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The high risk of tumor recurrence presents a big challenge in melanoma therapy. Photothermal therapy (PTT) has merged as a powerful weapon against tumor in recent years, which produces tumor-associated antigens (TAA) and recruits dendritic cells (DCs) to tumor sites through immunogenic cell death (ICD) for immune activation. However, due to the lack of activation signals of DCs, the immune effect induced by PTT is not sufficient to inhibit the recurrence and proliferation of tumor. To efficiently cooperate PTT and immunotherapy to circumvent tumor recurrence, here we constructed a polydopamine (PDA) based core-shell nanoplatform loading CpG ODNs to elicit robust photothermal ablation and antitumor immune responses. Cationized polydopamine coated with hyaluronic acid (HA) shell was proven an efficient photothermal agent that increased the surface temperature of tumor by 16 °C and induced ICD. CpG ODNs effectively induced maturation of DCs by elevating the expression of co-stimulating markers. PTT combined with CpG ODNs achieved a remarkable synergistic treatment effect in the maturation of DCs and activation of T cells in melanoma-bearing mice model compared with PTT or CpG ODNs alone. Furthermore, in a tumor recurrence model, photothermal-immune combination therapy increased the infiltration of CTLs in distant tumor compared with PTT or CpG ODNs alone. The combination therapy overcame insufficient immunity at distant tumor caused by PTT alone and relieved immunosuppression microenvironment of the tumor. Hence, the PDA based core-shell nanoplatform presents a potent photo-immunotherapy against proliferation and recurrence of melanoma. Statement of significance In order to solve the insufficient immunity induced by photothermal therapy (PTT), CpG ODNs were utilized to enhance the weak immune response mediated by PTT through inducing DCs maturation. Hence, we designed a polydopamine (PDA) based core-shell nanoplatform loading CpG ODNs followed by hyaluronic acid named PPP/CpG/HA to elicit robust photothermal ablation and antitumor immune responses. CpG ODNs were delivered to the tumor site through the targeting effect of the HA shell. The core-shell nanoplatform achieved a remarkable synergistic treatment effect in the maturation of DCs and activation of T cells, thereby overcoming insufficient immunity at distant tumor caused by PTT alone. The core-shell nanoplatform presents a potent photo-immunotherapy against proliferation and recurrence of melanoma.

The treatment options for cancer of unknown primary (CUP) are challenging due to the lack of knowledge about the primary sites, often resulting in a poor prognosis. The emerging next-generation sequencing (NGS) technique has provided a reliable approach to facilitate tumor primary site prediction and targetable gene alteration identification for CUP patients. In this report, we described a 63-year-old female patient who experienced recurrent CUP. NGS-based genetic profiling results revealed a pathogenic germline BRCA1 R71K mutation. Accordingly, the patient received the poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor olaparib treatment and demonstrated a favorable response to this treatment. Our case suggests that NGS holds great promise for providing improved diagnosis and treatment options to patients with CUP, warranting further clinical investigation.

When the historical data of the early phase trial and the interim data of the Phase III trial are available, we should use them to give a more accurate prediction in both futility and efficacy anal...

Elderly patients living in long-term care facilities have been restricted from leaving to comply with social distancing guidelines during the COVID-19 pandemic. This has led to a worsening of disorders, such as anxiety and depression. This study aims to understand the health benefits of an immersive garden experience to elderly nursing home residents with mild-to-moderate cognitive impairments. Virtual reality devices were used to provide immersive garden experiences for the residents who were unable to go outside. The heart rate and heart rate variability (HRV) data of the participants of the participants were collected using biofeedback instruments, and changes in the low frequency/high frequency (LF/HF) and the standard deviation of the NN interval (SDNN) values caused by immersive garden experiences were discussed. The results show that the immersive garden experiences were beneficial to these elderly residents. Within 6 min of completing the experiment, we found that the heart rates of participants had dropped slightly, while SDNN and HF values continued to rise. SDNN values before and after the experiment demonstrated a statistically significant improvement. Furthermore, participants expressed their satisfaction with the video intervention program. The results indicated that nursing homes can provide immersive landscape experiences to help increase HRV and SDNN of their elderly residents. This will not only help these residents recall beautiful memories of their past, but will also improve their quality of life. Supplementary Information The online version contains supplementary material available at 10.1007/s11355-021-00480-9.

Background Synovial sarcoma (SS) is a highly malignant tumor of unknown histological origin. This tumor can occur in various parts of the body, including those without synovial structures, but mainly in and around the joints, mostly in the lower extremities. Primary intracranial SSs are remarkably rare. This paper aims to report a case of primary intracranial SS with hemorrhage. Case summary A 35-year-old male patient suffered a headache and slurred speech during manual labor and was sent to the emergency department. Through imaging examination, the patient was considered to have high-grade glioma complicated with hemorrhage and was treated with craniotomy. Postoperative pathology revealed SS. positron emission tomography/computed tomography was performed, which ruled out the possibility of metastasis to the intracranial from other parts of the body. Postoperative radiotherapy was given to the patient, during which radiation necrosis occurred. Sixteen months after craniotomy, cranial magnetic resonance imaging revealed recurrence of the tumor. Conclusion Primary intracranial SS is a rare malignant tumor. Primary intracranial SS with hemorrhage and radiation necrosis should be carefully monitored during postoperative radiotherapy. Surgical resection of the tumor combined with postoperative radiotherapy and chemotherapy is currently used, but the prognosis is poor.

Aims: This study aims to explore the efficacy of punicalagin (PG) on diabetic cardiomyopathy (DCM), with a specific focus on the mechanisms underlying the effects of PG on mitochondrial fusion/fiss...

