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The acidic tumor microenvironment, a hallmark of many solid tumors, is primarily induced by the high glycolytic rate of tumor cells. To avoid acidosis, tumor cells ingeniously maintain an acidic extracellular pH while keeping a relatively alkaline intracellular pH. Overturning the unique pH gradient of tumor cells has exhibited to be a viable approach for cancer therapy. In this review, the formation and regulatory mechanisms of the acidic microenvironment in solid tumors will be firstly outlined. Subsequently, we will comprehensively summarize the latest advancements in anti-tumor therapy via using nanomedicines to manipulate the tumor pH gradient, including acidifying intracellular environment and alkalizing extracellular environment. Following this, we will discuss the future potential of strategies employing nanomedicines to reverse tumor pH gradient. This review aims to foster research on therapeutic approaches targeting the pH regulation of solid tumors and holds an optimistic outlook for the future development of this field., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: All authors have read and approved the manuscript. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Glutathione S-transferases (GSTs) are a crucial class of plant enzymes, playing pivotal roles in plant growth, development, and stress responses. However, studies on the functions and regulatory mechanisms of GSTs in plants remain relatively limited., Results: This study aimed to comprehensively identify and analyze GST proteins in rye. A total of 171 rye GST genes were identified and classified into four subfamilies, Tau, Phi, Theta, and Zeta, based on their sequence similarity and structural features. Notably, genes classified under the Tau subfamily were the most abundant at 118, while only one gene was under the Theta subfamily. Subsequent phylogenetic and collinearity analysis revealed 29 tandem duplications and 6 segmental duplication events. There were 13 collinear genes between rye and wheat, maize, and rice, demonstrating the expansion and evolution of the GST gene family. An analysis of the expression profiles of 20 representative ScGST genes in different tissues and under various environmental stresses was performed to further understand the functions and expression patterns of ScGST genes. The results showed that these genes exhibited the highest expression levels in stems, followed by fruits and leaves., Conclusions: This study provides a comprehensive identity, classification, and analysis of rye GST genes, which offer valuable insights into the functionality and regulatory mechanisms of the GST gene family in rye. Especially, ScGST39 was identified as a candidate gene because it was significantly upregulated under multiple stress conditions, indicating its potential crucial role in plant stress tolerance mechanisms., Competing Interests: Declarations. Ethics approval and consent to participate: This article does not contain any studies involving human participants or animals performed by the authors. These methods were carried out in accordance with relevant guidelines and regulations. All experimental protocols were approved by the Bio-Agriculture Institute of Shaanxi. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Objectives: This study aimed to investigate the impact of pregnancy and pre-existing comorbidities on COVID-19 infections and associated complications of hospitalisation and mortality in women of reproductive age (WRA). The study also compared the risk of severe COVID-19 complications between pregnant women (PW) and non-pregnant women (NPW) with and without pre-existing comorbidities. Special focus was placed on some understudied comorbidities of immunosuppression, chronic renal disease and chronic obstructive pulmonary disease (COPD)., Methods: The study utilized anonymized patient-related information for a population of 7,342,869 WRA from the Mexican Ministry of Health data repository on COVID-19. Descriptive variables were characterized using frequencies, percentages, means, and standard deviations. Adjusted odds ratios (aORs) were used to assess the associations between risk factors and outcomes of hospitalisation and mortality. The study covered the entire COVID-19 pandemic period from January 30, 2020, to May 5, 2023., Results: The findings revealed that PW were not more likely to get COVID-19 infections than NPW. PW with COVID-19 infections were more likely to require hospital admission, intubation treatments, and ICU admission compared to NPW with COVID-19. PW with immunosuppression had an increased odds ratio (aOR) of getting COVID-19 infections compared to NPW (PW: aOR = 1.0396; NPW: aOR = 0.8373). NPW with immunosuppression had higher risk of mortality (all-cause death: aOR = 1.7084; COVID-19-associated death: aOR = 1.4079) and hospitalisation (all-cause hospitalisation: aOR = 4.1328; COVID-19-associated hospitalisation: aOR = 3.0451) than NPW without immunosuppression. Renal disease was identified as a concerning pre-existing condition that increased the risks of COVID-19 associated mortality/hospitalizations and all-cause mortality/hospitalizations for both PW and NPW. NPW with renal disease had much higher odds ratio (aOR) of either COVID-19-associated-hospitalisations (NPW: aOR = 8.639; PW: aOR = 1.7603) or all-cause hospitalisations (NPW: aOR = 8.8594; PW: aOR = 1.786) than PW with renal disease., Conclusions: This study provides valuable insights into the impact of pregnancy and pre-existing comorbidities on COVID-19 outcomes in WRA. The findings underscore the importance of considering demographic factors and pre-existing comorbidities in the management of PW with COVID-19. The study also highlights the need for further research to understand the unique impacts of different comorbidities, particularly immunosuppression and renal disease, on COVID-19 outcomes in WRA., Competing Interests: Declarations Ethical approval This data was obtained in accordance with the Decree published in the Official Gazette of Mexico Government on Open Data, the General Directorate of Epidemiology [22]. Only anonymised patient-related information was available. No patient identifiable data were used. No ethical approval was necessary for this study because the data were publicly available. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: Kiwifruit, belonging to the genus Actinidia, represents a unique fruit crop characterized by its modern cultivars being genetically diverse and exhibiting remarkable variations in morphological traits and adaptability to harsh environments. However, the genetic mechanisms underlying such morphological diversity remain largely elusive., Results: We report the high-quality genomes of five Actinidia species, including Actinidia longicarpa, A. macrosperma, A. polygama, A. reticulata, and A. rufa. Through comparative genomics analyses, we identified three whole genome duplication events shared by the Actinidia genus and uncovered rapidly evolving gene families implicated in the development of characteristic kiwifruit traits, including vitamin C (VC) content and fruit hairiness. A range of structural variations were identified, potentially contributing to the phenotypic diversity in kiwifruit. Notably, phylogenomic analyses revealed 76 cis-regulatory elements within the Actinidia genus, predominantly associated with stress responses, metabolic processes, and development. Among these, five motifs did not exhibit similarity to known plant motifs, suggesting the presence of possible novel cis-regulatory elements in kiwifruit. Construction of a pan-genome encompassing the nine Actinidia species facilitated the identification of gene DTZ79_23g14810 specific to species exhibiting extraordinarily high VC content. Expression of DTZ79_23g14810 is significantly correlated with the dynamics of VC concentration, and its overexpression in the transgenic roots of kiwifruit plants resulted in increased VC content., Conclusions: Collectively, the genomes and pan-genome of diverse Actinidia species not only enhance our understanding of fruit development but also provide a valuable genomic resource for facilitating the genome-based breeding of kiwifruit., (© 2024. The Author(s).)

Background: Anti-HER2 therapies, including the HER2 antibody-drug conjugates (ADCs) trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-DXd), have led to improved survival outcomes in patients with HER2-overexpressing (HER2+) metastatic breast cancer. However, intrinsic or acquired resistance to anti-HER2-based therapies remains a clinical challenge in these patients, as there is no standard of care following disease progression. The purpose of this study was to elucidate the mechanisms of resistance to T-DM1 and T-DXd in HER2+ BC patients and preclinical models and identify targets whose inhibition enhances the antitumor activity of T-DXd in HER2-directed ADC-resistant HER2+ breast cancer in vitro and in vivo., Methods: Targeted DNA and whole transcriptome sequencing were performed in breast cancer patient tissue samples to investigate genetic aberrations that arose after anti-HER2 therapy. We generated T-DM1 and T-DXd-resistant HER2+ breast cancer cell lines. To elucidate their resistance mechanisms and to identify potential synergistic kinase targets for enhancing the efficacy of T-DXd, we used fluorescence in situ hybridization, droplet digital PCR, Western blotting, whole-genome sequencing, cDNA microarray, and synthetic lethal kinome RNA interference screening. In addition, cell viability, colony formation, and xenograft assays were used to determine the synergistic antitumor effect of T-DXd combinations., Results: We found reduced HER2 expression in patients and amplified DNA repair-related genes in patients after anti-HER2 therapy. Reduced ERBB2 gene amplification in HER2-directed ADC-resistant HER2+ breast cancer cell lines was through DNA damage and epigenetic mechanisms. In HER2-directed ADC-resistant HER2+ breast cancer cell lines, our non-biased RNA interference screening identified the DNA repair pathway as a potential target within the canonical pathways to enhance the efficacy of T-DXd. We validated that the combination of T-DXd with ataxia telangiectasia and Rad3-related inhibitor, elimusertib, led to significant breast cancer cell death in vitro (P < 0.01) and in vivo (P < 0.01) compared to single agents., Conclusions: The DNA repair pathways contribute to HER2-directed ADC resistance. Our data justify exploring the combination treatment of T-DXd with DNA repair-targeting drugs to treat HER2-directed ADC-resistant HER2+ breast cancer in clinical trials., (© 2024. The Author(s).)

Background: Limited research has explored the potential association between the Triglyceride-Glucose (TyG) and mortality, especially in individuals with Helicobacter pylori (H. pylori) infection. This study seeks to investigate the correlation between the TyG index and H. pylori infection and investigate whether the associations between the TyG index exposure and all-cause mortality are mediated by H. pylori infection., Methods: The study utilized data from the National Health and Nutrition Examination Survey (NHANES) 1999-2018, incorporating a final sample size of 2,187 participants. Both univariable and multivariable-adjusted logistic regression analyses were employed to examine the relationship between H. pylori infection and relevant covariates. To assess the association between TyG index, and all-cause mortality in individuals with or without H. pylori infection, Cox regression analysis, and restricted regression cubic spline analysis were implemented., Results: A significant positive correlation was observed between the TyG index and an elevated risk of H. pylori infection [OR 1.157, 95% CI (1.383 ~ 1.664)]. This correlation persisted even after adjusting for confounding factors [OR 1.189, 95% CI (1.003, 1.411), P < 0.05]. Furthermore, in patients with positive H. pylori infection, a noteworthy nonlinear correlation between the TyG index and all-cause mortality was identified (P = 0.0361). With an increase in the TyG index, all-cause mortality exhibited a corresponding rise, particularly following adjustment for all potential confounding factors. Conversely, in patients with negative H. pylori infection, no significant association was observed between the TyG index and all-cause mortality after adjusting for potential confounding factors., Conclusion: A higher TyG index was linked to increased H. pylori infection risks. Participants in the higher quantile group of the TyG index are positively associated with higher all-cause mortality compared to the higher quantile group of the TyG index in H. pylori-positive participants instead of H. pylori-negative participants., (© 2024. The Author(s).)

