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The immune profile in primary resected hypopharyngeal squamous cell carcinoma (HPSCC) and its prognostic value remain to be defined.We enrolled 100 patients with HPSCC underwent primary surgical resection at our department. HPSCC samples were examined using immunohistochemistry for the expressions of CD8, Foxp3, CD163, CD66B, programmed death ligand-1 (PD-L1), and interferon (IFN)-γ. The immune pattern of the tumor microenvironment (TME) was discriminated into inflamed and non-inflamed tumors based on the presence or absence of parenchymal CD8We found that 74% of HPSCC cases in our cohort were characterized by an immune-inflamed TME. Immune-inflamed patterns demonstrated an inferior survival with a significantly increased density of CD163The immune-inflamed pattern is the predominant preexisting immune phenotype in HPSCC and demonstrates immunosuppressive immune cell recruitment.

Background Bladder cancer is classified into high and low grades with different clinical treatments and prognoses. Thus, accurate preoperative evaluation of the histologic grade through imaging techniques is essential. Purpose To investigate the potential of amide proton transfer-weighted (APTw) MRI in evaluating the grade of bladder cancer and to evaluate whether APTw MRI can add value to diffusion-weighted imaging (DWI) at MRI. Materials and Methods In this single-center prospective study, participants with pathologic analysis-confirmed bladder cancer with no previous treatment, lesions larger than 10 mm, and adequate MRI quality were enrolled from July 2020 to September 2021 in a university teaching hospital. All participants underwent preoperative multiparametric MRI, including APTw MRI and DWI. The mean APTw and apparent diffusion coefficient (ADC) values of the primary tumor were measured independently by two radiologists. Receiver operating characteristic curves were generated to evaluate the diagnostic performance of these quantitative parameters. Results In total, 83 participants (mean age, 64 years ± 13 [SD]; 72 men) were evaluated: 51 with high-grade and 32 with low-grade bladder cancer. High-grade bladder cancer showed higher APTw values (6% [IQR, 4%-12%] vs 2% [IQR, 1%-3%]

The multicenter study aimed to explore the relationship between the growth pattern of liver metastases on preoperative MRI and early recurrence in patients with colorectal cancer liver metastases (CRCLM) after surgery.A total of 348 CRCLM patients from 3 independent centers were enrolled, including 130 patients with 339 liver metastases in the primary cohort and 218 patients in validation cohorts. Referring to the gross classification of hepatocellular carcinoma (HCC), the growth pattern of each liver metastasis on MRI was classified into four types: rough, smooth, focal extranodular protuberant (FEP), and nodular confluent (NC). Disease-free survival (DFS) curve was constructed using the Kaplan-Meier method.In primary cohort, 42 (12.4%) of the 339 liver metastases were rough type, 237 (69.9%) were smooth type, 29 (8.6%) were FEP type, and 31 (9.1%) were NC type. Those patients with FEP- and/or NC-type liver metastases had shorter DFS than those without such metastases (p0.05). However, there were no significant differences in DFS between patients with rough- and smooth-type liver metastases and those without such metastases. The patients with FEP- and/or NC-type liver metastases also had shorter DFS than those without such metastases in two external validation cohorts. In addition, 40.5% of high-risk-type (FEP and NC) liver metastases converted to low-risk types (rough and smooth) after neoadjuvant chemotherapy.The FEP- and NC-type liver metastases were associated with early recurrence, which may facilitate the clinical treatment of CRCLM patients.• In the primary cohort, patients with FEP- and NC-type metastases had shorter disease-free survival (DFS) and a higher intrahepatic recurrence rate than patients without such metastases in the liver. • In the primary cohort, there were no significant differences in DFS or intrahepatic recurrence rate between patients with rough- and smooth-type metastases and those without such metastases in the liver. • High-risk patients had shorter DFS and a higher intrahepatic recurrence rate than low-risk patients in primary and external validation cohorts.

Attention-deficit/hyperactivity disorder (ADHD) is a prevalent disorder of neurodevelopment in children. The diagnosis of ADHD mainly relies on the symptoms and some may be misdiagnosed due to age-based variation in behaviours. This study aimed to explore biomarkers that are greatly needed for the accurate diagnosis of ADHD.Seven hundred and forty-two samples were retrospectively investigated in three independent cohorts, screening, training, and validation, for circulation microRNA measurement using microarray, Taqman polymerase chain reaction, and regression analysis.A panel of five miRNAs (miR-4516, miR-6090, miR-4763-3p, miR-4281, and miR-4466) were identified as ADHD independent risk factors that provided a high diagnostic accuracy and specificity of ADHD (AUC = 0.940 and 0.927 in the training and validation datasets, respectively). This panel of miRNAs differentiated ADHD well from control groups. After clinical improvement by treatment, the panel of miRNAs in patients and AUC changed significantly and were close to those in healthy controls. Importantly, the targets of the miRNAs identified were commonly enriched in receptor signalling pathways, ion channels, and synapse structures.Our study identified a useful panel of miRNAs that have considerable clinical value in evaluating ADHD and provide important evidence for aberrant epigenetic regulation in ADHD.

ObjectivesThis study aimed to evaluate the willingness of patients with HIV/AIDS in Henan province to accept mobile information follow-up, to find the key factors that affect behavioral willingness to accept such follow-up, to explore the internal mechanism of the mobile service, and to provide a theoretical rationale for the further promotion of mobile follow-up.MethodsThis study used the technology acceptance model (TAM) as its main theoretical tool, which adopted a stratified random sampling method, and investigated 284 patients with HIV/AIDS in area six of Sanmenxia City. An on-site questionnaire survey method was adopted for this study. Confirmatory factor analysis was used for structural validity, with Cronbach's coefficient used for reliability. Data analysis mainly used SPSS23.0 and AMOS23.0 software.ResultsThe acceptance rate of the HIV/AIDS mobile follow-up service was 68.53%. In the study, product factors (PFs) were considered important in the indirect path of the TAM. Our TAM model suggested that high perceived usefulness (PU), perceived ease of use (PEU), and perceived innovativeness (PI) of the service were significant in improving mobile health (mHealth) acceptance among patients with HIV/AIDS in China. Subjective norms (SNs) also contributed to popularizing the service in the HIV/AIDS community. The model fitting was considered acceptable (root mean square error of approximation, RMSEA = 0.074; goodness of fit index, GFI = 0.905; comparative fit index, CFI = 0.963, and Tucker-Lewis index, TLI = 0.593).ConclusionPFs and SNs exerted an important influence on the behavioral intentions of the patients with HIV/AIDS who accepted mobile health. PU was another important factor affecting behavioral intention. The practicality of mHealth services was crucial. Convenience and the innovativeness of the experience with the service will be conducive to the promotion and use of mHealth follow-up services.

Background Posterior hypopharyngeal carcinoma indicates a poor prognosis. Previous treatments predicted negative influence to the pronunciation and swallowing function. The present study focuses on improving survival rate while improving quality of life. Aim To investigate on the surgical techniques of the preservation of laryngeal function of posterior hypopharyngeal carcinoma. Methods Eighteen patients with posterior hypopharyngeal carcinoma of T2-T3 were studied. All primary lesions were removed and the defects were repaired with the radial forearm free flap (RFFF). Results The 3-year overall survival rate was 51.9%. All patients could maintain daily caloric intake by feeding orally, and remove the gastric tube 28-61 days after operation. Assessed swallowing function by Fiberoptic endoscopic evaluations of swallowing. When eating solid food, 66.67% patients had food residue; no food entered airway, and all patients had Penetration-Aspiration Scale of level 1. As for liquid, 11.11% patients had level 5, 16.67% level 4, 27.78% level 2 and 44.44% level 1. Conclusions By preserving the integrity of larynx and superior laryngeal nerve with repairing the defects of posterior wall of hypopharynx with RFFF, patients with T2 and T3 stage posterior hypopharyngeal carcinoma could live a better quality of life.

