatics analysis investigating roles of ZNFs in STS was performed. Initially, we extracted raw datasets of differentially expressed ZNFs from GSE2719. Using a sequence of bioinformatics methods, we then investigated the prognostic significance, function, and molecular subtype of these differentially expressed ZNFs. In addition, CCK8 and plate clone formation assays were used to explore the effect of ZNF141 on STS cells. A total of 110 differentially expressed ZNFs were identified. Nine ZNFs (HLTF, ZNF292, ZNF141, LDB3, PHF14, ZNF322, PDLIM1, NR3C2, and LIMS2) were selected to establish an overall survival (OS) prediction model, and seven ZNFs (ZIC1, ZNF141, ZHX2, ZNF281, ZNHIT2, NR3C2, and LIMS2) were used to develop a progression-free survival (PFS) prediction model. Compared with patients with low-risk in the TCGA training and testing cohorts, as well as the GEO validation cohorts, patients with high-risk had poorer OS and PFS. Using nomograms constructed with the identified ZNFs predicting OS and PFS, we established a clinically useful model. Four distinct molecular subtypes with different prognostic and immune infiltration characteristics were identified. In vitro experiments showed that ZNF141 promoted the proliferation and viability of STS cells. In conclusion, ZNF-related models are useful as prognostic biomarkers, suggesting their potentials as therapeutic targets in STS. These findings will enable us to develop novel strategies treating STS, which will potentially improve outcomes of patients with STS.

Quantitative analysis of the minimum days of dietary survey to estimate dietary pesticide exposure: Implications for dietary pesticide sampling strategy.

Populations are exposed to pesticides through diet on a daily basis. However, there is no research guiding how to evaluate dietary pesticide exposure, and researchers used 1-day, 3-days, 7-days or even longer dietary survey to evaluate without any consensus. It is important for dietary pesticide evaluation to identify the minimum survey days. To increase knowledge of this, a data combination was applied between a two-wave consecutive repeated-measures study in Baoding City and the Fifth China Total Diet Study. Further policy consistency on pesticides were evaluated to explain its credibility. We computed the sensitivity and specificity to evaluate how well different days of dietary survey classify participants with high exposure, and calculated the minimum days required to estimate the participant-specific mean at different acceptable error range. With 1 day of dietary survey, the classification sensitivity was low (<0.6) for total HCH, endosulfan, chlordane, cyhalothrin, allethrin, and prallethrin; that for the other pesticides was high sensitivity (≥0.6). Sensitivity increased as the number of days increased, and the maximum marginal sensitivity increase (≥0.039) occurred from 1 to 2 days for all pesticides except phenothrin, whose maximum marginal sensitivity increase (0.042) occurred from 2 to 3 days. The specificity increased gradually from 0.8 to 0.9 from 1 to 7 days. Under the acceptable error range of 0.5%, 3-28 days were required for participant-specific mean estimation and 1-7 days were required when acceptable error range was shrunk in 1%. Only 1 day was enough if 5% error range was acceptable. In conclusion, 3 days in the study period was cost-effective to distinguish high exposure group, and it rose to 7 when estimating participant-specific mean from a conservative perspective. This study can serve as a reference to determine the minimum survey days for epidemiological studies employing dietary surveys.

The Application of Reference Dose Prediction Model to Human Health Water Quality Criteria and Risk Assessment.

Oral reference dose (RfD) is a key parameter for deriving the human health ambient water quality criteria (AWQC) for non-carcinogenic substances. In this study, a non-experimental approach was used to calculate the RfD values, which explore the potential correlation between toxicity and physicochemical characteristics and the chemical structure of pesticides. The molecular descriptors of contaminants were calculated using T.E.S.T software from EPA, and a prediction model was developed using a stepwise multiple linear regression (MLR) approaches. Approximately 95% and 85% of the data points differ by less than 10-fold and 5-fold between predicted values and true values, respectively, which improves the efficiency of RfD calculation. The model prediction values have certain reference values in the absence of experimental data, which is beneficial to the advancement of contaminant health risk assessment. In addition, using the prediction model constructed in this manuscript, the RfD values of two pesticide substances in the list of priority pollutants are calculated to derive human health water quality criteria. Furthermore, an initial assessment of the health risk was performed by the quotient value method based on the human health water quality criteria calculated by the prediction model.

Association between albumin corrected anion gap and 30-day all-cause mortality of critically ill patients with acute myocardial infarction: a retrospective analysis based on the MIMIC-IV database.

