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Qi-Zhu Feng,1– 3 Xian-Zhi Chen,2 Jie Sun,4 Man-Man Lu,5 Yong Wang,6 Qi Wang,4 Chao Zhang1,3 1Department of General Surgery, First Affiliated Hospital of Anhui Medical University, Hefei, 230032, Anhui, People’s Republic of China; 2Department of Breast Surgery, First Affiliated Hospital of Anhui University of Science and Technology (Huainan First People’s Hospital), Huainan, 232007, Anhui, People’s Republic of China; 3School of Continuing Education, Anhui Medical University, Hefei, 230032, Anhui, People’s Republic of China; 4Department of General Surgery, First Affiliated Hospital of Anhui University of Science and Technology (Huainan First People’s Hospital), Huainan, 232007, Anhui, People’s Republic of China; 5Department of Laboratory Medicine, First Affiliated Hospital of Anhui University of Science and Technology (Huainan First People’s Hospital), Huainan, 232007, Anhui, People’s Republic of China; 6Department of Medical Oncology, First Affiliated Hospital of Anhui University of Science and Technology (Huainan First People’s Hospital), Huainan, 232007, Anhui, People’s Republic of ChinaCorrespondence: Chao ZhangDepartment of General Surgery, First Affiliated Hospital of Anhui Medical University, Hefei, 230032, Anhui, People’s Republic of ChinaTel +86-13956053990Email zhangchaolove88@163.comObjective: To explore the influence of trastuzumab (TZ) combined with docetaxel (DTX) on serum tumor markers (TMs) in the treatment of human epidermal growth factor receptor 2-positive (HER-2+) breast cancer (BC) and to analyze the factors influencing therapeutic efficacy.Methods: Ninety-six patients with HER-2+ BC treated in the First Affiliated Hospital of Anhui University Of Science and Technology from January 2019 to December 2020 were selected. According to different treatment plans, the patients were divided into two arms with 48 cases each. The control group (CG) was treated with DTX, and the research group (RG) was given TZ combined with DTX (TZ+DTX). The two arms were compared regarding the following aspects: curative effects, adverse reaction, alterations of TMs and inflammatory factors (IFs), and quality of life. Logistic regression analysis was performed to analyze the factors affecting the efficacy of patients.Results: After treatment, the TMs carcinoembryonic antigen (CEA), carbohydrate antigen (CA)125 and CA15-3 were significantly lower in RG compared with CG. The levels of IFs C-reactive protein (CRP) and tumor necrosis factor-α (TNF-α) were also lower in CG. The overall response rate and the Karnofsky performance status (KPS) score were significantly higher in RG. No evident difference was observed in the total incidence of adverse reactions between the two arms. The high expression of CEA, CA125 and CA15-3 as well as DTX monotherapy increased the risk of adverse prognosis.Conclusion: TZ+DTX can effectively improve the clinical efficacy of HER-2+ BC patients and reduce their levels of serum TMs and IFs.Keywords: trastuzumab combined with docetaxel, HER-2+ breast cancer, tumor markers, analysis of therapeutic factors

Meng-meng Lu,1,2 Yuran Ge,1,2 Jing Qiu,1,2 Dan Shao,3 Yue Zhang,4 Jing Bai,4 Xiao Zheng,5 Zhi-min Chang,3 Zheng Wang,3 Wen-fei Dong,3 Chun-bo Tang1,2 1Department of Oral Implantology, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, 210029, China; 2Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, 210029, China; 3CAS Key Laboratory of Bio-Medical Diagnostics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, 215163, China; 4School of Materials Science and Engineering, Southeast University, Nanjing, 211189, China; 5Department of Pharmacology, Nanomedicine Engineering Laboratory of Jilin Province, College of Basic Medical Sciences, Jilin University, Changchun, 130021, China Background: Oral plaque biofilms pose a threat to periodontal health and are challenging to eradicate. There is a growing belief that a combination of silver nanoparticles and chlorhexidine (CHX) is a promising strategy against oral biofilms.Purpose: To overcome the side effects of this strategy and to exert maximum efficiency, we fabricated biodegradable disulfide-bridged mesoporous silica nanoparticles (MSNs) to co-deliver silver nanoparticles and CHX for biofilm inhibition.Materials and methods: CHX-loaded, silver-decorated mesoporous silica nanoparticles (Ag-MSNs@CHX) were fabricated after CHX loading, and the pH- and glutathione-responsive release profiles of CHX and silver ions along with their mechanism of degradation were systematically investigated. Then, the efficacy of Ag-MSNs@CHX against Streptococcus mutans and its biofilm was comprehensively assessed by determining the minimum inhibitory concentration, minimum bactericidal concentration, minimal biofilm inhibitory concentration, and the inhibitory effect on S. mutans biofilm formation. In addition, the biosafety of nanocarriers was evaluated by oral epithelial cells and a mouse model.Results: The obtained Ag-MSNs@CHX possessed redox/pH-responsive release properties of CHX and silver ions, which may be attributed to the redox-triggered matrix degradation mechanism of exposure to biofilm-mimetic microenvironments. Ag-MSNs@CHX displayed dose-dependent antibacterial activity against planktonic and clone formation of S. mutans. Importantly, Ag-MSNs@CHX had an increased and long-term ability to restrict the growth of S. mutans biofilms compared to free CHX. Moreover, Ag-MSNs@CHX showed less cytotoxicity to oral epithelial cells, whereas orally administered Ag-MSNs exhibited no obvious toxic effects in mice.Conclusion: Our findings constitute a highly effective and safe strategy against biofilms that has a good potential as an oral biofilm therapy. Keywords: biodegradable mesoporous silica nanoparticles, silver nanoparticles, chlorhexidine, GSH, pH-responsive release, biofilm, biocompatibility

Introduction and objectives The present study aimed to investigate different peripheral lymphocyte subsets in patients with severe hemophilia A (HA) and factor VIII (FVIII) inhibitor production. For this, age-matched cases of 19 FVIII inhibitor-positive (IP), 21 FVIII inhibitor-negative (IN) and 45 healthy controls were selected for study. Methods Flow cytometry was used to analyze the peripheral lymphocyte subsets, including T, B, natural killer (NK) and NKT cells. The T cell subsets included CD3 + CD4-CD8- [double negative T (DNT)], CD3 + CD4 + CD8+ [double-positive T (DPT)], CD3 + CD4 + CD8- and CD3 + CD4-CD8+ T cells. Pairwise comparisons of absolute lymphocyte subset values were conducted among the three groups. The cut-off value for absolute lymphocyte counts was determined using receiver operating characteristic curve analysis. Results The results demonstrated that the absolute values of DPT cells in the IN and IP groups were significantly lower than those in the healthy control group ( P = 0.007). The DNT values were also lower in severe HA patients with or without inhibitor than those in healthy subjects, but these differences were not statistically significant ( P = 0.053). In addition, the absolute value of CD4+ Th cells in the IP group was lower than that in the healthy controls ( P = 0.013). Although not statistically significant ( P = 0.064), the absolute values of NKT cells were higher in the IN group compared with the IP group, and higher in the IP group compared with the healthy control group. There were no statistically significant differences in total T, B, CD8 + and NK cells among the IN, IP and healthy control groups. The cut-off value for absolute CD4+ Th cells in the IN group was 598/µl, clinicians should be vigilant for possible FVIII inhibitor production, especially on days prior to FVIII exposure.

Objectives This two-center study aimed to establish a model for predicting the risk of lymph node metastasis in gastric cancer patients using machine learning (ML) and logistic regression (LR) algorithms, and to evaluate its predictive performance in clinical practice. Methods Data of a total of 369 patients who underwent radical gastrectomy in the Department of General Surgery of Affiliated Hospital of Xuzhou Medical University (Xuzhou, China) from March 2016 to November 2019 were collected and retrospectively analyzed as the training group. In addition, data of 123 patients who underwent radical gastrectomy in the Department of General Surgery of Jining First People's Hospital (Jining, China) were collected and analyzed as the verification group. Besides, 7 ML and logistic models were developed, including decision tree, random forest, support vector machine (SVM), gradient boosting machine (GBM), naive Bayes, neural network, and LR, in order to evaluate the occurrence of lymph node metastasis in patients with gastric cancer. The ML model was established following 10 cross-validation iterations within the training dataset, and subsequently, each model was assessed using the test dataset. The model's performance was evaluated by comparing the area under the receiver operating characteristic curve of each model. Results Compared with the traditional logistic model, among the 7 ML algorithms, except for SVM, the other models exhibited higher accuracy and reliability, and the influences of various risk factors on the model were more intuitive. Conclusion For the prediction of lymph node metastasis in gastric cancer patients, the ML algorithm outperformed traditional LR, and the GBM algorithm exhibited the most robust predictive capability.