The advantages of urgent-start peritoneal dialysis (PD) vis-a-vis urgent-start hemodialysis (HD) are not clear. We performed a systematic review and meta-analysis of studies comparing the two modalities. Databases of PubMed, Embase, Ovoid, and Google Scholar were searched up to November 1, 2020. The primary outcome was mortality, and secondary outcomes were dialysis-related infectious complications and mechanical complications. Risk ratios (RRs) were calculated for all outcomes. Seven studies were included. The pooled analysis revealed a statistically significant reduced risk of all-cause mortality in patients undergoing urgent-start PD as compared to urgent-start HD (RR: 0.61, 95% confidence interval [CI] [0.40, 0.94], I2 = 56.34%). A meta-analysis of dialysis-related infectious complications indicated no statistically significant difference between the two modalities (RR: 0.66, 95% CI [0.29, 1.50], I2 = 69.62%). Our analysis revealed a statistically significant reduced risk of mechanical complications in patients undergoing urgent-start PD (RR: 0.54, 95% CI [0.40, 0.73], I2 = 0%). To conclude, unadjusted data from observational studies are indicative of lower mortality and lower risk of mechanical complications with urgent-start PD versus urgent-start HD. The risk of infectious complications was not different between the two groups. Further studies with a larger sample size using propensity-matched cohorts are needed to strengthen current evidence.

Background The histological grade of bladder cancer (BCa) is an important factor associated with the treatment and prognosis. However, accurate determination of the preoperative histological grade of BCa remains a challenge. Purpose To investigate the diagnostic potential of synthetic MRI (SyMRI) in evaluating the histological grade of BCa. Study type Prospective. Subjects Sixty patients (48 men and 12 women; mean age, 65 ± 11 years) with pathologically confirmed BCa (33 with high-grade BCa and 27 with low-grade BCa) were enrolled. Field strength/sequence Diffusion-weighted imaging (DWI) acquired by a single-shot echo-planar sequence and SyMRI acquired by a multidynamic multiecho (MDME) sequence at 3.0 T. Assessment Preoperative quantitative longitudinal relaxation time (T1 ), transverse relaxation time (T2 ), proton density (PD), and apparent diffusion coefficient (ADC) values of BCa were independently measured by two radiologists. Statistical tests Interclass correlation coefficient (ICC), independent sample t-test, Mann-Whitney U test, Delong test, and receiver operating characteristic curve (ROC) analysis were used. Results Significant differences were found in the mean of all the T1 , T2 , PD, and ADC values between high- and low-grade BCa. The best diagnostic performance was found for the mean ADC value with an area under the ROC curve (AUC) of 0.869, while the AUC values of the mean PD, T1 , and T2 values were 0.755, 0.740, and 0.723, respectively. Data conclusion SyMRI may be a potential noninvasive technique for evaluating the histological grade of BCa. However, the overall diagnostic performance of SyMRI-derived parameters was inferior to the ADC value. Levels of evidence 2. Technical efficacy stage 2.

Background Kangaroo mother care (KMC) is an evidence-based intervention that reduces morbidity and mortality in preterm infants. However, it has not yet been fully integrated into health systems around the world. The aim of this study is to provide a cogent summary of the evidence base of the key barriers and facilitators to implementing KMC. Methods An umbrella review of existing reviews on KMC was adopted to identify systematic and scoping reviews that analysed data from primary studies. Electronic English databases, including PubMed, Embase, CINAHL and Cochrane Library, and three Chinese databases were searched from inception to 1 July 2022. Studies were included if they performed a review of barriers and facilitators to KMC. Quality assessment of the retrieved reviews was performed by at least two reviewers independently using the Joanna Briggs Institute (JBI) critical appraisal checklist and risk of bias was assessed with the Risk of Bias Assessment Tool for Systematic Reviews (ROBIS) tool. This umbrella review protocol was documented in the PROSPERO registry (CRD42022327994). Results We generated 531 studies, and after the removal of duplicates and ineligible studies, six eligible reviews were included in the analysis. The five themes identified were environmental factors, professional factors, parent/family factors, access factors, and cultural factors, and the factors under each theme were divided into barriers or facilitators depending on the specific features of a given scenario. Conclusions Support from facility management and leadership and well-trained medical staff are of great significance to the successful integration of KMC into daily medical practice, while the parents of preterm infants and other family members should be educated and encouraged in KMC practice. Further research is needed to propose strategies and develop models for implementing KMC.

Obstructive sleep apnea (OSA) has a high incidence and is harmful to health. It is characterized by repeated collapse of the upper airway. However, the mechanism underlying upper airway collapse is unclear.Patients with OSA and chronic tonsillitis were studied. Pathological changes in palatopharyngeus muscle were detected. The expression of peroxisome proliferator-activated receptor-γ co-activator-1α (PGC-1α) and nuclear respiratory factor-1 (NRF-1) in muscles was detected by PCR and Western blotting. Immunofluorescence staining was used to detect the expression of type I and type II myofibril.The structure of the palatopharyngeus muscle was changed, and the expression of PGC-1α and NRF-1 was decreased in the OSA group compared with that in the control group. The expression of PGC-1α, NRF-1, and type I myofibril in C2C12 myoblasts was decreased by intermittent hypoxia exposure. The expression of type I myofibril was decreased when knocking down PGC-1α.OSA patients exhibited pathological damage in palatopharyngeus muscle. PGC-1α was involved in the fiber type conversion in palatopharyngeus muscle caused by intermittent hypoxia.

Background The Vesical Imaging Reporting and Data System (VI-RADS) based on multiparametric MRI scans standardizes preoperative bladder cancer staging. However, limitations have been reported for VI-RADS, particularly for ureteral orifice tumors. Purpose To investigate the diagnostic performance and interobserver agreement of VI-RADS in evaluating muscle invasion for bladder tumors located at the ureteral orifice. Materials and Methods In this retrospective study, patients with histopathologically confirmed bladder cancer occurring at the ureteral orifice from January 2012 to November 2021 were analyzed. Two blinded radiologists independently scored multiparametric MRI scans according to VI-RADS. Interobserver agreement of the VI-RADS scores was evaluated with weighted κ analysis. Receiver operating characteristic curve analysis was used to evaluate the diagnostic performance of the VI-RADS scores in the prediction of muscle invasion. Results A total of 78 patients (mean age, 67 years ± 7 [SD]; age range, 46-90 years; 67 men) were included in the final analysis: 25 with non-muscle-invasive bladder cancer and 53 with muscle-invasive bladder cancer (MIBCa). At consensus reading, one (1%) case was scored as VI-RADS 1, 27 cases (35%) were scored as VI-RADS 2, six (8%) were scored as VI-RADS 3, 10 (13%) were scored as VI-RADS 4, and 34 (44%) were scored as VI-RADS 5. On comparison of the VI-RADS score with histopathologic findings, it was confirmed that the presence of muscle invasion was 0% (zero of one) for VI-RADS 1, 15% (four of 27) for VI-RADS 2, 83% (five of six) for VI-RADS 3, 100% (10 of 10) for VI-RADS 4, and 100% (34 of 34) for VI-RADS 5. The area under the receiver operating characteristic curve of VI-RADS in the detection of MIBCa was 0.96 (95% CI: 0.92, 1.00). Conclusion The Vesical Imaging Reporting and Data System could be used to accurately predict muscle invasion for bladder tumors occurring at the ureteral orifice. © RSNA, 2022

Amphisomes are intermediate/hybrid organelles produced through the fusion of endosomes with autophagosomes within cells. Amphisome formation is an essential step during a sequential maturation process of autophagosomes before their ultimate fusion with lysosomes for cargo degradation. This process is highly regulated with multiple protein machineries, such as SNAREs, Rab GTPases, tethering complexes, and ESCRTs, are involved to facilitate autophagic flux to proceed. In neurons, autophagosomes are robustly generated in axonal terminals and then rapidly fuse with late endosomes to form amphisomes. This fusion event allows newly generated autophagosomes to gain retrograde transport motility and move toward the soma, where proteolytically active lysosomes are predominantly located. Amphisomes are not only the products of autophagosome maturation but also the intersection of the autophagy and endo-lysosomal pathways. Importantly, amphisomes can also participate in non-canonical functions, such as retrograde neurotrophic signaling or autophagy-based unconventional secretion by fusion with the plasma membrane. In this review, we provide an updated overview of the recent discoveries and advancements on the molecular and cellular mechanisms underlying amphisome biogenesis and the emerging roles of amphisomes. We discuss recent developments towards the understanding of amphisome regulation as well as the implications in the context of major neurodegenerative diseases, with a comparative focus on Alzheimer's disease and Parkinson's disease.