Cisplatin (DDP) is a prevalent chemotherapeutic agent used in tumor therapy, yet DDP-induced acute kidney injury (AKI) severely limits its clinical application. Antioxidants as reactive oxygen species (ROS) scavengers can circumvent this adverse effect while leading to the decrease of efficacy to tumor. Herein, we report ultrasmall ruthenium nanoparticles (URNPs) as switchable ROS scavengers/generators to alleviate DDP-induced AKI and improve its therapeutic efficacy. In the physiological environment of the kidney, URNPs mimic multi-enzyme activities, such as superoxide dismutase and catalase, effectively protecting the renal cell and tissue by down-regulating the increased ROS level caused by DDP and alleviating AKI. Specifically, URNPs are oxidized by high levels of H 2 O 2 in the tumor microenvironment (TME), resulting in the generation of oxygen vacancies and Ru 3+ /Ru 4+ ions. This unique structure transformation endows URNPs to generate singlet oxygen ( 1 O 2 ) under laser irradiation and hydroxyl radicals (∙OH) through a Fenton-like reaction in tumor cell and tissue. The simultaneous generation of multifarious ROS effectively improves the efficacy of DDP in vitro and in vivo. This TME-responsive ROS scavenger/generator acts as an adjuvant therapeutic agent to minimize side effects and improve the efficacy of chemotherapy drugs, providing a new avenue to chemotherapy and facilitating clinical tumor therapy., (© 2024. The Author(s).)

Joint contracture is one of the common diseases clinically, and joint capsule fibrosis is considered to be one of the most important pathological changes of joint contracture. However, the underlying mechanism of joint capsule fibrosis is still controversial. The present study aims to establish an animal model of knee extending joint contracture in rats, and to investigate the role of hypoxia-mediated pyroptosis in the progression of joint contracture using this animal model. 36 male SD rats were selected, 6 of which were not immobilized and were used as control group, while 30 rats were divided into I-1 group (immobilized for 1 week following 7 weeks of free movement), I-2 group (immobilized for 2 weeks following 6 weeks of free movement), I-4 group (immobilized for 4 weeks following 4 weeks of free movement), I-6 group (immobilized for 6 weeks following 2 weeks of free movement) and I-8 group (immobilized for 8 weeks) according to different immobilizing time. The progression of joint contracture was assessed by the measurement of knee joint range of motion, collagen deposition in joint capsule was examined with Masson staining, protein expression levels of HIF-1α, NLRP3, Caspase-1, GSDMD-N, TGF-β1, α-SMA and p-Smad3 in joint capsule were assessed using western blotting, and the morphological changes of fibroblasts were observed by transmission electron microscopy. The degree of total and arthrogenic contracture progressed from the first week and lasted until the first eight weeks after immobilization. The degree of total and arthrogenic contracture progressed rapidly in the first four weeks after immobilization and then progressed slowly. Masson staining indicated that collagen deposition in joint capsule gradually increased in the first 8 weeks following immobilization. Western blotting analysis showed that the protein levels of HIF-1α continued to increase during the first 8 weeks of immobilization, and the protein levels of pyroptosis-related proteins NLRP3, Caspase-1, GSDMD-N continued to increase in the first 4 weeks after immobilization and then decreased. The protein levels of fibrosis-related proteins TGF-β1, p-Smad3 and α-SMA continued to increase in the first 8 weeks after immobilization. Transmission electron microscopy showed that 4 weeks of immobilization induced cell membrane rupture and cell contents overflow, which further indicated the activation of pyroptosis. Knee extending joint contracture animal model can be established by external immobilization orthosis in rats, and the activation of hypoxia-mediated pyroptosis may play a stimulating role in the process of joint capsule fibrosis and joint contracture., (© 2024. The Author(s).)

Background: Schistosomiasis is a disease primarily caused by eggs laid by pathogens called schistosomes. Among the schistosome species infecting humans, Schistosoma japonicum possesses the largest fecundity; each adult female produces an average of 3500 eggs per day. The lack of proper culture conditions supporting continuous oviposition in vitro has precluded detailed investigation of mechanisms regulating sexual maturation and egg production in Schistosoma japonicum., Methods: We optimized in vitro culture conditions by replacing reagents that are part of the classical ABC169 medium. Fast Blue BB staining and 4',6-diamidino-2-phenylindole (DAPI) labeling were applied to observe the sexual development status of the females. In vitro RNA interference (RNAi) technology was used to validate the capability of the modified medium. The detection of male β-alanyl-tryptamine (BATT) was conducted using liquid chromatography-mass spectrometry (LC-MS)., Results: Both m-AB169 (1640) and AB169 (1640) media are capable of facilitating the sexual development of paired virgin female S. japonicum, as well as sustaining the mature reproductive organs and egg production of adult S. japonicum for at least 22 days in vitro. M-AB169 (1640) provided a more stable condition for supporting the sexual maturity of female S. japonicum, as evidenced by the consistent initiation of egg production compared with AB169 (1640). Through a comparative analysis of S. japonicum and S. mansoni in diverse media, we demonstrated that these closely related species display distinct demands for their sexual development and egg production, suggesting a potential influence of nutritional factors on the observed variations in host ranges among different schistosome species. Importantly, we successfully identified the presence of the pheromone β-alanyl-tryptamine (BATT) in S. japonicum, previously identified in S. mansoni, highlighting its conserved role in schistosome reproductive development. Through the employment of double-stranded RNA (dsRNA) treatment to silence two genes that are involved in either the male (gli1, glioma-associated oncogene homolog 1) or female (vf1, vitellogenic factor 1) side in male-induced female reproductive development of S. mansoni, we confirmed that the combination of m-AB169 (1640) and RNAi technology has the capacity to facilitate in vitro studies of S. japonicum's reproductive and oviposition processes., Conclusions: We developed a novel medium, m-AB169 (1640), that not only maintains the mature reproductive organs and continuous oviposition of adult female Schistosoma japonicum for up to 22 days but also supports the reproductive development and subsequent egg-laying of virgin females after pairing with male worms. This study provides a valuable in vitro platform for functional studies of the mechanisms underlying the fascinating biology of the female sexual development and egg production of S. japonicum, which may accelerate the development of new strategies targeting schistosome egg production., (© 2024. The Author(s).)

Objective: This study investigated the clinical, imaging, and electroencephalogram (EEG) characteristics of methylmalonic acidemia (MMA) with nervous system damage as the primary manifestation., Methods: From January 2017 to November 2022, patients with nervous system injury as the main clinical manifestation, diagnosed with methylmalonic acidemia by metabolic and genetic testing, were enrolled and analyzed. Their clinical, imaging, and electroencephalogram data were analyzed., Results: A total of 18 patients were enrolled, including 15 males and 3 females. The clinical symptoms were convulsions, poor feeding, growth retardation, disorder of consciousness, developmental delay, hypotonia, and blood system changes. There were 6 cases (33%) of hydrocephalus, 9 (50%) of extracerebral space widened, 5 (27%) of corpus callosum thinning, 3 (17%) of ventricular dilation, 3 (17%) of abnormal signals in the brain parenchyma (frontal lobe, basal ganglia region, and brain stem), and 3 (17%) of abnormal signals in the lateral paraventricular. In addition, there were 3 cases (17%) of cerebral white matter atrophy and 1 (5%) of cytotoxic edema in the basal ganglia and cerebral peduncle. EEG data displayed 2 cases (11%) of hypsarrhythmia, 3 (17%) of voltage reduction, 12(67%) of abnormal discharge, 13 (72%) of abnormal sleep physiological waves or abnormal sleep structure, 1 (5%) of immature (delayed) EEG development, and 8 (44%) of slow background. There were 2 cases (11%) of spasms, 1 (5%) of atonic seizures, and 1 (5%) of myoclonic seizures. There were 16 patients (89%) with hyperhomocysteinemia. During follow-up, 1 patient was lost to follow-up, and 1 died. In total, 87.5% (14/16) of the children had varying developmental delays. EEG was re-examined in 11 cases, of which 8 were normal, and 3 were abnormal. Treatments included intramuscular injections of vitamin B12, L-carnitine, betaine, folic acid, and oral antiepileptic therapy. Acute treatment included anti-infective, blood transfusion, fluid replacement, and correcting acidosis. The other treatments included low-protein diets and special formula milk powder., Conclusion: Methylmalonic acidemia can affect the central nervous system, leading to structural changes or abnormal signals on brain MRI. Metabolic screening and genetic testing help clarify the diagnosis. EEG can reflect changes in brain waves during the acute phase., (© 2024. The Author(s).)

Multivalent drugs targeting homo-oligomeric viral surface proteins, such as the SARS-CoV-2 trimeric spike (S) protein, have the potential to elicit more potent and broad-spectrum therapeutic responses than monovalent drugs by synergistically engaging multiple binding sites on viral targets. However, rational design and engineering of nanoscale multivalent protein drugs are still lacking. Here, we developed a computational approach to engineer self-assembling trivalent microproteins that simultaneously bind to the three receptor binding domains (RBDs) of the S protein. This approach involves four steps: structure-guided linker design, molecular simulation evaluation of self-assembly, experimental validation of self-assembly state, and functional testing. Using this approach, we first designed trivalent constructs of the microprotein miniACE2 (MP) with different trimerization scaffolds and linkers, and found that one of the constructs (MP-5ff) showed high trimerization efficiency, good conformational homogeneity, and strong antiviral neutralizing activity. With its trimerization unit (5ff), we then engineered a trivalent nanobody (Tr67) that exhibited potent and broad neutralizing activity against the dominant Omicron variants, including XBB.1 and XBB.1.5. Cryo-EM complex structure confirmed that Tr67 stably binds to all three RBDs of the Omicron S protein in a synergistic form, locking them in the "3-RBD-up" conformation that could block human receptor (ACE2) binding and potentially facilitate immune clearance. Therefore, our approach provides an effective strategy for engineering potent protein drugs against SARS-CoV-2 and other deadly coronaviruses., (© 2024. The Author(s).)

