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The widespread adoption of smart terminals has significantly boosted the market potential for wearable electronic devices. Two-dimensional (2D) nanomaterials show great promise for flexible, wearable electronics of next-generation electronic materials and have potential in energy, optoelectronics, and electronics. First, this review focuses on the importance of functionalization/defects in 2D nanomaterials, a discussion of different kinds of 2D materials for wearable devices, and the overall structure–property relationship of 2D materials. Then, in this comprehensive review, we delve into the burgeoning realm of emerging applications for 2D nanomaterial-based flexible wearable electronics, spanning diverse domains such as energy, medical health, and displays. A meticulous exploration is presented, elucidating the intricate processes involved in tailoring material properties for specific applications. Each research direction is dissected, offering insightful perspectives and dialectical evaluations that illuminate future trajectories and inspire fruitful investigations in this rapidly evolving field. [ABSTRACT FROM AUTHOR]

The widespread adoption of smart terminals has significantly boosted the market potential for wearable electronic devices. Two-dimensional (2D) nanomaterials show great promise for flexible, wearable electronics of next-generation electronic materials and have potential in energy, optoelectronics, and electronics. First, this review focuses on the importance of functionalization/defects in 2D nanomaterials, a discussion of different kinds of 2D materials for wearable devices, and the overall structure–property relationship of 2D materials. Then, in this comprehensive review, we delve into the burgeoning realm of emerging applications for 2D nanomaterial-based flexible wearable electronics, spanning diverse domains such as energy, medical health, and displays. A meticulous exploration is presented, elucidating the intricate processes involved in tailoring material properties for specific applications. Each research direction is dissected, offering insightful perspectives and dialectical evaluations that illuminate future trajectories and inspire fruitful investigations in this rapidly evolving field. [ABSTRACT FROM AUTHOR]

Purpose: To assess the efficacy of double-balloon endoscopy (DBE) for the detection of small-bowel strictures in Crohn's disease (CD). Methods: This tertiary-referral hospital cohort study was conducted between January 2018 and May 2022. CD patients with symptoms of small-bowel stricture were enrolled sequentially. All of the patients were subjected to both computed tomography enterography (CTE) and DBE, and their symptoms of stricture were assessed using the Crohn's Disease Obstructive Score (CDOS). The diagnostic yield of DBE was compared to that of CTE, and the relationship between the DBE findings and CDOS was investigated. The factors influencing the DBE diagnosis were examined using Cox regression analysis. Results: This study included 165 CD patients. The CDOS scores were higher in 95 patients and lower in 70 patients. DBE detected 92.7% (153/165) and CTE detected 85.5% (141/165) of the strictures. The DBE diagnostic yields were 94.7% (90/95) in the high CDOS patients and 91.4% (64/70) in the low CDOS patients (P = 0.13). Patients with a history of abdominal surgery and abscess had a lower diagnosis rate in the multivariate analysis. Conclusion: DBE has been demonstrated to be an efficient diagnostic method for detecting small bowel strictures in CD patients. Additionally, there was no difference in the diagnostic yields between patients with low and high obstructive scores. [ABSTRACT FROM AUTHOR]

Background: In recent years, accumulating evidences have revealed that influenza A virus (IAV) infections induce significant differential expression of host long noncoding RNAs (lncRNAs), some of which play important roles in the regulation of virus-host interactions and determining the virus pathogenesis. However, whether these lncRNAs bear post-translational modifications and how their differential expression is regulated remain largely unknown. In this study, the transcriptome-wide 5-methylcytosine (m5C) modification of lncRNAs in A549 cells infected with an H1N1 influenza A virus was analyzed and compared with uninfected cells by Methylated RNA immunoprecipitation sequencing (MeRIP-Seq). Results: Our data identified 1317 upregulated m5C peaks and 1667 downregulated peaks in the H1N1 infected group. Gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that the differentially modified lncRNAs were associated with protein modification, organelle localization, nuclear export and other biological processes. Furthermore, conjoint analysis of the differentially modified (DM) and differentially expressed (DE) lncRNAs identified 143 'hyper-up', 81 'hypo-up', 6 'hypo-down' and 4 'hyper-down' lncRNAs. GO and KEGG analyses revealed that these DM and DE lncRNAs were predominantly associated with pathogen recognition and disease pathogenesis pathways, indicating that m5C modifications could play an important role in the regulation of host response to IAV replication by modulating the expression and/or stability of lncRNAs. Conclusion: This study presented the first m5C modification profile of lncRNAs in A549 cells infected with IAV and demonstrated a significant alteration of m5C modifications on host lncRNAs upon IAV infection. These data could give a reference to future researches on the roles of m5C methylation in virus infection. [ABSTRACT FROM AUTHOR]

Highlights: The low FODMAP diet is the most recommended dietary intervention for the clinical management of IBS symptoms. Bibliometrics analysis provides a comprehensive perspective and direction on global research trend and hotspot in the low FODMAP diet research. The restriction stage of the low FODMAP diet is superior to other dietary therapies for IBS in terms of symptom response, but it has a negative impact on the abundance of gut Bifidobacteria and diet quality. Identification of biomarkers to predict response to the low FODMAP diet has become the current research hotspot. Large, well-designed clinical research studies are needed in the future to investigate the long-term efficacy and safety of the low FODMAP diet, including FODMAP reintroduction and personalization stages. Background: According to national guidelines, a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) is a second-line therapy option for irritable bowel syndrome (IBS) and improves functional intestinal symptoms. Numerous noteworthy results have been published in this field over the past fifteen years. This study aims to analyze the global research trend and hotspot of the low FODMAP diet research, and provide a comprehensive perspective and direction for researchers. Methods: The Science Citation Index-Expanded of the Web of Science Core Collection (WoSCC) was used to identify low FODMAP diet-related articles and reviews. Three bibliometric programs (CiteSpace, VOSviewer, Scimago Graphic) were utilized to analyze and visualize the annual publications, authors, countries, institutions, journals, citations, and keywords. Results: In total, 843 documents related to the low FODMAP diet research were published in 227 journals by 3,343 authors in 1,233 institutions from 59 countries. The United States, which was the most engaged nation in international collaboration, had the largest annual production and the fastest growth. The most productive organization was Monash University, and the most fruitful researcher was Gibson PR. Nutrients ranked first in terms of the number of published documents. The article "A diet low in FODMAPs reduces symptoms of irritable bowel syndrome" (Halmos EP, 2014) received the most co-citations. Keywords that appear frequently in the literature mainly involve two main aspects: the clinical efficacy evaluation and mechanism exploration of the low FODMAP diet. The term "gut microbiota" stands out as the most prominent keyword among the burst keywords that have remained prevalent till date. Conclusion: The restriction stage of the low FODMAP diet is superior to other dietary therapies for IBS in terms of symptom response, but it has a negative impact on the abundance of gut Bifidobacteria and diet quality. Identification of biomarkers to predict response to the low FODMAP diet is of great interest and has become the current research hotspot. [ABSTRACT FROM AUTHOR]

Background: Both hepatitis C virus (HCV) infection and adiponectin are critically involved in metabolism. The reversal and associations of altering adiponectin levels after sustained virological responses (SVRs) following direct-acting antivirals (DAA) in HCV-infected patients remained elusive. Methods: A joint study was conducted in a prospective cohort of 427 HCV-infected patients and a line of HCV core transgenic mice. Results: Of 427, 358 had completed a course of DAA therapy and 353 had SVRs. At baseline, male sex (95% CI β: − 1.44 to − 0.417), estimated glomerular filtration rate (eGFR) (− 0.025 to − 0.008), triglycerides (− 0.015 to − 0.005), and fibrosis-4 levels (0.08–0.297) were associated with adiponectin levels; BMI (0.029–0.327) and triglycerides levels (0.01–0.03) were associated with homeostatic model assessment for insulin resistance (HOMA-IR) in HCV-infected patients. At 24-week post-therapy, in SVR patients, male sex (− 1.89 to − 0.5) and eGFR (− 0.02 to − 0.001) levels were associated with adiponectin levels, levels of BMI (0.094–0.335) and alanine transaminase (0.018–0.078) were associated with HOMA-IR; compared with baseline levels, adiponectin levels decreased (6.53 ± 2.77 vs. 5.45 ± 2.56 μg/mL, p < 0.001). In 12-month-old HCV core transgenic mice with hepatic steatosis, triglyceride levels (0.021–0.111) were associated with adiponectin levels, and hepatic adipopnectin expression was comparable with that of control mice. Conclusions: Triglycerides and hepatic fibrosis are associated with HCV-specific alteration of adiponectin levels, and adiponectin may affect insulin sensitivity through triglycerides during HCV infection. In DAA-treated patients, after SVR, adiponectin levels decreased and the linking function of triglycerides between adiponectin and insulin sensitivity vanished. Moreover, HCV core with hepatic steatosis might affect extrahepatic adiponectin expression through triglycerides. [ABSTRACT FROM AUTHOR]

Background: Proper sedation of patients, particularly elderly individuals, who are more susceptible to sedation-related complications, is of significant importance in endoscopic retrograde cholangiopancreatography (ERCP). This study aims to assess the safety and efficacy of a low-dose combination of midazolam, alfentanil, and propofol for deep sedation in elderly patients undergoing ERCP, compared to a group of middle-aged patients. Methods: The medical records of 610 patients with common bile duct stones who underwent elective ERCP under deep sedation with a three-drug regimen, including midazolam, alfentanil, and propofol at Shandong Provincial Third Hospital from January 2023 to September 2023 were retrospectively reviewed in this study. Patients were categorized into three groups: middle-aged (50–64 years, n = 202), elderly (65–79 years, n = 216), and very elderly (≥ 80 years, n = 192). Intraoperative vital signs and complications were compared among these groups. Results: The three groups showed no significant difference in terms of intraoperative variation of systolic blood pressure (P = 0.291), diastolic blood pressure (P = 0.737), heart rate (P = 0.107), peripheral oxygen saturation (P = 0.188), bispectral index (P = 0.158), and the occurrence of sedation-related adverse events including hypotension (P = 0.170) and hypoxemia (P = 0.423). Conclusion: The results suggest that a low-dose three-drug regimen consisting of midazolam, alfentanil, and propofol seems safe and effective for deep sedation of elderly and very elderly patients undergoing ERCP procedures. However, further studies are required to verify these findings and clarify the benefits and risks of this method. [ABSTRACT FROM AUTHOR]