Introduction This study compared treatment persistence and adherence among psoriatic arthritis (PsA) patients in the US who initiated an interleukin-12/23 inhibitor (IL-12/23i) versus those who initiated tumor necrosis factor inhibitors (TNFis), targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs), or interleukin-17 inhibitors (IL-17is). Methods Adults diagnosed with PsA with ≥ 1 claim for a targeted immune modulator were selected from the IBM MarketScan® Commercial and Medicare Supplemental databases (October 1, 2013–October 31, 2018). The date of the first claim was the index date. Patients had continuous health plan enrollment for ≥ 12 months pre-index and ≥ 12-month post-index period. Pairwise propensity score matching with nearest-neighbor technique was performed. Persistence duration, discontinuation rate, and the proportion of days covered (PDC) were evaluated in biologic/tsDMARD naïve patients who initiated TNFis, IL-17is, tsDMARDs, or IL-12/23i (reference group). Results There were 238 matched patient pairs for TNFi versus IL-12/23i, 238 pairs for tsDMARD versus IL-12/23i, and 189 pairs for IL-17is versus IL-12/23i. Duration of persistence was longer for the IL-12/23i cohort than for the TNFi (269 vs. 215 days, p

Hypothyroidism is a systemic metabolic deficiency syndrome caused by a deficiency in thyroid hormone or a decrease in the action of thyroid hormones. It has a high incidence among women of child-bearing age, and pregnant women with hypothyroidism may have a higher risk of birth defects.To explore the specific biological mechanism affecting the occurrence of hypothyroidism.This study determined key molecules by comparing and analyzing the difference in methylation levels between pre-pregnancy women and normal controls using the Illumina Infinium MethylationEPIC BeadChip.3493 Differential methylation positions (DMPs) related genes and 47 differentially methylated regions (DMRs) related genes were found between the Hypothyroidism group and the control group. Among them, miR-21 has been found to be closely related to thyroid hormone regulation. The results of enrichment analysis showed that the DMPs or DMRs-related genes are both significantly enriched in human T-cell leukemia virus 1 infection, osteoclast differentiation and sphingolipid signaling pathway, which were also closely related to the occurrence and development of hypothyroidism. In addition, the combined analysis of CNVs and DMRs showed that significant differences occurred near the regions of 16 M bp in chromosome 1 between the two groups, and the genes involved in these regions included NDUFS2, FCER1G and SHC1.This work screened molecular markers and key signaling pathways that are involved in the development of hypothyroidism in pre-pregnancy women, which may provide new targets for the research and diagnosis of hypothyroidism in the future.

To evaluate the diagnostic accuracy of preoperative contrast-enhanced ultrasound (CEUS) to detect extracapsular extension (ECE) and identify the relationship between ECE and nodule enhancement patterns in patients with papillary thyroid cancer (PTC). Patients with suspected thyroid cancer underwent ultrasound (US) and CEUS examinations. The US and CEUS features of the PTC nodules and thyroid capsule were recorded and classified individually. The accuracy of US and CEUS in detecting ECE was compared individually, and its relationship with various tumour enhancement patterns was analysed. The presence or absence of ECE and cervical lymph node metastasis (LNM) was confirmed pathologically. The final dataset included 119 patients with 124 PTC nodules. Seventy-two (60.5%) of these patients with PTC had no ECE (including 38 patients with single capsule invasion), while the remaining 52 had ECE. A significant difference was found in nodules with non-capsule invasion, single capsule invasion, and ECE between the cervical LNM and non-LNM groups (p < 0.01). Receiver operating characteristic curve analysis demonstrated that area under the curve (AUC) of ECE for cervical LNM was higher than that of capsule invasion (71.9% vs. 49.6%). Moreover, the CEUS images acquired to detect ECE showed higher AUC values than those of US images (79.4% vs. 65.8%) (p = 0.02). Among the PTC nodules with differential enhancement, hyper-enhanced nodules had the highest incidence of capsule invasion (41.9%), while hypo-enhanced ones had a higher incidence of ECE (47.4%). Compared with conventional US, CEUS is a more valuable and non-invasive imaging modality to detect ECE. • Single capsular invasion was a poor predictor of cervical lymph node metastasis, while extracapsular extension assessments were clinically significant for predicting cervical lymph node metastasis. • CEUS is better than conventional US in detecting extracapsular extension in papillary thyroid carcinoma (AUC: 79.4% vs. 65.8%) (p = 0.02). • Among the thyroid papillary carcinoma nodules with differential enhancement, hyper-enhanced nodules had the highest incidence of single capsule invasion (41.9%), while hypo-enhanced ones had a higher incidence of ECE (47.4%).

To investigate the therapeutic mechanism of action of transplanted stem cells and develop exosome-based nanotherapeutics for ischemic stroke, we assessed the effect of exosomes (Exos) produced by human umbilical cord mesenchymal stem cells (hUMSCs) on microglia-mediated neuroinflammation after ischemic stroke. Our results found that injected hUMSC-Exos were able to access the site of ischemic damage and could be internalized by cells both in vivo and in vitro. In vitro, treatment with hUMSC-Exos attenuated microglia-mediated inflammation after oxygen-glucose deprivation (OGD). In vivo results demonstrated that treatment with hUMSC-Exos significantly reduced infarct volume, attenuated behavioral deficits, and ameliorated microglia activation, as measured three days post-transient brain ischemia. Furthermore, miR-146a-5p knockdown (miR-146a-5p k/d Exos) partially reversed the neuroprotective effect of hUMSC-Exos. Our mechanistic study demonstrated that miR-146a-5p in hUMSC-Exos reduces microglial-mediated neuroinflammatory response through IRAK1/TRAF6 pathway. We conclude that miR-146a-5p derived from hUMSC-Exos can attenuate microglia-mediated neuroinflammation and consequent neural deficits following ischemic stroke. These results elucidate a potential therapeutic mechanism of action of mesenchymal stem cells and provide evidence that hUMSC-Exos represent a potential cell-free therapeutic option for ischemic stroke.

RIOK2 is an atypical kinase implicated in multiple human cancers. Although recent studies establish the role of RIOK2 in ribosome maturation and cell cycle progression, its biological functions remain poorly elucidated, hindering the potential to explore RIOK2 as a therapeutic target. Here, we report the discovery of

PURPOSE Few studies have explored the biomarkers for predicting the heterogeneous outcomes of patients with advanced pancreatic adenocarcinoma showing stable disease (SD) on the initial postchemotherapy computed tomography. We aimed to devise a radiomics signature (RS) to predict these outcomes for further risk stratification. MATERIALS AND METHODS Patients with advanced pancreatic adenocarcinoma and SD after chemotherapy were included. Pancreatic lesions on initial postchemotherapy computed tomography images were evaluated by radiomics analysis for predicting early death (≤ 1 year). RS was then internally and externally tested. The progression-free survival and objective response rate were compared between the low-risk and high-risk group of patients classified following RS. RESULTS Approximately 62.7% of patients receiving chemotherapy showed SD at first response evaluation in the primary cohort, which were 59.6% and 57.9% in internal and external testing cohorts, respectively. The RS predicted 1-year overall survival well, with areas under the receiver operating characteristic curve of 0.91 in the training cohort, 0.90 in the validation cohort, 0.84 in the internal testing cohort, and 0.87 in the external testing cohort. The high-risk group had a shorter median progression-free survival (7.3 months v 9.0 months, P = .016, in the training cohort; 5.9 months v 9.2 months, P = .026, in the internal testing cohort) and a lower objective response rate (2.2% v 24.0% in the training cohort) than the low-risk group. In addition, RS was not related to the clinical characteristics and chemotherapy regimens. CONCLUSION RS independently predicts the outcomes of patients with SD after chemotherapy well and can help to improve treatment decisions by identifying patients for whom current treatment may not be suitable.