Background: Microsatellite instability-high (MSI-H) is a unique genomic status in many cancers. However, its role in the genomic features and immunotherapy in cholangiocarcinoma (CCA) is unclear. This study aimed to systematically investigate the genomic characterization and immunotherapy efficacy of MSI-H patients with CCA., Methods: We enrolled 887 patients with CCA in this study. Tumor samples were collected for next-generation sequencing. Differences in genomic alterations between the MSI-H and microsatellite stability (MSS) groups were analyzed. We also investigated the survival of PD-1 inhibitor-based immunotherapy between two groups of 139 patients with advanced CCA., Results: Differential genetic alterations between the MSI-H and MSS groups included mutations in ARID1A, ACVR2A, TGFBR2, KMT2D, RNF43, and PBRM1 which were enriched in MSI-H groups. Patients with an MSI-H status have a significantly higher tumor mutation burden (TMB) (median 41.7 vs. 3.1 muts/Mb, P < 0.001) and more positive programmed death ligand 1 (PD-L1) expression (37.5% vs. 11.9%, P < 0.001) than those with an MSS status. Among patients receiving PD-1 inhibitor-based therapy, those with MSI-H had a longer median overall survival (OS, hazard ratio (HR) = 0.17, P = 0.001) and progression-free survival (PFS, HR = 0.14, P < 0.001) than patients with MSS. Integrating MSI-H and PD-L1 expression status (combined positive score ≥ 5) could distinguish the efficacy of immunotherapy., Conclusions: MSI-H status was associated with a higher TMB value and more positive PD-L1 expression in CCA tumors. Moreover, in patients with advanced CCA who received PD-1 inhibitor-based immunotherapy, MSI-H and positive PD-L1 expression were associated with improved both OS and PFS., Trial Registration: This study was registered on ClinicalTrials.gov on 07/01/2017 (NCT03892577)., (© 2024. The Author(s).)

Background: The present study identified survival and progression-free rates and evaluated prognostic factors for IVB stage cervical cancer in patients that presented with synchronous oligometastases (sync-oligometastases) who received definitive irradiation for primary and metastatic sites., Methods: The study retrospectively included 60 patients with newly diagnosed stage IVB cervical cancer. Patients received definitive radiation for both primary and metastatic sites through Volumetric Modulated Arc Therapy (VMAT) or intensity modulated radiation therapy (IMRT) followed by three dimensional-intracavitary/interstitial brachytherapy at our institution between July 2014 to December 2020. All patients were staged based on the International Federation of Gynecology and Obstetrics (FIGO) 2018 guidelines. Overall survival (OS), progression-free survival (PFS), and patient prognostic factors were analyzed., Results: The 60 patients who received curative-intent irradiation for primary and metastatic sites showed a 5-year OS rate of 51.4% and a 5-year PFS rate of 25.9%. The median PFS was 52.3 months, and the median OS had not been reached. Lymphatic metastases had a better OS compared with hematogenous metastases (3-year OS rates: 57.2% vs. 20%, p = 0.017). Patients with one metastasis site showed a more favorable prognosis than patients with ≥ 2 metastases sites (3-year OS rates: 60.4% vs. 20.6%, p = 0.003). Patients that presented with tumors larger than 4 cm in diameter before treatment demonstrated a poorer prognosis (5-year OS rates: 41.2% vs. 65.2%, p = 0.029; 5-year PFS rates: 10.4% vs. 53.7%, p = 0.021)., Conclusion: Definitive irradiation for both primary and oligo-metastatic sites for selected IVB patients is a feasible treatment strategy. Metastatic type, number of metastatic sites, and pre-treatment tumor diameter were significant prognostic factors. Neoadjuvant chemotherapy, the lymph nodal metastatic type (supraclavicular or inguinal), and number of lymphatic metastatic sites failed to reach statistical significance as prognostic factors., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Knee osteoarthritis (KOA) is an age-related degenerative disease characterized by abrasion of articular cartilage. Tongbi Huoluo Decoction (TBHLD) has been transformed from the famous traditional Chinese medicine Duhuo Jisheng Decoction, which can effectively alleviate pain symptoms in KOA. However, the active components and mechanisms of TBHLD in treating KOA have not yet been elucidated. The purpose of the study was to demonstrate the molecular mechanism of TBHLD in treating KOA., Methods: The components and targets of TBHLD and KOA were collected from multiple databases, and the protein to protein interaction (PPI) network was constructed. Next, we performed topological calculation and enrichment analysis. Besides, we performed virtual screening for molecular docking and molecular dynamics simulation (MDS). Furthermore, the vitro and vivo experiments were performed to evaluate the validity and mechanism of TBHLD., Results: 206 active components and 187 potential targets were screened from Tongbi Huoluo Decoction. A total of 50 intersecting genes were identified between TBHLD and KOA, 20 core targets were calculated by network topology analysis. The core targets were enriched in the ECM interaction pathways. The results of virtual screening for molecular docking and MDS showed that the active components of TBHLD had steady binding conformations with core genes. Moreover, we identified 32 differential serum components in TBHLD-containing serum using LC-MS, including 22 upregulated and 10 downregulated serum components. TBHLD improved the proliferation activity of OA chondrocytes, decreased the expression of Col1a1, Col1a2, Mmp2, Mmp13 in OA chondrocytes, ameliorated the cartilage lesions and restored the cartilage abrasion., Conclusion: TBHLD inhibited degradation of cartilage ECM by regulating the expression of type I collagens and Mmps to ameliorate cartilage degeneration in KOA., (© 2023. The Author(s).)

Background: RP11-296E3.2 is a novel long noncoding RNA (lncRNA) associated with colorectal cancer (CRC) metastasis, that was reported in our previous clinical studies. However, the mechanisms of RP11-296E3.2 in colorectal tumorigenesis remain elusive., Methods: RNA sequencing (RNA-seq), Fluorescence in situ hybridization (FISH), Transwell assays and others, were performed to evaluate the function of RP11-296E3.2 for proliferation and metastasis in vitro. In situ and metastatic tumor models were performed to evaluate the function of RP11-296E3.2 for proliferation and metastasis in vivo. RNA-pulldown, RNA-interacting protein immunoprecipitation (RIP), tissue microarray (TMA) assay, a luciferase reporter assay, chromatin immunoprecipitation (ChIP) and others were performed to explore the mechanisms by which RP11-296E3.2 regulates CRC tumorigenesis., Results: RP11-296E3.2 was confirmed to be associated with CRC cell proliferation and metastasis in vitro and in vivo. Mechanistically, RP11-296E3.2 directly bound to recombinant Y-Box Binding Protein 1 (YBX1) and enhanced signal transducer and activator of transcription 3 (STAT3) transcription and phosphorylation. YBX1 promoted the CRC cell proliferation and migration, while knockdown of RP11-296E3.2 attenuated the effects of YBX1 on CRC cell proliferation, and metastasis and the expression of several related downstream genes. We are the first to discover and confirm the existence of the YBX1/STAT3 pathway, a pathway dependent on RP11-296E3.2., Conclusion: Together, these novel findings show that the RP11-296E3.2/YBX1 pathway promotes colorectal tumorigenesis and progression by activating STAT3 transcription and phosphorylation, and suggest that RP11-296E3.2 is a potential diagnostic biomarker and therapeutic target in CRC., (© 2023. The Author(s).)

Background: A variety of external factors might seriously degrade PET image quality and lead to inconsistent results. The aim of this study is to explore a potential PET image quality assessment (QA) method with deep learning (DL)., Methods: A total of 89 PET images were acquired from Peking Union Medical College Hospital (PUMCH) in China in this study. Ground-truth quality for images was assessed by two senior radiologists and classified into five grades (grade 1, grade 2, grade 3, grade 4, and grade 5). Grade 5 is the best image quality. After preprocessing, the Dense Convolutional Network (DenseNet) was trained to automatically recognize optimal- and poor-quality PET images. Accuracy (ACC), sensitivity, specificity, receiver operating characteristic curve (ROC), and area under the ROC Curve (AUC) were used to evaluate the diagnostic properties of all models. All indicators of models were assessed using fivefold cross-validation. An image quality QA tool was developed based on our deep learning model. A PET QA report can be automatically obtained after inputting PET images., Results: Four tasks were generated. Task2 showed worst performance in AUC,ACC, specificity and sensitivity among 4 tasks, and task1 showed unstable performance between training and testing and task3 showed low specificity in both training and testing. Task 4 showed the best diagnostic properties and discriminative performance between poor image quality (grade 1, grade 2) and good quality (grade 3, grade 4, grade 5) images. The automated quality assessment of task 4 showed ACC = 0.77, specificity = 0.71, and sensitivity = 0.83, in the train set; ACC = 0.85, specificity = 0.79, and sensitivity = 0.91, in the test set, respectively. The ROC measuring performance of task 4 had an AUC of 0.86 in the train set and 0.91 in the test set. The image QA tool could output basic information of images, scan and reconstruction parameters, typical instances of PET images, and deep learning score., Conclusions: This study highlights the feasibility of the assessment of image quality in PET images using a deep learning model, which may assist with accelerating clinical research by reliably assessing image quality., (© 2023. The Author(s).)

Background: N6-methyladenosine (m6A) modification is involved in tumorigenesis and progression as well as closely correlated with stem cell differentiation and pluripotency. Moreover, tumor progression includes the acquisition of stemness characteristics and accumulating loss of differentiation phenotype. Therefore, we integrated m6A modification and stemness indicator mRNAsi to classify patients and predict prognosis for LGG., Methods: We performed consensus clustering, weighted gene co-expression network analysis, and least absolute shrinkage and selection operator Cox regression analysis to identify an m6A regulation- and mRNAsi-related prognostic index (MRMRPI). Based on this prognostic index, we also explored the differences in immune microenvironments between high- and low-risk populations. Next, immunotherapy responses were also predicted. Moreover, single-cell RNA sequencing data was further used to verify the expression of these genes in MRMRPI. At last, the tumor-promoting and tumor-associated macrophage polarization roles of TIMP1 in LGG were validated by in vitro experiments., Results: Ten genes (DGCR10, CYP2E1, CSMD3, HOXB3, CABP4, AVIL, PTCRA, TIMP1, CLEC18A, and SAMD9) were identified to construct the MRMRPI, which was able to successfully classify patients into high- and low-risk group. Significant differences in prognosis, immune microenvironment, and immunotherapy responses were found between distinct groups. A nomogram integrating the MRMRPI and other prognostic factors were also developed to accurately predict prognosis. Moreover, in vitro experiments illustrated that inhibition of TIMP1 could inhibit the proliferation, migration, and invasion of LGG cells and also inhibit the polarization of tumor-associated macrophages., Conclusion: These findings provide novel insights into understanding the interactions of m6A methylation regulation and tumor stemness on LGG development and contribute to guiding more precise immunotherapy strategies., (© 2023. The Author(s).)