Background: With the increased empirical interest in the positive significance of improving nurses' sense of professional benefits, there is a requirement for measures of nurses' perceived professional benefit (NPPB). Our objective was to develop and psychometrically test a brief Nurses' Perceived Professional Benefit Questionnaire (NPPBQ).Methods: After expert consultation and nurse interviews, a primary questionnaire was developed for an exploratory factor analysis (EFA). The seventeen items of the NPPBQ were used for verification of the theorized factor structure and content validity using a confirmatory factor analysis (CFA). The NPPBQ's concurrent validity was evaluated. Three samples of nurses were collected in Shanghai, Hangzhou and Nanjing between November 2017 and August 2018.Results: The results of the EFA and CFA verified the five dimensions of nurses' occupational benefit discovery. The results demonstrated that the NPPBQ has adequate internal consistency and is fully consistent with the theorized factor structure. This 5-factor solution explained an adequate percentage of the total variance. The Cronbach's alpha of each dimension of the NPPBQ was good. The concurrent validity was significantly correlated with all aspects of the Maslach Burnout Inventory (MBI).Conclusion: The results suggest that the NPPBQ is a psychometrically sound measure for evaluating perceived professional benefits among a wide range of nurses. [ABSTRACT FROM AUTHOR]

Halopiger salifodinae strain KCY07-B2, isolated from a salt mine in Kuche county, Xinjiang province, China, belongs to the family Halobacteriaceae. It is a strictly aerobic, pleomorphic, rod-shaped, Gram-negative and extremely halophilic archaeon. In this work, we report the features of the type strain KCY07-B2, together with the draft genome sequence and annotation. The draft genome sequence is composed of 83 contigs for 4,350,718 bp with 65.41 % G + C content and contains 4204 protein-coding genes and 50 rRNA genes. [ABSTRACT FROM AUTHOR]

Introduction: Osteoporosis leads to more serious consequences in men than in women, but less is known about its impacts on health-related quality of life (HRQoL) of men, and whether the anti-osteoporosis treatment can improve HRQoL of men with osteopenia/osteoprosis. Methods: We enrolled men with primary osteoporosis and age-matched healthy controls. We collected medical history, serum levels of carboxyl-terminal type I collagen telopeptide, procollagen type I propeptides, and bone mineral density of patients. All patients and controls completed the short-form 36 (SF-36) questionnaires. Changes in HRQoL of osteopenia/osteoporosis men were prospectively evaluated after alendronate or zoledronic acid treatment. Results: A total of 100 men with primary osteoporosis or osteopenia and 100 healthy men were included. The patients were divided into three subgroups: osteopenia (n = 35), osteoporosis (n = 39) and severe osteoporosis (n = 26). Men with osteoporosis or severe osteoporosis had impaired HRQoL in domains of physical health compared to healthy controls. HRQoL scores in physical health related domains of patients with severe osteoporosis were significantly lower compared to healthy controls, and were the poorest among the three subgroups of patients. Fragility fracture history was correlated with lower SF-36 scores about physical health. In 34 men with newly diagnosed osteoporosis receiving bisphosphonates treatment, HRQoL scores were significantly improved in domains of physical health after treatments. Conclusions: The HRQoL is significantly impaired in men with osteoporosis, and the more severe the osteoporosis, the poorer the HRQoL. Fragility fracture is an important influencing factor of deteriorated HRQoL. Bisphosphonates treatment is beneficial to improve HRQoL of osteopenia/osteoporosis men. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the clinical availability and stability of histological endometrial dating as a tool for personalized frozen-thawed embryo transfer (pFET) in patients with repeated implantation failure (RIF) in natural cycles. Methods: A total of 1245 RIF patients were recruited to the present study. All of the patients received an endometrial dating evaluation on day 7 post-ovulation (PO + 7) to guide their first pFET. The second and third pFETs were executed according to histological examination (again employing biopsy) or by reference to previous results. Subsequent pregnancy outcomes for all of the cycles were ultimately tracked. Results: The out-of-phase rate for RIF patients was 32.4% (404/1245) and the expected dating rate (the probability of the expected endometrial dating aligning with repeat biopsy) for endometrial dating reevaluation was as high as 94.3% (50/53). The clinical pregnancy rates of first, second, and third pFETs were 65.3%, 50.0%, and 44.4%, respectively; and the cumulative clinical pregnancy rate attained 74.9% after three transfers. Endometrial dating reevaluations met expectations with more than a 2-year duration in three cases and elicited favorable clinical outcomes. Conclusion: We validated the relatively high stability of the histological endometrial dating platform—including the out-of-phase rate and the expected dating rate of reevaluation in patients with RIF—by expanding the sample size. The pFET, based on histological endometrial dating, was of acceptable clinical value and was worthy of promotion in patients with unexplained RIF. [ABSTRACT FROM AUTHOR]

Background: Endocrine resistance driven by sustained activation of androgen receptor (AR) signaling pathway in advanced prostate cancer (PCa) is fatal. Characterization of mechanisms underlying aberrant AR pathway activation to search for potential therapeutic strategy is particularly important. Rac GTPase-activating protein 1 (RACGAP1) is one of the specific GTPase-activating proteins. As a novel tumor proto-oncogene, overexpression of RACGAP1 was related to the occurrence of various tumors. Methods: Bioinformatics methods were used to analyze the relationship of expression level between RACGAP1 and AR as well as AR pathway activation. qRT-PCR and western blotting assays were performed to assess the expression of AR/AR-V7 and RACGAP1 in PCa cells. Immunoprecipitation and immunofluorescence experiments were conducted to detect the interaction and co-localization between RACGAP1 and AR/AR-V7. Gain- and loss-of-function analyses were conducted to investigate the biological roles of RACGAP1 in PCa cells, using MTS and colony formation assays. In vivo experiments were conducted to evaluate the effect of RACGAP1 inhibition on the tumor growth. Results: RACGAP1 was a gene activated by AR, which was markedly upregulated in PCa patients with CRPC and enzalutamide resistance. AR transcriptionally activated RACGAP1 expression by binding to its promoter region. Reciprocally, nuclear RACGAP1 bound to the N-terminal domain (NTD) of both AR and AR-V7, blocking their interaction with the E3 ubiquitin ligase MDM2. Consequently, this prevented the degradation of AR/AR-V7 in a ubiquitin-proteasome-dependent pathway. Notably, the positive feedback loop between RACGAP1 and AR/AR-V7 contributed to endocrine therapy resistance of CRPC. Combination of enzalutamide and in vivo cholesterol-conjugated RIG-I siRNA drugs targeting RACGAP1 induced potent inhibition of xenograft tumor growth of PCa. Conclusion: In summary, our results reveal that reciprocal regulation between RACGAP1 and AR/AR-V7 contributes to the endocrine resistance in PCa. These findings highlight the therapeutic potential of combined RACGAP1 inhibition and enzalutamide in treatment of advanced PCa. [ABSTRACT FROM AUTHOR]

Background: Cellular states of different immune cells can affect the activity of the whole immune microenvironment. Methods: Here, leveraging reference profiles of microenvironment cell states that were constructed based on single-cell RNA-seq data of melanoma, we dissected the composition of microenvironment cell states across 463 skin cutaneous melanoma (SKCM) bulk samples through CIBERSORT-based deconvolution of gene expression profiles and revealed high heterogeneity of their distribution. Correspondence analysis on the estimated cellular fractions of melanoma bulk samples was performed to identify immune phenotypes. Based on the publicly available clinical survival and therapy data, we analyzed the relationship between immune phenotypes and clinical outcomes of melanoma. Results: By analysis of the relationships among those cell states, we further identified three distinct tumor microenvironment immune phenotypes: "immune hot/active", "immune cold-suppressive" and "immune cold-exhausted". They were characterized by markedly different patterns of cell states: most notably the CD8 T Cytotoxic state, CD8 T Mixed state, B non-regulatory state and cancer-associated fibroblasts (CAFs), depicting distinct types of antitumor immune response (or immune activity). These phenotypes had prognostic significance for progression-free survival and implications in response to immune therapy in an independent cohort of anti-PD1 treated melanoma patients. Conclusions: The proposed strategy of leveraging single-cell data to dissect the composition of microenvironment cell states in individual bulk tumors can also extend to other cancer types, and our results highlight the importance of microenvironment cell states for the understanding of tumor immunity. [ABSTRACT FROM AUTHOR]

Background: Breast cancer is the most common cancer affecting women across the world. Tumor endothelial cells (TECs) and malignant cells are the major constituents of the tumor microenvironment (TME), but their origin and role in shaping disease initiation, progression, and treatment responses remain unclear due to significant heterogeneity. Methods: Tissue samples were collected from eight patients presenting with breast cancer. Single-cell RNA sequencing (scRNA-seq) analysis was employed to investigate the presence of distinct cell subsets in the tumor microenvironment. InferCNV was used to identify cancer cells. Pseudotime trajectory analysis revealed the dynamic process of breast cancer angiogenesis. We validated the function of small extracellular vesicles (sEVs)-derived protein phosphatase 1 regulatory inhibitor subunit 1B (PPP1R1B) in vitro experiments. Results: We performed single-cell transcriptomics analysis of the factors associated with breast cancer angiogenesis and identified twelve subclusters of endothelial cells involved in the tumor microenvironment. We also identified the role of TECs in tumor angiogenesis and confirmed their participation in different stages of angiogenesis, including communication with other cell types via sEVs. Overall, the research uncovered the TECs heterogeneity and the expression levels of genes at different stages of tumor angiogenesis. Conclusions: This study showed sEVs derived from breast cancer malignant cells promote blood vessel formation by activating endothelial cells through the transfer of PPP1R1B. This provides a new direction for the development of anti-angiogenic therapies for human breast cancer. [ABSTRACT FROM AUTHOR]