Objective Tripartite motif-containing protein 11 (TRIM11), an E3 ubiquitin ligase, possesses a pro-tumor property. Still, the detailed functions of TRIM11 remain not well characterized in prostate cancer. Methods PC-3 and DU145 prostate cancer cells were transfected with small interfering RNAs (siRNAs) or lentiviruses for TRIM11 deficiency or overexpression, and microRNA-5193 (miR-5193) mimics were utilized for overexpressing miR-5193. Proliferation, apoptosis, migration, and invasion were examined through CCK-8, colony formation, flow cytometry, wound healing, and transwell assays. MAP kinase-extracellular signal-regulated kinase (MEK1/2) and extracellular signal-regulated kinase (ERK)1/2 activities were detected via immunoblotting. Murine xenograft models were established. Interactions of TRIM11 with miR-5193 were demonstrated via dual luciferase reporter. Results TRIM11 deficiency or miR-5193 overexpression exerted antiprostate cancer effects through suppression of proliferation, migration, and invasion as well as enhancement of apoptosis in PC-3 and DU145 cells. The mechanisms by which TRIM11 deficiency or miR-5193 overexpression involved the inactivation of MEK1/2 and ERK1/2. miR-5193 downregulated TRIM11 expressions in prostate cancer cells, and their interactions were confirmed. Further, up-regulated miR-5193 weakened the effects of TRIM11 overexpression on enhancing proliferation, migration, invasion, and activity of MEK1/2 and ERK1/2 as well as alleviating apoptosis of prostate cancer cells. In murine xenograft models, TRIM11 upregulation facilitated tumor growth, which was alleviated by miR-5193 overexpression. Conclusion These findings described the oncogenic role of TRIM11 in prostate cancer biology, which was post-transcriptionally modulated by miR-5193.

Background To investigate the differences between physicians in target delineation in intensity-modulated radiation therapy for nasopharyngeal carcinoma as well as their impact on target dose coverage. Methods Ninety-nine in-hospital patients were randomly selected for retrospective analysis, and the target volumes were delineated by 2 physicians. The target volumes were integrated with the original plans, and the differential parameters, including the Dice similarity coefficient (DSC), Hausdorff distance (HD), and Jaccard similarity coefficient (JSC) were recorded. The dose–volume parameters to evaluate target dose coverage were analyzed by superimposing the same original plan to the 2 sets of images on which the target volumes were contoured by the 2 physicians. The significance of differences in target volumes and dose coverage were evaluated using statistical analysis. Results The target dose coverage for different sets of target volumes showed statistically significant differences, while the similarity metrics to evaluate geometric target volume differences did not. More specifically, for PGTVnx, the median DSC, JSC, and HD were 0.85, 0.74, and 11.73, respectively; for PCTV1, the median values were 0.87, 0.77, and 11.78, respectively; for PCTV2, the median values were 0.90, 0.82, and 16.12, respectively. For patients in stages T3-4, DSC, and JSC were reduced but HD was increased compared to those in stages T1-2. Dosimetric analysis indicated that, for the target volumes, significant differences between the 2 physicians were found in D95, D99, and V100 for all the target volumes (ie, PGTVnx, PCTV1, and PCTV2) across the whole group of patients, as well as in patients with disease stages T3-4 and T1-2. Conclusions The target volumes delineated by the 2 physicians had a high similarity, but the maximal distances between the outer contours of the 2 sets were significantly different. In patients with advanced T stages, significant differences in dose distributions were found, stemming from the deviations of target delineation.

This study examines the interannual variability of the North Pacific high during boreal summer of 1979–2008 to understand how its leading modes are related to the two types of El Niño–Southern Oscillation (ENSO). In the observations, the first empirical orthogonal function mode (EOF1) is characterized by an in-phase variation between the western Pacific subtropical high (WPSH) and the northeastern Pacific subtropical high (NPSH), while the second mode (EOF2) is characterized by an out-of-phase WPSH–NPSH variation. The EOF1 mode dominates during the post early-1990s period and is a forced response to sea surface temperature (SST) variations over the maritime continent and tropical central Pacific (CP) regions related to developing CP ENSOs. Its in-phase WPSH–NPSH relationship is established through the ENSO-induced meridional atmospheric circulation, Pacific–North American pattern and eddy–zonal flow interaction over the North Pacific. In contrast, the EOF2 mode dominates prior to the early-1990s and is partially a forced response to tropical Indian Ocean (IO) and eastern Pacific (EP) SST variations related to decaying EP ENSOs and partially a coupled atmosphere–ocean response to western North Pacific SST variations. Of the 28 Atmospheric Model Intercomparison Project models, most (71 %) realistically simulate the EOF1 mode but only a few (14 %) simulate the EOF2 mode. The roughly 50 % underestimation in the strength of the EOF2 mode is due to model deficiencies in properly representing the atmospheric circulation responses to the IO and EP SST variations. This deficiency may be related to underestimations of the strength of the mean Walker circulation in the models.

Objective: Polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes (POEMS) syndrome is a rare monoclonal plasma cell proliferation disorder. At present, there is no unified treatment for POEMS syndrome. Here, we describe one case with POEMS syndrome with obvious neurological symptoms diagnosed in September 2020. We made a meta-­analysis to assess the efficacy of treatment strategies in recent years. Methods: We retrospectively analyzed the diagnosis and treatment of this patient, and searched relevant articles in PubMed, Embase, and MEDLINE databases using MedicalSubject Headings (MeSH) (eg, POEMS, Therapy, Drug Therapy, Biological Therapy, Combined Modality Therapy, Hematopoietic Stem Cell Transplantation, Immunotherapy, Molecular Targeted Therapy, Chemoradiotherapy, and Salvage Therapy) and free words, and performed the statistical analysis. Results: The patient's efficacy evaluation was complete response (CR) after treatment with ixazomib combined with autologous stem cell transplantation (ASCT). Overall, 20 articles consist of 6 clinical trials, 14 retrospective studies, and 936 patients were included in this meta-analysis. There was no significant difference in complete hematologic response (CR H ) rate between people who underwent ASCT and those who did not. However, ASCT might have a better survival rate. Conclusions: Ixazomib combined with ASCT therapy may be a safe and effective method for patients with POEMS syndrome.

Among all malignancies worldwide, gastric cancer is the fifth most common cancer with the third highest mortality rate. One of the main reasons for the low survival rate is the recurrence and metastasis that occurs in many patients after surgery. Numerous studies have shown that abnormal TRIM33 expression is associated with the progression of malignant tumors. TRIM33 can function either as a tumor suppressor or tumor promoter in different cancers. Our data showed that TRIM33 was highly expressed in stomach cancer, and in human gastric cancer tissues, low expression of TRIM33 was associated with poor prognosis in patients with gastric cancer. To clarify the function of TRIM33 in survival and epithelial–mesenchymal transition in gastric cancer cells, we investigated the effect of TRIM33 knockdown in several gastric cancer cell lines. Downregulation of TRIM33 in BGC-823 and SGC-7901 cells enhanced the proliferation, colony formation, and migratory ability of these gastric cancer cells. It also promoted epithelial–mesenchymal transition; transfection of cells with siRNA targeting TRIM33 led to the upregulation of vimentin and N-Cadherin expression, and downregulation of E-Cadherin expression. Meanwhile, the transforming growth factor beta pathway was activated: levels of transforming growth factor beta were elevated and the expressions of p-Smad2, Smad2, Smad3, and Smad4 were activated. To confirm the role of TRIM33 in vivo, a xenograft model was established in nude mice. Immunohistochemical analysis identified that the protein levels of TRIM33, p-Smad2, Smad2, Smad3, Smad4, vimentin, and N-Cadherin were increased, and E-Cadherin levels were decreased, in xenograft tumors from the si-TRIM33 group. Taken together, these results suggest that TRIM33 may be a potential marker for the diagnosis and prognosis of gastric cancer. Furthermore, it may also serve as a novel target for gastric cancer treatment.