BACKGROUND: Smoking is a risk factor for many diseases. PURPOSE: This study explored the relationship between current or past smoking and pressure injury (PI) risk through a systematic review and meta-analysis. METHODS: The databases PubMed, Web of Science, and China National Knowledge Infrastructure were searched for the years between 2001 and 2020. Quality of evidence was estimated by the Newcastle-Ottawa Scale. The random effects model was applied to assess the odds ratios (OR) and 95% confidence intervals (CI); pooled adjusted OR and 95% CI, subgroup analysis, publication bias, sensitivity analyses, and meta-regression analysis were performed. RESULTS: Fifteen (15) studies (12 retrospective and 3 prospective) comprising data on 11 304 patients were eligible for inclusion in the review. The meta-analysis demonstrated that smoking increased the risk of PI (OR = 1.498; 95% CI, 1.058-2.122), and the pooled adjusted OR (1.969) and 95% CI (1.406-2.757) confirmed this finding. Publication bias was not detected by funnel plot, Begg’s test (P = .322), or Egger’s test (P = .666). Subgroup analyses yielded the same observations in both retrospective (OR = 1.607; 95% CI, 1.043-2.475) and prospective (OR = 1.218; 95% CI, 0.735-2.017) studies. The results were consistent across sensitivity analyses (OR = 1.07; 95% CI, 1.043-2.475). Relevant heterogeneity moderators were not identified by meta-regression analysis with PI incidence (P = .466), years of patient data included (P = .637), mean patient age (P = .650), and diabetes mellitus diagnosis (P = .509). CONCLUSION: This study found that individuals who are current or formers smokers have an almost 1.5 times higher risk of PI development than do those who do not smoke.

Chikungunya fever is an acute infectious disease caused by the chikungunya virus (CHIKV) that is characterized by fever, rash, and joint pain. CHIKV has infected millions of people in Africa, Asia, America, and Europe since it re-emerged in the Indian Ocean region in 2004. Here, we report an outbreak of Chikungunya fever that occurred in Ruili of Yunnan Province, a city located on the border between China and Myanmar, in September 2019. The outbreak lasted for three months from September to December. Overall, 112 cases were confirmed by a real-time reverse-transcription polymerase chain reaction in the Ruili People's Hospital, and they showed apparent temporal, spatial, and population aggregation. Among them, 91 were local cases distributed in 19 communities of Ruili City, and 21 were imported cases. The number of female patients was higher than that of male patients, and most patients were between 20 and 60 years old. The main clinical manifestations included joint pain (91.96%), fever (86.61%), fatigue (58.04%), chills (57.14%), rash (48.21%), headache (39.29%), and so forth. Biochemical indexes revealed increased C-reactive protein (63.39%), lymphopenia (57.17%), increased hemoglobin (33.04%), neutrophilia (28.57%), and thrombocytopenia (16.07%). Phylogenetic analysis of the complete sequences indicated that the CHIKV strains in this outbreak belonged to the Indian Ocean clade of the East/Central/South African genotype. We speculated that this chikungunya outbreak might be caused by CHIKV-infected persons returning from Myanmar, and provided a reference for the formulation of effective treatment and prevention measures.

Aim: To screen novel biomarkers in serum of syphilis patients using a mass spectrometry-based method. Materials & methods: Sera were collected from 18 syphilis patients and divided into three groups. Every six serum samples (before and after treatment) in each group were pooled and detected by mass spectrometry. Results: Twenty-five unique peptides corresponding to 15 Treponema pallidum proteins were discovered. Among them, Tp0369 was discovered as a promising biomarker candidate in this study. Tp0524 and Tp0984 levels decreased 0.38-fold and 0.51-fold after BPG treatment, respectively, which may be related to disease outcomes of syphilis. Conclusion: These findings confirmed the presence of detectable T. pallidum protein in patients' serum, which could promote the development of syphilis diagnostics.

Aim The aim of this study is to develop and test radiomics models based on magnetic resonance imaging (MRI) to preoperatively and respectively predict the T stage, perineural invasion, and microvascular invasion of extrahepatic cholangiocarcinoma (eCCA) through a non-invasive approach. Methods This research included 101 eCCA patients (29–83 years; 45 females and 56 males) between August 2011 and December 2019. Radiomics features were retrospectively extracted from T1-weighted imaging, T2-weighted imaging, diffusion-weighted imaging, and apparent diffusion coefficient map using MaZda software. The region of interest was manually delineated in the largest section on four MRI images as ground truth while keeping 1–2 mm margin to tumor border, respectively. Pretreatment, dimension reduction method, and classifiers were used to establish radiomics signatures for assessing three pathological characteristics of eCCA. Finally, independent training and testing datasets were used to assess radiomics signature performance based on receiver operating characteristic curve analysis, accuracy, precision, sensitivity, and specificity. Results This study extracted 1208 radiomics features from four MRI images of each patient. The best performing radiomics signatures for assessing the T stage, perineural invasion, and microvascular invasion were respectively produced by L1_normalization + linear discriminant analysis (LDA) + logistic regression, Box_Cox transformer + LDA + K-nearest neighbor, and L2_normalization + LDA + AdaBoost. The area under the curve values of the radiomics signatures for predicting the training and testing cohorts in each subgroup were respectively 1 and 0.962 (T stage), 1 and 1 (both perineural invasion and microvascular invasion). Conclusion These proposed radiomic models based on MR images had powerful performance and high potential in predicting T stage, perineural, and microvascular invasion of eCCA. Reporting guidelines/Research design Prognostic study.

It is commonly agreed, flexible work arrangements (FWA) could bring many benefits to both employees and employers. With the increased prevalence of team-based work structures, collaborative jobs wi...

Left ventricular hypertrophy (LVH) is the most common target organs damage in the hypertension patients. Abnormal low (≤0.9) or high (≥1.40) ankle brachial index (ABI) are associated with an increased risk of cardiovascular events. However, the relationships between a high ABI in the normal range (0.9–1.4) and LVH in Han Chinese hypertension are not entirely elucidated. This study included 3953 hypertension patients aged 40–75 years among Han Chinese. Hypertension was defined as systolic blood pressure≥140 mm Hg, diastolic blood pressure≥90 mm Hg, or history of antihypertensive drug use. Left ventricular mass (LVM) was measured by transthoracic echocardiography. LVH was diagnosed by using the criteria of LVM ≥49.2 g/m2.7 for men and 46.7 g/m2.7 for women. Our study suggested that the ABI was higher in patients with LVH than in those without (1.13±0.11, 1.11±0.11, p