Background: The maximum likelihood activity and attenuation (MLAA) reconstruction algorithm has been proposed to jointly estimate tracer activity and attenuation at the same time, and proven to be a promising solution to the CT attenuation correction (CT-AC) artifacts in PET images. This study aimed to perform a quantitative evaluation and clinical validation of the MLAA method., Methods: A uniform cylinder phantom filled with 18 F-FDG solution was scanned to optimize the reconstruction parameters for the implemented MLAA algorithm. 67 patients who underwent whole-body 18 F-FDG PET/CT scan were retrospectively recruited. PET images were reconstructed using MLAA and clinical standard OSEM algorithm with CT-AC (CT-OSEM). The mean and maximum standardized uptake values (SUVmean and SUVmax) in regions of interest (ROIs) of organs, high uptake lesions and areas affected by metal implants and respiration motion artifacts were quantitatively analyzed., Results: In quantitative analysis, SUVs in patient's organ ROIs between two methods showed R 2 ranging from 0.91 to 0.98 and k ranging from 0.90 to 1.06, and the average SUVmax and SUVmean differences between two methods were within 10% range, except for the lung ROI, which was 10.5% and 16.73% respectively. The average SUVmax and SUVmean differences of a total of 117 high uptake lesions were 7.25% and 7.10% respectively. 20 patients were identified to have apparent respiration motion artifacts in the liver in CT-OSEM images, and the SUVs differences between two methods measured at dome of the liver were significantly larger than measured at middle part of the liver. 10 regions with obvious metal artifacts were identified in CT-OSEM images and the average SUVmean and SUVmax differences in metal implants affected regions were reported to be 52.90% and 56.20% respectively., Conclusions: PET images reconstructed using MLAA are clinically acceptable in terms of image quality as well as quantification and it is a useful tool in clinical practice, especially when CT-AC may cause respiration motion and metal artifacts. Moreover, this study also provides technical reference and data support for the future iteration and development of PET reconstruction technology of SUV accurate quantification., (© 2023. The Author(s).)

Background: Interspecific postzygotic reproduction isolation results from large genetic divergence between the subgenomes of established hybrids. Polyploidization immediately after hybridization may reset patterns of homologous chromosome pairing and ameliorate deleterious genomic incompatibility between the subgenomes of distinct parental species in plants and animals. However, the observation that polyploidy is less common in vertebrates raises the question of which factors restrict its emergence. Here, we perform analyses of the genome, epigenome, and gene expression in the nascent allotetraploid lineage (2.95 Gb) derived from the intergeneric hybridization of female goldfish (Carassius auratus, 1.49 Gb) and male common carp (Cyprinus carpio, 1.42 Gb), to shed light on the changes leading to the stabilization of hybrids., Results: We firstly identify the two subgenomes derived from the parental lineages of goldfish and common carp. We find variable unequal homoeologous recombination in somatic and germ cells of the intergeneric F 1 and allotetraploid (F 22 and F 24 ) populations, reflecting high plasticity between the subgenomes, and rapidly varying copy numbers between the homoeolog genes. We also find dynamic changes in transposable elements accompanied by genome merger and duplication in the allotetraploid lineage. Finally, we observe the gradual decreases in cis-regulatory effects and increases in trans-regulatory effects along with the allotetraploidization, which contribute to increases in the symmetrical homoeologous expression in different tissues and developmental stages, especially in early embryogenesis., Conclusions: Our results reveal a series of changes in transposable elements, unequal homoeologous recombination, cis- and trans-regulations (e.g. DNA methylation), and homoeologous expression, suggesting their potential roles in mediating adaptive stabilization of regulatory systems of the nascent allotetraploid lineage. The symmetrical subgenomes and homoeologous expression provide a novel way of balancing genetic incompatibilities, providing a new insight into the early stages of allopolyploidization in vertebrate evolution., (© 2022. The Author(s).)

Background: G protein-coupled receptor (GPCR) is the most targeted protein family by the FDA-approved drugs. GPCR-kinase 3 (GRK3) is critical for GPCR signaling. Our genomic analysis showed that GRK3 expression correlated with poor prognosis of gastric adenocarcinoma (GAC) patients. However, GRK3's functions and clinical utility in GAC progression and metastases are unknown., Methods: We studied GRK3 expression in normal, primary, and metastatic GAC tissues. We identified a novel GRK3 inhibitor, LD2, through a chemical-library screen. Through genetic and pharmacologic modulations of GRK3, a series of functional and molecular studies were performed in vitro and in vivo. Impact of GRK3 on YAP1 and its targets was determined., Results: GRK3 was overexpressed in GAC tissues compared to normal and was even higher in peritoneal metastases. Overexpression (OE) of GRK3 was significantly associated with shorter survival. Upregulation of GRK3 in GAC cells increased cell invasion, colony formation, and proportion of ALDH1 + cells, while its downregulation reduced these attributes. Further, LD2 potently and specifically inhibited GRK3, but not GRK2, a very similar kinase to GRK3. LD2 highly suppressed GAC cells' malignant phenotypes in vitro. Mechanistically, GRK3 upregulated YAP1 in GAC tissues and its transcriptional downstream targets: SOX9, Birc5, Cyr61 and CTGF. Knockdown (KD) YAP1 rescued the phenotypes of GRK3 OE in GAC cells. GRK3 OE significantly increased tumor growth but LD2 inhibited tumor growth in the PDX model and dramatically suppressed peritoneal metastases induced by GRK3 OE., Conclusions: GRK3, a poor prognosticator for survival, conferred aggressive phenotype. Genetic silencing of GRK3 or its inhibitor LD2 blunted GRK3-conferred malignant attributes, suggesting GRK3 as a novel therapeutic target in advanced GAC., (© 2022. The Author(s).)

Background: International guidelines advocate providing prompt structured education to individuals with diabetes at diagnosis. However, among the few eligible structured education programs, heterogeneous intervention regimens and inconsistent findings were reported. Eligible programs for Chinese individuals with diabetes are lacking. This study aimed to investigate the effects of a nurse-led integrative medicine-based structured education program on self-management behaviors, glycemic control and self-efficacy among individuals with newly diagnosed type 2 diabetes., Methods: Employing a randomized controlled trial, 128 individuals with type 2 diabetes diagnosed in the preceding three to nine months were recruited from four university-affiliated tertiary hospitals in Xi'an City, Northwest China, and randomly allocated to the intervention or control groups after baseline assessments. Participants in the intervention group received a 4-week nurse-led integrative medicine-based structured education program, which is theoretically based on the Health Belief Model and Self-Efficacy Theory, in line with updated diabetes management guidelines, and informed by relevant systematic reviews. Participants in the control group received routine care. Self-management behaviors and self-efficacy were measured with the Summary of Diabetes Self-Care Activities and the Diabetes Management Self-Efficacy Scale at baseline, immediate post-intervention and 12 weeks following the intervention while Glycated Hemoglobin A was measured at baseline and the 12th-week follow-up. The intervention effects were estimated using the generalized estimating equation models., Results: Participants in the intervention group exhibited significantly better self-management performance in specific diet regarding intake of fruits and vegetables at both follow-ups (β = 1.02, p = 0.011 and β = 0.98, p = 0.016, respectively), specific diet regarding intake of high-fat foods at the immediate post-intervention follow-up (β = 0.83, p = 0.023), blood glucose monitoring at the 12th-week follow-up (β = 0.64, p = 0.004), foot care at both follow-ups (β = 1.80, p <  0.001 and β = 2.02, p <  0.001, respectively), and medication management at both follow-ups (β = 0.83, p = 0.005 and β = 0.95, p = 0.003, respectively). The intervention also introduced significant improvements in Glycated Hemoglobin A (β = - 0.32%, p <  0.001), and self-efficacy at both follow-ups (β = 8.73, p <  0.001 and β = 9.71, p <  0.001, respectively)., Conclusions: The nurse-led integrative medicine-based structured education program could produce beneficial effects on multiple diabetes self-management behaviors, glycemic control and self-efficacy., Trial Registration: This study was retrospectively registered in the ClinicalTrials.gov . on 25/08/2017; registration number: NCT03261895 ., (© 2022. The Author(s).)

Background: The study aimed to investigate the difference in refractive status and ocular parameters between ptotic and fellow eyes in patients with unilateral congenital ptosis., Methods: Thirty patients (53% males, age 22.00 ± 11.41 years) with unilateral congenital ptosis diagnosed and treated at the First Affiliated Hospital of Sun-yat Sen University were enrolled and underwent detailed refractive examinations from March 2019 to February 2022. Ocular biometric measurements were performed by an IOL Master 700 biometer. The differences in refractive error characteristics, best-corrected visual acuity (BCVA), and ocular parameters including axial length (AL), central corneal thickness (CCT), aqueous depth (AQD), anterior chamber depth (ACD), lens thickness (LT), and keratometry values between ptotic and fellow eyes were analysed., Results: A lower BCVA (logMAR, median (IQR), 0.00 (- 0.13,0.00), P = 0.009) and a higher incidence of amblyopia (n (%), 7(23%), P = 0.016) were observed in ptotic eyes. The CCT of ptotic eyes was greater than that of fellow eyes (mean ± SD, 539.83 ± 26.73 μm, P < 0.001). The keratometry values at the flat axis (K1) and mean corneal power (Km) were smaller in ptotic eyes (mean ± SD, 42.11 ± 1.49 D, 42.68 ± 1.52 D, respectively, both P = 0.001). There was no significant difference in AL between ptotic and fellow eyes., Conclusions: Congenital ptosis influences ocular parameters, mainly causing a thicker and flatter cornea. Patients with unilateral congenital ptosis might have lower BCVA in the ptotic eyes., (© 2022. The Author(s).)