Objectives: To develop a nomogram for predicting calf muscle veins thrombosis (CMVT) in stroke patients during rehabilitation. Methods: We enrolled 360 stroke patients from the Rehabilitation Medicine Center from December 2015 to February 2019. Of the participants, 123 were included in the CMVT group and 237 in the no CMVT group. The least absolute shrinkage and selection operator (LASSO) regression model was applied to optimize feature selection for the model. Multivariable logistic regression analysis was applied to construct a predictive model. Performance and clinical utility of the nomogram were generated using the Harrell's concordance index, calibration curve, and decision curve analysis (DCA). Results: Age, Brunnstrom stage (lower extremity), D-dimer, and antiplatelet therapy were associated with the occurrence of CMVT. The prediction nomogram showed satisfactory performance with a concordance index of 0.718 (95% CI: 0.663-0.773) in internal verification. The Hosmer–Lemeshow test, P = .217, suggested that the model was of goodness-of-fit. In addition, the DCA demonstrated that the CMVT nomogram had a good clinical net benefit. Conclusions: We developed a nomogram that could help clinicians identify high-risk groups of CMVT in stroke patients during rehabilitation for early intervention.

Abstract. Background:. Posttraumatic headache (PTH) after traumatic brain injury (TBI) is a common clinical symptom, which refers to a headache that occurs after TBI. Acupuncture is often used for the treatment of such patients in China, and significant clinical effects have been achieved. However, to date, its efficacy has not been methodically evaluated. The purpose of this systematic review is to provide evidence to prove the effectiveness of acupuncture in the treatment of PTH in patients with TBI. Methods:. This systematic review will be conducted in accordance with the preferred reporting items for systematic review and meta-analysis protocols. The following electronic databases will be searched from their inception to February 2022: PubMed, Web of Science, Embase, PsycINFO, the Cochrane Library, and Chinese databases such as Chinese Biomedical Literature (CBM), Chinese Medical Current Content (CMCC), Chinese Scientific Journal Database (VIP), WanFang Database, and China National Knowledge Infrastructure (CNKI). No language restrictions will be applied to the search strategy. Randomized controlled trials and cohort and case-control studies that met the inclusion and exclusion criteria will be included in this study. The meta-analysis will be performed using RevMan 5.3 software. Each session of this systematic review will be conducted independently by 2 members. Results:. This review evaluates the efficacy of acupuncture in the treatment of PTH after TBI. Conclusion:. This review provides substantial evidence for the clinical application of acupuncture in PTH treatment after TBI. Ethics and dissemination:. Since the data in this study will be retrieved from published trials, therefore the Patient Consent Statement and Ethical Approval are not required. We will disseminate our results by publishing the research in a peer-reviewed journal. Trail registration number:. The protocol was registered in INPLASY (INPLASY 202220073).

The ocean-atmosphere coupling in the northeastern subtropical Pacific is dominated by a Pacific meridional mode (PMM), which spans between the extratropical and tropical Pacific and plays an important role in connecting extratropical climate variability to the occurrence of El Niño. Analyses of observational data and numerical model experiments were conducted to demonstrate that the PMM (and the subtropical Pacific coupling) experienced a rapid strengthening in the early 1990s and that this strengthening is related to an intensification of the subtropical Pacific high caused by a phase change of the Atlantic multidecadal oscillation (AMO). This PMM strengthening favored the development of more central Pacific (CP)-type El Niño events. The recent shift from more conventional eastern Pacific (EP) to more CP-type El Niño events can thus be at least partly understood as a Pacific Ocean response to a phase change in the AMO.

This study reveals a possible cause of model bias in simulating the western Pacific subtropical high (WPSH) variability via an examination of an Atmospheric Model Intercomparison Project (AMIP) simulation produced by the atmospheric general circulation model (AGCM) developed at Taiwan's Central Weather Bureau (CWB). During boreal summer, the model overestimates the quasi-biennial (2-3 yr) band of WPSH variability but underestimates the low-frequency (3-5 yr) band of variability. The overestimation of the quasi-biennial WPSH sensitivity is found to be due to the model's stronger sensitivity to the central Pacific El Niño-Southern Oscillation (CP ENSO) that has a leading periodicity in the quasi-biennial band. The model underestimates the low-frequency WPSH variability because of its weaker sensitivity to the eastern Pacific (EP) ENSO that has a leading periodicity in the 3-5-yr band. These different model sensitivities are shown to be related to the relative strengths of the mean Hadley and Walker circulations simulated in the model. An overly strong Hadley circulation causes the CWB AGCM to be overly sensitive to the CP ENSO, while an overly weak Walker circulation results in a weak sensitivity to the EP ENSO. The relative strengths of the simulated mean Hadley and Walker circulations are critical to a realistic simulation of the summer WPSH variability in AGCMs. This conclusion is further supported using AMIP simulations produced by three other AGCMs, including the CanAM4, GISS-E2-R, and IPSL-CM5A-MR models.

Co-development of the cardiovascular and pulmonary systems is a recent evolutionary adaption to terrestrial life that couples cardiac output with the gas exchange function of the lung. Here we show that the murine pulmonary vasculature develops even in the

Introduction: To explore association of excision repair cross-complementing 5 ( ERCC5 ) genetic polymorphisms with cirrhosis and liver cancer. Methods: A total of 365 patients were enrolled, including control group (n = 133), cirrhosis group (n = 122), and liver cancer group (n = 110). The genotyping of ERCC5 rs2016073, rs751402, rs2094258, rs2296147, and rs2296148 was measured by using MassARRAY iPLEX technology. Results: There were no significant differences in gender and drinking among the 3 groups ( P > .05). There were significant differences among the 3 groups in both age-group ≤60 and >60 subgroup patients. Locus rs2016073 was significantly different among 3 groups, and genotype GG (n = 0) was not observed in liver cancer group. As for locus rs751402, there were significant differences among 3 groups, and genotype AA (n = 0) was not observed in liver cancer group. As for locus rs2094258, there were no significant differences among 3 groups. Locus rs2296147 showed no significant differences among 3 groups ( P > .05), but genotype CC was not observed in liver cancer group (n = 0). As for locus rs2296148, there were significant differences among 3 groups, and genotype TC (n = 0) was not observed in cirrhosis group. Regression analysis found locus rs751402 had significant difference between control group and cirrhosis group, patients with genotype AA and genotype GG were more likely to have cirrhosis than those with genotype GA. Conclusion: Our study suggested that genotype AA, genotype GG of ERCC5 locus rs751402, and genotype TC of locus rs2296148 may be important targets for cirrhosis, while ERCC5 polymorphisms (rs2016073 and ERCC5 polymorphisms, rs2016073 with genotype GG, and rs751402 with genotype AA) may be potential markers for liver cancer.

Coiled-coil motifs are ubiquitous mediators of specific protein-protein interactions through the formation of interlocking hydrophobic seams between α-helical chains. Residues that form these seams occur at the first (a) and fourth (d) positions of a characteristic 7-aa repeat and are primarily aliphatic. The potential of aromatic residues to promote helix association in a coiled coil was explored by engineering a "Trp-zipper" protein with Trp residues at all 14 a and d positions. The protein forms a discrete, stable, α-helical pentamer in water at physiological pH. Its 1.45-Å crystal structure reveals a parallel, five-stranded coiled coil, a previously uncharacterized type of "knobs-into-holes" packing interaction between interfacial Trp side chains, and an unusual ≈8-Å-diameter axial channel lined with indole rings that is filled with polyethylene glycol 400 and water and sulfate ion molecules. The engineered Trp-zipper pentamer enlarges current views of coiled-coil assembly, molecular recognition, and protein engineering, and may serve as a soluble model for membrane ion channels. [ABSTRACT FROM AUTHOR]

Purpose: Cyclin D1 has been identified as a proto-oncogene associated with the uncontrolled proliferation of tumor cells. This systematic review and meta-analysis aims to estimate the prognostic significance of cyclin D1 in multiple myeloma (MM) patients. Method: We searched for qualified data in PubMed, Embase, and Web of Science up to February 2020. Data quality was assessed by the Newcastle-Ottawa scale (NOS). Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were used to evaluate the relationship between cyclin D1 expression and overall survival (OS), progression-free survival (PFS)/event-free survival (EFS) in patients with MM. Result: A total of 13 studies involving 961 patients were included. Overall, pooled analysis revealed significant heterogeneity between cyclin D1 expression and the prognosis of MM (OS, HR = 1.08, 95% CI: 0.71-1.64, I 2 = 67.9%; PFS/EFS, HR = 0.97, 95% CI: 0.49-1.93, I 2 = 85.8%). Subgroup analysis revealed that the prolongation of OS was relevant to increased expression of cyclin D1 in MM patients in the relapsed and refractory group (OS, HR = 0.46, 95% CI: 0.24-0.90). Another subgroup assessment of OS established that MM patients with CCND1 overexpression in the bortezomib group had longer survival time (HR = 0.30, 95% CI: 0.11-0.82), whereas, those overexpressing CCND1 in the conventional chemotherapy group had poor prognosis (HR = 2.19, 95% CI: 1.18-4.08). We also found that increased cyclin D1 expression correlated favorably with PFS in the autologous stem cell transplantation (ASCT) (HR = 0.45, 95% CI: 0.28-0.73) or reverse transcription-polymerase chain reaction (RT-PCR) group (HR = 0.41, 95% CI: 0.26-0.64). Conclusion: The result of this meta-analysis suggested that CCND1 overexpression might be a predictive biomarker for MM patients when treated with bortezomib, receiving ASCT, or in relapsed and refractory period.