Triple-negative breast cancer (TNBC) is an aggressive, difficult-to-treat subtype of cancer with a poor prognosis; there is an urgent need for effective, targeted molecular therapies. The cyclin D/cyclin-dependent kinase (CDK)4/6–retinoblastoma protein (Rb) pathway plays a critical role in regulating cell cycle checkpoints, a process which is often disrupted in cancer cells. Selective CDK4/6 inhibitors can prevent retinoblastoma protein phosphorylation by invoking cell cycle arrest in the first growth phase (G1), and may therefore represent an effective treatment option. In this article, we review the molecular mechanisms and therapeutic efficacy of CDK4/6 inhibitors in combination with other targeted therapies for the treatment of triple-negative breast cancer. Three selective CDK4/6 inhibitors have so far received the approval of the Food and Drug Administration (FDA) for patients with estrogen receptor (ER)+/human epidermal growth factor receptor 2 (HER2) breast cancer. Trilaciclib, a small molecule short-acting inhibitor of CDK4/6, has also been approved recently for people with small cell lung cancer, and is also expected to be clinically effective against breast cancer. Although the efficacy of CDK4/6 inhibitors in patients with triple-negative breast cancer remains uncertain, their use in conjunction with other targeted therapies may improve outcomes and is therefore currently being explored. Identifying biomarkers for response or resistance to CDK4/6 inhibitor treatment may optimize the personalization of treatment strategies for this disease. Ongoing and future clinical trials and biomarker studies will shed further light on these topics, and help to realize the full potential of CDK4/6 inhibitor treatment in triple-negative breast cancer.

Since the imbalance of gene expression has been demonstrated to tightly related to breast cancer (BRCA) genesis and growth, common genes expressed of BRCA were screened to explore the essence in-between. In current work, most common differentially expressed genes (DEGs) in various subtypes of BRCA were identified. Functional enrichment analysis illustrated the driving factor of deactivation of the cell cycle and the oocyte meiosis, which critically triggers the development of BRCA. Herein, we constructed a 12-gene prognostic risk model relative to differential gene expression. Subsequently, the K-M curves, analysis on time-ROC curve and Cox regression were performed to assess this risk model by determining the respective prognostic value, and the prediction performance were ascertained for both training and validation cohorts. In addition, multivariate Cox regression was analysed to reveal the independence between risk score and prognostic stage, and the accuracy and sensitivity of prognosis are particularly improved after clinical indicators are included into the analysis. In summary, this study offers novel insights into the imbalance of gene expression within BRCA, and highlights 12 selected genes associated with patient prognosis. The risk model can help individualize treatment for patients at different risks, and propose precise strategies and treatments for BRCA therapy.

Background. Acupuncture is considered a complementary therapy for atopic eczema. The aim of this scoping review is to identify, examine, and summarize the potential acupoint prescriptions and outcome reporting regarding the clinical trials of acupuncture for eczema. Methods. We searched different databases from inception to September 30, 2020. The data were screened and extracted to identify the potential acupuncture prescription and examine the variation in outcome reporting, outcome measurement instruments (OMIs), and measurement time points in clinical trials of acupuncture. Results. A total of 116 clinical studies were included. The acupoint combination of LI11 and SP10 was used frequently. The core acupoint association networks were acupoints LI11, SP10, ST36, SP6, and LI4. For clinical trials of acupuncture, a total of 6 outcome distinct domains were identified in the 32 outcome measurements. The most frequently reported outcome was the eczema area, which was reported 97 times (83.6%, 97/116). Immune system outcomes were assessed in 15 outcome measurements, which totally reported 37 times. Adverse events were reported 51 times. TCM syndrome, which could reflect the characteristics of TCM, was reported 4 times. 29 outcomes (90.6%, 29/32) were provided definitions or OMIs. Among these outcomes, the outcome measurement times ranged from 0 to 34. Conclusions. This scoping review provides potential knowledge that should be considered as priority in future research of acupuncture for eczema.

With the ability to activate certain signaling pathways, chemokines and their receptors may facilitate tumor progression at key steps, including proliferation, immunomodulation, and metastasis. Nevertheless, their prognostic value and regulatory mechanism warrant thorough studies in liver cancer. Here, by screening the expression profiles of all known chemokines in independent liver cancer cohorts, we found that CCL23 was frequently downregulated at mRNA and protein levels in liver cancer. Decreased CCL23 correlated with shortened patient survival, enrichment of signatures related to cancer stem cell property, and metastatic potential. In addition to serving as a tumor suppressor through recruiting CD8+ T cell infiltration in liver cancer, CCL23 could repress cancer cell proliferation, stemness, and mobility. Mechanistically, the expression of CCL23 was transcriptionally regulated by ESR1. On the other hand, CCL23 could suppress the activation of AKT signaling and thus promote the expression of ESR1, forming a feedback loop in liver cancer cells. Collectively, these findings reveal that loss of CCL23 drives liver cancer progression by coordinating immune evasion and metastasis initiation. Targeting the ESR1/CCL23/CCR1/AKT regulatory axis could be an effective therapeutic strategy., Downregulated expression of CCL23 is associated with poor prognosis in liver cancer. Loss of CCL23 drives liver cancer progression by coordinating immune evasion and metastasis initiation. Mechanistic study reveals an ESR1/CCL23/CCR1/AKT feedback loop.

Thermal management is critical in modern electronic systems. Efforts to improve heat dissipation have led to the exploration of novel semiconductor materials with high thermal conductivity, including boron arsenide (BAs) and boron phosphide (BP). However, the integration of such materials into devices and the measurement of their interface energy transport remain unexplored. Here, we show that BAs and BP cooling substrates can be heterogeneously integrated with metals, a wide-bandgap semiconductor (gallium nitride, GaN) and high-electron-mobility transistor devices. GaN-on-BAs structures exhibit a high thermal boundary conductance of 250 MW m−2 K−1, and comparison of device-level hot-spot temperatures with length-dependent scaling (from 100 μm to 100 nm) shows that the power cooling performance of BAs exceeds that of reported diamond devices. Furthermore, operating AlGaN/GaN high-electron-mobility transistors with BAs cooling substrates exhibit substantially lower hot-spot temperatures than diamond and silicon carbide at the same transistor power density, illustrating their potential for use in the thermal management of radiofrequency electronics. We attribute the high thermal management performance of BAs and BP to their unique phonon band structures and interface matching. Boron arsenide and boron phosphide cooling substrates can be integrated with other materials, including the wide-bandgap semiconductor gallium nitride, creating structures that exhibit high thermal boundary conductances and high-electron-mobility transistors that exhibit low hot-spot temperatures.