Background: Cancer stem-like traits contribute to prostate cancer (PCa) progression and metastasis. Deciphering the novel molecular mechanisms underlying stem-like traits may provide important insight for developing novel therapeutics. Methods: Immunohistochemistry and immunofluorescence assays in prostatic tissues; gain- and loss-of-function analyses using ectopic overexpression and shRNAs in PCa cell lines; measurements of tumorigenic and stemness properties, and transcription in vitro and in vivo; transcriptional analysis in public databases. Results: We identified that overexpression of BTF3 in PCa tissues and BTF3 expression highly correlates to stem-like traits. Cancer stem-like characteristics in PCa including self-renewal and metastatic potential were impaired by BTF3 loss and promoted by BTF3 overexpression. Mechanistically, BTF3 could stabilize BMI1, which is a crucial regulator of prostate stem cell self-renewal. More importantly, our data revealed that BTF3 is highly predictive of poor prognosis and may help in risk stratification of PCa patients. Conclusions: BTF3 promotes PCa progression though modeling stem-like traits in PCa. BTF3 represents a stratification marker in PCa progression and outcomes. [ABSTRACT FROM AUTHOR]

Background: The present survey evaluated the incidence of perioperative cardiac arrests in a Chinese tertiary general teaching hospital over ten years. Methods: The incidence of cardiac arrest that occurred within 24 h of anaesthesia administration was retrospectively identified in the Third Affiliated Hospital of Sun Yat-Sen University between August 2007 and October 2017. Overall, 152,513 anaesthetics were included in the study period. Data collected included patient characteristics, American Society of Anaesthesiologists (ASA) physical status score, surgical specialty and anaesthesia technique. Cardiac arrests were assigned to one of three groups: “anaesthesia-related”, “anaesthesia-contributing” or “anaesthesia-unrelated”. Results: In total, 104 cardiac arrests (6.8:10,000) and 34 deaths (2.2:10,000) were obtained. Among them, eleven cardiac arrests events were anaesthesia-related, resulting in an incidence of 0.7 per 10,000 anaesthetics. Sixteen cardiac arrests events were found to be anaesthesia-contributing, resulting in an incidence of 1.0 per 10,000 anaesthetics. Cardiovascular adverse events were the major events that contributed to anaesthesia-related cardiac arrest. Differences were found between events related and unrelated to anaesthesia with regard to ASA physical status and anaesthesia technique (P < 0.05). Conclusions: Anaesthesia-related cardiac arrest occurred in 11 of 104 cardiac arrests within 24 h of anaesthesia administration. Most cardiac arrests related to anaesthesia were due to cardiovascular events, including arrhythmia and hypotension after intravenous narcotic, as well as haemorrhage. ASA physical status of at least 3 and subarachnoid block appeared to be relevant risk factors for anaesthesia-related cardiac arrest. [ABSTRACT FROM AUTHOR]

Background: Breast cancer is the most common cancer affecting women across the world. Tumor endothelial cells (TECs) and malignant cells are the major constituents of the tumor microenvironment (TME), but their origin and role in shaping disease initiation, progression, and treatment responses remain unclear due to significant heterogeneity. Methods: Tissue samples were collected from eight patients presenting with breast cancer. Single-cell RNA sequencing (scRNA-seq) analysis was employed to investigate the presence of distinct cell subsets in the tumor microenvironment. InferCNV was used to identify cancer cells. Pseudotime trajectory analysis revealed the dynamic process of breast cancer angiogenesis. We validated the function of small extracellular vesicles (sEVs)-derived protein phosphatase 1 regulatory inhibitor subunit 1B (PPP1R1B) in vitro experiments. Results: We performed single-cell transcriptomics analysis of the factors associated with breast cancer angiogenesis and identified twelve subclusters of endothelial cells involved in the tumor microenvironment. We also identified the role of TECs in tumor angiogenesis and confirmed their participation in different stages of angiogenesis, including communication with other cell types via sEVs. Overall, the research uncovered the TECs heterogeneity and the expression levels of genes at different stages of tumor angiogenesis. Conclusions: This study showed sEVs derived from breast cancer malignant cells promote blood vessel formation by activating endothelial cells through the transfer of PPP1R1B. This provides a new direction for the development of anti-angiogenic therapies for human breast cancer. [ABSTRACT FROM AUTHOR]

Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) and immunosuppressive therapy (IST) are two major competing treatment strategies for acquired aplastic anemia (AA). Whether allo-HSCT is superior to IST as a front-line treatment for patients with AA has been a subject of debate. To compare the efficacy and safety of allo-HSCT with that of IST as a front-line treatment for patients with AA, we performed a meta-analysis of available studies that examined the impact of the two major competing treatment strategies for AA. Results: Fifteen studies including a total of 5336 patients were included in the meta-analysis. The pooled hazard ratio (HR) for overall survival (OS) was 0.4 (95% CI 0.074–0.733, P = 0.016, I2 = 58.8%) and the pooled HR for failure-free survival (FFS) was 1.962 (95% CI 1.43–2.493, P = 0.000, I2 = 0%). The pooled relative risk (RR) for overall response rate (ORR) was 1.691 (95% CI 1.433–1.996, P = 0.000, I2 = 11.6%). Conclusion: Although survival was significantly longer among AA patients undergoing first-line allo-HSCT compared to those undergoing first-line IST, the selection of initial treatment for patients with newly diagnosed AA still requires comprehensive evaluation of donor availability, patient age, expected quality of life, risk of disease relapse or clonal evolution after IST, and potential use of adjunctive eltrombopag. [ABSTRACT FROM AUTHOR]

Background: Orofacial pain (OFP) is a highly prevalent disorder in mainland China that predisposes to an associated physical and psychological disability. There is lack of a good properties mainland Chinese version of instrument to examine OFP. This study aims to cross-cultural adaptation and evaluate psychometrics properties of the Manchester Orofacial Pain Disability Scale (MOPDS) in mainland Chinese Mandarin context. Methods: Translation and cross-cultural adaption of the mainland Chinese version MOPDS were conducted following accepted guidelines of self-report measures. Chinese college students (N = 1039) completed the mainland Chinese version of the MOPDS for item analysis, reliability and validity tests, and measurement invariance analysis, and after a one-month interval, around 10% of the sample (n = 110) were invited to retest. To conduct the CFA and measurement invariance analysis, Mplus 8.4 was used. IBM SPSS Statistics 26 software were used for all additional studies. Results: We found that the mainland Chinese version of MOPDS contains 25 items, divided into two categories: physical disability and psychological disability. The scale demonstrated excellent internal reliability, test-retest reliability, and validity. The measurement invariance results proved that the scale could be applied to people of different gender, age, and health consultation status. Conclusions: The results demonstrated the mainland Chinese version of MOPDS has good psychometric properties and can be used to measure the level of physical and psychological disability of Chinese OFP peoples. [ABSTRACT FROM AUTHOR]

Background: Hereditary spherocytosis (HS) is a common inherited hemolytic anemia, caused by mutations in five genes that encode erythrocyte membrane skeleton proteins. The red blood cell (RBC) lifespan could directly reflect the degree of hemolysis. In the present cohort of 23 patients with HS, we performed next-generation sequencing (NGS) and Levitt's carbon monoxide (CO) breath test to investigate the potential genotype-degree of hemolysis correlation. Results: In the present cohort, we identified 8 ANK1,9 SPTB,5 SLC4A1 and 1 SPTA1 mutations in 23 patients with HS, and the median RBC lifespan was 14(8–48) days. The median RBC lifespan of patients with ANK1, SPTB and SLC4A1 mutations was 13 (8–23), 13 (8–48) and 14 (12–39) days, respectively, with no statistically significant difference (P = 0.618). The median RBC lifespan of patients with missense, splice and nonsense/insertion/deletion mutations was 16.5 (8–48), 14 (11–40) and 13 (8–20) days, respectively, with no significant difference (P = 0.514). Similarly, we found no significant difference in the RBC lifespan of patients with mutations located in the spectrin-binding domain and the nonspectrin-binding domain [14 (8–18) vs. 12.5 (8–48) days, P = 0.959]. In terms of the composition of mutated genes, 25% of patients with mild hemolysis carried ANK1 or SPTA1 mutations, while 75% of patients with mild hemolysis carried SPTB or SLC4A1 mutations. In contrast, 46.7% of patients with severe hemolysis had ANK1 or SPTA1 mutations and 53.3% of patients with severe hemolysis had SPTB or SLC4A1 mutations. However, there was no statistically significant difference in the distribution of mutated genes between the two groups (P = 0.400). Conclusion: The present study is the first to investigate the potential association between genotype and degree of hemolysis in HS. The present findings indicated that there is no significant correlation between genotype and degree of hemolysis in HS. [ABSTRACT FROM AUTHOR]

Background: Antiviral intervention in hepatitis B virus (HBV)-infected pregnant women can effectively reduce mother-to-child transmission. However, the immunological characteristics of pregnant women with chronic HBV infection and the effects of antiviral intervention during pregnancy on maternal immune response remain unknown. We aimed to investigate these effects by comparing mothers who received antiviral intervention during pregnancy with those who did not. Methods: Pregnant women positive for hepatitis B surface antigen and hepatitis B e-antigen (HBsAg+ HBeAg+) were enrolled at delivery, including 34 received prophylactic antiviral intervention during pregnancy (AVI mothers) and 15 did not (NAVI mothers). T lymphocyte phenotypes and functions were analysed using flow cytometry. Results: At delivery, maternal regulatory T cell (Treg) frequency in AVI mothers was significantly higher than that in NAVI mothers (P < 0.002), and CD4+ T cells in AVI mothers displayed a decreased ability to secrete IFN-γ (P = 0.005) and IL-21 (P = 0.043), but an increased ability to secrete IL-10 and IL-4 (P = 0.040 and P = 0.036), which represented a higher Treg frequency, enhanced Th2 response and suppressed Th1 response. Treg frequency among AVI mothers was correlated negatively with serum HBsAg and HBeAg levels. After delivery, the ability of CD4+ T cells or CD8+ T cells to secrete IFN-γ or IL-10 was similar and no significant difference in Treg frequency was found between the two groups. Conclusions: Prophylactic antiviral intervention during pregnancy has an effect on T cell immunity in pregnant women, which was characterised by increased maternal Treg frequency, enhanced Th2 response and suppressed Th1 response at delivery. [ABSTRACT FROM AUTHOR]