This study aimed to explore the influences of microRNA-195 (miRNA-195)/Rap2C/MAPK in the proliferation and apoptosis of small cell lung cancer (SCLC) cells. QRT-PCR analysis were executed to evaluate miRNA-195 expression in lung cancer tissues and SCLC cells, and the western blot was implemented to monitor Rap2C protein level and uncovered whether the MAPK signaling pathway in lung cancer tissues and SCLC cells was activated. The CCK-8 experiment was performed to detect cell proliferation ability, and the flow cytometry was utilized to examine cell apoptosis level. Luciferase reporter gene system was executed to disclose the interaction between miRNA-195 and Rap2C. Subcutaneous implantation mouse models of SCLC cells were constructed to detect cell proliferation in vivo, and Kaplan-Meier method calculated patient survival. The expression of Rap2C was higher in lung cancer tissues and SCLC cells than in normal tissues and cells, while the expression of miRNA-195 was lower in lung cancer tissues and SCLC cells than in normal tissues and cells. miRNA-195 lower expression predicted showed reduced overall survival in lung cancer patients. Further loss of function and enhancement experiments revealed that miRNA-195 overexpression could significantly inhibit SCLC cell proliferation and promote cell apoptosis by upregulation of Bax and down-regulation of bcl-2; Luciferase reporter assay demonstrated that miRNA-195 could bind to Rap2C mRNA and inhibit its expression, Rap2C overexpression also related to the poorer prognosis of lung patients. Knockdown of Rap2C suppressed cell proliferation and expedited apoptosis. In addition, overexpression of Rap2C reversed miRNA-195-induced apoptosis and proliferation inhibition. Furthermore, miRNA195 prohibited the activation of MAPK signaling pathway by down-regulating Rap2C. These consequences indicated that miRNA-195 promotes the apoptosis and inhibits the proliferation of small cell lung cancer (SCLC) cells via inhibiting Rap2C protein-dependent MAPK signal transduction

Purpose: A meta-analysis was conducted to evaluate the diagnostic performance of contrast-enhanced ultrasonography using the contrast agent SonoVue to differentiate benign from malignant breast lesions. Method: A comprehensive search of the literature was performed using the Embase, PubMed, and Web of Science databases to retrieve studies published before February 2020. Data were extracted, and pooled sensitivity, specificity, and diagnostic odds ratios were calculated with meta-analysis software. Heterogeneity was evaluated via the Q test and I 2 statistic. Meta-regression and subgroup analyses were applied to evaluate potential sources of heterogeneity. Publication bias was assessed using the Deeks’ funnel plot asymmetry test. A summary receiver operating characteristic curve (SROC) was constructed. Results: A total of 27 studies including 5378 breast lesions subjected to CEUS examination with SonoVue were included in the meta-analysis. The pooled sensitivity and specificity values were 0.90 (95% confidence interval [CI], 0.88–0.91; inconsistency index [ I 2 ] = 75.7%) and 0.83 (95% CI, 0.82–0.85; I 2 = 91.0%), respectively. The pooled diagnostic odds ratio was 48.35% (95% CI, 31.22–74.89; I 2 = 77.6%). The area under the summary receiver operating characteristic curve (AUC) was 0.9354. Meta-regression analysis revealed the region of patient residence and dose of contrast agent as potential sources of heterogeneity (P < .01). Subgroup analysis showed a higher area under the summary receiver operating characteristic curve for European and higher contrast agent dose subgroups (P < .05). Conclusion: Contrast-enhanced ultrasonography with SonoVue displays high sensitivity, specificity, and accuracy when differentiating benign from malignant breast lesions. Despite its current limitations, this technique presents a promising tool for diagnosing breast lesions in clinical practice.

Lupus nephritis (LN) is an immunoinflammatory glomerulonephritis associated with renal involvement in systemic lupus erythematosus (SLE). Given the close relationship between plasma amino acids (AAs) and renal function, this study aimed to elucidate the plasma AA profiles in LN patients and identify key AAs and diagnostic patterns that distinguish LN patients from those with SLE and healthy controls. Participants were categorized into three groups: normal controls (NC), SLE, and LN. Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was employed to quantify AA levels in human plasma. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were utilized to identify key AAs. The diagnostic capacity of the models was assessed using receiver operating characteristic (ROC) curve analysis and area under the ROC curve (AUC) values. Significant alterations in plasma AA profiles were observed in LN patients compared to the SLE and NC groups. The OPLS-DA model effectively separated LN patients from the SLE and NC groups. A joint model using histidine (His), lysine (Lys), and tryptophan (Trp) demonstrated exceptional diagnostic performance, achieving an AUC of 1.0 with 100% sensitivity, specificity, and accuracy in predicting LN. Another joint model comprising arginine (Arg), valine (Val), and Trp also exhibited robust predictive performance, with an AUC of 0.998, sensitivity of 93.80%, specificity of 100%, and accuracy of 95.78% in distinguishing between SLE and LN. The joint forecasting models showed excellent predictive capabilities in identifying LN and categorizing lupus disease status. This approach provides a novel perspective for the early identification, prevention, treatment, and management of LN based on variations in plasma AA levels., (© 2024. The Author(s).)

This study aimed to explore the mediating effects of ADL and depression on the relationship between sleep quality and HRQOL among older people in rural China, while also exploring the moderating impact of loneliness. The study gathered data from a household survey conducted among 1587 Chinese rural older adults (mean age = 73.63 years). The collected data was analyzed using SPSS version 23.0 software (IBM, New York, USA) and the PROCESS macro version 4.0 program. The findings indicated a significant correlation between sleep quality, ADL, depression, loneliness and HRQOL. ADL and depression exhibited a chain mediation effect on the relationship between sleep quality and HRQOL. Notably, the association between sleep quality and HRQOL was entirely mediated by ADL and depression. Additionally, loneliness acted as a moderator in the relationship between ADL and HRQOL. The findings of this study suggest that interventions focusing on sleep quality should prioritize strategies for enhancing older adults' ADL and depression as integral components of promoting older adults' HRQOL., (© 2024. The Author(s).)

Background: Bone metastases are rare in oral squamous cell carcinoma (OSCC). It has not been defined on the risk and prognosis of OSCC patients with bone metastases. The purpose of this study was to assess the factors associated with the development and prognosis of bone metastases among OSCC patients., Methods: Demographic and clinicopathological characteristics of OSCC patients diagnosed between 2010 and 2019 was retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. To explore risk factors for developing bone metastases and prognosis, the univariate and multivariate logistic and Cox regression analysis were performed, further the predictive nomogram models were constructed., Results: The incidence rate of bone metastases in newly diagnosed OSCC patients was 0.91 % (95 %CI 0.81% -1.02 %). Ultimately, 137 OSCC patients with bone metastases and 19,469 OSCC patients without bone metastases were included in the present study. Pathological grade, primary site, T/N stage and distant organ metastases (liver/lung/brain) were independently associated with the risk of developing bone metastases among OSCC patients. The C-index of a constructed risk-predicting nomogram was 0.86 (95 %CI 0.83-0.89). Multivariate Cox regression analysis indicated that lung metastases, the use of surgery as well as chemotherapy were three independent prognostic factors. The C-indexes of constructed risk-predicting nomograms were 0.70 (95 %CI 0.65-0.75), 0.68 (95 %CI 0.63-0.73) for OS and CSS, respectively. Calibration plots demonstrated an agreementbetween the established nomogram's predicted survival and actual survival. In addition, decision curve analysis (DCA) indicated these established nomograms had considerable net benefits and clinical utilities., Conclusion: This study defined the risk and prognostic factors for bone metastases among OSCC patients and the established nomograms were well calibrated for discrimination to predict bone metastasis development and prognosis., Competing Interests: Declaration of competing interest All authors declare no potential conflict of interest., (Copyright © 2024. Published by Elsevier Masson SAS.)