Patient–ventilator asynchrony (PVA) is commonly encountered during mechanical ventilation of critically ill patients. Estimates of PVA incidence vary widely. Type, risk factors, and consequences of PVA remain unclear. We aimed to measure the incidence and identify types of PVA, characterize risk factors for development, and explore the relationship between PVA and outcome among critically ill, mechanically ventilated adult patients admitted to medical, surgical, and medical-surgical intensive care units in a large academic institution staffed with varying provider training background. A single center, retrospective cohort study of all adult critically ill patients undergoing invasive mechanical ventilation for ≥ 12 h. A total of 676 patients who underwent 696 episodes of mechanical ventilation were included. Overall PVA occurred in 170 (24%) episodes. Double triggering 92(13%) was most common, followed by flow starvation 73(10%). A history of smoking, and pneumonia, sepsis, or ARDS were risk factors for overall PVA and double triggering (all P P P

A deep and comprehensive understanding of factors that contribute to cancer initiation, progression, and evolution is of essential importance. Among them, the serine/threonine and tyrosine kinase-like kinases, also known as receptor interacting proteins (RIPs) or receptor interacting protein kinases (RIPKs), is emerging as important tumor-related proteins due to its complex regulation of cell survival, apoptosis, and necrosis. In this review, we mainly review the relevance of RIP to various malignant digestive neoplasms, including esophageal cancer, gastric cancer, colorectal cancer, hepatocellular carcinoma, gallbladder cancer, cholangiocarcinoma, and pancreatic cancer. Consecutive research on RIPs and its relationship with malignant digestive neoplasms is required, as it ultimately conduces to the etiology and treatment of cancer.

The burden of non-communicable diseases (NCDs) has increased in China. However, the contribution of dietary risks to the NCD burden has not been evaluated. This study aimed to estimate the burden of ischemic heart disease (IHD) and colorectal cancer (CRC) attributable to a diet low in fiber in China from 1990 to 2017. China data from the Global Burden of Disease Study (GBD) 2017 were used to assess the age-, sex-, and province-specific mortality and disability-adjusted life-years (DALYs) of IHD and CRC related to a diet low in fiber. In 2017, a diet low in fiber contributed 170,143 [95% uncertainty interval (UI): 99,623–256,806] IHD deaths and 25,561 (95% UI: 13,726–39,215) CRC deaths, with the population attributable fractions (PAFs) were 9.7 and 13.7%, respectively. Males had higher risk-attributable mortality and DALY rates for IHD and CRC than females. An upward trend with age in rates of mortality and DALY was observed. All-age risk-attributable mortality and DALY rates increased significantly by 111.4 and 53.2% for IHD, and 94.4 and 59.6% for CRC from 1990 to 2017, respectively; however, the corresponding age-standardized rates for IHD and CRC showed relatively stable trends. Heilongjiang, Xinjiang, and Inner Mongolia were ranked as the top three provinces in terms of total risk-attributable NCD burden in 2017. China has a large and growing NCD burden attributable to a diet low in fiber. Greater priority in disease prevention and control should be given to male and older adults throughout China, particularly in some western provinces.

Transit-oriented development (TOD) housing aims to provide housing in locations with good public transportation network, and where residents can work, study and pursue leisure nearby. With this goal, TOD housing could create a more sustainable and time-saving living environment. However, a controversy then arises as these benefits may mean that TOD housing may be pushed to higher price brackets through demand and commercialisation. Although there is much research on TOD and non-transit-oriented development (non-TOD) housing the analysis of revealed and stated preference for TOD house demand and supply is rare. Using stated preference data, results derived from three different groups of residents in Adelaide–‘Corridor Population’, ‘Working Population’ and ‘Mawson Lakes Population’ (a transit-oriented development [TOD] group)–are compared, revealing their different housing needs and demands. All three modelled populations show similar preference patterns regarding housing type, distance to the train station and housing affordability, but some differences are evident. The Corridor Population and Working Population seek houses closer to bus stops, while the Mawson Lakes Population desires housing with high-frequency train services and more activities nearby. The power of the modelling approach to identify factors pertinent for policy development is clearly demonstrated. Refereed/Peer-reviewed

Background Congenital heart disease (CHD) is the most common congenital defect in human beings. The purpose of this article is to investigate impact of an integrated management mode of 'prenatal diagnosis-postnatal treatment' on birth, surgery, prognosis and complications associated with critical CHD (CCHD) in newborns. Methods A retrospective analysis of the medical records of newborns diagnosed with CCHD were divided into two groups: prenatal diagnosis and postnatal diagnosis. The demographics, clinical characteristics, surgical status, prognosis and complications of the two groups were compared and the differences identified. Results Among the 290 newborns with CCHD, 97 (33.4%) were prenatally diagnosed and 193 (66.6%) were postnatally diagnosed. Newborns in the prenatal diagnostic group were hospitalized immediately after birth, whereas the median age of admission was 6.00 (3.00-12.00) days in postnatal diagnostic group, P=0.000. In terms of postnatal symptoms and signs, the incidence of anhelation, cyanosis and cardiac murmur was higher in the postnatal diagnostic group. The rates of preoperative intubation, postoperative open chest exploration and treatment abandonment were higher in the postnatal diagnostic group. The postnatal diagnostic group was more prone to postoperative complications, such as pneumonia and hypoxic-ischemic brain damage. The preoperative mortality [0 (0.0%) vs. 12 (6.2%), P=0.028] in the prenatal diagnostic group was lower than that in the postnatal diagnostic group. And the one-year survival rate of the prenatal diagnostic group was higher (log-rank test P=0.034). Conclusions The integrated management mode of prenatal diagnosis-postnatal treatment can improve postnatal symptoms, reduces complications, reduces preoperative mortality and increases one-year survival rates in newborns with CCHD.