BACKGROUND: The anion gap (AG) has been linked to the prognosis of many cardiovascular disorders. However, the correlation between albumin-corrected anion gap (ACAG) and 30 d all-cause mortality of intensive care patients with acute myocardial infarction (AMI) is unclear. Furthermore, owing to the lack of studies, it is also unknown whether ACAG is more accurate than AG in predicting the mortality of AMI. METHODS: The Medical Information Mart for Intensive Care IV (MIMIC IV) dataset was used to provide patient data in this retrospective cohort study. ACAG is computed using the formulae: [4.4-{albumin (g/dl)}] × 2.5 + AG. The primary outcome was 30 d all-cause mortality intensive care patients with AMI. To explore the prognostic worthiness of ACAG, the receiver operating characteristic curve, smooth curve fitting, Cox regression model, and Kaplan survival analysis was performed. RESULTS: We enrolled 2,160 patients in this study. ACAG had a better predictive value for 30 d all-cause mortality than AG, with an area under the curve of 0.66. The association between ACAG levels and overall mortality was nonlinear. In our model, after correcting for confounding factors, the ACAG was the independent predictor for 30 d all-cause mortality (HR 1.75, 95%CI 1.24, 2.47). ACAG K-M estimator curve analyses revealed that the group with ACAG ≥ 21.75 mmol/l had poor survival rate than the other group. CONCLUSIONS: High serum ACAG levels were a significant risk factor for 30 d all-cause mortality in critically ill patients with AMI. ACAG concentration and 30 d all-cause mortality had a nonlinear relationship. ACAG had better predictive value in identifying 30 d all-cause mortality of patients with AMI in ICU than the AG.

Association of estimated glomerular filtration rate and all-cause mortality in acute pancreatitis: a retrospective analysis.

BACKGROUND: Our primary objective was to explore the association between estimated glomerular filtration rate (eGFR) and all-cause mortality in acute pancreatitis (AP) admission to intensive care units. METHODS: This study is a retrospective cohort analysis based on the Medical Information Mart for Intensive Care III database. The eGFR was calculated based on Chronic Kidney Disease Epidemiology Collaboration equation. Cox models with restricted cubic spline functions were used to evaluated the association of eGFR with all-cause mortality. RESULTS: The mean eGFR was 65.93 ± 38.56 ml/min/1.73 m2 in 493 eligible patients. 28-day mortality was 11.97% (59/ 493), which decreased by 15% with every 10 ml/min/1.73 m2 increase in eGFR. The adjusted hazard ratio (95% confidence interval) was 0.85 (0.76-0.96). A non-linear association was proved between eGFR and all-cause mortality. When eGFR < 57 ml/min/1.73 m2, there was a negative correlation between eGFR and 28-day mortality, hazard ratio (95% CI) was 0.97 (0.95, 0.99). The eGFR was also negatively correlated with in-hospital and in-ICU mortality. Subgroup analysis confirmed that the association between eGFR and 28-day mortality in different characteristics was stable. CONCLUSIONS: The eGFR was negatively correlated with all-cause mortality in AP when eGFR is less than the threshold inflection point.

Geometry-mediated bridging drives nonadhesive stripe wound healing.

Wound healing through reepithelialization of gaps is of profound importance to the medical community. One critical mechanism identified by researchers for closing non-cell-adhesive gaps is the accumulation of actin cables around concave edges and the resulting purse-string constriction. However, the studies to date have not separated the gap-edge curvature effect from the gap size effect. Here, we fabricate micropatterned hydrogel substrates with long, straight, and wavy non-cell-adhesive stripes of different gap widths to investigate the stripe edge curvature and stripe width effects on the reepithelialization of Madin-Darby canine kidney (MDCK) cells. Our results show that MDCK cell reepithelization is closely regulated by the gap geometry and may occur through different pathways. In addition to purse-string contraction, we identify gap bridging either via cell protrusion or by lamellipodium extension as critical cellular and molecular mechanisms for wavy gap closure. Cell migration in the direction perpendicular to wound front, sufficiently small gap size to allow bridging, and sufficiently high negative curvature at cell bridges for actin cable constriction are necessary/sufficient conditions for gap closure. Our experiments demonstrate that straight stripes rarely induce cell migration perpendicular to wound front, but wavy stripes do; cell protrusion and lamellipodia extension can help establish bridges over gaps of about five times the cell size, but not significantly beyond. Such discoveries deepen our understanding of mechanobiology of cell responses to curvature and help guide development of biophysical strategies for tissue repair, plastic surgery, and better wound management.

Neoadjuvant therapy with camrelizumab plus gemcitabine and cisplatin for patients with muscle-invasive bladder cancer: A multi-center, single-arm, phase 2 study.