Inorganic aerosol is the main component of haze days in winter over Tianjin. In this study, two typical high concentrations of secondary inorganic aerosol (SIA) processes, defined as CASE1 and CASE2, were selected during polluted days in January 2020 over Tianjin, and the effects of meteorological factors, regional transport, and chemical processes were comprehensively investigated combined with observations and numerical models (WRF-NAQPMS). The average SIA concentrations in CASE1 and CASE2 were 76.8 μg·m -3 and 66.0 μg·m -3 , respectively, and the nitrate concentration was higher than that of sulfate and ammonium, which were typical nitrate-dominated pollution processes. Meteorological conditions played a role in inorganic aerosol formation. The temperature of approximately -6-0℃ and 2-4℃ and the relative humidity of 50%-60% and 80%-100% would be suitable conditions for the high SIA concentration (&gt;80 μg·m -3 ) in CASE1, whereas the temperature of approximately 2-4℃ and the relative humidity of 60%-70% would be suitable in CASE2. The average contribution rates of external sources to SIA in the CASE1 and CASE2 processes were 62.3% and 22.1%, which were regional transport-dominant processes and local emission-dominant processes, respectively. The contribution of the local emission of CASE1 to nitrate and sulfate was 16.2 μg·m -3 and 8.2 μg·m -3 , respectively, higher than that of external sources (31.7 μg·m -3 and 8.8 μg·m -3 ). the local contribution of CASE2 to nitrate and sulfate was 29.3 μg·m -3 and 25.1 μg·m -3 , respectively, whereas the contribution from external sources was 8.1 μg·m -3 and 9.4 μg·m -3 , respectively. The quantitative result indicated that local formation and regional transport resulted in higher nitrate concentration than sulfate in CASE1, in contrast to only local sources in CASE2. The gas phase reaction was the main source of inorganic aerosol formation, contributing 48.9% and 57.8% in CASE1 and CASE2, respectively, whereas the heterogeneous reactions were also important processes, with contribution rates of 48.1% and 42.2% to SIA. The effect of aqueous phase reaction was negligible.

PD-1/PD-L1 signaling is a key factor of local immunosuppression in the tumor microenvironment. Immune checkpoint inhibitors targeting PD-1/PD-L1 signaling have achieved tremendous success in clinic. However, several types of cancer are particularly refractory to the anti-PD-1/PD-L1 treatment. Recently, a series of studies reported that IFN-γ can stimulate cancer cells to release exosomal PD-L1 (exoPD-L1), which possesses the ability to suppress anticancer immune responses and is associated with anti-PD-1 response. In this review, we introduce the PD-1/PD-L1 signaling, including the so-called 'reverse signaling'. Furthermore, we summarize the immune treatments of cancers and pay more attention to immune checkpoint inhibitors targeting PD-1/PD-L1 signaling. Additionally, we review the action mechanisms and regulation of exoPD-L1. We also introduce the function of exoPD-L1 as biomarkers. Finally, we review the methods for analyzing and quantifying exoPD-L1, the therapeutic strategies targeting exoPD-L1 to enhance immunotherapy and the roles of exoPD-L1 beyond cancer. This comprehensive review delves into recent advances of exoPD-L1 and all these findings suggest that exoPD-L1 plays an important role in both cancer and other fields., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lu and Yang.)

A novel and interesting controllable spirocyclization of unsaturated barbiturates with enamino esters for the assembly of cyclopentenyl and pyrrolinyl spirobarbiturates has been developed under ball-milling conditions. The present protocol features high chemoselectivity and efficiency, excellent functional group tolerance and mild reaction conditions.

Background: The impact of esophageal dysmotility among patients with post-fundoplication esophageal symptoms is not fully understood. This study aimed to investigate secondary peristalsis and esophagogastric junction (EGJ) opening biomechanics using functional lumen imaging probe (FLIP) panometry in symptomatic post-fundoplication patients., Methods: Eighty-seven adult patients post-fundoplication who completed FLIP for symptomatic esophageal evaluation were included. Secondary peristaltic contractile response (CR) patterns and EGJ opening metrics (EGJ distensibility index (EGJ-DI) and maximum EGJ diameter) were evaluated on FLIP panometry and analyzed against high-resolution manometry (HRM), patient-reported outcomes, and fundoplication condition seen on esophagram and/or endoscopy., Key Results: FLIP CR patterns included 14 (16%) normal CR, 30 (34%) borderline CR, 28 (32%) impaired/disordered CR, 13 (15%) absent CR, and 2 (2%) spastic reactive CR. Compared with normal and borderline CRs (i.e., CR patterns with distinct, antegrade peristalsis), patients with impaired/disordered and absent CRs demonstrated significantly greater time since fundoplication (2.4 (0.6-6.8) vs. 8.9 (2.6-14.5) years; p = 0.002), greater esophageal body width on esophagram (n = 50; 2.3 (2.0-2.8) vs. 2.9 (2.4-3.6) cm; p = 0.013), and lower EGJ-DI (4.3 (2.7-5.4) vs. 2.6 (1.7-3.7) mm 2 /mmHg; p = 0.001). Intact fundoplications had significantly higher rates of normal CRs compared to anatomically abnormal (i.e., tight, disrupted, slipped, herniated) fundoplications (9 (28%) vs. 5 (9%); p = 0.032), but there were no differences in EGJ-DI or EGJ maximum diameter., Conclusions & Inferences: Symptomatic post-fundoplication patients were characterized by frequent abnormal secondary peristalsis after fundoplication, potentially worsening with time after fundoplication or related to EGJ outflow resistance., (© 2024 The Authors. Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)

Objective: To investigate the association between portal vein thrombosis and rebleeding after non-urgent endoscopic treatment of esophagogastric varices. Methods: The cirrhotic patients with esophagogastric varices diagnosed in the People's Hospital of Zhengzhou University from January 2017 to March 2023 were retrospectively collected. The patients were divided into thrombotic group and non-thrombotic group according to the presence or absence of portal vein thrombosis. The failure rate of endoscopic treatment and rebleeding rate in different periods were compared between the two groups. Receiver operating characteristic (ROC) curve was used to select the best cutoff value of gastric varicose diameter that affected total rebleeding during follow-up in both groups. The influencing factors of rebleeding within 12 and 36 months in both groups were analyzed, and the influencing factors of rebleeding within 36 months in thrombus group were further analyzed. Results: A total of 106 patients were enrolled, including 53 patients in the thrombotic group [male 37, female 16, aged 18-78 (54±13) years] and 53 patients in the non-thrombotic group [male 37, female 16, aged 27-83 (55±12) years]. The follow-up time of the two groups were (20±15) and (25±15) months, respectively. The total rebleeding rate in the thrombotic group was higher than that in the non-thrombotic group [30.2% (16/53) vs 13.2% (7/53), P ˂0.05]. The rebleeding rates within 6, 12, 24 and 36 months in the thrombotic group were higher than those in the non-thrombotic group [18.9% (10/53) vs 5.7% (3/53), 18.9% (10/53) vs 5.7% (3/53), 28.3% (15/53) vs 9.4% (5/53), 30.2% (16/53) vs 11.3% (6/53), all P ˂0.05]. The best cut-off value of the diameter of gastric varices that affects the total rebleeding in the two groups was 10.4 mm (10 mm was selected as the best cut-off value for the convenience of practical clinical application). Hemoglobin ˂ 85 g/L ( HR =0.202, 95% CI : 0.043-0.953, P =0.043), 10 mm ˂ the diameter of GV ≤ 15 mm ( HR =5.321, 95% CI : 1.161-24.390, P =0.031) and endoscopic variceal ligation combined with endoscopic tissue adhesive injection (EVL+ETAI) ( HR =7.172, 95% CI : 1.910-26.930, P =0.004) were the risk factors for the first gastroesophageal variceal rebleeding within 12 months after non-urgent endoscopic treatment. EVL+ETAI ( HR =3.811, 95% CI : 1.441-10.084, P =0.007) and portal vein thrombosis ( HR =4.026, 95% CI : 1.483-10.932, P =0.006) were the risk factors for the first gastroesophageal variceal rebleeding within 36 months after non-urgent endoscopic treatment. The study found that, 10 mm ˂ the diameter of GV ≤ 15 mm ( HR =7.503, 95% CI : 1.568-35.890, P =0.012) was the risk factor for rebleeding within 36 months in the thrombotic group. Conclusion: Portal vein thrombosis is a risk factor for rebleeding after non-urgent endoscopic treatment of esophagogastric varices.