Objectives: This study aimed to investigate the gene expression of angiogenic marker in surgically treated jawbones and femur on a rat model administrated with zoledronic acid., Results: No soft tissue fenestration or bone exposure was found in femur. Delayed soft tissue healing was found in both ZA group (3 in mandible, 4 in maxilla) and control group (1 in mandible, 2 in maxilla), while exposed bone was found only in the ZA group (1 in maxilla, 2 in mandible). RT-PCR analysis demonstrated no significant difference in gene expression of angiogenetic markers between ZA-treated and control groups in femur and mandible. In the maxilla, the expression of VEGFA and VEGFR-2 in medium-term ZA group was significantly down-regulated compared with that in the control. The ZA treatment does not change significantly the expression of the angiogenic factors in femur and mandible, but significantly downregulates the expression in maxilla in this rat model. The angiogenesis inhibition may contribute to the development of MRONJ but does not play a key role., (© 2021. The Author(s).)

Background: Despite inconsistent findings, accumulative evidence has shown abnormalities of the key antioxidant enzyme, superoxide dismutase (SOD), in patients with schizophrenia. However, few studies explored SOD in late-life schizophrenia (LLS). Our work aimed to investigate changes in SOD activity and the relationship between SOD activity and psychotic symptoms or cognitive deficits in LLS., Methods: 32 geriatric male patients with schizophrenia (age ≥ 60) and 28 age-matched male normal controls were recruited in the study. We assessed cognitive functions with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), evaluated the severity of clinical symptoms with the Positive and Negative Syndrome Scale (PANSS), and measured the plasma levels of SOD., Results: Patients with LLS presented with higher total levels of SOD compared to the controls (81.70 vs. 65.26 U/ml, p < .001). Except for the visuospatial index, the cognitive performance was significantly worse on RBANS total and other domain scores in the schizophrenia group than the control group. In the schizophrenia group, SOD levels were positively correlated with subscores of general psychopathology and negative symptoms and total scores of the PANSS (all p < .05), and inversely associated with performance in immediate memory, language, and RBANS total scores (all p < .05)., Conclusions: Our findings suggest that patients with LLS display disturbances in the antioxidant system, which may underlie the pathological process of cognitive impairments and negative symptoms in the late stage of schizophrenia. Supplementing with antioxidants could be a potential treatment., (© 2021. The Author(s).)

Background: Infancy is the of a child's visual development. Refractive errors, especially myopia, are a common vision disorder. Thus, the purpose of this study was to explore refractive errors and risk factors for myopia among infants aged 1-18 months in Tianjin, China., Methods: A total of 583 infants aged 1-18 months participated in this cross-sectional study at Tianjin Women's and Children's Health Center in China from February 2019 to November 2020. Each infant received a complete ophthalmologic examination, and myopia-related risk factors were investigated using a questionnaire., Results: A total of 583 eligible infants participated in this study, including 312 (53.5%) boys and 271 (46.5%) girls. There were 164 (28.1%) premature born infants. The mean age was 6.59 ± 4.84 months (range, 1-18 months). The mean spherical equivalent (MSE) for the right eye was 1.81 D ± 1.56 D, with no difference related to sex (P = 0.104). Refractive state showed an average hyperopia of +2.74 ± 1.74 D at early ages, followed by a trend toward less hyperopia, finally reaching +1.35 ± 1.44 D at the age of 18 months (P ≤0.001). The overall prevalence rates of myopia (MSE ≤ -0.50 D), emmetropia (-0.50 D

Background: With the increased understanding of heart disease, microvascular angina (MVA) is receiving greater attention from clinicians. Studies have shown that patients with MVA have significantly higher major cardiovascular events and all-cause mortality than the control population, and the search for effective treatments is of great clinical importance. Both basic and clinical studies have shown that Qi-Jing Hui-Xin Decoction (QJHX) can relieve angina symptoms and improve clinical efficacy, but there is a lack of high-quality clinical studies to provide a research basis. This article introduces the evaluation protocol of QJHX for the adjunctive treatment of MVA., Methods/design: This is a prospective randomized controlled trial. The trial will enroll 150 patients with MVA. On the basis of Western drug treatment, patients will be randomized into two groups, and the experimental group will receive QJHX treatment for 12 weeks and follow-up at 24 week. The primary indicators are the clinical efficacy of angina pectoris and the evidence of traditional Chinese medicine (TCM) efficacy. Secondary indicators are the Seattle Angina Scale score, serum lipid levels, electrocardiogram, and echocardiogram diagnosis. Additional indicators are endothelial function and immunoinflammatory factors. Adverse events will be monitored throughout the trial., Discussion: Integrated traditional Chinese and Western medicine is commonly used for angina in China. This study will evaluate the clinical effectiveness and safety of adding QJHX based on standardized Western medications. The results of the trial will provide high-level clinical research-based evidence for the application of QJHX in MVA., Trial Registration: Chinese Clinical Trial Registry ChiCTR1900027015 . Registered on 28 October 2019., (© 2021. The Author(s).)

Background: Coronary heart disease (CHD) has become one of the biggest health problems in the world. Stable angina is a common clinical type of CHD with poor prognosis and high mortality. Although there are various interventions for stable angina, none of them can significantly reduce mortality. Both basic and clinical research have shown that Suxiao Jiuxin Pill (SJP) can relieve the symptoms of angina pectoris and improve the clinical efficacy, but there is a lack of high-quality clinical research to provide research-based evidence. We design a randomized, double-blind, placebo-controlled trial to evaluate the efficacy of SJP for stable angina., Methods/design: This is a prospective, randomized, double-blind, placebo-controlled, and multicenter trial. The trial will enroll 324 participants with chronic stable angina (Qi Stagnation and Blood Stasis syndrome). All participants will have received the conventional therapy of chronic stable angina. Participants will be randomized into two groups, conventional therapy plus SJP group and conventional therapy plus placebo group. Eligible participants will receive either SJP or placebo (five pills administered orally, three times daily) in addition to conventional treatment for 24 weeks. The primary outcomes are the symptom improvement rate of angina from baseline to 4 weeks after inclusion and major adverse cardiovascular events (MACE). The secondary outcomes are angina classification (CCS), improvement of traditional Chinese medicine (TCM) syndromes, Seattle Angina Scale score, the dosage of emergency drugs and the stopping rate, and electrocardiogram (EKG) efficacy. Adverse events will be monitored throughout the trial., Discussion: Integrated traditional Chinese and Western Medicine is commonly used for angina in China. This study will evaluate the clinical effectiveness and safety of SJP for angina. The results of the trial will provide high-level clinical research-based evidence for the application of SJP instable angina., Trial Registration: This study protocol was registered on 14 March 2019. The registration number is ChiCTR1900021876 on the Chinese Clinical Trial Registry., (© 2021. The Author(s).)

Background: Long noncoding RNA (lncRNA), urothelial carcinoma-associated 1 (UCA1) is aberrantly expressed in multiple cancers and has been verified as an oncogene. However, the underlying mechanism of UCA1 in the development of gastric cancer is not fully understood. In the present study, we aimed to identify how UCA1 promotes gastric cancer development., Methods: The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) data were used to analyze UCA1 and myosin VI (MYO6) expression in gastric cancer. Western blot and quantitative real-time PCR (QPCR) were performed to test the expression level of the UCA1/miR-145/MYO6 axis in gastric cancer cell lines and tissues. The roles of the UCA1/miR-145/MYO6 axis in gastric cancer in vitro and in vivo were investigated by CCK-8 assay, flow cytometry, siRNAs, immunohistochemistry, and a mouse xenograft model. The targeted relationship among UCA1, miR-145, and MYO6 was predicted using LncBase Predicted v.2 and TargetScan online software, and then verified by luciferase activity assay and RNA immunoprecipitation., Results: UCA1 expression was higher but miR-145 expression was lower in gastric cancer cell lines or tissues, compared to the adjacent normal cell line or normal tissues. Function analysis verified that UCA1 promoted cell proliferation and inhibited cell apoptosis in the gastric cancer cells in vitro and in vivo. Mechanistically, UCA1 could bind directly to miR-145, and MYO6 was found to be a downstream target gene of miR-145. miR-145 mimics or MYO6 siRNAs could partly reverse the effect of UCA1 on gastric cancer cells., Conclusions: UCA1 accelerated cell proliferation and inhibited cell apoptosis through sponging miR-145 to upregulate MYO6 expression in gastric cancer, indicating that the UCA1/miR-145/MYO6 axis may serve as a potential therapeutic target for gastric cancer.

Background: Venous thromboembolism (VTE) is a significant complication after joint arthroplasty. Diabetes is related to a few changes in coagulation and fibrinolysis that may lead to thrombophilia. We aimed to investigate the incidence of postoperative VTE and associated risk factors among patients with diabetes undergoing total hip (THA) or total knee anthroplasty (TKA) in a single centre in China., Methods: Patients with diabetes who underwent THA or TKA from January 2016 to December 2018 (n = 400) at Beijing Jishuitan Hospital were recruited in this study. Lower limb venous Doppler ultrasound was performed before and after surgery to confirm deep venous thrombosis (DVT). Computer tomography pulmonary angiography was done to confirm pulmonary embolism (PE) for those with new postoperative DVT and typical symptoms of PE. A multivariate logistic regression model was conducted to examine factors associated with the development of postoperative VTE., Results: The overall incidence of postoperative VTE in patients with diabetes after THA or TKA was 46.8 % (187 out of 400). Among the 187 VTE patients, 7.5 % (14 out of 187) had proximal vein thrombosis and 92.5 % (173 out of 187) had distal vein thrombosis. No PE occurred. Female patients and patients undergoing TKA had higher incidence of postoperative VTE. Patients who developed postoperative VTE were older, and had higher levels of preoperative D-Dimer and Caprini score. A high level of preoperative D-dimer (OR = 2.11, 95 %CI = 1.35-3.30) and the surgery of TKA (OR = 2.29, 95 %CI = 1.29-4.01) significantly increased the risk of developing postoperative VTE. Postoperative initiation of concomitant mechanical prophylaxis and low molecular weight heparin (LMWH) was protective for postoperative VTE (OR = 0.56, 95 %CI = 0.37-0.86)., Conclusions: VTE is common in patients with diabetes undergoing joint arthroplasty. Patients undergoing TKA or with a high level of preoperative D-dimer are at a considerable risk of developing postoperative VTE. There may be a protective role of postoperative initiation of concomitant mechanical prophylaxis and LMWH for VTE.