N6-Methyladenosine (m6A), one of the post-transcriptional modifications of RNA, is important in hepatocellular carcinoma (HCC). However, the mechanism of its regulation remains elusive. We here show that exposure of HCC cells to sulfatide significantly reduced the total mRNA m6A modification. Interestingly, METTL3 protein was robustly acetylated and the binding of METTL3 to MTF1 mRNA, METTL14 or WTAP was weakened in cells treated with sulfatide. Further investigation of the METTL3 complex revealed recruitment of the deacetylase scaffold SIN3B, but a diminished level of histone deacetylase HDAC2, which might enhance the acetylation of METTL3. The m6A abundance in MTF1 mRNA was markedly decreased in cells after sulfatide treatment. The expression of MTF1, a zinc-dependent transcription factor, was significantly strengthened with reduced m6A modification. Sulfatide prolonged the half-life of MTF1 mRNA, while the mutation (A to C) on 7 methylation sites in the 3'UTR of MTF1 mRNA enhanced MTF1 mRNA stability. 3-deaza-adenosine, an m6A methylation inhibitor, significantly reduced the m6A modification of MTF1 mRNA but extended its half-life time. Importantly, overexpression of MTF1 prompted HCC cell proliferation and was associated with poor prognosis. In conclusion, the METTL3-METTL14-WTAP complex was regulated by acetylation induced by sulfatide to control MTF1 m6A methylation and its mRNA transcription, which was important for the tumor growth and migration of HCC.

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is highly contagious and has resulted in a protracted pandemic. Infections caused by new coronavirus strains, primarily Delta and Omicron and currently highly prevalent globally. In response to the epidemic, countries, and cities implemented isolation and quarantine guidance, such as limiting social contact, which have affected the lifestyles and quality of life of the population. Parental feeding behaviors may vary as a result of factors such as prolonged home isolation of parents and children, lack of supplies during isolation, and stress. This study was designed to assess the available evidence and its implications for parental feeding practices in the context of COVID-19. We screened and reviewed research published in five electronic databases between 2020 and 2022, and eight studies met the selection criteria. Parents were observed to use a variety of feeding practices, including high levels of coercive control and reduction of rules and limits according to Vaughn’s food parenting constructs. The findings suggest that parental feeding practices are changing as a result of the pandemic and that more research is needed to further explore how to provide supportive feeding guidance to parents during emergencies in order to jointly promote child health.

To investigate the clinicopathological and molecular features of colorectal cancer (CRC) with synchronous adenoma and to describe features of synchronous adenomas in CRC patients.Single-centre retrospective cohort of 180 patients were included. The clinicopathological and endoscopic data were collected. The expression mismatch repair (MMR) proteins were detected by immunohistochemistry. The determination of microsatellite instability (MSI) was performed by multiple fluorescence PCR, and the mutations of genes were detected by real-time PCR.Among all cases, 49 were diagnosed as CRC with synchronous adenoma, and 131 were diagnosed as solitary CRC. Some of the differences between the groups are: higher incidence was found in male (71.4 vs. 52.6%,Gender, a habit of drinking and other neoplastic diseases are risk factors for the development of a synchronous adenoma. With a low rate of BRAF mutations, the responses to monoclonal antibody and prognosis of patients with synchronous adenomas may be better than that of solitary CRC.

Data on average iodine requirements for the Chinese population are limited following implementation of long-term universal salt iodisation. We explored the minimum iodine requirements of young adults in China using a balance experiment and the ‘iodine overflow’ hypothesis proposed by our team. Sixty healthy young adults were enrolled to consume a sequential experimental diet containing low, medium and high levels of iodine (about 20, 40 and 60 μg/d, respectively). Each dose was consumed for 4 d, and daily iodine intake, excretion and retention were assessed. All participants were in negative iodine balance throughout the study. Iodine intake, excretion and retention differed among the three iodine levels (P < 0·01 for all groups). The zero-iodine balance derived from a random effect model indicated a mean iodine intake of 102 μg/d, but poor correlation coefficients between observed and predicted iodine excretion (r 0·538 for μg/d data) and retention (r 0·304 for μg/d data). As iodine intake increased from medium to high, all of the increased iodine was excreted (‘overflow’) through urine and faeces by males, and 89·5 % was excreted by females. Although the high iodine level (63·4 μg/d) might be adequate in males, the corresponding level of 61·6 μg/d in females did not meet optimal requirements. Our findings indicate that a daily iodine intake of approximately half the current recommended nutrient intake (120 μg/d) may satisfy the minimum iodine requirements of young male adults in China, while a similar level is insufficient for females based on the ‘iodine overflow’ hypothesis.

The platysma skin flap was used for laryngeal reconstruction after vertical partial laryngectomy to improve the postoperative voice quality of patients with T2 and T3 glottic laryngeal carcinoma. Sixty-nine patients with unilateral T2 and T3 glottic laryngeal carcinoma were included. Forty-six patients received vertical partial laryngectomy, and a platysma skin flap was used for laryngeal reconstruction. The other 23 patients underwent transoral laser microsurgery. Subjective and objective examinations were performed to evaluate laryngeal morphology after the surgery. Acceptable voice quality was achieved for 46 patients who underwent vertical partial laryngectomy. Flap vibrational waves occurred in 19 cases (41.3%). The platysma skin flap is an ideal tissue for the reconstruction of articulation structure in open surgery of T2 and T3 unilateral glottic laryngeal carcinoma.

Undifferentiation is a key feature of nasopharyngeal carcinoma (NPC), which presents as a unique opportunity for intervention by differentiation therapy. In this study, we found that SOX1 inhibited proliferation, promoted differentiation, and induced senescence of NPC cells, which depended on its transcriptional function. RNA-Seq-profiling analysis showed that multiple undifferentiated markers of keratin family, including KRT5, KRT13, and KRT19, were reduced in SOX1 overexpressed NPC cells. Interestingly, gene ontology (GO) analysis revealed genes in SOX1 overexpressed cells were enriched in extracellular functions. The data of LC/MS untargeted metabolomics showed that the content of retinoids in SOX1 overexpressed cells and culture medium was both higher than that in the control group. Subsequently, we screened mRNA level of genes in retinoic acid (RA) signaling or metabolic pathway and found that the expression of UDP-glucuronosyltransferases was significantly decreased. Furtherly, UGT2B7 could rescue the differentiation induced by SOX1 overexpression. Inhibition of UGTs by demethylzeylasteral (T-96) could mimic SOX1 to promote the differentiation of NPC cells. Thus, we described a mechanism by which SOX1 regulated the differentiation of NPC cells by activating retinoid metabolic pathway, providing a potential target for differentiation therapy of NPC.

Objectives: To assess long-term (2-year) biologic treatment patterns of psoriatic arthritis (PsA) patients who initiated adalimumab, certolizumab pegol, etanercept, golimumab, or ustekinumab.Method...