Abstract: Dystrophic epidermolysis bullosa pruriginosa (DEB-Pr) is a rare subtype of dystrophic epidermolysis bullosa, and traditional treatments have limited efficacy. Dupilumab has demonstrated remarkable efficacy in relieving pruritus. In this case study, after traditional treatment failed, providers recommended the patient begin dupilumab to treat his pruritus. The patient was administrated a loading dose of 600 mg of dupilumab and a dose of 300 mg every 2 weeks. The Dermatology Life Quality Index and Pruritic Numeric Rating Scale were used to assess the patient's situation. After several months, the patient's DEB-Pr was considered in remission. Dupilumab may be a better choice than immunosuppressants for the treatment of pruritus in patients with DEB-Pr., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Crohn's disease (CD) is caused by immune, environmental, and genetic factors. It can involve the entire gastrointestinal tract, and although its prevalence is rapidly increasing its etiology remains unclear. Emerging biological and small-molecule drugs have advanced the treatment of CD; however, a considerable proportion of patients are non-responsive to all known drugs. To achieve a breakthrough in this field, innovations that could guide the further development of effective therapies are of utmost urgency. In this review, we first propose the innovative concept of pan-lymphatic dysfunction for the general distribution of lymphatic dysfunction in various diseases, and suggest that CD is the intestinal manifestation of pan-lymphatic dysfunction based on basic and clinical preliminary data. The supporting evidence is fully summarized, including the existence of lymphatic system dysfunction, recognition of the inside-out model, disorders of immune cells, changes in cell plasticity, partial overlap of the underlying mechanisms, and common gut-derived fatty and bile acid metabolism. Another benefit of this novel concept is that it proposes adopting the zebrafish model for studying intestinal diseases, especially CD, as this model is good at presenting and mimicking lymphatic dysfunction. More importantly, the ensuing focus on improving lymphatic function may lead to novel and promising therapeutic strategies for CD., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

The mixotrophic cultivation of microalgae in wastewater has attracted extensive attention due to its many advantages. In this study, acetate, which can be prepared by hydrolysis of aquaculture waste, was used as exogenous organic matter to promote the growth of Chlorella pyrenoidosa cultured in aquaculture wastewater. Microalgae cultivation was carried out in a membrane photobioreactor (MPBR) with continuous inflow and outflow mode. The results showed that exogenous acetate greatly promoted the mixotrophic growth of C. pyrenoidosa. When the dosage of acetate reached 1.0 g L -1 , the relative growth rate of microalgae in the logarithmic stage reached 0.31 d -1 , which was 4.4 times that of the control. As a result, exogenous acetate also promoted the removal of nutrients from aquaculture wastewater. During the stable operation stage of the MPBR with acetate added in the influent, an average of 87.41%-93.93% nitrogen and 76.34%-88.55% phosphorus was removed from the aquaculture wastewater containing 19.41 mg L -1 total inorganic nitrogen and 1.31 mg L -1 total inorganic phosphorus. However, it was worth noting that adding exogenous acetate also led to an increase in the membrane resistance of the membrane module in the MPBR. Membrane resistance was mainly composed of internal resistance (R i ) and cake resistance (R c ), and with the increase of acetate content in the influent, their proportion in the total resistance gradually increased. R i contributed the major membrane resistance and was most affected by acetate dosage. R i reached 32.04 × 10 12  m -1 with 1 g L -1 acetate, which accounted for 69.49% of total resistance. Moreover, with the increase of influent acetate concentration of the MPBRs, both the number of insoluble contaminants and dissolved organic contaminants in the membrane modules increased. In addition, the composition of proteins, polysaccharides, and humus in dissolved organic contaminants was close to that in extracellular polymeric substances and soluble microbial products secreted by microalgae. These results suggested that the membrane fouling of membrane modules was closely related to the algal biomass content in the MPBRs. The above results provided a theoretical basis for reducing membrane fouling of MPBR., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

This study aimed to explore the moderating role of socioeconomic status (SES) in the association between multimorbidity and health-related quality of life (HRQOL) among cancer patients in Anhui China. A total of 560 cancer patients were recruited for the cross-section study. Socio-demographic and clinical characteristics were analyzed using descriptive statistics. Tobit regression analysis was employed to investigate the relationship between multimorbidity and HRQOL as well as to assess the moderating effect of SES. The research findings indicated that 76.61% of cancer patients experienced multimorbidity, with psychological multimorbidity being the most prevalent (45.54%), followed by physical-psychological multimorbidity (20.89%). Moreover, physical-psychological multimorbidity had the most substantial adverse effect on HRQOL ( P < .001). The presence of multimorbidity was correlated with a significant decline in HRQOL, with a 17.5% ( P < .001) decrease in HRQOL for each additional multimorbidity. Additionally, SES played a significant role in moderating the impact of multimorbidity on HRQOL in cancer patients. (Marginal effect = -0.022, P < .01). The high SES group exhibited a higher overall HRQOL than the low SES group (Marginal effect = 0.068, P < .001). And with the increase of multimorbidity, HRQOL in the higher SES showed a more pronounced downward trend, compared with the lower SES ( β = -.270 vs β = -.201, P < .001). Our findings underscore the importance of preventing and managing multimorbidity in cancer patients, particularly those with low SES. Furthermore, it is essential to consider the impact of the rapid decline in HRQOL as the number of multimorbidity increases in individuals with higher SES. It is imperative to explore interdisciplinary and continuous collaborative management models., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Adoptive cell therapy using T cell receptor-engineered T cells (TCR-T) is a promising approach for cancer therapy with an expectation of no significant side effects. In the human body, mature T cells are armed with an incredible diversity of T cell receptors (TCRs) that theoretically react to the variety of random mutations generated by tumor cells. The outcomes, however, of current clinical trials using TCR-T cell therapies are not very successful especially involving solid tumors. The therapy still faces numerous challenges in the efficient screening of tumor-specific antigens and their cognate TCRs. In this review, we first introduce TCR structure-based antigen recognition and signaling, then describe recent advances in neoantigens and their specific TCR screening technologies, and finally summarize ongoing clinical trials of TCR-T therapies against neoantigens. More importantly, we also present the current challenges of TCR-T cell-based immunotherapies, e.g., the safety of viral vectors, the mismatch of T cell receptor, the impediment of suppressive tumor microenvironment. Finally, we highlight new insights and directions for personalized TCR-T therapy., (© 2023. The Author(s).)