Background: Gastric adenocarcinoma with peritoneal carcinomatosis (PC) is therapy resistant and leads to poor survival. To study PC in depth, there is an urgent need to develop representative PC-derived cell lines and metastatic models to study molecular mechanisms of PC and for preclinical screening of new therapies., Methods: PC cell lines were developed from patient-derived PC cells. The tumorigenicity and metastatic potential were investigated by subcutaneously (PDXs) and orthotopically. Karyotyping, whole-exome sequencing, RNA-sequencing, and functional studies were performed to molecularly define the cell lines and compare genomic and phenotypic features of PDX and donor PC cells., Results: We established three PC cell lines (GA0518, GA0804, and GA0825) and characterized them in vitro. The doubling times were 22, 39, and 37 h for GA0518, GA0804, and GA0825, respectively. Expression of cancer stem cell markers (CD44, ALDH1, CD133 and YAP1) and activation of oncogenes varied among the cell lines. All three PC cell lines formed PDXs. Interestingly, all three PC cell lines formed tumors in the patient derived orthotopic (PDO) model and GA0518 cell line consistently produced PC in mice. Moreover, PDXs recapitulated transcriptomic and phenotypic features of the donor PC cells. Finally, these cell lines were suitable for preclinical testing of chemotherapy and target agents in vitro and in vivo., Conclusion: We successfully established three patient-derived PC cell lines and an improved PDO model with high incidence of PC associated with malignant ascites. Thus, these cell lines and metastatic PDO model represent excellent resources for exploring metastatic mechanisms of PC in depth and for target drug screening and validation by interrogating GAC for translational studies.

Background: Lymphangioleiomyomatosis (LAM) is a rare multisystem disease characterized by cystic lung disease and extrapulmonary manifestations, including lymphatic system disorder. The objective of this study was to investigate the findings of 68 Ga-NOTA-Evans Blue (NEB) PET/CT in LAM and compare it with that of 99m Tc-ASC lymphoscintigraphy., Methods: Ten patients diagnosed with LAM according to the American Thoracic Society/Japanese Respiratory Society guidelines for LAM were recruited in this study. PET/CT acquisition was performed at 20 to 40 min after subcutaneous injection of 68 Ga-NEB into the first interdigital spaces of both feet (0.3 ml, 37 MBq/foot). All subjects also underwent 99m Tc-antimony sulfide colloid (ASC) lymphoscintigraphy within a week for comparison., Results: 68 Ga-NEB PET/CT displayed various lymphatic system abnormalities in 10 (100%) of 10 patients. These included pulmonary lymphatic abnormalities in 10 (100%) of 10 patients, enlarged lymph nodes in 5 (50%), lymphangioleiomyomas in 2 (20%), dilation of the lumbar trunk and/or iliac lymph vessels in 5 (50%), thoracic duct dilation in 2 (20%), chylous effusion in 1 (10%). For pulmonary lymphatic abnormalities, the positive rates of 68 Ga-NEB PET/CT and 99m Tc-ASC lymphoscintigraphy were 100% (10/10) and 10% (1/10), respectively (P < 0.001). As for the 7 patients with extrapulmonary lymphatic manifestations, 68 Ga-NEB PET/CT also presented more information than 99m Tc-ASC lymphoscintigraphy., Conclusion: 68 Ga-NEB PET/CT visualized pulmonary lymphatic abnormality and displayed extrapulmonary lymphatic system disorders of LAM, and might play a role in the diagnosis and evaluation of the disease. 68 Ga-NEB PET/CT is advantageous over conventional 99m Tc-ASC lymphoscintigraphy in LAM by providing more detailed information of lymphatic dysfunction.

Background: Dynamic PET with kinetic modeling was reported to be potentially helpful in the assessment of hepatic malignancy. In this study, a kinetic modeling analysis was performed on hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) from dynamic FDG positron emission tomography/computer tomography (PET/CT) scans., Methods: A reversible two-tissue compartment model with dual blood input function, which takes into consideration the blood supply from both hepatic artery and portal vein, was used for accurate kinetic modeling of liver dynamic 18 F-FDG PET imaging. The blood input functions were directly measured as the mean values over the VOIs on descending aorta and portal vein respectively. And the contribution of hepatic artery to the blood input function was optimization-derived in the process of model fitting. The kinetic model was evaluated using dynamic PET data acquired on 24 patients with identified hepatobiliary malignancy. 38 HCC or ICC identified lesions and 24 healthy liver regions were analyzed., Results: Results showed significant differences in kinetic parameters [Formula: see text], blood supplying fraction [Formula: see text], and metabolic rate constant [Formula: see text] between malignant lesions and healthy liver tissue. And significant differences were also observed in [Formula: see text], [Formula: see text], [Formula: see text] and [Formula: see text] between HCC and ICC lesions. Further investigations of the effect of SUV measurements on the derived kinetic parameters were conducted. And results showed comparable effectiveness of the kinetic modeling using either SUVmean or SUVmax measurements., Conclusions: Dynamic 18F-FDG PET imaging with optimization-derived hepatic artery blood supply fraction dual-blood input function kinetic modeling can effectively distinguish malignant lesions from healthy liver tissue, as well as HCC and ICC lesions.

Background: Although more and more attention has been paid to the psychological consequences of the lockdown policy amongst pregnant women, the underlying mechanism linking the lockdown policy to maternal depression has not been studied in the context of China. This study aimed to explore the association between the lockdown policy and maternal depressive symptoms, and whether such association was mediated by internet use and/or family support., Methods: This cross-sectional study used multi-stage sampling techniques in central and western China. Data were collected from 1266 pregnant women using a structtured questionnaire that measured internet use, family support, and depressive symptoms. The Patient Health Questionnaire-9 (PHQ-9) was used to measure depressive symptoms. Internet use was measured by length of usage and varierity of purpose for internet use. Family support was measureed by spousal support and parental support. The structural equation modelling was employed to conduct mediation analysis to test the specificity of the hypothetical paths., Results: Overall, 527 respondents (41.63%) presented depressive symptoms. The lockdown policy was negatively associated with depressive symptoms in pregnant women (β = - 0.925, 95% CI = -1.510, - 0.360). The impact of the lockdown policy on depressive symptoms was partially mediated by internet use (β = 1.589, 95% CI = 0.730, 2.807) and family support (β = - 0.162, 95% CI = - 0.341, - 0.017), accounting for 42.67% of the total effect., Conclusions: The lockdown policy was generally associated with fewer depressive symptoms in pregnant women. The lockdown policy increased maternal depressive symptoms through increased internet use, but decreased maternal depressive symptoms through enhanced family support. The findings suggest that the psychological consequence of the lockdown policy may vary across different populations, and warrant the need to take into consideration the features of subgroups.

Background: Measles outbreaks have threatened the global elimination and eradication of measles in recent years. Measles virus (MeV)-specific antibodies are successful in clearing MeV infection. Follicular helper T (Tfh) cells play a crucial role in promoting antibody production. This study investigated the potential role of Tfh cells in peripheral blood mononuclear cells (PBMCs) from children with acute MeV infection., Results: The frequencies of CXCR5 + CD4 + Tfh, ICOS high Tfh, and PD-1 high Tfh cells in PBMCs and levels of IL-6 and IL-21 in plasma were significantly elevated in patients with acute MeV infection. Moreover, a positive correlation was discovered among the frequency of ICOS high Tfh cells, plasma levels of IL-21 and optical density (OD) values of MeV-specific IgM antibodies in the patients with acute MeV infection. However, elevated plasma MeV-specific NAb titres were not associated with the frequency of Tfh, ICOS high Tfh, or PD-1 high Tfh cells in the patients with acute MeV infection., Conclusion: These results suggest that an elevated Tfh cell frequency and associated molecules possibly play a key role in children with acute MeV infection, which contributes to the prevention and treatment of MeV infection in children.

Background: Primiparous mothers who lack of experience and knowledge of child caring, are usually overwhelmed by multifarious stressors and challenges. Although professional support is needed for primiparas, there is a gap between the necessary high-quality services and the currently provided poor services. This study aimed to explore Chinese primiparous mothers' views on professional services, identify barriers to utilizing professional support, and further understand mothers' expectations of and preferences for the delivery of professional services., Method: A descriptive phenomenological study design was utilized in this study, and semi-structured interviews were conducted with 28 primiparous mothers who had given birth in the first year period before the interview and were selected from two community health centres in Xi'an city, Shaanxi Province, Northwest China. Each conversational interview lasted between 20 and 86 min. Colaizzi's seven-step phenomenological approach was used to analyse the data., Results: Three major themes were identified: (a) dissatisfaction with current professional services for postpartum mothers, (b) likelihood of health care professional help-seeking behaviour, (c) highlighting the demands for new health care services. The related seven sub-themes included being disappointed with current hospital services; distrusting services provided by community health centres, private institutes and commercial online platforms; preferring not seeking help from professionals as their first choice; hesitating to express their inner discourse to professionals; following confinement requirement and family burden prevents mothers from seeking professional help; experiencing urgent needs for new baby-care-related services; and determining the importance of mothers' needs. The necessity of professional support in the first month after childbirth was strongly emphasized by the participants. Online professional guidance and support were perceived as the best way to receive services in this study., Conclusion: The results of this descriptive phenomenological study suggested that the current maternal and child health care services were insufficient and could not meet primiparous mothers' need. The results also indicated that identifying barriers and providing services focused on mothers' needs may be an effective strategy to enhance primiparous mothers' well-being, and further suggested that feasibility, convenience, and the cultural adaptability of health care services should be considered during the delivery of postpartum interventions.