Aim and Objective: Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a common chronic kidney disease that leads to End-Stage Renal Disease (ESRD). The key target of this therapy is to prevent the progression of kidney failure. Tolvaptan could slow kidney cyst growth and are proven highly effective. The aims of this analysis are to perform a systematic review, estimate and evaluate the efficacy and safety of tolvaptan in ADPKD patients. Materials and Methods: Randomized controlled trials of tolvaptan in ADPKD were identified in PubMed, Ovid, Web of Science and the Cochrane Library electronic database. The changes observed in kidney function, treatment efficiency and the incidence of adverse events between the tolvaptan and placebo groups were compared. Data were analyzed by the RevMan software. Results: Eight trials, including 7 double-blinded randomised controlled trials and 1 quasi RCT involving 1,536 patients were extracted. Significant differences in the annual rate of change in the total kidney volume TKV at any stages of CKD (MD = -3.32, 95%CI =-4.57,-2.07, I2 =70%) and the glomerular filtration rate (MD = 1.4, 95%CI = 0.83,1.97, I2 =0%) were observed between the tolvaptan group and the placebo group. Subgroup analysis of patients in different CKD stages also showed the same conclusion. There was an increase in the urine osmolality, and 24-hour urine volume in patients receiving tolvaptan. Tolvaptan reduced the rate of serious hypertension and kidney pain events in ADPKD patients. At higher doses, it increased the rate of adverse events (liver injuries, thirst, pollakiuria, and nocturia). There was no significant risk of bias in the included studies. Conclusions: Tolvaptan has a beneficial effect on ADPKD, but is associated with an increase in adverse events at high doses when compared with the placebo. Further RCTs on tolvaptan may be required to support this conclusion.

Although there has been increasing interest in aesthetical approaches for treating patients with papillary thyroid carcinoma (PTC), there have been no studies comparing the safety and effectiveness of gasless endoscopic selective lateral neck dissection (SLND) via the anterior chest approach (ACA) with that of conventional open surgery (OPEN) for papillary thyroid carcinoma. A total of 91 patients with PTC who underwent either gasless endoscopic thyroidectomy, central compartment neck dissection and SLND via the ACA or conventional open surgery between Nov. 2008 to Dec. 2018 were included. Primary outcomes and demographic data were compared between the two groups. Thirty-one patients were in the ACA group and 60 were in the OPEN group. The ACA group was younger and had a longer operative time but less intraoperative hemorrhage (P

Despite the increasing number of inflammatory bowel disease (IBD) patients using traditional Chinese medicine (TCM), relatively few studies have examined their experiences with TCM in the Chinese healthcare context. The aim of this study was to explore these experiences from the perspective of IBD patients. Adopting a qualitative descriptive method, IBD patients from several comprehensive hospitals in Hangzhou, Zhejiang were recruited through purposive sampling. Data were collected using semistructured interviews and analyzed by a conventional content analysis method. The results are presented thematically. Fourteen IBD patients participated in the study. They often used TCM, such as Chinese herbal medicine, retention enemas of Chinese medicine, and acupuncture, as a complementary therapy instead of as an alternative to conventional therapies. Three themes emerged from the analysis: triggers for initiating TCM, the experienced efficacies of TCM, and disturbances caused by TCM use. The IBD patients initiate TCM treatment due to the unsatisfactory effects of conventional therapies and TCM culture. However, the efficacies of TCM are subjective and slow acting and vary across individuals. There are communication gaps between physicians and patients concerning TCM. Thus, healthcare professionals are encouraged to gain more knowledge on these therapies and employ a participatory decision-making style based on this understanding.

Mitochondrial defects are a hallmark of early pathophysiology in Alzheimer's disease, with pathologically phosphorylated tau reported to induce mitochondrial toxicity. Mitophagy constitutes a key pathway in mitochondrial quality control by which damaged mitochondria are targeted for autophagy. However, few details are known regarding the intersection of mitophagy and pathologies in tauopathy. Here, by applying biochemical and cell biological approaches including time-lapse confocal imaging in live tauopathy neurons, combined with gene rescue experiments via stereotactic injections of adeno-associated virus particles into tauopathy mouse brains, electrophysiological recordings and behavioural tests, we demonstrate for the first time that mitochondrial distribution deficits at presynaptic terminals are an early pathological feature in tauopathy brains. Furthermore, Parkin-mediated mitophagy is extensively activated in tauopathy neurons, which accelerates mitochondrial Rho GTPase 1 (Miro1) turnover and consequently halts Miro1-mediated mitochondrial anterograde movement towards synaptic terminals. As a result, mitochondrial supply at tauopathy synapses is disrupted, impairing synaptic function. Strikingly, increasing Miro1 levels restores the synaptic mitochondrial population by enhancing mitochondrial anterograde movement and thus reverses tauopathy-associated synaptic failure. In tauopathy mouse brains, overexpression of Miro1 markedly elevates synaptic distribution of mitochondria and protects against synaptic damage and neurodegeneration, thereby counteracting impairments in learning and memory as well as synaptic plasticity. Taken together, our study reveals that activation of the Parkin pathway triggers an unexpected effect-depletion of mitochondria from synaptic terminals, a characteristic feature of early tauopathy. We further provide new mechanistic insights into how parkin activation-enhanced Miro1 degradation and impaired mitochondrial anterograde transport drive tauopathy-linked synaptic pathogenesis and establish a foundation for future investigations into new therapeutic strategies to prevent synaptic deterioration in Alzheimer's disease and other tauopathies.

Neurons are highly polarized and post-mitotic cells with the specific requirements of neurotransmission accompanied by high metabolic demands that create a unique challenge for the maintenance of cellular homeostasis. Thus, neurons rely heavily on autophagy that constitutes a key quality control system by which dysfunctional cytoplasmic components, protein aggregates, and damaged organelles are sequestered within autophagosomes and then delivered to the lysosome for degradation. While mature lysosomes are predominantly located in the soma of neurons, the robust, constitutive biogenesis of autophagosomes occurs in the synaptic terminal via a conserved pathway that is required to maintain synaptic integrity and function. Following formation, autophagosomes fuse with late endosomes and then are rapidly and efficiently transported by the microtubule-based cytoplasmic dynein motor along the axon toward the soma for lysosomal clearance. In this review, we highlight the recent knowledge of the roles of autophagy in neuronal health and disease. We summarize the available evidence about the normal functions of autophagy as a protective factor against neurodegeneration and discuss the mechanism underlying neuronal autophagy regulation. Finally, we describe how autophagy function is affected in major neurodegenerative diseases with a special focus on Alzheimer's disease, Parkinson's disease, and Amyotrophic Lateral Sclerosis.

Desmoplasia is a hallmark of intrahepatic cholangiocarcinoma (ICC), which constitutes a barrier to infiltration of lymphocyte, but not myeloid cells. Given that dense desmoplastic stroma has been reported to be a barrier to infiltration of lymphocyte, but not myeloid cells. We here investigated whether fibroblastic FAP influenced ICC progression via non-T cell-related immune mechanisms. We demonstrated fibroblastic FAP expression was critical for STAT3 activation and CCL2 production, and ICC-CAFs were the primary source of CCL2 in human ICC microenvironment by using ICC-Fbs from six ICC patients. Fibroblastic knockdown of FAP significantly impaired the ability of ICC-CAFs to promote ICC growth, MDSCs infiltration and angiogenesis, which was restored by adding exogenous CCL2. Furthermore, interestingly, the tumor-promoting effect of fibroblastic FAP is dependent on MDSCs via secretion of CCL2, as depletion of Gr-1+ cells reversed the restoring effects of exogenous CCL2 on tumor growth and angiogenesis. In vitro migration assay confirmed that exogenous CCL2 could rescue the impaired ability of ICC-Fbs to attract Gr-1+ cells caused by fibroblastic FAP knockdown. In contrast, fibroblastic FAP knockdown had no effect on ICC cell proliferation and apoptotic resistance. Depletion MDSCs by anti-Gr-1 monoclonal antibody in subcutaneous transplanted tumor model abrogated tumor promotion by ICC-CAFs suggested that the pro-tumor function of Fibroblastic FAP relied on MDSCs. Mechanical, flow cytometry and chamber migration assay were conducted to find Fibroblastic FAP was required by the ability of ICC-CAFs to promote MDSC migration directly. Moreover, fibroblastic FAP knockdown had no effect on cell proliferation and apoptotic resistance. Here, we revealed the T-cell independent mechanisms underlying the ICC-promoting effect of fibroblastic FAP by attracting MDSCs via CCL2, which was mainly attributed to the ability of FAP to attract MDSCs and suggests that specific targeting fibroblastic FAP may represent a promising therapeutic strategy against ICC.