Background: Jaw-bone defects caused by various diseases lead to aesthetic and functional complications, which can seriously affect the life quality of patients. Current treatments cannot fully meet the needs of reconstruction of jaw-bone defects. Thus, the research and application of bone tissue engineering are a "hot topic." As seed cells for engineering of jaw-bone tissue, oral cavity-derived stem cells have been explored and used widely. Models of jaw-bone defect are excellent tools for the study of bone defect repair in vivo. Different types of bone defect repair require different stem cells and bone defect models. This review aimed to better understand the research status of oral and maxillofacial bone regeneration. Main text: Data were gathered from PubMed searches and references from relevant studies using the search phrases "bone" AND ("PDLSC" OR "DPSC" OR "SCAP" OR "GMSC" OR "SHED" OR "DFSC" OR "ABMSC" OR "TGPC"); ("jaw" OR "alveolar") AND "bone defect." We screened studies that focus on "bone formation of oral cavity-derived stem cells" and "jaw bone defect models," and reviewed the advantages and disadvantages of oral cavity-derived stem cells and preclinical model of jaw-bone defect models. Conclusion: The type of cell and animal model should be selected according to the specific research purpose and disease type. This review can provide a foundation for the selection of oral cavity-derived stem cells and defect models in tissue engineering of the jaw bone. [ABSTRACT FROM AUTHOR]

Background: BMP9-stimulated DPSCs, SCAPs and PDLSCs are effective candidates for repairing maxillofacial bone defects in tissue engineering, while the most suitable seed cell source among these three hDMSCs and the optimal combination of most suitable type of hDMSCs and BMP9 have rarely been explored. Moreover, the orthotopic maxillofacial bone defect model should be valuable but laborious and time-consuming to evaluate various candidates for bone regeneration. Thus, inspired from the maxillofacial bone defects and the traditional in vivo ectopic systems, we developed an intrabony defect repair model to recapitulate the healing events of orthotopic maxillofacial bone defect repair and further explore the optimized combinations of most suitable hDMSCs and BMP9 for bone defect repair based on this modified ectopic system. Methods: Intrabony defect repair model was developed by using decellularized bone matrix (DBM) constructs prepared from the cancellous part of porcine lumbar vertebral body. We implanted DBM constructs subcutaneously on the flank of each male NU/NU athymic nude mouse, followed by directly injecting the cell suspension of different combinations of hDMSCs and BMP9 into the central hollow area of the constructs 7 days later. Then, the quality of the bony mass, including bone volume fraction (BV/TV), radiographic density (in Hounsfield units (HU)) and the height of newly formed bone, was measured by micro-CT. Furthermore, the H&E staining and immunohistochemical staining were performed to exam new bone and new blood vessel formation in DBM constructs. Results: BMP9-stimulated periodontal ligament stem cells (PDLSCs) exhibited the most effective bone regeneration among the three types of hDMSCs in DBM constructs. Furthermore, an optimal dose of PDLSCs with a specific extent of BMP9 stimulation was confirmed for efficacious new bone and new blood vessel formation in DBM constructs. Conclusions: The reported intrabony defect repair model can be used to identify optimized combinations of suitable seed cells and biological factors for bone defect repair and subsequent development of efficacious bone tissue engineering therapies. [ABSTRACT FROM AUTHOR]

Background: The reduction in androgen level gives rise to a decrease in bone mineral density (BMD) and muscle strength, but the exact mechanisms are unclear. We investigated the roles of novel cytokines of sclerostin and irisin on bone and muscle of orchiectomized rats.Methods: Twenty 3-month-old male rats were randomized to receive sham or orchiectomy (ORX) operation. Rats were euthanized after 8 weeks of surgery, and serum levels of sclerostin and irisin were measured by enzyme-linked immunosorbent assay at baseline and execution. Grip strength was measured by a grip strength tester at baseline and before execution. BMD and bone microarchitecture were measured by microcomputed tomography. The samples of bone and muscle were harvested at execution. Bone biomechanics were measured by three-point bending tests and vertebral body indentation tests. Bone and muscle histological features were analyzed by hematoxylin and eosin stain, Von Kossa's stain and tartrate resistant acid phosphatase stain. Simple linear regression analyses were used to analyze the relationships between serum levels of sclerostin, irisin and grip strength and BMD of ORX rats.Results: Serum sclerostin level increased from 279 ± 44 pg/mL to 586 ± 57 pg/mL since baseline to 8 weeks after ORX (P = 0.002), which was significantly higher than that in sham rats (406 ± 20 pg/mL at execution) (P = 0.012). Serum irisin level decreased from 4.12 ± 0.20 ng/mL to 3.55 ± 0.29 ng/mL since baseline to 8 weeks of ORX (P = 0.048), which was significantly lower than sham rats (4.84 ± 0.37 pg/mL at execution) (P = 0.013). Trabecular BMD, parameters of bone microarchitecture, bone strength, grip strength and the myofibers size of soleus muscles were significantly lower in ORX rats than in sham group. Grip strength was positively correlated with femoral trabecular BMD (r = 0.713, P < 0.001) and bone volume/total volume (r = 0.712, P < 0.001) in all rats. The serum sclerostin level was negatively correlated to femoral trabecular BMD (r = -0.508, P = 0.022) and grip strength (r = -0.492, P = 0.028). Serum irisin level was positively correlated with femoral trabecular BMD (r = 0.597, P = 0.005), but no obvious correlation was found between irisin level and muscle strength in all rats.Conclusions: Reduced BMD, impaired bone microarchitecture, weak strength of bone and muscle, and thin myofibers were induced by androgen deficiency of ORX rats. Serum sclerostin and irisin levels were significantly changed after ORX, which might be closely correlated with the occurrence of osteoporosis and sarcopenia in ORX rats. [ABSTRACT FROM AUTHOR]

Bone tissue engineering (BTE) is a promising method for the repair of difficult-to-heal bone tissue damage by providing three-dimensional structures for cell attachment, proliferation, and differentiation. Traditional Chinese medicine (TCM) has been introduced as an effective global medical program by the World Health Organization, comprising intricate components, and promoting bone regeneration by regulating multiple mechanisms and targets. This study outlines the potential therapeutic capabilities of TCM combined with BTE in bone regeneration. The effective active components promoting bone regeneration can be generally divided into flavonoids, alkaloids, glycosides, terpenoids, and polyphenols, among others. The chemical structures of the monomers, their sources, efficacy, and mechanisms are described. We summarize the use of compounds and medicinal parts of TCM to stimulate bone regeneration. Finally, the limitations and prospects of applying TCM in BTE are introduced, providing a direction for further development of novel and potential TCM. [ABSTRACT FROM AUTHOR]

Background: Foods have a considerable influence on human health and were directly related to glycemic control for diabetes patients. However, little is known about the effects of biscuits, a traditional food consumed in large amounts in several countries, on diabetic retinopathy. This study aimed to explore the association between biscuit consumption and diabetic retinopathy prevalence in adults of the United States population. Methods: A cross-sectional study with 1904 participants from the National Health and Nutrition Examination Survey database were included in this population-based, cross-sectional study. The association between different consumption frequencies of biscuit and diabetic retinopathy prevalence was evaluated using a binary logistic regression model. Trend test, stratified and interaction analyses were also performed. Results: After possible confounders including sex, age, ethnicity, education, marital status, family poverty income ratio, smoking and alcohol consumption habit, fasting blood glucose level, hemoglobin A1c level, diagnosis of diabetes, insulin use, blood pressure, body mass index were adjusted, the participants who consumed biscuit 1–11 times a year, 1–3 times a month, and more than once a week had a 139.8% (95% confidence interval, 1.003–5.734), 182.1% (95% confidence interval, 1.106–7.191), and 236.2% (95% confidence interval, 1.335–9.844) higher risk of diabetic retinopathy prevalence, respectively, compared with those who never ate biscuit. For male, non-Hispanic, and overweight (body mass index ≥ 25 kg/m2) subgroups, the trend test demonstrated that the diabetic retinopathy prevalence significantly elevated with increased frequency of biscuit consumption (Ptrend = 0.021, 0.009, and 0.002, respectively). The interaction analysis suggested that no aforementioned confounders played an interactive role in the relationship between biscuit consumption and diabetic retinopathy prevalence. Conclusions: The risk of diabetic retinopathy was positively associated with biscuit consumption. Moreover, for male, non-Hispanic, or overweight individuals, the risk of diabetic retinopathy significantly increased with the frequency of biscuit consumption. [ABSTRACT FROM AUTHOR]

Background: This study compared the survival outcomes of different surgical approaches to determine the optimal approach for gastric cardia adenocarcinoma (GCA) and aimed to standardize the surgical treatment guidelines for GCA. Methods: A total of 7103 patients with GCA were enrolled from our previously established gastric cardia and esophageal carcinoma databases. In our database, when the epicenter of the tumor was at or within 2 cm distally from the esophagogastric junction, the adenocarcinoma was considered to originate from the cardia and was considered a Siewert type 2 cancer. The main criteria for the enrolled patients included treatment with radical surgery, no radio- or chemotherapy before the operation, and detailed clinicopathological information. Follow-up was mainly performed by telephone or through home interviews. According to the medical records, the surgical approaches included transthoracic, thoracoabdominal, and transabdominal approaches. Kaplan–Meier and Cox proportional hazards regression models were applied to correlate the surgical approach with survival in patients with GCA. Results: There were marked differences in age and tumor stage among the patients who underwent the three surgical approaches (P < 0.001). Univariate analysis showed that survival was related to sex, age, tumor stage, and N stage (P < 0.001 for all). Cox regression model analysis revealed that thoracoabdominal approach (P < 0.001) and transabdominal approach (P < 0.001) were significant risk factors for poor survival. GCA patients treated with the transthoracic approach had the best survival (5-year survival rate of 53.7%), and survival varied among the different surgical approaches for different tumor stages. Conclusion: Thoracoabdominal approach and transabdominal approach were shown to be poor prognostic factors. Patients with (locally advanced) GCA may benefit from the transthoracic approach. Further prospective randomized clinical trials are necessary. [ABSTRACT FROM AUTHOR]