Background: Although body image (BI) disturbance is a common problem that often contributes to poor health-related quality of life (HRQoL) among women with breast cancer following surgery, the mediating role of BI (as a self-perceptive factor) in the relationship between needs and HRQoL after controlling for socio-demographic factors remains unclear. The purpose of this study was to identify the mediating role of BI between post-surgery needs and HRQoL after controlling for socio-demographic factors among women with breast cancer., Methods: In this cross-sectional study, the primary outcome was HRQoL (as measured with the 36-item Short-Form Health Survey version 2 [SF-36v2] and Functional Assessment of Cancer Therapy-Breast version 4.0 [FACT-Bv4.0]). The secondary outcomes included needs (measured in terms of needs importance [NI] and needs satisfaction [NS]) and BI. Structural equation modeling was used to identify the mediating role of BI between needs and HRQoL while considering socio-demographics., Results: The 406 eligible patients reported poor HRQoL, and approximately half reported important unmet needs and poor BI. NI, NS, and socio-demographics had differing direct effects on BI and HRQoL, and contrasting indirect effects on HRQoL via BI. NI, NS, surgery type, presence of chronic disease, and BI explained 4% of the variance in the SF-36v2 physical component summary score; NI, NS, surgery type, residence, and BI explained 20% of the variance in the mental component summary score; and NI, NS, marital status, employment status, radiotherapy, and BI explained 33% of the variance in the FACT-Bv4.0 total score., Conclusions: After surgery, women with breast cancer have poor HRQoL and BI, and important unmet needs. BI mediates the relationship between needs and HRQoL after controlling for socio-demographics. The present findings provide information for developing comprehensive BI-based needs interventions and preparing targeted health-management programs for patients with breast cancer.

Background: Osteoporotic vertebral compression fractures (OVCF) is a common and often debilitating complication of osteoporosis, leading to significant morbidity and increased mortality. Percutaneous vertebroplasty (PVP) and Percutaneous kyphoplasty (PKP) are recommendable surgical treatments for OVCF., Objective: To evaluate PVP/PKP utilisation and their related direct medical costs for OVCF treatment in China from the payer perspective., Methods: A population-based medical claims database of a metropolitan city in China was analysed from the payer perspective, which included all inpatient claims from 01/01/2015 to 31/12/2017. All vertebral fractures patients that met the eligibility criteria (aged ≥50 years old, having vertebral fracture diagnosis, without unrelated diseases diagnoses such as tumour and scoliosis, received PVP/PKP) were deemed as OVCF patients. Baseline characteristics, surgery rate, length of stay in hospital, time to re-surgery, and costs (including costs per hospitalisation and annual costs) were described. Survival analysis function was used to estimate the re-surgery rate., Results: Of the 50,686 patients with OVCF identified, 14,527 (28.66%) received a total number of 15,599 records of PVP/PKP surgeries from 2015 to 2017. Mean age was 75 at the first surgery captured in the database analysis period; females accounted for 79.54% of all cases. The median length of surgery stay was 9 days. Cumulative re-surgery rates were 1.22% in 30 days, 2.58% in 90 days, 3.61% in 183 days, 5.42% in 1 year, and 7.95% in 2 years. There was no significant difference in re-surgery rate between PVP and PKP (p = 0.3897). The median time to the re-surgery was 139 days. Mean costs per PVP/PKP-related hospitalisation were 35,906 CNY/5122 USD (34,195 CNY/4878USD for PVP, 44,414 CNY/6336 USD for PKP, p < 0.01). The overall costs of hospitalisation averaged 186.61 million CNY (26.62 million USD) per year in this metropolitan city., Conclusion: From 2015 to 2017, nearly one-third of OVCF inpatients received PVP/PKP and the re-surgery rate was 7.95%. PVP/PKP procedures for OVCF place a high economic burden for both the healthcare system and patients. Early detection and treatment of patients with osteoporosis are critical in China.

Background: The prevalence of type 2 diabetes has grown significantly in China. However, little is known about the survival outcome of people with type 2 diabetes and diabetic kidney disease (DKD). The purpose of this study is to examine the survival of this population and the risk factors for mortality in one suburb cohort of Beijing, China., Methods: Four hundred and forty-five people with DKD (48.8% male, age at onset of diabetes 48.8 ± 11.0 years, age at enrollment 57.5 ± 11.6 years) were enrolled in one suburb of Beijing, China between January 1st, 2003 and December 31st, 2015. Mortality ascertainment was censored by December 31st, 2015. Survival analysis was performed by Kaplan-Meier analysis, and Cox proportional hazards regression models were served for risk factor analysis of mortality. The Chiang method was used to estimate life expectancy by age., Results: A total of 78 deaths were identified during the 3232 person-years of follow-up. Multivariate Cox regression analysis showed significantly higher risks of mortality with respect to older age, higher systolic blood pressure (SBP), lower body mass index (BMI) and lower estimated glomerular filtration rate (eGFR). The life expectancy at age of 50 was estimated to be 12.3 (95%, CI: 9.0-16.1) years. Circulatory disease was the leading cause of death in this population (accounting for 43.6% of all deaths), followed by diabetic complications (33.3%) and respiratory disease (6.4%)., Conclusions: Data from one Chinese cohort from 2003 through 2015 showed that people with DKD faced higher risk of death and shorter life expectancy. Factors significantly increasing risk of death included older age, higher SBP, lower BMI and lower eGFR. There is an urgent need to early detection, closely monitoring and effective intervention on DKD.

Background: An increasing number of extremely preterm (EP) infants have survived worldwide. However, few data have been reported from China. This study was designed to investigate the short-term outcomes of EP infants at discharge in Guangdong province., Methods: A total of 2051 EP infants discharged from 26 neonatal intensive care units during 2008-2017 were enrolled. The data from 2008 to 2012 were collected retrospectively, and from 2013 to 2017 were collected prospectively. Their hospitalization records were reviewed., Results: During 2008-2017, the mean gestational age (GA) was 26.68 ± 1.00 weeks and the mean birth weight (BW) was 935 ± 179 g. The overall survival rate at discharge was 52.5%. There were 321 infants (15.7%) died despite active treatment, and 654 infants (31.9%) died after medical care withdrawal. The survival rates increased with advancing GA and BW (p < 0.001). The annual survival rate improved from 36.2% in 2008 to 59.3% in 2017 (p < 0.001). EP infants discharged from hospitals in Guangzhou and Shenzhen cities had a higher survival rate than in others (p < 0.001). The survival rate of EP infants discharged from general hospitals was lower than in specialist hospitals (p < 0.001). The major complications were neonatal respiratory distress syndrome, 88.0% (1804 of 2051), bronchopulmonary dysplasia, 32.3% (374 of 1158), retinopathy of prematurity (any grade), 45.1% (504 of 1117), necrotizing enterocolitis (any stage), 10.1% (160 of 1588), intraventricular hemorrhages (any grade), 37.4% (535 of 1431), and blood culture-positive nosocomial sepsis, 15.7% (250 of 1588). The multivariate logistic regression analysis indicated that improved survival of EP infants was associated with discharged from specialist hospitals, hospitals located in high-level economic development region, increasing gestational age, increasing birth weight, antenatal steroids use and a history of premature rupture of membranes. However, twins or multiple births, Apgar ≤7 at 5 min, cervical incompetence, and decision to withdraw care were associated with decreased survival., Conclusions: Our study revealed the short-term outcomes of EP infants at discharge in China. The overall survival rate was lower than the developed countries, and medical care withdrawal was a serious problem. Nonetheless, improvements in care and outcomes have been made annually.

Background: PVT1 has emerged as an oncogene in many tumor types. However, its role in Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) is unknown. The aim of this study was to assess the role of PVT1 in BE/EAC progression and uncover its therapeutic value against EAC., Methods: PVT1 expression was assessed by qPCR in normal, BE, and EAC tissues and statistical analysis was performed to determine the association of PVT1 expression and EAC (stage, metastases, and survival). PVT1 antisense oligonucleotides (ASOs) were tested for their antitumor activity in vitro and in vivo., Results: PVT1 expression was up-regulated in EACs compared with paired BEs, and normal esophageal tissues. High expression of PVT1 was associated with poor differentiation, lymph node metastases, and shorter survival. Effective knockdown of PVT1 in EAC cells using PVT1 ASOs resulted in decreased cell proliferation, invasion, colony formation, tumor sphere formation, and reduced proportion of ALDH1A1 + cells. Mechanistically, we discovered mutual regulation of PVT1 and YAP1 in EAC cells. Inhibition of PVT1 by PVT1 ASOs suppressed YAP1 expression through increased phosphor-LATS1and phosphor-YAP1 while knockout of YAP1 in EAC cells significantly suppressed PVT1 levels indicating a positive regulation of PVT1 by YAP1. Most importantly, we found that targeting both PVT1 and YAP1 using their specific ASOs led to better antitumor activity in vitro and in vivo., Conclusions: Our results provide strong evidence that PVT1 confers an aggressive phenotype to EAC and is a poor prognosticator. Combined targeting of PVT1 and YAP1 provided the highest therapeutic index and represents a novel therapeutic strategy.

Background: Portal vein tumor thrombosis (PVTT) in hepatocellular carcinoma (HCC) is a sign of advanced stage disease, which is associated with poor prognosis. Liver resection (LR) may provide better prognosis in selected patients. In the present study, we aimed to assess information from HCC patients with PVTT who died within 3 months or 2 years after LR in order to identify preoperative factors correlated to short-term or long-term survival, by which inappropriate selection of patients for LR might be avoided in the future., Methods: A retrospective cohort study consisting of 487 consecutive cases of HCC patients with PVTT was performed from 2008 to 2010 at Eastern Hepatobiliary Surgery Hospital. Medical records, including laboratory values, imaging results and treatment information, were obtained from participants. Study endpoints were survival at 3 months and 2 years post-hepatectomy. Logistic regression analysis was utilized to determine the significant pre-operative factors influencing short-term or long-term survival., Results: In multivariable analysis, α-fetoprotein, total bilirubin and radiologic ascites were significantly associated with short-term survival, while α-fetoprotein level, clinical significant portal hypertension, extent of PVTT and tumor differentiation were factors significantly associated with long-term survival., Conclusions: The independent risk factors of poor short-term survival were the liver function-associated, such as factors radiologic ascites and total bilirubin, while tumor differentiation indicating the tumor biology was associated with longer-term survival. In addition, α-fetoprotein was a risk factor associated with both short-term and longer-term survivals.