Background To explore the therapeutic effect of topical 5-Aminolevulinic Acid photodynamic therapy (ALA-PDT) on laryngeal papillomatosis (LP) treatment. Methods 13 patients with LP underwent topical ALA-PDT after tumor resection (CO2laser or/and microdebrider resection). All patients were irradiated 3–4 times. After ALA-PDT treatment, the laryngoscopic examination was performed every 1–2 months to observe the therapeutic effect. Results All 13 patients were followed up for more than 1 year. Eleven cases (84.6%) showed no recurrence; two cases (15.4%) had relapses. One child developed III° inspiratory dyspnea caused by laryngeal mucosal edema and need endotracheal intubation again. Four patients had adhesion of the anterior commissure of the vocal cord. The detection rate of HPV infections was 76.9% and two patients had multiple HPV subtype co-infection. Conclusions The preliminary effect of topical ALA-PDT significantly reduces recurrence and improves the cure rate of LP. Further research on this treatment is still required.

To compare the clinical effect of acupuncture combined with wheat-grain moxibustion and oral sertraline hydrochloride dispersible tablets in the treatment of mild to moderate postpartum depression.Sixty patients with mild to moderate postpartum depression were randomly divided into an observation group and a control group, 30 cases in each group. Both groups were treated with psychotherapy. The control group was treated with oral sertraline hydrochloride dispersible tablets, 50 mg each time, once a day; the observation group was treated with acupuncture at Qihai (CV 6), Zusanli (ST 36), Xuehai (SP 10), Hegu (LI 4), Sanyinjiao (SP 6), Taixi (KI 3), etc. combined with wheat-grain moxibustion at Xinshu (BL 15), Pishu (BL 20), Ganshu (BL 18) and Shenshu (BL 23), once every other day, 3 times a week. Both groups were treated for 4 weeks as a course, with 2 consecutive courses of treatment. Before and after treatment and follow-up of 3 months after the end of treatment, the Hamilton depression scale (HAMD), Edinburgh postnatal depression scale (EPDS) and World Health Organization quality of life-BREF (WHOQOL-BREF) score of the two groups were compared, and the clinical effect was assessed.After treatment and during follow-up, the HAMD and EPDS scores of the two groups were lower than before treatment (Acupuncture combined with wheat-grain moxibustion can improve the depressive symptoms of patients with mild to moderate postpartum depression and improve their quality of life, and the clinical effect is more lasting and stable than oral sertraline hydrochloride dispersible tablets.

Objective: To examine the incremental mental health care resource utilization (MHRU) and barriers to receiving mental health services among adults with a major depressive episode (MDE) and suicidal ideation or behavior with intent. Methods: Data from adult participants in the 2017 National Survey on Drug Use and Health were used to identify 3 cohorts: MDE (determined by Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition [DSM-5] criteria) with suicidal ideation or behavior with intent (MDSI), MDE, and non-MDE. MHRU and barriers to receiving mental health services were compared among cohorts using logistic regression models. Results: The MDSI cohort had significantly higher odds (adjusted odds ratio [95% confidence interval]) of receiving mental health-related inpatient care, outpatient care, prescription medications, and any treatment versus the MDE cohort (10.2 [7.1-14.6], 2.4 [1.7-3.4], 2.4 [1.8-3.3], and 2.6 [1.8-3.7], respectively) and the non-MDE cohort (40.3 [27.3-59.5], 20.0 [14.5-27.7], 17.2 [12.9-22.9], and 19.6 [14.1-27.1], respectively). Compared to the MDE cohort, the MDSI cohort was significantly more likely to report barriers to receiving mental health services (2.6 [2.0-3.4]), with the largest differences between cohorts related to fear of negative impact (3.9 [2.8-5.4]). Additionally, 30.6% of the MDSI cohort and 47.0% of the MDE cohort did not receive any mental health treatment in the past year. Conclusions: Although respondents in the MDSI cohort reported substantially higher MHRU across all categories, they also reported greater barriers to receiving care than those in the MDE cohort. This study documents the extensive burden and unmet need in the MDSI population.

The ecological health assessment of lakes, reservoirs and wetlands can provide decision-making basis for ecosystem restoration and management. We selected 20 typical lakes, reservoirs and wetlands sampling points in Tianjin, based on physical, chemical, and biological community indicators data (zooplankton, phytoplankton, benthos, fish, large aquatic plants, riparian plants) obtained during the survey from August to September 2018. We constructed an index of ecological integrity (IEI) including physical integrity, chemical integrity, and biological integrity to evaluate their ecological health. The reference points were selected based on three aspects using standardized methods: habitat environmental quality index (QHEI), water quality status, and disturbance of human activities. The analytic hierarchy process was used to calculate the weight of the three indicators. The evaluation results of the ecological integrity of typical lakes, reservoirs and wetlands in Tianjin were finally obtained. The results showed that: 1) Among all the samples, "healthy" points accounted for 5.0%, "good" points accounted for 20.0%, "general" points accounted for 35.0%, "worse" points accounted for 30.0%, and "poor" points accounted for 10.0%. Ecological health status of typical lakes, reservoirs and wetlands in Tianjin was at a general level, with a trend that the west was better than the east with significant spatial differences. 2) Reference points were selected based on the combination of habitat score, water quality conditions, and human activity disturbance. Water quality indicators could reduce subjectivity when selecting reference points and promote the application of ecological integrity evaluation. 3) The applicability verification results showed that IEI could better characterize the health status of each point, and the discrimination efficiency was obvious, which was suitable for evaluating the ecological health of lakes, reservoirs and wetlands.对湖库湿地进行生态健康评价,可为湖库湿地生态系统修复和管理提供决策依据。本文以天津市为例,选取20个典型的湖库湿地采样点,基于2018年8—9月期间调查获取的物理、化学和生物群落指标(浮游动物、浮游植物、底栖动物、鱼类、水生大型植物、河岸带植物)数据,构建包含物理完整性、化学完整性和生物完整性在内的生态完整性指数(IEI)对采样点生态健康状况进行评价。根据栖息地环境质量(QHEI)、水质状况和人类活动干扰3方面选取参照点,采用标准化方法筛选候选指标,应用层次分析法计算各指标权重,最终得出天津市典型湖库湿地生态完整性评价结果。结果表明: 1)所有样点中,“健康”点位占5.0%,“较好”点位占20.0%,“一般”点位占35.0%,“较差”点位占30.0%,“差”点位占10.0%。天津市典型湖库湿地生态健康状况整体处于一般水平,呈现出西部优于东部的趋势,空间差异显著;2)基于栖息地评分、水质状况与人类活动干扰相结合选取参照点是可行的,依据水质指标可降低选择参照点时的主观性;3)适用性验证结果表明,IEI可较好表征各点位的健康状况,区分效率明显,适用于评价研究区湖库湿地生态健康状况。.

To observe the effect of auricular acupuncture on reduction rate of sertraline hydrochloride, and to explore the long-term efficacy of auricular acupuncture in patients with depression.Seventy-two patients with depression were randomly divided into an observation group (36 cases, 1 case dropped off) and a control group (36 cases, 2 cases dropped off). The patients in the control group were treated with conventional dosage reduction method, that is, the dosage of sertraline hydrochloride was reduced by 25% every week until the dosage was stopped completely on the premise of no aggravation of depressive symptoms. Based on the conventional dosage reduction method used in the control group, the patients in the observation group were treated with auricular acupuncture at Xin (COThe dosage of sertraline hydrochloride in the observation group was less than that in the control group after 2, 3, 4 weeks of dosage reduction and during follow-up (Auricular acupuncture could effectively reduce the dosage of sertraline hydrochloride, improve the dosage reduction rate, reduce the incidence of withdrawal syndrome and reduce the risk of long-term recurrence in patients with depression.