Background: Hereditary spastic paraplegia (HSP) is a group of neurodegenerative diseases characterized by lower-limb spastic paraplegia with highly genetic and clinical heterogeneity. However, the clinical sign of spastic paraplegia can also be seen in a variety of hereditary neurologic diseases with bilateral corticospinal tract impairment. The purpose of this study is to identify the disease spectrum of spastic paraplegia, and to broaden the coverage of genetic testing and recognize clinical, laboratorial, electrophysiological and radiological characteristics to increase the positive rate of diagnosis.Methods: Twenty-seven cases were screened out to have definite or suspected pathogenic variants from clinically suspected HSP pedigrees through HSP-associated sequencing and/or expanded genetic testing. One case was performed for enzyme detection of leukodystrophy without next-generation sequencing. In addition, detailed clinical, laboratorial, electrophysiological and radiological characteristics of the 28 patients were presented.Results: A total of five types of hereditary neurological disorders were identified in 28 patients, including HSP (15/28), leukodystrophy (5/28), hereditary ataxia (2/28), methylmalonic acidemia/methylenetetrahydrofolate reductase deficiency (5/28), and Charcot-Marie-tooth atrophy (1/28). Patients in the HSP group had chronic courses, most of whom were lower limbs spasticity, mainly with axonal neuropathy, and thinning corpus callosum, white matter lesions and cerebellar atrophy in brain MRI. In the non-HSP groups, upper and lower limbs both involvement was more common. Patients with homocysteine remethylation disorders or Krabbe's disease or autosomal recessive spastic ataxia of Charlevoix-Saguenay had diagnostic results in laboratory or imaging examination. A total of 12 new variants were obtained.Conclusions: HSP had widespread clinical and genetic heterogeneity, and leukodystrophy, hereditary ataxia, Charcot-Marie-Tooth atrophy and homocysteine remethylation disorders accounted for a significant proportion of the proposed HSP. These diseases had different characteristics in clinical, laboratorial, electrophysiological, and radiological aspects, which could help differential diagnosis. Genetic analysis could ultimately provide a clear diagnosis, and broadening the scope of genetic testing could improve the positive rate of diagnosis. [ABSTRACT FROM AUTHOR]

Background: ITPR1 is a key gene for autophagy, but its biological function is still unclear, and there are few studies on the correlation between ITPR1 gene expression and the occurrence and development of breast cancer.Methods: Analyze the expression of ITPR1 through online databases such as Oncomine and TIMER. Kaplan-Meier plotter and other databases were used to evaluate the impact of ITPR1 on clinical prognosis. The expression of ITPR1 in analysis of 145 cases of breast cancer and 30 cases of adjacent normal tissue was detected by Immunohistochemistry. Statistical analysis was used to evaluate the clinical relevance and prognostic significance of abnormally expressed proteins. And the Western Blot was used to detect the expression of ITPR1 between breast cancer tissues and cells. The TIMER database studied the relationship between ITPR1 and cancer immune infiltration. And used the ROC plotter database to predict the response of ITPR1 to chemotherapy, endocrine therapy and anti-HER2 therapy in patients with breast cancer.Results: Compared with normal breast samples, ITPR1 was significantly lower in patients with breast cancer. And the increased expression of ITPR1 mRNA was closely related to longer overall survival (OS), distant metastasis free survival (DMFS), disease specific survival (DSS) and relapse free survival (RFS) in breast cancer. And the expression level of ITPR1 was higher in patients treated with chemotherapy than untreated patients. In addition, the expression of ITPR1 was positively correlated with related gene markers of immune cells in different types of breast cancer, especially with BRCA basal tissue breast cancer.Conclusion: ITPR1 was lower expressed in breast cancer. The higher expression of ITPR1 suggested favorable prognosis for patients. ITPR1 was related to the level of immune infiltration, especially in BRCA-Basal patients. All research results indicated that ITPR1 might affect breast cancer prognosis and participate in immune regulation. In short, ITPR1 might be a potential target for breast cancer therapy. [ABSTRACT FROM AUTHOR]

Background: Long non-coding RNAs (lncRNAs) have been reported to be vital factors to affect the expression of genes and proteins. Also, it has been proved that the abnormal expression or mutation of lncRNAs stands as a signal of metastasis and proliferation of cancer. Nevertheless, the majority of lncRNAs still need to be explored in abundant cancers especially in oral squamous cell carcinoma (OSCC). Methods: RT-qPCR assays were applied to test the expression of RNAs. Mechanism assays were performed to verify the combination among NORAD, TPM4 and miR-577. Also, functional assays were conducted to verify the function of RNAs on OSCC cells. Results: LncRNA NORAD was highly expressed in OSCC tissues and cells. NORAD silencing repressed the biological behaviors of OSCC cells. MiR-577 was found in OSCC with low expression, and RIP assays illustrated that NORAD, miR-577 and TPM4 coexisted in RNA-induced silencing complexes. Rescue assays proved that the overexpression of TPM4 could recover the effect of NORAD silencing on OSCC progression. Conclusions: It was revealed that NORAD functioned as a tumor promoter to sponge miR-577 thus elevating TPM4 in OSCC, which indicated that NORAD was worthy to be studied as a target for the treatment of OSCC. [ABSTRACT FROM AUTHOR]

Background: Prone position ventilation is a widely used lung protection ventilation strategy. The strategy is more convenient to implement in children compared to adults. Due to the precise mechanism of improving oxygenation function, development of pediatric prone ventilation technology has been largely focused on children with acute respiratory distress syndrome. There is a paucity of high-quality studies investigating the effects of prone position ventilation after pediatric cardiac surgery. The purpose of this study is to evaluate the feasibility and effectiveness of prone position ventilation in infants who develop postoperative acute lung injury after surgery for congenital heart disease.Methods: A single-center, randomized controlled trial of pediatric patients with acute lung injury after surgery for congenital heart disease who will receive prone position ventilation or usual care (control group). A total of 68 children will be enrolled according to the inclusion criteria. The main outcome measures will be lung compliance and oxygenation index. The secondary outcomes will be duration of mechanical ventilation, length of stay in cardiac intensive care unit, reintubation rate, and complication rate.Discussion: This study will investigate the feasibility and effectiveness of prone position ventilation techniques in children who develop postoperative acute lung injury after surgery for congenital heart disease. The results may help inform strategies to improve airway management after surgery for congenital heart disease.Trial Registration: ClinicalTrials.gov NCT04607993 . Initially registered on 29 October 2020. [ABSTRACT FROM AUTHOR]

With the in-depth exploration on cancer therapeutic nanovaccines, increasing evidence shows that the poor delivery of nanovaccines to lymphoid organs has become the culprit limiting the rapid induction of anti-tumor immune response. Unlike the conventional prophylactic vaccines that mainly form a depot at the injection site to gradually trigger durable immune response, the rapid proliferation of tumors requires an efficient delivery of nanovaccines to lymphoid organs for rapid induction of anti-tumor immunity. Optimization of the physicochemical properties of nanovaccine (e.g., size, shape, charge, colloidal stability and surface ligands) is an effective strategy to enhance their accumulation in lymphoid organs, and nanovaccines with dynamic structures are also designed for precise targeted delivery of lymphoid organs or their subregions. The recent progress of these nanovaccine delivery strategies is highlighted in this review, and the challenges and future direction are also discussed. [ABSTRACT FROM AUTHOR]

Background: Postpartum alanine transaminase (ALT) flares occur frequently in chronic hepatitis B virus (HBV)-infected mothers with antepartum antiviral therapy (AVT). We aimed to characterize the T cell immunity in HBV-infected mothers experiencing postpartum ALT flares.Methods: Twenty HBV-infected pregnant women who received AVT at 26-28 weeks of gestation were enrolled and followed up until 15-18 weeks postpartum. Among the 20 HBV-infected pregnant women, 6 experienced postpartum ALT flare (AF mothers), while 14 did not (NAF mothers). T lymphocyte phenotypes and functions were analyzed using flow cytometry.Results: Compared to NAF mothers, the quantitative HBsAg levels in AF mothers decreased significantly at 6-8 or 15-18 weeks postpartum. Significant differences in HBeAg levels between these groups were only found at delivery. Regulatory T cell (Treg) numbers in AF mothers were lower than those of NAF mothers before AVT; however, there were no significant differences in Treg numbers at other follow-up points. Expression of other T cell phenotypes were similar between the two groups. T cells in AF mothers produced more pro-inflammatory cytokines (IFN-γ, IL-21, TNF-α, IL-2) or less anti-inflammatory cytokine (IL-10) than those in NAF mothers before, during, or after antiviral treatment. The ratio of IFN-γ to IL-10 producing by CD4+ T cells or CD8+ T cells was higher in AF mothers than that in NAF mothers during pregnancy or after delivery.Conclusions: The characteristics of T cell immunity was distinct between mothers with postpartum ALT flare and those without ALT flare from pregnancy to postpartum, which indicated that T cell immunity might get involved in postpartum ALT flare. [ABSTRACT FROM AUTHOR]