Background Blood-brain barrier (BBB) breakdown, as an early biomarker for vascular mild cognitive impairment (vMCI), has only been validated by a few studies. The aim of this study was to investigate whether compromised BBB integrity is involved in vMCI patients, and detect the relationship between BBB breakdown and cognitive function. BBB leakage in vMCI was explored, and the relationship between BBB leakage and cognitive function was discussed in this study. Methods This is a cross-sectional study involving 26 vMCI patients and 21 sex- and age-matched healthy controls. Dynamic contrast-enhanced-magnetic resonance imaging was performed for all participants, to determine BBB leakage. Leakage volume, leakage rate, and fractional blood plasma volume (Vp) in the grey and white matter were evaluated. Neuropsychological tests were used to determine cognitive function. Leakage rate, leakage volume, and Vp in different brain locations, including deep grey matter, cortical grey matter, white matter hyperintensity, and normal-appearing white matter were compared between the two groups. Results Multivariable linear regression analyses revealed that in all regions of interest, the leakage rate was significantly higher in vMCI patients relative to controls. Leakage volume in normal-appearing white matter and white matter hyperintensity were significantly higher, while Vp in normal-appearing white matter, deep grey matter, and cortical grey matter were significantly lower in vMCI patients. Moreover, Montreal Cognitive Assessment scores decreased with the increase of leakage rate in white matter hyperintensity. Conclusion Increased BBB permeability was detected in vMCI patients and was related to cognitive decline, which suggested that BBB breakdown might be involved in cognitive dysfunction pathogenesis.

Image-based separation of coal and gangue is susceptible to the external environment. This paper studies the effects of illuminance and external moisture on grayscale and texture features of coal a...

BACKGROUND Thymic-enteric adenocarcinoma with positive expression of CDX2 and CK20 is rare in adults, with only 16 reported cases. However, standard treatment options for this type of thymic adenocarcinoma has not yet been established. Therefore, we report a case of stage IV thymic-enteric adenocarcinoma treated with radiotherapy, chemotherapy, and anti-angiogenesis therapy. CASE SUMMARY We report a case of thymic-enteric adenocarcinoma occurring in a 44-year-old woman. The tumor was considered unresectable owing to its invasiveness. The patient was treated with six cycles of oxaliplatin (130 mg/m2, day 1) and capecitabine (1000 mg/m2 BID, days 1-14). During the first three cycles of chemotherapy, concurrent radiotherapy (60 Gy/30 fractions) and anti-angiogenic therapy using apatinib were recommended. The primary tumor achieved partial remission based on the Response Evaluation Criteria in Solid Tumors. During follow-up, there was no evidence of disease relapse, except a high serum CA19-9 level. The patient is alive and regularly followed. Based on the previous literature and the present case, we believe that early diagnosis of thymic-enteric adenocarcinoma is important. CONCLUSION XELOX (capecitabine plus oxaliplatin) combined with radiotherapy is an optional therapy for inoperable thymic-enteric adenocarcinoma.

BACKGROUND: Current mechanical ventilation practice and the use of treatment adjuncts in patients requiring extracorporeal membrane oxygenation (ECMO) for refractory hypoxemia (RH) vary widely and their impact on outcomes remains unclear. In 2015, we implemented a standardized approach to protocolized ventilator settings and guide the escalation of adjunct therapies in patients with RH. This study aimed to investigate ICU mortality, its associated risk factors, and mechanical ventilation practice before and after the implementation of a standardized RH guideline in patients requiring venovenous ECMO (VV-ECMO). METHODS: This was a single-center, retrospective cohort study of patients undergoing VV-ECMO due to RH respiratory failure between January 2008 and March 2015 (before RH protocol implementation) and between April 2015 and October 2019 (after RH protocol implementation). RESULTS: A total of 103 subjects receiving VV-ECMO for RH were analyzed. After implementation of the RH protocol, more subjects received prone positioning (6.7% vs 23.3%, P = .02), and fewer received high-frequency oscillatory ventilation than before launching the RH protocol (0% vs 13.3%, P = .01). Plateau pressure was also lower before initiation of ECMO (P = .04) and at day 1 during ECMO (P = .045). Driving pressure was consistently lower at days 1, 2, and 3 after ECMO initiation: median 13.0 (interquartile range [IQR] 10.6–18.0) vs 16.0 (IQR 14.0–20.0) cm H2O at day 1 (P = .003); 13.0 (IQR 11.0–15.9) vs 15.5 (IQR 12.0–20.0) cm H2O at day 2 (P = .03); and 12.0 (IQR 10.0–14.5) vs 15.0 (IQR 12.0–19.0) cm H2O at day 3 (P = .005). CONCLUSIONS: The implementation of a standardized RH guideline improved compliance with a lung-protective ventilation strategy and utilization of the prone position and was associated with lower driving pressure during the first 3 days after ECMO initiation in subjects with refractory hypoxemia.

Purpose Drug resistance is one of the main causes of chemotherapy failure in patients with small cell lung cancer (SCLC), and extensive biological studies into chemotherapy drug resistance are required. Materials and Methods In this study, we performed lncRNA microarray, in vitro functional assays, in vivo models and cDNA microarray to evaluate the impact of lncRNA in SCLC chemoresistance. Results The results showed that KCNQ1OT1 expression was upregulated in SCLC tissues and was a poor prognostic factor for patients with SCLC. Knockdown of KCNQ1OT1 inhibited cell proliferation, migration, chemoresistance and promoted apoptosis of SCLC cells. Mechanistic investigation showed that KCNQ1OT1 can activate transforming growth factor-β1 mediated epithelial-to-mesenchymal transition in SCLC cells. Conclusion Taken together, our study revealed the role of KCNQ1OT1 in the progression and chemoresistance of SCLC, and suggested KCNQ1OT1 as a potential diagnostic and prognostic biomarker in SCLC clinical management.

To study the relationship between daily activity level and cognitive function in community-dwelling elderly. We collected demographic features, cognitive function, activity level and self-rating depression scale scores in 53 community-dwelling olderly aged 60 years or above. The activity level and moderate-to-vigorous physical activity (MVPA) time were assessed by using the accelerometer for 7 consecutive days. We compared activity level, MVPA time and depression scores between cognitive impaired and normal groups. Cognitive functions were compared in groups with different MVPA level, and the correlation between cognitive function and MVPA time was analysed. Of the 53 subjects, 27 had varying degrees of cognitive impairment. Individuals with cognitive impairment shown significantly shorter MVPA time and higher depression score compared to the cognitive normal group (P < 0.05). After controlling for confounding factors (age, BMI), MVPA time was associated with cognitive function (r = 0.358, P = 0.009). The memory factor score correlated with MVPA time (r = 0.357, P = 0.012) and mean activity level (r = 0.287, P = 0.046). Moderate-to-vigorous physical activity in the elderly was positively related to their cognitive function. Strengthening daily activities may beneficial for the elderly to maintain better cognitive function.