Background: T helper 2 (Th2) cells are thought to play critical roles in allergic conjunctivitis (AC). They release inflammatory cytokines to promote an allergic response in AC. Due to individual heterogeneity and long-term chronic management, current therapies do not always effectively control AC. Mesenchymal stem cells (MSCs) have been shown to be effective in treating allergy-related disorders, but it is unclear how exactly the Th2-mediated allergic response is attenuated. This study aims to elucidate the therapeutic effect and mechanism of the human umbilical cord MSCs (hUCMSCs) in a mouse model of experimental AC (EAC)., Methods: A mouse EAC model was established by inoculating short ragweed (SRW) pollen. After the SRW pollen challenge, the mice received a single subconjunctival or tail vein injection of 2 × 10 6 hUCMSCs, or subconjunctival injection of hUCMSCs conditioned medium (hUCMSC-CM), and dexamethasone eye drops was used as positive control; subsequent scratching behavior and clinical symptoms were assessed. Immunostaining and flow cytometry were carried out to show allergic reactions and the activation of CD4 + T cell subsets in the conjunctiva and cervical lymph nodes (CLNs). Gene expression was determined by RNA-seq and further verified by qRT-PCR and Western blot. Co-culture assays were performed to explore the regulatory role of hUCMSCs in the differentiation of CD4 + naive T cells (Th0) into Th2 cells., Results: Subconjunctival administration of hUCMSCs resulted in fewer instances of scratching and lower inflammation scores in EAC mice compared to the tail vein delivery, hUCMSC-CM and control groups. Subconjunctival administration of hUCMSCs reduced the number of activated mast cells and infiltrated eosinophils in the conjunctiva, as well as decreased the number of Th2 cells in CLNs. After pretreatment with EAC mouse serum in vitro to mimic the in vivo milieu, hUCMSCs were able to inhibit the differentiation of Th0 into Th2 cells. Further evidence demonstrated that repression of Th2 cell differentiation by hUCMSCs is mediated by CRISPLD2 through downregulation of STAT6 phosphorylation. Additionally, hUMCSCs were able to promote the differentiation of Th0 cells into regulatory T cells in CLNs of EAC mice., Conclusions: Subconjunctival injection of hUCMSCs suppressed the Th2-allergic response and alleviated clinical symptoms. This study provides not only a potential therapeutic target for the treatment of AC but also other T cell-mediated diseases., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Obesity plays a vital role in the occurrence and development of non-alcoholic steatohepatitis (NASH). However, the underlining mechanism is still unclear, where adipose tissue (AT) derived exosomes may actively participate. MicroRNAs (miRNAs) are commonly secreted from exosomes for cell communication. Though the regulation of miR-103 on insulin sensitivity has been reported, the specific role of AT-derived exosomes miR-103 in NASH is still vague and further investigation may provide novel therapeutic choices., Aim: To determine the specific role of AT-derived exosomes miR-103 in developing NASH through various methods., Methods: The expression levels of miR-103 in the AT-derived exosomes and livers were detected and compared between NASH mice and control. The effect of miR-103 on NASH progression was also explored by antagonizing miR-103, including steatosis and inflammation degree changes. The interaction between miR-103 and the autophagy-related gene phosphatase and tensin homolog (PTEN) was confirmed by dual-luciferase reporter assay. The role of the interaction between miR-103 and PTEN on autophagy was verified in NASH-like cells. Finally, the effects of miR-103 from adipose-derived exosomes on NASH and autophagy were analyzed through animal experiments., Results: The expression of miR-103 was increased in NASH mice, compared to the control, and inhibition of miR-103 could alleviate NASH. The results of the dual-luciferase reporter assay showed miR-103 could interact with PTEN. MiR-103-anta decreased p-AMPKa, p-mammalian target of rapamycin (mTOR), and p62 but increased the protein levels of PTEN and LC3-II/I and the number of autophagosomes in NASH mice. Similar results were also observed in NASH-like cells, and further experiments showed PTEN silencing inhibited the effect of miR-103-anta. AT derived-exosome miR-103 aggravated NASH and increased the expressions of p-AMPKa, p-mTOR, and p62 but decreased the protein levels of PTEN and LC3-II/I and the number of autophagosomes in mice., Conclusion: AT derived-exosome increased the levels of miR-103 in the liver, and miR-103 aggravated NASH. Mechanically, miR-103 could interact with PTEN and inhibit autophagy., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

The regulation of protein kinase B (AKT) phosphorylation by Tripartite motif-containing protein 31 (TRIM31) is implicated as an essential mechanism in the progression of many malignant tumors. Nevertheless, the function of the TRIM31/AKT pathway in oral squamous cell carcinoma (OSCC) remains elusive. Here, immunohistochemistry analysis of human OSCC tissue microarrays indicated significantly higher levels of TRIM31 and phosphorylated AKT (p-AKT) in OSCC tumors than in adjacent tissue samples. Also, we detected a positive association between TRIM31 expression and clinical OSCC development. In in vitro studies, TRIM31 knockdown severely impaired OSCC cell growth, invasion, and migration. By contrast, TRIM31 overexpression improved these cell behaviors, while subsequent AKT inhibition abrogated the effect. In vivo tumorigenesis experiments using nude mice also validated the effects of TRIM31/AKT signaling in tumor growth. Furthermore, TRIM31 upregulation facilitated glucose uptake, as well as lactate and adenosine triphosphate production of OSCC cells, while such positive effects on glycolysis and malignant cell phenotypes were reversed by treatment with AKT or glycolysis inhibitors. In conclusion, TRIM31 may improve OSCC progression by enhancing AKT phosphorylation and subsequent glycolysis. Hence, TRIM31 has the potential as a treatment target in OSCC.

Small cell lung cancer (SCLC) remains a lethal disease with a dismal overall survival rate of 6% despite promising responses to upfront combination chemotherapy. The key drivers of such rapid mortality include early metastatic dissemination in the natural course of the disease and the near guaranteed emergence of chemoresistant disease. Here, we found that we could model the regression and relapse seen in clinical SCLC in vitro. We utilized time-course resolved RNA-sequencing to globally profile transcriptome changes as SCLC cells responded to a combination of cisplatin and etoposide-the standard-of-care in SCLC. Comparisons across time points demonstrated a distinct transient transcriptional state resembling embryonic diapause. Differential gene expression analysis revealed that expression of the PEA3 transcription factors ETV4 and ETV5 were transiently upregulated in the surviving fraction of cells which we determined to be necessary for efficient clonogenic expansion following chemotherapy. The FGFR-PEA3 signaling axis guided the identification of a pan-FGFR inhibitor demonstrating in vitro and in vivo efficacy in delaying progression following combination chemotherapy, observed inhibition of phosphorylation of the FGFR adaptor FRS2 and corresponding downstream MAPK and PI3K-Akt signaling pathways. Taken together, these data nominate PEA3 transcription factors as key mediators of relapse progression in SCLC and identify a clinically actionable small molecule candidate for delaying relapse of SCLC., (© 2022. The Author(s).)

Purpose: This study aimed to investigate the efficacy of piezosurgery (PI) in promoting immediate clotting after flapless extraction in patients undergoing dual antiplatelet therapy (DAPT)., Methods: In this randomized controlled trial, 80 DAPT patients were equally divided into the PI and turbine handpiece (TH) groups. Accordingly, flapless extraction of a single tooth using PI or TH was performed on each patient, and the immediate clotting status was evaluated. The results of the preoperative hematological examinations, surgery-related variables and postoperative complications were recorded for analysis., Results: Both groups presented with low platelet aggregation and similar coagulation functions. The PI group exhibited a higher proportion of patients with normal intra-alveolar clotting (≤30 min) (70% vs. 40%, P = 0.007) and fewer intraoperative complications (25% vs. 47.5%, P = 0.036) than that in the TH group. Logistic regression analysis indicated that the applied instrument was an independent risk factor for prolonged immediate bleeding (odds ratio = 3.10, 95% confidence interval: 1.20-8.00, P = 0.019). Intergroup differences were insignificant in terms of the other surgery-related variables and postoperative complications, except for the longer surgical duration in the PI group., Conclusion: The application of PI may contribute to better immediate clotting in DAPT patients after flapless extraction compared with the use of TH.

Background: Obesity is associated with an increased risk of developing Crohn's disease (CD), higher disease activity, and comparatively worse clinical outcomes., Aim: To investigate the role of mesenteric adipose tissue-derived exosomes in the pathogenesis of CD aggravation in obese individuals., Methods: First, we induced colitis in mice initiated on high-fat and normal diets and compared the severity of colitis. We then extracted and identified exosomes from mesenteric adipose tissue and determined the levels of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in mesenteric adipose tissue-derived exosomes and the colon. Next, we demonstrated an interaction between MALAT1 and the miR-15a-5p/activating transcription factor 6 (ATF6) axis. Finally, we explored the effects of mesenteric adipose tissue-derived exosomes extracted from mice fed a high-fat or normal diet on the severity of 2,4,6-trinitrobe-nzenesulfonic acid (TNBS)-induced colitis and ATF6-related endoplasmic reticulum stress pathways., Results: High-fat diet was found to aggravate TNBS-induced colitis in mice. The expression of MALAT1 in mesenteric adipose tissue-derived exosomes of high-fat diet-fed mice increased. The increased expression of MALAT1 in colon tissue exacerbated TNBS-induced colitis and activated the ATF6 endoplasmic reticulum stress pathway. This effect was partially reversed by the reduced expression of MALAT1 and overexpression of miR-15a-5p., Conclusion: Mesenteric adipose tissue-derived exosome-encapsulated long noncoding RNAs MALAT1 targets the colon and aggravates TNBS-induced colitis in obese mice, which may potentially act on the miR-15a-5p/ATF6 axis and activate endoplasmic reticulum stress., Competing Interests: Conflict-of-interest statement: There are no conflicts of interest to report., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Malignant myoepithelioma of the head and neck (HNMM) is a rare malignancy, and its characteristics and survival rates have not been well-defined. This study aimed to define the epidemiology of HNMM and identify the prognostic factors associated with the disease. Data on all patients diagnosed with HNMM between 1991 and 2016 were gathered from the Surveillance Epidemiology and End Results (SEER) database. The demographics, clinicopathological characteristics, treatment, and prognoses of the patients were described. Cox regression analysis was used to identify the prognostic factors, and the prognostic nomograms for overall survival (OS) and disease-specific survival (DSS) were constructed. A total of 333 cases of HNMM were identified. The average age at diagnosis was 60.6 years, and 50.1% of the patients were men. After diagnosis, 46.2% of patients underwent surgery alone, 43.5% of patients underwent surgery and radiotherapy, and 3.6% of patients received only radiotherapy. Survival analysis showed that the 5-year OS and DSS for all HNMM patients were 69.7 and 82.1%, respectively. In the multivariate analysis model, the undifferentiated pathological grade (P <0.05) and M1 in the M category (P <0.01) were independent prognostic factors for poor OS and DSS, whereas the use of surgical resection was an independent favorable prognostic factor for both OS and DSS (P <0.05). The prognostic nomograms for OS and DSS prediction were constructed; the C-index values for OS and DSS prediction were 0.78 (95% CI 0.70-0.86) and 0.79 (95% CI 0.67-0.90), respectively. In conclusion, this SEER data-based study demonstrated that HNMM patients often had a favorable prognosis, and distant metastasis, pathological grade, and the use of surgery contributed to their survival. Furthermore, we developed a prognostic nomogram to predict OS and DSS for HNMM patients to aid physicians in the clinical management of this rare disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Deng, Liu, Luo, Lu and Yang.)