Background: Klebsiella pneumoniae (K. pneumoniae) is a common pathogen associated with hospital and community-onset infections. This study aimed to compare the clinical and microbiological characteristics of nosocomial, healthcare-associated (HCA), and community-acquired (CA) K. pneumoniae infections. Methods: Clinical data were extracted from electronic medical records and analyzed retrospectively. Antimicrobial susceptibility and extended-spectrum beta-lactamase (ESBL) production were determined for all identified strains. Carbapenemase and ESBL genes were amplified by PCR. Genotyping of carbapenem-resistant K. pneumoniae (CRKP) and ESBL-producing strains was performed by pulsed-field gel electrophoresis (PFGE). Results: Of 379 K. pneumoniae infections, 98 (25.9%) were nosocomial, 195 (51.5%) were healthcare-associated, and 86 (22.6%) were community-acquired. Hematological malignancy (OR = 4.467), and hypertension (OR = 2.08) and cerebral vascular disease (OR = 2.486) were associated with nosocomial and HCA infections respectively, when compared to CA infections. Overall, the incidence of antimicrobial resistance for the majority of agents tested was similar between nosocomial and HCA infections (P > 0.05) and both groups had a higher incidence than CA infections (P < 0.05). Moreover, 95.1% (78/82) of CRKP strains were isolated from the nosocomial and HCA groups. The blaKPC was the most prevalent carbapenemase gene among CRKP strains (80.5%, 66/82). ESBL-producing strains were prevalent among nosocomial (40.8%), HCA (35.9%) and CA groups (24.4%). The blaCTX-M-9-group and blaCTX-M-1-group genes were predominant in nosocomial (65.0%) and CA strains (66.7%), respectively. PFGE results showed ESBL-producing and CRKP strains were genetically diverse. Identical PFGE profiles were observed among HCA and nosocomial strains. Conclusions: Nosocomial and HCA K. pneumoniae infections presented similar clinical features and antimicrobial resistance, and both two types of infections were different to CA infections. CRKP and ESBL-producing strains were disseminated mainly in HCA and nosocomial groups, and showed a clonal diversity. The cross transmission of CRKP was existed among HCA and nosocomial patients. This finding suggests that similar empirical therapy should be considered for patients with nosocomial and HCA K. pneumoniae infections and bacterial resistance surveillance of these infections is necessary. [ABSTRACT FROM AUTHOR]

Background: NSCLC patients with EGFR mutation were at a higher incidence of developing brain metastasis (BM). Patients with BM are associated with high mortality. Reducing BM incidence becomes increasingly significant for NSCLC patients to achieve prolonged survival. The aim of the study was to explore the possible risk factors of developing metachronous BM during EGFR-TKIs treatment, and to identify the potential candidates for prophylactic cranial irradiation (PCI) or the first-line Osimertinib treatment. Methods: A total of 157 consecutive EGFR-mutated advanced NSCLC patients without BM at initial diagnosis in our institution from 2012 and 2018 were retrospectively reviewed. Comparisons of OS were performed based on BM status. The cumulative incidence of metachronous BM was calculated by the Kaplan-Meier method, and the independent risk factors of metachronous BM were investigated by multivariate analysis. Results: Patients developing metachronous BM had worse survival (mOS: 22.1 months) than patients not-developing BM (mOS: 44.8 months). Moreover, the multivariate analysis indicated that age ≤ 49 years (P = 0.035), number of extracranial metastases (P = 0.013), and malignant pleural effusion (P = 0.002) were independent risk factors of metachronous BM. Furthermore, the 1-year actuarial incidence of developing metachronous BM in patients with no risk factor (n = 101), 1 risk factor (n = 46), and 2 risk factors (n = 10) were 7.01, 14.61, and 43.75%, respectively (P < 0.001). Conclusions: Patients developing metachronous BM during EGFR-TKIs treatment have worse outcomes. Our results suggested that EGFR-mutated advanced NSCLC patients with ≥1 risk factors were candidates for PCI or the first-line Osimertinib treatment. [ABSTRACT FROM AUTHOR]

Background: NSCLC patients with EGFR mutation were at a higher incidence of developing brain metastasis (BM). Patients with BM are associated with high mortality. Reducing BM incidence becomes increasingly significant for NSCLC patients to achieve prolonged survival. The aim of the study was to explore the possible risk factors of developing metachronous BM during EGFR-TKIs treatment, and to identify the potential candidates for prophylactic cranial irradiation (PCI) or the first-line Osimertinib treatment.Methods: A total of 157 consecutive EGFR-mutated advanced NSCLC patients without BM at initial diagnosis in our institution from 2012 and 2018 were retrospectively reviewed. Comparisons of OS were performed based on BM status. The cumulative incidence of metachronous BM was calculated by the Kaplan-Meier method, and the independent risk factors of metachronous BM were investigated by multivariate analysis.Results: Patients developing metachronous BM had worse survival (mOS: 22.1 months) than patients not-developing BM (mOS: 44.8 months). Moreover, the multivariate analysis indicated that age ≤ 49 years (P = 0.035), number of extracranial metastases (P = 0.013), and malignant pleural effusion (P = 0.002) were independent risk factors of metachronous BM. Furthermore, the 1-year actuarial incidence of developing metachronous BM in patients with no risk factor (n = 101), 1 risk factor (n = 46), and 2 risk factors (n = 10) were 7.01, 14.61, and 43.75%, respectively (P < 0.001).Conclusions: Patients developing metachronous BM during EGFR-TKIs treatment have worse outcomes. Our results suggested that EGFR-mutated advanced NSCLC patients with ≥1 risk factors were candidates for PCI or the first-line Osimertinib treatment. [ABSTRACT FROM AUTHOR]

Background: Progression of Colorectal cancer (CRC) is influenced by single or compounded environmental factors. Accumulating evidence shows that microbiota can influence the outcome of cancer immunotherapy. T cell, one of the main populations of effector immune cells in antitumor immunity, has been considered as a double-edged sword during the progression of CRC. Our previous studies indicate that traditional Chinese herbs (TCM) have potential anticancer effects in improving quality of life and therapeutic effect. However, little is known about the mechanism of TCM formula in cancer prevention. Methods: Here, we used C57BL/6 J ApcMin/+ mice, an animal model of human intestinal tumorigenesis, to investigate the gut bacterial diversity and their mechanisms of action in gastrointestinal adenomas, and to evaluate the effects of Yi-Yi-Fu-Zi-Bai-Jiang-San (YYFZBJS) on of colon carcinogenesis in vivo and in vitro. Through human-into-mice fecal microbiota transplantation (FMT) experiments from YYFZBJS volunteers or control donors, we were able to differentially modulate the tumor microbiome and affect tumor growth as well as tumor immune infiltration. Results: We report herein, YYFZBJS treatment blocked tumor initiation and progression in ApcMin/+ mice with less change of body weight and increased immune function. Moreover, diversity analysis of fecal samples demonstrated that YYFZBJS regulated animal's natural gut flora, including Bacteroides fragilis, Lachnospiraceae and so on. Intestinal tumors from conventional and germ-free mice fed with stool from YYFZBJS volunteers had been decreased. Some inflammation' expression also have been regulated by the gut microbiota mediated immune cells. Intestinal lymphatic, and mesenteric lymph nodes (MLN), accumulated CD4+ CD25+ Foxp3 positive Treg cells were reduced by YYFZBJS treatment in ApcMin/+ mice. Although YYFZBJS had no inhibition on CRC cell proliferation by itself, the altered Tregs mediated by YYFZBJS repressed CRC cancer cell growth, along with reduction of the phosphorylation of β-catenin. Conclusions: In conclusion, we demonstrated that gut microbiota and Treg were involved in CRC development and progression, and we propose YYFZBJS as a new potential drug option for the treatment of CRC. Video abstract [ABSTRACT FROM AUTHOR]

Background: Family caregivers of elderly patients with spinal tumours experience considerable pain and burden during the care process. This study aims to investigate the factors associated with caregiver burden in family caregivers of elderly patients with spinal tumours.Methods: A total of 220 elderly patients with spinal tumours (age ≥ 65 years) hospitalized at the spine centre of our hospital from January 2015 to December 2017 and their family caregivers were recruited for this cross-sectional study. All participants completed a sociodemographic questionnaire. Caregiver burden, social support and self-efficacy were assessed by the Chinese version of the Zarit Burden Interview (ZBI), the Social Support Rating Scale (SSRS) and the General Self-Efficacy Scale (GSE), respectively. The factors related to caregiver burden were analysed by multivariate analysis. P < 0.05 was considered statistically significant.Results: The 216 elderly patients with spinal tumours were 71.59 ± 8.49 years old, and their caregivers were 70.46 ± 9.13 years old. A total of 170 patients were cared for by their spouses, who accounted for 78.7% of all caregivers. The ZBI score for the family caregivers was 35.5 ± 7.5, and most caregivers (84.5%) reported a moderate or heavy burden. The factors related to caregiver burden included patient paralysis, the primary cancer site, chemotherapy and/or radiation, cognitive dysfunction, functional status, monthly income, pain score, caregivers' SSRS score, and GSE score.Conclusions: Most family caregivers of elderly patients with spinal tumours have a considerable caregiver burden. Interventions based on social support and self-efficacy can help reduce caregiver burden. [ABSTRACT FROM AUTHOR]

Background: Acupoint selection is a key factor in the treatment of diseases and has not been well studied. The aim of this trial is to explore the differences in efficacy between compatible acupoints and a single acupoint for patients with functional dyspepsia (FD).Methods: This randomized controlled trial will be conducted in the First Affiliated Hospital of Changchun University of Chinese Medicine in China. Two hundred and sixteen FD patients will be randomly assigned to the compatible acupoints group, single acupoint group, or sham acupuncture group. This trial will include a 1-week baseline period, a 4-week treatment period, and a 4-week follow-up period. During the 4-week treatment period, patients will receive 20 sessions of acupuncture (weekly cycles of one session per day for 5 consecutive days followed by a 2-day break). The primary outcome will be a change in the Nepean Dyspepsia Life Quality Index from baseline to after the 4-week treatment period. Secondary outcome measures will include the dyspeptic symptom sum score, Overall Treatment Effect questionnaire, and 36-item Short Form survey. Adverse events also will be recorded. Ultraweak photon emission and metabolomics tests will be performed at baseline and at the end of treatment to explore the mechanisms of the differences between compatible acupoints and a single acupoint.Discussion: The results of this trial will allow us to compare the difference in efficacy between compatible acupoints and a single acupoint. The findings from this trial will be published in peer-reviewed journals.Trial Registration: Acupuncture-Moxibustion Clinical Trial Registry, AMCTR-IPC-18000176, registered on 4 March 2019; Chinese Clinical Trial Registry, ChiCTR1900023983, registered on 23 June 2019. [ABSTRACT FROM AUTHOR]