BACKGROUND: Neoadjuvant chemotherapy followed by radical cystectomy (RC) is the standard of care for patients with muscle-invasive bladder cancer (MIBC). However, treatment outcomes are suboptimal. Camrelizumab, a PD-1 blockade, has shown benefits in several tumors. This study aimed to investigate the efficacy and safety of neoadjuvant camrelizumab in combination with gemcitabine plus cisplatin (GC) followed by RC for MIBC patients. METHODS: This was a multi-center, single-arm study that enrolled MIBC patients with a clinical stage of T2-4aN0-1M0, and scheduled for RC. Patients received three 21-day cycles of camrelizumab 200 mg on day 1, gemcitabine 1000 mg/m2 on day 1 and 8, and cisplatin 70 mg/m2 on day 2, followed by RC. The primary endpoint was pathologic complete response (pCR, pT0N0). RESULTS: From May 2020 to July 2021, 43 patients were enrolled and received study medications at nine centers in China. Three of them were deemed ineligible and excluded from efficacy analysis but included in safety analysis. In total 10 patients were unevaluable as they declined RC (two due to adverse events [AEs] and eight due to patient's willingness). Among 30 evaluable patients, 13 patients (43.3%) achieved pCR, and 16 patients (53.3%) achieved pathologic downstaging. No AEs leading to death were observed. The most common AEs were anemia (69.8%), decreased white blood cell count (65.1%), and nausea (65.1%). Immune-related AEs were all grade 1 or 2. Pathologic response was not correlated with PD-L1 expression status or tumor mutation burden. Individual genes as a biomarker for pathologic response were not identified. CONCLUSIONS: Neoadjuvant treatment with camrelizumab and GC regimen demonstrated preliminary anti-tumor activity for MIBC patients with manageable safety profiles. The study met its primary endpoint, and the following randomized trial is ongoing.

Medical Image Classification Using Light-weight CNN with Spiking Cortical Model Based Attention Module.

In the field of disease diagnosis where only a small dataset of medical images may be accessible, the light-weight convolutional neural network (CNN) has become popular because it can help to avoid the over-fitting problem and improve computational efficiency. However, the feature extraction capability of the light-weight CNN is inferior to that of the heavy-weight counterpart. Although the attention mechanism provides a feasible solution to this problem, the existing attention modules, such as the squeeze and excitation module and the convolutional block attention module, have insufficient non-linearity, thereby influencing the ability of the light-weight CNN to discover the key features. To address this issue, we have proposed a spiking cortical model based global and local (SCM-GL) attention module. The SCM-GL module analyzes the input feature maps in parallel and decomposes each map into several components according to the relation between pixels and their neighbors. The components are weighted summed to obtain a local mask. Besides, a global mask is produced by discovering the correlation between the distant pixels in the feature map. The final attention mask is generated by combining the local and global masks, and it is multiplied by the original map so that the important components can be highlighted to facilitate accurate disease diagnosis. To appreciate the performance of the SCM-GL module, this module and some mainstream attention modules have been embedded into the popular light-weight CNN models for comparison. Experiments on the classification of brain MR, chest X-ray, and osteosarcoma image datasets demonstrate that the SCM-GL module can significantly improve the classification performance of the evaluated light-weight CNN models by enhancing the ability of discovering the suspected lesions and it is generally superior to state-of-the-art attention modules in terms of accuracy, recall, specificity and F1 score.

Abscopal effect triggered by radiation sequential mono-immunotherapy resulted in a complete remission of PMMR sigmoid colon cancer.

Background: Radiation therapy combined with immune checkpoint inhibitors (ICIs) has recently turned into an appealing and promising approach to enhance the anti-tumor immunity and efficacy of immunological drugs in many tumors. Abscopal effect induced by radiation is a phenomenon that often leads to an efficient immunity response. In this study, we investigated whether the combination of the immunogenic effects derived from radiotherapy sequential ICIs-based therapy could increase the incidence of abscopal effects, and improve the survival rates. Case presentation: We described a clinical case regarding a 35-year-old male patient who was admitted to our hospital with a diagnosis of adenocarcinoma of the sigmoid colon and synchronous multiple liver metastases following a surgical resection. The molecular pathological examination showed immune-desert phenotype and proficient mismatch repair (pMMR). The patient was treated with adjuvant chemotherapy after surgery, however, after 7 months, multiple metastasis in the pelvic lymph nodes were diagnosed. Unfortunately, the tumor progressed despite multiple cycles of chemotherapy combined with cetuximab or bevacizumab. Within the follow-up treatment, the patient was administered with only 50Gy/25F of radiation dose to treat the anastomotic lesions. Subsequently, mono-sindilizumab was used as systemic therapy, leading to a rapid reduction of all pelvic lesions and complete clinical remission. So far, the patient survived for more than 20 months under continuous mono-sindilizumab treatment and is still in complete remission. Conclusion: A localized radiotherapy combined with a sindilizumab-based systemic therapy may overcome the immune resistance of pMMR metastatic colorectal cancer (mCRC), thus obtaining greater efficacy of the therapy. Its mechanism may be related to the abscopal effect obtained by the synergistic use of radiation and sindilizumab, which should be further investigated in the future.