Background: Body image is a complex post-treatment concern among female patients with breast cancer, and various tools have been developed and applied to measure this multifaceted issue. However, these available tools were developed in other countries and only a few have been modified into Chinese versions. Furthermore, body-image evaluation instruments that are specific to Chinese mainland female patients with breast cancer have not been devised yet. Therefore, we developed the Body Image Self-rating Questionnaire for Breast Cancer for Chinese mainland female patients with breast cancer., Methods: We performed two rounds of the Delphi technique and a cross-sectional pilot survey. Items were selected using a Likert scale (1-5) to determine ratings of importance (i.e., the significance of the item from experts' perspective; coefficients of variation ≤0.25), internal consistency reliability (Cronbach's α ≥ 0.70), convergent validity (hypothesized item-subscale correlations ≥0.40), and discriminant validity (stronger correlations of the item with the hypothesized subscale than for other subscales). All decisions on items were made based on statistical analysis results, experts' recommendations, and in-depth discussion among researchers., Results: Twenty-five eligible experts completed the two Delphi rounds (mean age: 42.20 ± 8.90 years). Over half the experts were professors (56%, n = 14) or worked as clinical staff (68%, n = 17). Twenty (mean age = 49.55 ± 10.01 years) and 50 patients (mean age = 48.44 ± 9.98 years) completed the first- and second-round survey, respectively. Over half the patients had a tertiary education level, were married, and were employed. Regarding the revised questionnaire (comprising 33 items across seven subscales), the expert panelists' ratings of each item met the criteria (Kendall's W = 0.238, p < .001). Five subscales had a Cronbach's α value over 0.60 (range: 0.62-0.69) and two subscales were over 0.80 (range: 0.84-0.88). All items satisfied the criteria for convergent and discriminant validity., Conclusions: The findings of this study provide evidence of a suitable tool for body image evaluation among Chinese mainland female patients with breast cancer. Studies with larger sample sizes should be conducted to validate this questionnaire in this patient population.

Background: Breast cancer and its treatment-related adverse effects are harmful to physical, psychological, and social functioning, leading to health-related quality of life (HRQoL) impairment in patients. Many programs have been used with this population for HRQoL improvement; however, few studies have considered the physical, psychological, and social health domains comprehensively, and few have constructed multimodal standard nursing interventions based on specific theories. The purpose of this trial is to examine the effect of a health belief model (HBM)-based multimodal standard nursing program (MSNP) on HRQoL in female patients with breast cancer., Methods: This is a two-arm single-blind cluster randomized controlled trial (cRCT) in clinical settings. Twelve tertiary hospitals will be randomly selected from the 24 tertiary hospitals in Xi'an, China, and allocated to the intervention arm and control arm using a computer-generated random numbers table. Inpatient female patients with breast cancer from each hospital will receive either MSNP plus routine nursing care immediately after recruitment (intervention arm), or only routine nursing care (control arm). The intervention will be conducted by trained nurses for 12 months. All recruited female patients with breast cancer, participating clinical staff, and trained data collectors from the 12 hospitals will be blind with respect to group allocation. Patients of the control arm will not be offered any information about the MSNP during the study period to prevent bias. The primary outcome is HRQoL measured through the Functional Assessment of Cancer Therapy-Breast version 4.0 at 12 months. Secondary outcomes include pain, fatigue, sleep, breast cancer-related lymphedema, and upper limb function, which are evaluated by a visual analogue scale, the circumference method, and the Constant-Murley Score., Discussion: This trial will provide important evidence on the effectiveness of multimodal nursing interventions delivered by nurses in clinical settings. Study findings will inform strategies for scaling up comprehensive standard intervention programs on health management in the population of female patients with breast cancer., Trial Registration: Chictr.org.cn ChiCTR-IOR-16008253 (April 9, 2016).

Background: A disintegrin and metalloprotease 8 (ADAM8) has been reported to be associated with various malignancies. However, no studies have examined ADAM8 association in colorectal cancer (CRC). The aim of this study was to investigate the expression and function of ADAM8 in CRC., Methods: Expression level of ADAM8 in CRC was evaluated by quantitative RT-PCR, western blot and immunohistochemical staining analysis. The role of ADAM8 in colorectal carcinogenesis was evaluated by in vitro assays. The correlations between ADAM8 status and clinicopathological features including survival were analyzed., Results: ADAM8 was highly expressed in CRC tissues compared with adjacent normal tissues. Knockdown of ADAM8 in two CRC cell lines resulted in reduced cellular growth and proliferation, and increased apoptosis. Immunohistochemistry analysis showed no significant correlations of ADAM8 protein expression with clinicopathologic features. Survival analysis indicated that patients with ADAM8-positive tumors had worse 5-year overall survival (OS, p = 0.037) and 5-year disease free survival (DFS, p = 0.014) compared with those with ADAM8-negative tumors. Multivariate analysis indicated ADAM8 expression was an independent prognostic factor for both OS and DFS (both p< 0.001). Subgroup analysis showed that 5-year OS of colon cancer, T3-T4 stage and N0 stage was worse for patients with ADAM8-positive tumors than those with ADAM8-negative tumors (p < 0.05). The 5-year DFS in colon cancer, T3-T4 stage, N0 stage, TNM stage II, adenocarcinoma, moderate differentiation and male patient subgroups was also worse for patients with ADAM8-positive tumors than those with ADAM8-negative tumors (p < 0.05)., Conclusions: Our results show that ADAM8 is overexpressed in CRC, promotes cell growth and correlates with worse OS and DFS, and thus could serve as a biomarker for individual CRC patient therapy.

Background: Enhancer of zeste homolog 2 (EZH2), a member of the polycomb group proteins, has been shown to promote cancer progression and breast cancer stem cell (CSC) expansion. Breast CSCs are associated with resistance to radiation in inflammatory breast cancer (IBC), a rare but aggressive variant of breast cancer. In this retrospective study, we examined the clinical role of EZH2 in locoregional recurrence (LRR) of IBC patients treated with radiation., Patients and Methods: 62 IBC patients who received radiation (7 pre-operative, 55 post-operative) and had adequate follow up to assess LRR were the subject of this study. Positive EZH2 status was defined as nuclear immunohistochemical staining in at least 10% of invasive cancer cells. Association of EZH2 expression with clinicopathologic features were evaluated using the Chi-square statistic and actuarial LRR free survival (LRFS) was determined using the Kaplan-Meier method., Results: The median follow-up for this cohort was 33.7 months, and the 5-year overall LRFS rate was 69%. Of the 62 patients, 16 (25.8%) had LRR, and 15 out of 16 LRR occurred in EZH2 expressing cases. Univariate analysis indicated that patients who had EZH2-positive IBC had a significantly lower 5-year locoregional free survival (LRFS) rate than patients who had EZH2-negative IBC (93.3% vs. 59.1%; P = 0.01). Positive EZH2 expression was associated significantly with negative ER status (97.1% in ER- vs 48.1% in ER+; P < 0.0001) and triple-negative receptor status (P = 0.0001) and all triple-negative tumors were EZH2-positive. In multivariate analysis, only triple negative status remained an independent predictor of worse LRFS (hazard ratio 5.64, 95% CI 2.19 - 14.49, P < 0.0001)., Conclusions: EZH2 correlates with locoregional recurrence in IBC patients who received radiation treatment. EZH2 expression status may be used in addition to receptor status to identify a subset of patients with IBC who recur locally in spite of radiation and may benefit from enrollment in clinical trials testing radiosensitizers.

Background: Gastritis cystica profunda (GCP) is an uncommon disease characterized by multiple cystic gastric glands within the submucosa of the stomach., Case Description: Here, we present a case of a 63-year-old man with intermittent epigastric discomfort in whom gastroscopy revealed multiple irregular elevated nodular lesions with smooth surfaces at the anterior of the antrum. Surgical resection of the nodular lesions was performed, and the diagnosis of gastritis cystica profunda (GCP) was confirmed by histological examination. Another elevated nodular lesion approximately 10 mm in diameter with an ulcer was found on the gastric side of the remnant stomach near the resection side from 6 to 24 months after the surgical resection. Endoscopic ultrasonography (EUS) and repeated biopsies of the new elevated lesion were performed. Homogeneous, anechoic masses originating from the submucosa without gastric adenocarcinoma in histological examination showed GCP recurrence may occur., Conclusions: We report a case of GCP recurrence within 6 months after surgical resection. GCP should be considered in the differential diagnosis of elevated lesions in the stomach.

Background: Human papillomavirus (HPV) infection is a major risk factor for the development of nearly all cases of cervical cancer worldwide. The presence of HPV DNA in cases of esophageal squamous-cell carcinoma (ESCC) has been reported repeatedly from Shantou, China, and other regions with a high incidence of esophageal carcinoma (EC). However, unlike in cervical squamous-cell carcinoma (CSCC), in ESCC, the characteristics of HPV are unclear. Thus, the role of high-risk HPV types in the carcinogenesis of ESCC remains uncertain., Methods: Seventy cases of ESCC with 60 controls and 39 cases of CSCC with 54 controls collected from patients in Shantou region in China were compared for the distributions of HPV-16, -18 and -58; viral load; and viral integration using real-time PCR assay and HPV-16 expression using immunostaining., Results: The detection rates and viral loads of HR-HPV infection were significantly lower in ESCC than in CSCC (50.0% vs. 79.48%, P = 0.005; 2.55 ± 3.19 vs. 361.29 ± 441.75, P = 0.002, respectively). The combined integration level of HPV-16, -18 and -58 was slightly lower in ESCC than in CSCC (P = 0.022). HPV-16 expression was detected in 59.26% of ESCC tissue and significantly associated with tumour grade (P = 0.027)., Conclusions: High levels of HR-HPV expression and integration may be an indicator of the risk of ESCC, at least for patients in the Shantou region of China. However, a relatively low HPV copy number and infection rate in ESCC is unlikely to play an essential a role in the carcinogenesis of ESCC as in cervical cancer. Factors other than HR-HPV infection may contribute to the carcinogenesis of ESCC.