Background: Nursing intervention following discharge is a long-term rehabilitation process that is essential for improving hip joint function and quality of life in affected patients. This study aimed to assess the effect of nursing intervention via WeChat on the rehabilitation of patients after total hip arthroplasty (THA). Methods: We conducted a retrospective analysis of 232 patients who underwent THA at our hospital from January 2013 to October 2015. Of the 232 patients, 114 received nursing intervention via telephone (Group A), and 118 received nursing intervention via WeChat (Group B). Furthermore, the Harris hip score and Short-Form 36 (SF-36) health survey score were used to evaluate hip joint function and quality of life in patients in the two groups at discharge and 1, 3 and 6 months following discharge. Moreover, the functional independence measure was applied to assess the recovery of joint function in the patients. Results: No significant difference was observed in the Harris hip score and the SF-36 health survey score between the two groups at discharge and 1 month following discharge (p > 0.05). However, the Harris hip score and SF-36 health survey score were lower in group A than in group B at 3 and 6 months following discharge (p < 0.05). Furthermore, no obvious difference was observed in terms of functional independence between the two groups at discharge (p > 0.05). However, more individuals were completely independent in group B than in group A at 1, 3 and 6 months following discharge (p < 0.05). Conclusions: Nursing intervention via WeChat can improve the effect of rehabilitation after THA and promote the recovery of joint function in patients. [ABSTRACT FROM AUTHOR]

Background: Limited studies have evaluated the effectiveness of pharmacist interventions on outpatient prescription. The goal of this study was to evaluate the clinical and economic impacts of pharmacist interventions on randomly sampled outpatient prescriptions.Method: Outpatient prescriptions of our hospital were sampled automatically and reviewed by pharmacists since 2011. Pharmacists intervened in inappropriate prescriptions (IPs) real-timely, and summarized and analyzed the information monthly. Cost-benefit analysis was performed to estimate the economic benefit of the pharmacist intervention.Results: From 2011 to 2016, pharmacists reviewed 101,271 prescriptions and intervened in 5155 prescriptions. With the interventions of pharmacists, the number of IPs decreased from 1845 to 238, while the inappropriate percentage decreased from 12.60 to 1.22%. The inappropriate rates of different departments and the types decreased annually. IPs were mainly from the Department of Medicine and Department of Surgery and category 1 (Non-indicated medications) in all years. The benefit-to-cost ratios of pharmacist interventions were always more than 1. In the same years, the benefit-to-cost ratios in public payments were higher than those with insurance and self-payment.Conclusion: This form of pharmacist intervention constitutes a method that showed positive clinical and economic benefits and is worth expanding in large hospitals. Pharmacists should pay more attention on prescriptions in department of surgery or prescriptions with public payments. [ABSTRACT FROM AUTHOR]

Background: Theranostic perfluorocarbon nanoprobes have recently attracted attention due to their fascinating versatility in integrating diagnostics and therapeutics into a single system. Furthermore, although 17β-estradiol (E2) is a potential anti-hypertrophic drug, it has severe non-specific adverse effects in various organs. Therefore, we have developed cardiomyocyte-targeted theranostic nanoprobes to achieve concurrent targeted imaging and treatment of cardiac hypertrophy. Results: We had successfully synthesized E2-loaded, primary cardiomyocyte (PCM) specific peptide-conjugated nanoprobes with perfluorocarbon (PFP) as a core (PCM-E2/PFPs) and demonstrated their stability and homogeneity. In vitro and in vivo studies confirmed that when exposed to low-intensity focused ultrasound (LIFU), these versatile PCM-E2/PFPs can be used as an amplifiable imaging contrast agent. Furthermore, the significantly accelerated release of E2 enhanced the therapeutic efficacy of the drug and prevented systemic side effects. PCM-E2/PFPs + LIFU treatment also significantly increased cardiac targeting and circulation time. Further therapeutic evaluations showed that PCM-E2/PFPs + LIFU suppressed cardiac hypertrophy to a greater extent compared to other treatments, revealing high efficiency in cardiac-targeted delivery and effective cardioprotection. Conclusion: Our novel theranostic nanoplatform could serve as a potential theranostic vector for cardiac diseases. [ABSTRACT FROM AUTHOR]

Background: In traditional Chinese culture, liver disease is believed to underlie excessive daytime sleepiness (EDS). Consequently, Chinese patients with complaints of EDS and physicians who treat them suspect that a liver abnormality is present. If liver disease is ruled out, these patients are often discharged without treatment. Gastroesophageal reflux disease (GERD) is a common disorder also associated with EDS. This pilot study was undertaken to determine the prevalence of GERD among Taiwanese patients with complaints of EDS suspected to be related to liver disease but in whom no evidence for the latter was found.Methods: From July 2009 to December 2009, 121 outpatients who presented to or were referred to the Department of Gastroenterology and Hepatology of the Chiayi Gung Memorial Hospital for evaluation of a complaint of EDS thought to be due to liver disease were examined. Demographic data were collected, and physical examinations and liver function tests were performed. Forty-eight patients had liver disease and were excluded. The Chinese Epworth Sleepiness Scale questionnaire (Chinese ESS) and the Chinese Gastroesophageal Reflux Disease Questionnaire (CGERDQ) were then administered to 73 included patients.Results: More than half (56.2%) of the included patients were found to suffer from GERD. Patients with symptoms of GERD had higher mean CGERDQ scores than patients without symptoms of the disorder (18.88 ± 5.49 and 5.56 ± 3.57, respectively; P < 0.001). Patients with symptoms of GERD also had higher mean Chinese ESS scores than patients without symptoms (8.80 ± 5.49 and 3.13 ± 3.50, respectively; P < 0.001). Chinese ESS scores indicative of EDS were observed in 48.8% of patients with symptoms of GERD and in 3.1% of those without symptoms (P < 0.001). Differences between the two groups retained their significance after controlling for potential confounders.Conclusions: A significant percentage of Taiwanese patients who complained of EDS and were admitted to our Hepatology/Gastroenterology Department due to a suspicion of liver disease actually had symptoms of GERD. Further studies are needed to ascertain whether treatment of GERD will effectively resolve EDS in these patients. [ABSTRACT FROM AUTHOR]

Background: Since the 1990s, families from the ecologically hostile mountainous southern areas of Ningxia Province, China, have been migrating to the northern areas of the province. This study compared the prevalence of behavioral problems among migrant adolescents to those among host adolescents (adolescents from the northern areas) and adolescents in the region of origin (adolescents from the southern areas), to determine whether ecological migration is related to adolescent behavioral problems, and possible changes in such problems over time. Methods: We used the Children and Adolescents Ecological Migration Survey on Mental Health, administered to 4805 students aged 12–16 years and their parents between 2012 and 2014 (W1), of whom 1753 students and their parents completed the follow-up between 2014 and 2017 (W2). Parents answered questions related to adolescent behavioral problems, main source of family income, parents' desire to reverse migrate, improved standard of living, and parents' educational attainment, while children completed the Eysenck Personality Questionnaire and a classroom environment questionnaire. Results: The prevalence of behavioral problems among the migrant adolescents (28.04%) was significantly higher than among host adolescents (21.59%) or adolescents in the region of origin (24.37%; p < 0.001) at W1. After adjusting for gender and age, parents' work outside the home was the main source of family income (OR = 1.42, 95% CI = 1.13–1.78), and adolescents' learning burden (OR = 1.04, 95% CI = 1.01–1.06) in school negatively influenced behavioral problems. Strong student-teacher relationships (OR = 0.97,95% CI = 0.94–0.99) and parents who had no intention to move back to the original residence (OR = 0.70, 95% CI = 0.52–0.94) exerted a protective effect at W1; at W2, a protective effect was associated with improved living conditions (OR = 0.39–0.55, 95% CI = 0.25–0.84). The extent of behavioral problems among migrant adolescents significantly decreased after two years. Conclusion: Ecological migration will increase children's behavioral problems in the early stage, with various factors influencing the extent of these problems. [ABSTRACT FROM AUTHOR]

Background: Neutral lipid storage disease with myopathy (NLSDM) is a rare clinical heterogeneous disorder caused by mutations in the patatin-like phospholipase domain-containing 2 (PNPLA2) gene. NLSDM usually presents skeletal myopathy, cardiomyopathy and the multiple organs dysfunction. Around 50 cases of NLSDM have been described worldwide, whereas the comprehensive understanding of this disease are still limited. We therefore recruit NLSDM patients from 10 centers across China, summarize the clinical, muscle imaging, pathological and genetic features, and analyze the genotype-phenotype relationship.Results: A total of 45 NLSDM patients (18 men and 27 women) were recruited from 40 unrelated families. Thirteen patients were born from consanguineous parents. The phenotypes were classified as asymptomatic hyperCKemia (2/45), pure skeletal myopathy (18/45), pure cardiomyopathy (4/45), and the combination of skeletal myopathy and cardiomyopathy (21/45). Right upper limb weakness was the early and prominent feature in 61.5% of patients. On muscle MRI, the long head of the biceps femoris, semimembranosus and adductor magnus on thighs, the soleus and medial head of the gastrocnemius on lower legs showed the most severe fatty infiltration. Thirty-three families were carrying homozygous mutations, while seven families were carrying compound heterozygous mutations. A total of 23 mutations were identified including 11 (47.8%) point mutations, eight (34.8%) deletions and four (17.4%) insertions. c.757 + 1G > T, c.245G > A and c.187 + 1G > A were the three most frequent mutations. Among four groups of phenotypes, significant differences were shown in disease onset (< 20 years versus ≥20 years old, p = 0.003) and muscle pathology (with rimmed vacuoles versus without rimmed vacuoles, p = 0.001). PNPLA2 mutational type or functional defects did not show great impact on phenotypes.Conclusion: We outline the clinical and genetic spectrum in a large cohort of NLSDM patients. Selective muscle fatty infiltration on posterior compartment of legs are characteristic of NLSDM. Chinese patients present with distinctive and relative hotspot PNPLA2 mutations. The disease onset age and pathological appearance of rimmed vacuoles are proved to be related with the clinical manifestations. The phenotypes are not strongly influenced by genetic defects, suggesting the multiple environmental risk factors in the development of NLSDM. [ABSTRACT FROM AUTHOR]