IntroductionUnexpected premature delivery and separation from preterm infants are common problems that parents of preterm infants must handle with. Parents of preterm infants may suffer from severe psychological distress. Family-centred care (FCC) can effectively ease parents’ psychological distress and strengthen connections between parents and their preterm infants. The purpose of this systematic review will be to systematically review and evaluate the impacts of FCC interventions on the mental health of parents of preterm infants and the parent–infant relationship.Methods and analysisThis protocol for this systematic review will be conducted in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocol. We will search databases including PubMed, Embase, The Cochrane Library, CINAHL, Web of Science, PsycINFO, Scopus and ProQuest, CNKI, SinoMed and Wanfang Data from 1 July 2012 to 1 July 2022. An additional search of OpenGrey will be conducted to identify grey literature. Randomised controlled trials related to FCC inventions for preterm infants≤37 weeks’ gestational age and their parents will be included, and the outcome measures will be parental mental health and parent–infant interaction. Two reviewers will independently conduct title and abstract screening, full-text screening, data extraction and study quality assessment. Risk of bias for the studies will be evaluated using the Cochrane Collaboration Risk of Bias V.2.0. Any disagreements will be solved by a third reviewer to reach a consensus. If appropriate, a meta-analysis will be conducted to assess the effect of FCC on parental mental health and parent–infant relationship.Ethics and disseminationResearch ethics approval will not be required for this review since it will not involve the collection of primary data and will only use published literature. The results will be disseminated in a peer-reviewed journal through publication or by presentation at relevant academic conference.PROSPERO registration numberCRD42022299203.

Silicosis is an occupational disease caused by inhalation of silica dust, which is hallmarked by progressive pulmonary fibrosis associated with poor prognosis. Wnt/β-catenin signaling is implicated in the development of fibrosis and is a therapeutic target for fibrotic diseases. Previous clinical studies of patients with pneumoconiosis, including silicosis, revealed an increased concentration of circulating WNT3A and DKK1 proteins and inflammatory cells in bronchoalveolar lavage compared with healthy subjects. The present study evaluated the effects of adenovirus-mediated transduction of

Background and aims We previously demonstrated that cancer-associated fibroblasts (CAFs) promote tumor growth via recruiting of myeloid-derived suppressor cells (MDSCs). 5-lipoxygenase (5-LO) is highly expressed in myeloid cells and critical for synthesizing leukotriene B4 (LTB4), which is involved in tumor progression via acting its receptor Leukotriene B4 receptor type 2 (BLT2). In this study, we investigated whether and how CAFs regulate MDSC function to enhance cancer stemness, the driving force of the cancer aggressiveness and chemotherapy refractoriness, in highly desmoplastic intrahepatic cholangiocarcinoma (ICC). Approach and results RNA-sequencing analysis revealed enriched metabolic pathways but decreased inflammatory pathways in cancer MDSCs compared with blood MDSCs from ICC patients. Co-injection of ICC patient-derived CAFs promoted cancer stemness in an orthotopic ICC model, which was blunted by MDSC depletion. Conditioned media (CM) from CAF-educated MDSCs drastically promoted tumorsphere formation efficiency and stemness marker gene expression in ICC cells. CAF-CM stimulation increased expression and activity of 5-LO in MDSCs while 5-LO inhibitor impaired the stemness-enhancing capacity of MDSCs in vitro and in vivo. Furthermore, IL-6 and IL-33 mainly expressed by CAFs mediated hyperactivated 5-LO metabolism in MDSCs. We identify the LTB4-BLT2 axis as the critical downstream metabolite signaling of 5-LO in promoting cancer stemness, as treatment with LTB4 that were elevated in CAF-educated MDSCs or blockade of BLT2 that was preferentially expressed in stem-like ICC cells significantly reduced stemness-enhancing effects of CAF-educated MDSCs. Finally, BLT2 blockade augmented chemotherapeutic efficacy in ICC patient derived-xenograft (PDX) models. Conclusions Our study reveals a previously unrecognized role for CAFs in orchestrating the optimal cancer stemness-enhancing microenvironment by educating MDSCs and suggests 5-LO/LTB4-BLT2 axis as promising therapeutic targets for ICC chemoresistance by targeting cancer stemness.

Tumor complexity makes the development of highly sensitive tumor imaging probes an arduous task. Here, we construct a peptide-based near-infrared probe that is responsive to fibroblast activation protein-α (FAP-α), and specifically forms nanofibers on the surface of cancer-associated fibroblasts (CAFs) in situ. The assembly/aggregation-induced retention (AIR) effect results in enhanced accumulation and retention of the probe around the tumor, resulting in a 5.5-fold signal enhancement in the tumor 48 h after administration compared to that of a control molecule that does not aggregate. The probe provides a prolonged detectable window of 48 h for tumor diagnosis. The selective assembly of the probe results in a signal intensity over four- and fivefold higher in tumor than in the liver and kidney, respectively. With enhanced tumor imaging capability, this probe can visualize small tumors around 2 mm in diameter.

Thalassemia is one of the most common genetic diseases in southern China. Accurate population frequency data regarding the occurrence and distribution of thalassemia is important for designing appropriate prevention strategies of thalassemia.The aim of this study is to reveal the prevalence and the mutation spectrum of thalassemia in neonates in the Wuhan region of central China.About 3796 neonates in Wuhan area of China were analyzed by hematological and genetic analysis.About 2174 subjects were genetically diagnosed as thalassemia carriers or patients, including 1415 cases of α-thalassemia (65.89%), 731 cases of β-thalassemia (33.62%), and 28 cases of α-composite β-thalassemia (1.29%). A total of 11 genotypes and 6 gene mutations were identified in α-thalassemia anomalies, with -There was high heterogeneity and extensive spectrum of thalassemia in the neonates in Wuhan populations. The findings will be useful for genetic counseling and prenatal diagnosis of thalassemia in the Wuhan region.

Brain metastasis (BM) is associated with poor prognosis in patients with non-small cell lung cancer (NSCLC). We sought to identify microRNAs (miRNAs) that could serve as biomarkers to differentiate NSCLC patients with and without BM. Logistic regression was conducted with 122 NSCLC patients (60 without BM, 62 with BM) to assess the association between miRNAs and BM. We confirmed several risk factors for BM and revealed that serum miR-330-3p levels are higher in NSCLC patients with BM than that without BM. Overexpression of miR-330-3p promoted proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) of NSCLC cells in vitro and NSCLC tumorigenesis in vivo. Knocking down miR-330-3p suppressed this metastatic phenotype. We identified putative miR-330-3p target genes by comparing mRNA microarray analysis data from A549 cells after miR-330-3p knockdown with candidate miR-330-3p target genes predicted by public bioinformatic tools and luciferase reporter assays. We found that GRIA3 is a target of miR-330-3p and that miR-330-3p stimulates EMT progress by mediating GRIA3-TGF-β1 interaction. Our results provide novel insight into the role of miR-330-3p in NSCLC metastasis, and suggest miR-330-3p may be a useful biomarker for identifying NSCLC with metastatic potential.

Background To investigate whether the relative computed tomography (CT) value (rCT) of adjacent pancreatic parenchyma can distinguish focal‐type autoimmune pancreatitis (fAIP) from pancreatic ductal adenocarcinoma (PDAC). Methods A total of 13 patients with fAIP and 20 patients with PDAC were included in this study. The rCT was calculated as the ratio of the CT value of adjacent pancreatic parenchyma to that of muscle. The diagnostic performance of rCT for discriminating fAIP from PDAC was evaluated using receiver operating characteristic (ROC) analysis. Results Both fAIP and PDAC presented hyper‐fibrosis histologically and delayed enhancement on CT examination. Moreover, the pancreatic parenchyma of fAIP presented serious inflammation. The mean rCT of the parenchyma was significantly lower in fAIP than in PDAC in all phases. The best diagnostic performance of the rCT value was found in the pancreatic phase, with an area under the ROC curve of 0.912, while the areas under the ROC curve of the portal and delayed phases were 0.812 and 0.754, respectively. The optimal cut‐off value for distinguishing fAIP from PDAC was 1.62 in the pancreatic phase. Conclusions The rCT of the pancreatic parenchyma during the pancreatic phase may be a feasible CT feature for differentiating fAIP from PDAC., Similar imaging features such as regional enlargement of the pancreas and delayed enhancement became a big challenge to differentiate focal‐type autoimmune pancreatitis (fAIP) from PDAC. In this study, we found that the pancreatic parenchyma of fAIP presented severe inflammation. Moreover, the mean relative computed tomography values of the pancreatic parenchyma were lower in fAIP than that in PDAC in all phases.