Knowledge mapping and visualization analysis of pelvic organ prolapse repair with mesh from 2001 to 2021.

Aims: In recent decades, extensive attention has been paid to the application of mesh to repair pelvic floor defects. However, a large body of related literature has not been system summarized. The purpose of this study is to summarize and visualize the literature on pelvic organ prolapse (POP) repair with mesh using bibliometrics. Methods: Medical literature regarding POP repair with mesh were searched and obtained in the Web of Science™ Core (WoSCC) database from 2001 to 2021. Microsoft Excel 2020, CiteSpace and VOSviewer were used to conduct the bibliometric and knowledge-map analysis. Results: In the past 20 years, a total of 2,550 articles and reviews have been published in 35 journals, and the published and cited results show a growing trend. Cosson M and International Urogynecology Journal were the authors and journals with the highest output, respectively. The United States, France and the United Kingdom are among the top three countries/organizations in relevant publications in worldwide. 584 key words in the literature are divided into 8 clusters, which are mainly related to prolapse type, risk factors, surgical methods, imaging, quality of life and bioengineering. Using clinical research and tissue engineering technology to reduce mesh complications is the current hot spot in this field. Conclusion: Reasonable application of mesh and avoiding mesh complications are still the most concerned topics in POP research. Although clinical research, surgical improvement, biological mesh and bioengineering technology have shown promising results, it is still urgent to carry out clinical transformation application research.

Extracellular vesicles, hyperadhesive von willebrand factor, and outcomes of gastric cancer: a clinical observational study.

Von Willebrand factor (VWF) is an adhesive ligand critical for maintaining hemostasis. However, it has also been increasingly recognized for its role in cancer development because it has been shown to mediate the adhesion of cancer cells to endothelial cells, promote the epithelial-mesenchymal transition, and enhance angiogenesis. We have previously shown that gastric cancer cells synthesize VWF, which mediates the interaction between the cancer and endothelial cells to promote cancer growth. Here, we report results from a clinical observational study that demonstrate the association of VWF in plasma and on the surface of extracellular vesicles (EVs) with the pathological characteristics of gastric cancer. We found that patients with gastric cancer had elevated and intrinsically hyperadhesive VWF in their peripheral blood samples. VWF was detected on the surface of EVs from cancer cells, platelets, and endothelial cells. Higher levels of these VWF-bound EVs were associated with cancer aggression and poor clinical outcomes for patients. These findings suggest that VWF+ EVs from different cell types serve collectively as a new class of biomarkers for the outcome assessment of gastric cancer patients.

Identification and in vitro functional assessment of 10 CYP2C9 variants found in Chinese Han subjects.

Cytochrome P450 2C9 (CYP2C9) participates in about 15% of clinical drug metabolism, and its polymorphism is associated with individual drug metabolism differences, which may lead to the adverse drug reactions (ADRs). In this study, 1163 Chinese Han individuals were recruited to investigate their distribution pattern of CYP2C9 gene and find out the variants that may affect their drug metabolic activities. We successfully developed a multiplex PCR amplicon sequencing method and used it for the genetic screening of CYP2C9 in a large scale. Besides the wild type CYP2C9*1, totally 26 allelic variants of CYP2C9 were detected, which included 16 previously reported alleles and 10 new non-synonymous variants that had not been listed on the PharmVar website. The characteristics of these newly detected CYP2C9 variants were then evaluated after co-expressing them with CYPOR in S. cerevisiae microsomes. Immunoblot analysis revealed that except for Pro163Ser, Glu326Lys, Gly431Arg and Ile488Phe, most of newly detected variants showed comparable protein expression levels to wild type in yeast cells. Two typical CYP2C9 probe drugs, losartan and glimepiride, were then used for the evaluation of metabolic activities of variants. As a result, 3 variants Thr301Met, Glu326Lys, and Gly431Arg almost lost their catalytic activities and most of other variants exhibited significantly elevated activities for drug metabolism. Our data not only enriches the knowledge of naturally occurring CYP2C9 variants in the Chinese Han population, but also provides the fundamental evidence for its potential clinical usage for personalized medicine in the clinic.