Chlorophyll (Chl) plays a crucial role in plant photosynthesis. The geranylgeraniol reductase gene ( CHLP ) participates in the terminal hydrogenation of chlorophyll biosynthesis. Although there are many studies related to the genome-wide analysis of Populus trichocarpa , little research has been conducted on CHLP family genes, especially those concerning growth and photosynthesis. In this study, three CHLP genes were identified in Populus . The evolutionary tree indicated that the CHLP family genes were divided into six groups. Moreover, one pair of genes was derived from segmental duplications in Populus . Many elements related to growth were detected by cis -acting element analysis of the promoters of diverse PtrCHLPs . Furthermore, PtrCHLPs exhibit different tissue expression patterns. In addition, PtrCHLP3 is preferentially expressed in the leaves and plays an important role in regulating chlorophyll biosynthesis. Silencing of PtrCHLP3 in poplar resulted in a decrease in chlorophyll synthesis in plants, thus blocking electron transport during photosynthesis. Furthermore, inhibition of PtrCHLP3 expression in poplar can inhibit plant growth through the downregulation of photosynthesis. Ultimately, PtrCHLP3 formed a co-expression network with photosynthesis and chlorophyll biosynthesis-related genes, which synergistically affected the growth and photosynthesis of poplars. Thus, this study provides genetic resources for the improved breeding of fast-growing tree traits., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 He, Shi, Chen, Li, Niu, Feng, Lu, Tian, Zhang, Lin, Chen, Liu and Wan.)

Cadmium, a toxic heavy metal, seriously affects human health and ecological security. The cation/H + exchanger (CAX) family is a unique metal transporter that plays a crucial role in Cd acquisition, transfer, and remission in plants. Although there are many studies related to the genome-wide analysis of Populus trichocarpa, little research has been done on the CAX family genes, especially concerning Cd stress. In this study, genome-wide analysis of the Populus CAX family identified seven stress-related CAX genes. The evolutionary tree indicated that the CaCA family genes were grouped into four clusters. Moreover, seven pairs of genes were derived by segmental duplication in poplars. Cis-acting element analysis identified numerous stress-related elements in the promoters of diverse PtrCAXs. Furthermore, some PtrCAXs were up-regulated by drought, beetle, and mechanical damage, indicating their possible function in regulating stress response. Under cadmium stress, all CAX genes in the roots were up-regulated. Our findings suggest that plants may regulate their response to Cd stress through the TF-CAXs module. Comprehensively investigating the CAX family provides a scientific basis for the phytoremediation of heavy metal pollution by Populus., (Copyright © 2022. Published by Elsevier B.V.)

Objective: To compare the morphological and compositional characteristics of carotid plaques in two cohorts (2002-2005 and 2012-2015) of Chinese patients using magnetic resonance vessel wall imaging., Methods: Symptomatic patients with carotid atherosclerotic plaques who underwent carotid vessel wall magnetic resonance imaging between 2002-2005 and 2012-2015 were retrospectively recruited. Plaque morphology [including mean wall area, wall thickness, and maximum normalized wall index (NWI)] and composition [including calcification, intraplaque hemorrhage, and lipid-rich necrotic core (LRNC)] in symptomatic carotid arteries were evaluated and compared between patients in these two time periods., Results: A total of 258 patients, including 129 patients in the 2002-2005 cohort and 129 patients in the 2012-2015 cohort, were recruited. Statin use (49.6% vs. 32.6%, P = 0.004) and hypertension (76.0% vs. 62.8%, P = 0.015) were significantly more common in the 2012-2015 cohort than in the 2002-2005 cohort. Patients in the 2012-2015 cohort also exhibited significantly low plaque burden parameters (all P < 0.05), as well as a lower prevalence (68.2% vs. 89.9%, P < 0.001) and volume percentages of LRNC (11.2% ± 14.2% vs. 25.7% ± 17.7%, P < 0.001). These differences remained significant after adjustment for clinical factors. The differences in the volume percentages of LRNC also remained significant after an additional adjustment for maximum NWI ( P < 0.001)., Conclusions: Patients in the 2012-2015 cohort had a lower plaque burden and volume percentages of LRNC in symptomatic carotid arteries than those in the 2002-2005 cohort. These findings indicate that carotid plaques in the recent cohort had a lower severity and vulnerability., (Copyright and License information: Journal of Geriatric Cardiology 2021.)

A detailed knowledge of gene function in the monarch butterfly is still lacking. Here we generate a genome assembly from a Mexican nonmigratory population and used RNA-seq data from 14 biological samples for gene annotation and to construct an atlas portraying the breadth of gene expression during most of the monarch life cycle. Two thirds of the genes show expression changes, with long noncoding RNAs being particularly finely regulated during adulthood, and male-biased expression being four times more common than female-biased. The two portions of the monarch heterochromosome Z, one ancestral to the Lepidoptera and the other resulting from a chromosomal fusion, display distinct association with sex-biased expression, reflecting sample-dependent incompleteness or absence of dosage compensation in the ancestral but not the novel portion of the Z. This study presents extended genomic and transcriptomic resources that will facilitate a better understanding of the monarch's adaptation to a changing environment.

Background: Extreme temperature events have been observed to appear more frequently and with greater intensity in Taiwan in recent decades due to climate change, following the global trend. Projections of temperature extremes across different climate zones and their impacts on related mortality and adaptation have not been well studied., Methods: We projected site-specific future temperature extremes by statistical downscaling of 8 global climate models followed by Bayesian model averaging from 2021 to 2060 across Taiwan under the representative concentration pathway (RCP) scenarios RCP2.6, RCP4.5, and RCP8.5. We then calculated the attributable mortality (AM) in 6 municipalities and in the eastern area by multiplying the city/county- and degree-specific relative risk of mortality according to the future population projections. We estimated the degree of adaptation to heat by slope reduction of the projected AM to be comparable with that in 2018., Results: The annual number of hot days with mean temperatures over 30 °C was predicted to have a substantial 2- to 5-fold increase throughout the residential areas of Taiwan by the end of 2060 under RCP8.5, whereas the decrease in cold days was less substantial. The decrease in cold-related mortality below 15 °C was projected to outweigh heat-related mortality for the next two decades, and then heat-related mortality was predicted to drastically increase and cross over cold-related mortality, surpassing it from 2045 to 2055. Adjusting for future population size, the percentage increase in heat-related deaths per 100,000 people could increase by more than 10-fold under the worst scenario (RCP8.5), especially for those over 65 years old. The heat-related impacts will be most severe in southern Taiwan, which has a tropical climate. There is a very high demand for heat-adaptation prior to 2050 under all RCP scenarios., Conclusions: Spatiotemporal variations in AM in cities in different climate zones are projected in Taiwan and are expected to have a net negative effect in the near future before shifting to a net positive effect from 2045 to 2055. However, there is an overall positive and increasing trend of net effect for elderly individuals under all the emission scenarios. Active adaptation plans need to be well developed to face future challenges due to climate change, especially for the elderly population in central and southern Taiwan., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)