The aim of this study was to investigate associations between age-dependent variations in isolated systolic/diastolic hypertension (ISH/IDH) with target organ damage in chronic kidney disease (CKD). A cross-sectional study was conducted among 2,459 CKD patients with ambulatory blood pressure monitoring. Blood pressure was categorized into four groups: normotension, ISH, IDH, and systolic-diastolic hypertension. The outcome measurements were left ventricular mass index (LVMI), estimated glomerular filtration rate(eGFR), and urinary albumin creatinine ratio (ACR). Older patients (≥60-years-old) had a higher prevalence of ISH and a lower prevalence of IDH than younger patients (

Objective In this study, we explored the effect of semaphorin5A (SEMA5A) on RA pathogenesis and its specific TSP1 domain on pannus formation. Methods The expression of SEMA5A was detected in the synovium, the fibroblast-like synoviocytes (FLSs) and the SF of RA patients and healthy controls (HCs) by real-time quantitative PCR (q-PCR), immunohistochemistry staining, western blot and ELISA. SEMA5A-mAb intervention was performed to appraise the severity of joints in the CIA model. Transcriptome sequencing and bioinformatics analysis in SEMA5A-transfected FLSs from HCs were performed to screen differentially expressed genes after SEMA5A overexpression. An MTT assay in RA-FLSs, a chicken embryo allantoic membrane experiment and a tube formation experiment were used to clarify the influence of SEMA5A on cell proliferation and angiogenesis. Furthermore, a rescue experiment verified the function of the TSP1 domain of SEMA5A in the progress of RA with Sema5a−/− CIA mice. Results The expression of SEMA5A increased in RA compared with that in HCs. Simultaneously, SEMA5A-mAbs significantly attenuated joint injury and the inflammatory response in CIA models. In addition, transcriptome sequencing and angiogenesis-related experiments verified the ability of SEMA5A to promote FLS proliferation and angiogenesis. Moreover, TSP1 was proved to be an essential domain in SEMA5A-induced angiogenesis in vitro. Additionally, rescue of TSP1-deleted SEMA5A failed to reduce the severity of arthritis in a CIA model constructed with Sema5a −/− mice. Conclusion In summary, upregulation of SEMA5A was first confirmed in pathological lesions of RA patients. Furthermore, treatment with SEMA5A-mAbs attenuated the progress of RA in the CIA model. Moreover, TSP1 was indicated as the key domain of SEMA5A in the promotion of pannus formation in RA.

Background: In the phase III MONARCH plus study (NCT02763566) the cyclin-dependent kinase (CDK) 4&6 inhibitor abemaciclib in combination with non-steroidal aromatase inhibitors (NSAI) or with fulvestrant compared with placebo demonstrated its efficacy and acceptable safety profile at interim analysis in postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) locoregionally recurrent or metastatic breast cancer. One of the most common treatment-emergent adverse event (TEAE) was diarrhea, typically low grade and of early onset. We will further characterize abemaciclib-associated diarrhea and describe its management in MONARCH plus trial. Methods: MONARCH plus study included two cohorts of patients. Cohort A enrolled patients with initial treatment of endocrine therapy, received abemaciclib or placebo plus NSAI (anastrozole or letrozole); Cohort B enrolled patients who progressed on prior endocrine therapy, receiving abemaciclib or placebo plus fulvestrant. The relative dose intensity was defined as the percentage of actual dose received relative to the planned dose. The severity of diarrhea was reported by investigators and graded according to Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0). Further analysis on diarrhea included time to onset, duration, supportive medication and dose modifications. Progression-free survival (PFS) was defined as time from randomization to death or progression (RECIST v1.1), and a stratified Cox proportional hazard model was used to estimate the hazard ratio (HR) between study intervention arm and placebo arm. Results: The median relative dose intensity of abemaciclib in abemaciclib plus NSAI arm and abemaciclib plus fulvestrant arm were 96.77% and 96.30% respectively. In abemaciclib plus NSAI arm and abemaciclib plus fulvestrant arm, the median time to onset of first reported diarrhea was 7 and 6 days and majority of diarrhea events occurred early (66.3% and 71.2% of patients reported diarrhea in Cycle 1 respectively). Diarrhea was typically of low grade (3.9% and 1.9% of patients reported Grade 3 in abemaciclib plus NSAI arm and abemaciclib plus fulvestrant arm, no Grade 4 diarrhea was reported in either arm). Median duration of grade ≥ 3 diarrhea was 2.5 and 3.5 days. Diarrhea was managed by dose adjustments and/or supportive medication (Table 1). Dose reductions were present in 2.0% and 2.9% of patients, and anti-diarrhea therapy was received in 30.2% and 32.7% of patients with abemaciclib plus NSAI and abemaciclib plus fulvestrant arm, respectively. As data cutoff, most diarrhea events were reported as resolved, and the incidence dropped below 10% (Grade 2) and 1% (Grade 3) by Cycle 2 in both arms and kept low incidence over time. Compared to the placebo arm, patients treated with abemaciclib combination who reported diarrhea within the first 7 days (abemaciclib + NSAI, HR [95% CI]: 0.289 [0.166, 0.502]; abemaciclib + fulvestrant, HR [95% CI]: 0.371 [0.213, 0.647]) had significant improvement in PFS. Conclusion: Majority of diarrhea events were of low grade in severity and well managed by anti-diarrheal medications, dose omissions or/and dose reductions in MONARCH plus patients. Table 1. Summary of dose adjustments and supportive medications in patients experiencing diarrheaCohort ACohort BAbemaciclib + NSAIAbemaciclib + FulvestrantN = 205N = 104Diarrhea (any grade), n (%)164 (80.0)82 (78.8)1105 (51.2)52 (50.0)251 (24.9)28 (26.9)38 (3.9)2 (1.9)Outcome, number of events, n796333Recovered/resolved, n (%)757 (95.1)318 (95.5)Not recovered/resolved, n (%)17 (2.1)7 (2.1)Treatment change, n (%)Dose reduction4 (2.0)3 (2.9)Dose omission3 (1.5)3 (2.9)Treatment discontinuation00Anti-diarrhea therapies, n (%)62 (30.2)34 (32.7)loperamide48 (23.4)21 (20.2)berberine6 (2.9)6 (5.8) Citation Format: Zefei Jiang, Xichun Hu, Qingyuan Zhang, Tao Sun, Yongmei Yin, Huiping Li, Min Yan, Zhongsheng Tong, Christina Pimentel Oppermann, Yunpeng Liu, Romulo Costa, Man Li, Xi Chen, Ying Cheng, Quchang Ouyang, Ning Liao, Xiaojia Wang, Xinhong Wu, Jifeng Feng, Roberto Hegg, Govindbabu Kanaka Setty, Amit Agarwal, Jyoti Bajpai, Jing Cheng, Gustavo Girotto, Chanchal Goswami, Wenjing Hu, Jian Huang, MA Coccia Portugal, Jin Yang, Rongsheng Zheng, Fabio Andre Franke, Qiang Liu, Yunjiang Liu, Yongkui Lu, Cristiano Souza, Shiying Yu, Nalini Kilara, Harsha Panchal, Ashish Singh, Shona Nag, Jian Liu, Bernardo Rapoport, Neonyana Keorapetse Rebecca Tabane, Hongxia Wang, Ning Wang, Rubing Han, Wanli Zhang. Management of abemaciclib associated diarrhea in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer: Analysis of the MONARCH plus study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS13-25.