Objective: To describe the prevalence and costs of anxiety and depression among moderate-to-severe psoriasis (PsO) patients in a commercially-insured US population. Methods: The IBM MarketScan Commercial database was used to select adults with moderate-to-severe PsO (≥1 PsO diagnosis and ≥1 systemic or biologic medication) within each calendar year from 2014 to 2016. Adults with no diagnosis of PsO or similar disorders were randomly selected (2014–2016) and matched 1:1 to PsO patients to compare the prevalence of anxiety and depression each year. Moderate-to-severe PsO patients identified in 2014 with continuous enrollment through 2015 were stratified into those with treated anxiety and/or depression (≥1 anxiety or depression diagnosis plus any anxiolytics, antidepressants, or antipsychotics within 30 days) vs those without anxiety/depression, and then matched 1:1 to determine the incremental burden of treated anxiety/depression among PsO patients. All-cause and PsO-related healthcare costs were compared between the matched cohorts using generalized linear models. Results: In total, 69,644 matched PsO and non-PsO patients were identified in 2014, 61,478 in 2015, and 66,880 in 2016. The prevalence of anxiety/depression among PsO patients increased more than for matched controls, from 18.2% vs 12.2% in 2014 (p p p p p p Conclusions: The prevalence of psychiatric disorders is higher among PsO patients than the general population, and the incremental burden of treated anxiety/depression is substantial. Further research is needed, but PsO treatments that improve psychiatric symptoms such as anxiety/depression may benefit patients and reduce their economic burden.

An early diagnosis of interstitial lung disease (ILD) is important for guiding treatments of rheumatoid arthritis (RA)-associated ILD (RA-ILD) in clinical settings. The non-canonical Wnt signaling representative ligand Wnt5a was recently found to involve in idiopathic pulmonary fibrosis (IPF) and pathogenesis of RA. The goal of this study was to examine the clinical relevance of Wnt5a in RA-ILD. In this report, the clinical relevance of plasma Wnt5a protein was evaluated in 40 RA-ILD patients and 41 non-ILD RA cohorts. The results showed an elevated Wnt5a protein in plasmas of RA-ILD patients compared with non-ILD RA patients (p 0.01), which was positively correlated with the plasma level of rheumatoid factor (RF). Of note, more abundant Wnt5a was also found in patients with usual interstitial pneumonia (UIP) than those with nonspecific interstitial pneumonia (NSIP) and other ILD patterns. More importantly, the disease severity was correlated with the circulating Wnt5a as ascertained by high-resolution computed tomography (HRCT)-UIP scores. The multiple-factor non-conditional logistic regression analysis further revealed that the age, RA duration, smoking and plasma Wnt5a were risk factors with clinical significance for RA-ILD. Interestingly, more Wnt5a-positive patients were identified in RA-ILD smokers relative to RA-ILD never-smokers, and longer smoking duration was strongly correlated with Wnt5a in RA-ILD patients. In consistence, ROC curve also suggested that the Wnt5a was a potential candidate biomarker for identifying patients with RA-UIP. These results demonstrate that the circulating Wnt5a may be a risk factor and potential biomarker for identifying UIP and accessing the severity and progression of ILD in RA patients.

To investigate the effects of lncRNA GAS5 on the proliferation, migration, invasion and apoptosis of brain glioma cells. The expression levels of lncRNA GAS5 and GSTM3 in normal glial cells (HEB) and glioma cells (U251 and U87) were detected by RT-qPCR and western blot, respectively. Glioma cells were transfected with ctrl vector, pcDNA-GAS5, siRNA ctrl (siNC) or GSTM3 siRNA and the effects of lncRNA GAS5 and GSTM3 on the proliferation, migration, invasion and apoptosis of glioma cells were detected by CCK-8 assay, transwell assay and Caspase 3/7 activity assay, respectively. The expression of lncRNA GAS5 was significantly decreased in glioma cell lines U251 and U87 compared with normal glial cells HEB (p

Factors underlying the selection of antipsychotics for patients with schizophrenia are poorly understood. This study investigated variables associated with initiation of treatment with the long-acting injectables paliperidone palmitate (LAI-PP) and aripiprazole LAI (LAI-AP) in Medicaid patients with schizophrenia. Adults with at least one medical or pharmacy claim for LAI-PP or LAI-AP from 1 January 2013 to 31 December 2016 were selected from the IBM® MarketScan® Medicaid Database. The date of the first LAI-PP or LAI-AP claim was the index date. Patients who had at least two medical claims, on different days, for a schizophrenia diagnosis and at least 12 months of continuous health plan enrollment prior to index date were included in the analysis. Multivariable logistic regression was performed to determine the factors associated with the initiation of LAI-PP versus LAI-AP. Of included patients, 5501 initiated LAI-PP and 1449 initiated LAI-AP. Patients more likely to initiate LAI-PP versus LAI-AP were older, male, or African American (all p

BACKGROUND In traditional Chinese medicine, acupuncture has been used to treat angina due to coronary artery disease (CAD). The aim of this systematic review of the literature and meta-analysis was to identify published randomized controlled trials (RCTs) that quantified the effectiveness of adjunctive acupuncture treatment in patients with angina due to CAD who were also treated with Western or Chinese medicine. MATERIAL AND METHODS A systematic review of the literature included a search of the PubMed, Embase, Cochrane library, and China National Knowledge Infrastructure (CNKI) databases, from their inception to September 2018. Published findings from RCTs were included that investigated the effectiveness of acupuncture as an adjunctive treatment for angina due to CAD in combination with Western or traditional Chinese medicine. The odds ratio (OR) and 95% confidence interval (CI) were calculated using the random-effects model to determine the outcomes of markedly and moderately effective rates for the use of acupuncture. RESULTS Twenty-four published RCTs were identified that included 1,916 patients with CAD. Patients who received adjunctive acupuncture treatment had a significantly increased markedly effective rate. However, the moderately effective rate between adjunctive acupuncture combined with standard treatment for angina and standard treatment alone was not statistically significant. Sensitivity analysis showed that the pooled results for the markedly and moderately effective rates were robust. Subgroup analysis in most subsets supported the main findings. CONCLUSIONS Meta-analysis supported a positive treatment effect for the use of acupuncture when used as adjunctive therapy in patients with angina due to CAD.

Objective To investigate the effect of paraquat (PQ) exposure on gene expression in neural stem cells as well as structures and functions of vascular endothelial cells. Methods RNA-Seq was used to explore the differentially expressed genes in human umbilical cord blood-neural stem cells (HUCB-NSCs) at different stages (eg, proliferation, early and late differentiation) in the presence of PQ. The effects of PQ on human umbilical vein endothelial cells (HUVECs), including cell proliferation, apoptosis, cytokines secretion, and expression of tight junction proteins, were assessed with CCK-8, flow cytometry, ELISA, and western blot analysis, individually. Results A total of 53 genes were up-regulated and 61 genes were down-regulated in PQ treated HUCB-NSCs, including seven genes associated with the differentiation of neural stem cells, for example, Gfap, S100B, Oct4, Gdf3, Sox1, Pax6, and Ngn1. PQ treatment significantly reduced the proliferation of HUVECs, inhibited cytokines secretion (VEGF, BFGF) and expressions of tight junction-associated protein (Claudin 1, Occludin, ZO-1), as well as induced significant apoptosis. Conclusion Our study suggests that PQ impairs the development of nervous system by regulating the expression of genes associated with neural stem cell differentiation, as well as the structure and function of vascular endothelial cells, which together lead to abnormality in the nervous system.