Background: Myocardial infarction (MI) is a common cause of mortality in people. Mesenchymal stem cell (MSC) has been shown to exert therapeutic potential to treat myocardial infarction (MI). However, in patients with diabetes, the diabetic environment affected MSCs activity and could impair the efficacy of treatment. Interleukin-10 (IL-10) has been shown to attenuate MI by suppressing inflammation. In current study, the combination of MSC transplantation with IL-10 was evaluated in a diabetic mice model with MI. Methods: We engineered bone marrow derived MSCs (BM-MSCs) to overexpress IL-10 by using CRISPR activation. We established the diabetic mice model with MI and monitored the IL-10 expression after BM-MSCs transplantation. We also evaluated the effects of BM-MSCs transplantation on inflammatory response, cell apoptosis, cardiac function and angiogenesis. Results: CRISPR activation system enabled overexpression of IL-10 in BM-MSCs. Transplantation of BM-MSCs overexpressing IL-10 resulted in IL-10 expression in heart after transplantation. Transplantation of BM-MSCs overexpressing IL-10 inhibited inflammatory cell infiltration and pro-inflammatory cytokines production, improved cardiac functional recovery, alleviated cardiac injury, decreased apoptosis of cardiac cells and increased angiogenesis. Conclusion: In summary, we have demonstrated the therapeutic potential of IL-10 overexpressed BM-MSCs in the treatment of MI in diabetic mice. [ABSTRACT FROM AUTHOR]

Background: The current prognosis of thymic epithelial tumors (TETs) is according to the World Health Organization (WHO) histologic classification and the Masaoka staging system. These methods of prognosis have certain limitations in clinical application and there is a need to seek new method for determining the prognosis of patients with TETs. To date, there have been no studies done on the use of DNA methylation biomarkers for prognosis of TETs. The present study was therefore carried out to identify DNA methylation biomarkers that can determine the overall survival in patients with TETs. Methods: Bioinformatic analysis of TCGA 450 K methylation array data, transcriptome sequencing data, WHO histologic classification and Masaoka staging system was performed to identify differentially expressed methylation sites between thymoma and thymic carcinoma as well as the different DNA methylation sites associated with the overall survival in patients with TETs. Using pyrosequencing, 4 different methylation sites (cg05784862, cg07154254, cg02543462, and cg06288355) were sequenced from tumor tissues of 100 Chinese patients with TETs. A prognostic model for TETs was constructed using these four methylation sites. Results: The TCGA dataset showed 5155 and 6967 hyper- and hypomethylated CpG sites in type A–B3 group and type C group, respectively, of which 3600 were located within the gene promoter regions. One hundred thirty-four genes were silenced by promoter hypermethylation and 174 mRNAs were upregulated. Analysis of univariate and multivariate Cox regression showed significant association between the methylation levels of 187 sites and the overall survival in patients with TETs. cg05784862(KSR1), cg07154254(ELF3), cg02543462(ILRN), and cg06288355(RAG1) were identified as independent prognostic factors for overall survival in patients with TETs after adjusting for Masaoka staging in 100 Chinese patients. The prognostic model which consists of the four abovementioned genes had higher accuracy for predicting the 5-year overall survival in patients with TETs as compared to the Masaoka clinical staging. (Time-dependent ROC analysis AUC 1.000 vs 0.742, P = 2.7 × 10−6). Conclusions: The methylation levels of cg05784862(KSR1), cg07154254(ELF3), cg02543462(ILRN), and cg06288355(RAG1) sites are associated with the progression of TETs and may serve as new biomarkers for predicting the overall survival in patients with TETs. [ABSTRACT FROM AUTHOR]

Background: Lung cancer stem cells have the ability to self-renew and are resistant to conventional chemotherapy. MicroRNAs (miRNAs) regulate and control the expression and function of many target genes; therefore, miRNA disorders are involved in the pathogenesis of human diseases, such as cancer. However, the effects of miRNA dysregulation on tumour stemness and drug resistance have not been fully elucidated. miR-181b has been reported to be a tumour suppressor miRNA and is associated with drug-resistant non-small cell lung cancer. Methods: Cancer stem cell (CSC)-like properties were tested by a cell proliferation assay and flow cytometry; miR-181b expression was measured by real-time PCR; and Notch2 and related proteins were detected by Western blotting and immunohistochemistry. A mouse xenograft model was also established. Results: In this study, we found that ectopic miR-181b expression suppressed cancer stem cell properties and enhanced sensitivity to cisplatin (DDP) treatment by directly targeting Notch2. miR-181b could inactivate the Notch2/Hes1 signalling pathway. In addition, tumours from nude mice treated with miR-181b were significantly smaller than tumours from mice treated with control agomir. Decreased miR-181b expression and increased Notch2 expression were observed to have a significant relationship with overall survival (OS) and CSC-like properties in non-small cell lung cancer (NSCLC) patients. Conclusions: This study elucidates an important role of miR-181b in the regulation of CSC-like properties, suggesting a potential therapeutic target for overcoming drug resistance in NSCLC. [ABSTRACT FROM AUTHOR]

Background: The highly refractory nature of non-small cell lung cancer (NSCLC) to chemotherapeutic drugs is an important factor resulting in its poor prognosis. Recent studies have revealed that tumour necrosis factor alpha-induced protein 8 (TNFAIP8) is involved in various biological and pathological processes of cells, but their underlying mechanisms in processes ranging from cancer development to drug resistance have not been fully elucidated. Methods: TNFAIP8 expression in clinical NSCLC samples was examined through immunohistochemistry (IHC). After adjusting for patients' characteristics with propensity score matching, Kaplan-Meier analysis and Cox regression analysis were performed for comparison of patients' survival according to the TNFAIP8 level. Lentiviral transfection with TNFAIP8-specific shRNAs was used to establish stable TNFAIP8 knockdown (TNFAIP8 KD) NCI-H460, A549 and cis-diamminedichloroplatinum II resistant A549 (A549/cDDP) cell lines. Cell proliferation and viability were assessed by CCK-8 assay. Cell cycle was examined by flow cytometry. Multiple pathways regulated by TNFAIP8 KD were revealed by microarray analysis. Results: We found that high TNFAIP8 expression was associated with advanced pT stage, advanced pTNM stage, lymph node metastasis and unfavourable survival in NSCLC patients. TNFAIP8 shRNAs reduced in vitro cancer cell proliferation and in vivo tumor growth. Additionally, TNFAIP8 KD increased the sensitivity of NSCLC cells to cisplatin in vitro and in vivo. Conversely, up-regulation of TNFAIP8 promoted the proliferation and drug resistance to cisplatin of NSCLC cells. TNFAIP8 influences cancer progression pathways involving the MDM2/p53 pathway. Indeed, we observed that TNFAIP8 KD mediated the MDM2 downregulation and the p53 ubiquitination, thereby decreasing the degradation of p53 protein. shRNA p53 reversed TNFAIP8 shRNA-mediated regulation of cell proliferation, cell cycle, cisplatin sensitivity, and expression levels of RAD51, a DNA repair gene. Conclusion: Our work uncovers a hitherto unappreciated role of TNFAIP8 in NSCLC proliferation and cisplatin chemoresistance that is mediated through the MDM2/p53 pathway. These findings might offer potential therapeutic targets for reversing cisplatin resistance in NSCLC patients with high TNFAIP8 expression. [ABSTRACT FROM AUTHOR]

Background: Accelerated hypofractionated radiotherapy can shorten total treatment time and overcome the accelerated repopulation of tumour cells during radiotherapy. This therapeutic approach has demonstrated good efficacy in the treatment of locally advanced non-small-cell lung cancer (NSCLC). However, the optimal fractionation scheme remains uncertain. The purpose of this phase I trial was to explore the maximum tolerated dose (MTD) of accelerated hypofractionated three-dimensional conformal radiotherapy (3-DCRT) (at 3 Gy/fraction) administered in combination with concurrent vinorelbine (NVB) and carboplatin (CBP) chemotherapy for unresectable stage III NSCLC.Methods: Previously untreated cases of unresectable stage III NSCLC received accelerated hypofractionated 3-DCRT, delivered at 3 Gy per fraction, once daily, with five fractions per week. The starting dose was 66 Gy and an increment of 3 Gy was utilized. Higher doses continued to be tested in patient groups until the emergence of dose-limiting toxicity (DLT). The MTD was regarded as the dose that was one step below the dose at which DLT occurred. Patients received at least one cycle of a concurrent two-drug chemotherapy regimen of NVB and CBP.Results: A total of 13 patients were enrolled and progressed through three dose escalation groups: 66 Gy, 69 Gy, and 72 Gy. No treatment-related deaths occurred. The major adverse events included radiation oesophagitis, radiation pneumonitis, and neutropenia. Nausea, fatigue, and anorexia were commonly observed, although the magnitude of these events was typically relatively minor. Among the entire group, four instances of DLT were observed, including two cases of grade 3 radiation oesophagitis, one case of grade 3 radiation pneumonitis, and one case of grade 4 neutropenia. All of these cases of DLT occurred in the 72 Gy group. Therefore, 72 Gy was designated as the DLT dose level, and the lower dose of 69 Gy was regarded as the MTD.Conclusions: For unresectable stage III NSCLC 69 Gy (at 3 Gy/fraction) was the MTD of accelerated hypofractionated 3-DCRT administered in combination with concurrent NVB and CBP chemotherapy. The toxicity of this chemoradiotherapy regimen could be tolerated. A phase II trial is recommended to further evaluate the efficacy and safety of this regimen. [ABSTRACT FROM AUTHOR]