With the deepening of people’s research on event anaphora, a large number of methods will be used in the identification and resolution of event anaphora. Although there has been some progress in the resolution of the current event, the difficult problems have not yet been completely resolved. This study analyzes the English information anaphora resolution based on SVM and machine learning algorithms and uses the CNN three-layer network as the basis to model the structure. Moreover, this study improves the semantic features by adding semantic roles and analyzes and compares the performance of the improved semantic features with those before the improvement. In addition, this study combines semantic features to compare and analyze each feature combination and uses a dual candidate model to improve the system. Finally, this study analyzes the experimental results. The results show that the performance of the system using the dual candidate model is better than that of the single candidate model system.

Using Manas riverbed sediment in Northwest China as filter media, a comprehensive study was conducted on the hydraulic performance of the mesh filter, including filtration performance and sewage performance, head loss and sewage time. Relationship among filter head loss, sewage time, flow rate, sand content, filter aperture and particle gradation was established. The results showed that at the filter aperture of 0.100 mm and the influent flow rates of 160 m3/h, 180 m3/h, 200 m3/h and 220 m3/h, the corresponding maximum head loss was 8.97 m, 11 m, 12.95 m and 15.81 m, respectively. With the increase in the influent flow rate, the head loss increased. Influent flow rate, sewage flow rate, sand content, filter aperture and particle gradation jointly affected the sewage time. The sewage time was determined to be in the range of 20–45 s. Mathematical expressions for head loss and sewage time were established through theoretical analysis and verified by the test results. The results showed that the error for the head loss and sewage time between the predicted and experimental results was less than 10%, and the regression coefficient was higher than 0.95. It has been demonstrated that the proposed equations of head loss and sewage time can be used to evaluate self-priming screen filters under various working conditions. From the results, when the sewage time was 45 s, the mesh filter can achieve a higher sewage effect and ensure the efficient operation of the next filtration cycle.

Peiyan Ni,1– 3 Manli Liu,1– 3 Dequan Wang,1– 3 Yang Tian,1– 3 Liansheng Zhao,1– 3 Jinxue Wei,1– 3 Xueli Yu,1– 3 Xueyu Qi,1– 3 Xiaojing Li,1– 3 Hua Yu,1– 3 Rongjun Ni,1– 3 Xiaohong Ma,1– 3 Wei Deng,1– 3 Wanjun Guo,1– 3 Qiang Wang,1– 3 Tao Li1– 4 1The Psychiatric Laboratory, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 2Mental Health Center, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 3Huaxi Brain Research Center, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 4Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangzhou, People’s Republic of ChinaCorrespondence: Tao LiThe Psychiatric Laboratory, West China Hospital, Sichuan University, 28 Dian Xin Nan Road, Chengdu, Sichuan, 610041, People’s Republic of ChinaTel/Fax +86-28-85423561Email litaohx@scu.edu.cnIntroduction: Schizophrenia, bipolar disorder (BD), and major depressive disorder are three common mental disorders. Although their diagnosis and treatment differ, they partially overlap.Methods: To explore the similarities and characteristics of these three psychiatric diseases, an intelligence quotient (IQ) assessment was performed to evaluate cognitive deficits. Relative catechol-O-methyltransferase (COMT) expression in peripheral blood mononuclear cells was examined in all three groups compared with healthy controls (HCs).Results: The results indicated that patients with any of the three psychiatric diseases presented IQ deficits, and that the first-episode schizophrenia (FES) group had even lower cognitive function than the other two groups. The relative COMT expression decreased in the FES group and increased in the BD group compared with the HC group. The correlation analysis of COMT expression level and IQ scores showed a positive correlation between relative COMT expression and full-scale IQ in the HC group. However, this correlation disappeared in all three psychiatric diseases studied.Conclusion: In conclusion, this cross-disease strategy provided important clues to explain lower IQ scores and dysregulated COMT expression among three common mental illnesses.Keywords: first-episode schizophrenia, FES, bipolar disorder, BD, first-episode major depressive disorder, MDD, catechol-O-methyltransferase, COMT, intelligence quotient, IQ

Hong Kong is a metropolitan city. Owing to its historical background as a former British colony, it is characterised by a mixture of Chinese and Western cultures. While most housing estates’ names ...

BackgroundMetastasis-Associated in Colon Cancer 1(MACC1) is a validated biomarker for metastasis and is linked to survival. Although extensive experimental evidence indicates an association between MACC1 and diverse cancers, no pan-cancer analyses have yet been performed for this marker, and the role of MACC1 in immunology remains unknown. Material and MethodsIn our study, we performed the analysis of MACC1 expression and its influence on prognosis using multiple databases, including TIMER2, GEPIA2, Kaplan-Meier plotter. MACC1 promoter methylation levels were evaluated using the UALCAN database. Based on the TCGA database, we explored the relationship between MACC1 and tumor mutational burden (TMB), microsatellite instability (MSI), immune checkpoints using the R programming language. We evaluated the association between MACC1 and immune infiltration via TIMER and UALCAN. ResultsOur results revealed that abnormal DNA methylation may be an important cause for the different expression of MACC1 across cancer types. Meanwhile, we explored the potential oncogenic roles of MACC1 and found significant prognostic value. MACC1 may be related to T-cell function and the polarization of tumor-associated macrophages, especially in STAD and LGG. Its expression was associated with immune infiltration and was found to be closely related to immune checkpoint-associated genes, especially CD274 and SIGLEC15, indicating that MACC1 may be a potential immune therapeutic target for several malignancies. Our paper reveals for the first time the relationship between MACC1 and cancer immunology. ConclusionsMACC1 might act as a predictor for the immune response in cancer patients, and could also represent a new potential immunotherapeutic target.

Objective: To systematically explore the effect and mechanism of traditional Chinese herbs in the treatment of allergic rhinitis. Methods: Magnolia flower, xanthium fruit, astragalus root, paniculate cynanchum, scutellaria root, cicada molting, stephania root, small centipeda herb, and licorice root as traditional Chinese herbs are widely used to treat allergic rhinitis. With multiple database integration and entity grammar systems, a molecular interaction network of traditional Chinese herbs for treating allergic rhinitis was established. Bioinformatics approaches were adopted to integrate relevant data and biological information by multiple databases. Molecular interaction network of Chinese herbs for treating allergic rhinitis was constructed based on entity grammar systems model. The network was then used for elucidating the anti-allergic rhinitis mechanism of the Chinese herbs on the molecular level. The subnetworks were also extracted to explicitly display the pathway and targets where effective components acted on. Results: Traditional Chinese herbs could influence various pathological aspects in allergic rhinitis including the production of pro-inflammatory substances, such as histamine and cytokine interleukin-4 (IL-4), interleukin-13 (IL-13), lowering immunoglobulin E (IgE) level or blocking antigen binding, altering the biological processes of IgE, modulating the balance of T helper (Th) or other cells by cell proliferation and differentiation, mediating cell–cell signaling and second-messenger-mediated signaling, stabilizing the cell membrane, and affecting regulation of cellular defense response. Conclusion: The research theoretically confirms the mechanism of anti-allergic rhinitis by traditional Chinese herbs, provides important fundamental research information for treatment of allergic rhinitis, and may serve as a reference for new drug development and effective ingredients of compatibility.

Genome‐wide 5hmC profiling in cell‐free DNA acquired from CRC patients, adenoma patients, and healthy individuals revealed that the differential 5hmC‐modified regions were gathered into four clusters with no overlap, although there are a few overlapped genes shared between the different clusters. CRC patients with adenoma history showed exclusive 5hmC‐gain characteristics, which was consistent with the ‘parallel’ evolution hypothesis in adenoma., Approximately 85% colorectal cancers (CRCs) are thought to evolve through the adenoma‐to‐carcinoma sequence associated with specific molecular alterations, including the 5‐hydroxymethylcytosine (5hmC) signature in circulating cell‐free DNA (cfDNA). To explore colorectal disease progression and evaluate the use of cfDNA as a potential diagnostic factor for CRC screening, here, we performed genome‐wide 5hmC profiling in plasma cfDNA and tissue genomic DNA (gDNA) acquired from 101 samples (63 plasma and 38 tissues), collected from 21 early‐stage CRC patients, 21 AD patients, and 21 healthy controls (HC). The gDNA and cfDNA 5hmC signatures identified in gene bodies and promoter regions in CRC and AD groups were compared with those in HC group. All the differential 5hmC‐modified regions (DhMRs) were gathered into four clusters: Disease‐enriched, AD‐enriched, Disease‐lost, and AD‐lost, with no overlap. AD‐related clusters, AD‐enriched and AD‐lost, displayed the unique 5hmC signals in AD patients. Disease‐enriched and Disease‐lost clusters indicated the general 5hmC changes when colorectal lesions occurred. Cancer patients with a confirmable adenoma history segmentally gathered in AD‐enriched clusters. KEGG functional enrichment and GO analyses determined distinct differential 5hmC‐modified profiles in cfDNA of HC individuals, AD, and CRC patients. All patients had comprehensive 5hmC signatures where Disease‐enriched and Disease‐lost DhMR clusters demonstrated similar epigenetic modifications, while AD‐enriched and AD‐lost DhMR clusters indicated complicated subpopulations in adenoma. Analysis of CRC patients with adenoma history showed exclusive 5hmC‐gain characteristics, consistent with the ‘parallel’ evolution hypothesis in adenoma, either developed through the adenoma‐to‐carcinoma sequence or not. These findings deepen our understanding of colorectal disease and suggest that the 5hmC modifications of different pathological subtypes (cancer patients with or without adenoma history) could be used to screen early‐stage CRC and assess adenoma malignancy with large‐scale follow‐up studies in the future.

ssemination and development of information has occurred, and this has had a positive impact on audiences. Research on the integration and develop-ment of traditional media with new media is recent, and has been focused, across the world, on the educational context. This study most specifically looks at art education. Or art teachers in further and higher education, the use of electronic media may not only lead to better work, creatively, but al-so more efficient real-time interaction, and the more effective collection of student feedback. Modern students’ lifestyles and the teaching environment they are subject to, have created the basis for convergence media; within such an environment, cultural knowledge can be more quickly and conven-iently accessed. Based on an analysis of innovative art education teaching methods within this era of convergent media, this paper proposes a design framework for the sharing of such high-quality teaching resources and the design of a shared teaching platform; these proposals are informed by the use of the ‘extreme value’ method to optimize the allocation of high-quality teaching resources in the framework design during the sharing process. The identification of an objective function can be effective in this context. The participation of an objective function within resource allocation can better guarantee that the best teachers can arrange the teaching programs that are most effective for particular courses --- so that high-quality teaching pro-grams can be better spread across the media available and so that the stu-dents can better accept and absorb this new teaching mode.

International organizations such as the International Monetary Fund and the World Bank raise concerns about the financial sustainability issues of pension systems. These issues have attracted increasing attention because of the challenges presented by lower growth and financial market volatility, making it harder for governments to fulfil their promises on pension policies (Ebbinghaus, 2011). In order to tackle these challenges, it is not uncommon that governments reform pension schemes with an emphasis on individual responsibility (Yeh et al., 2018). They particularly stress the earnings-related pension measures as an important means to assist people to accumulate pension income (Foster, 2014). Employees are the target group for measures relating to earnings-related pension measures. The amount of pension income accumulated through these measures is highly related to employees’ earnings.

Macrophages are a double-edged sword with potential cancer-promoting and anticancer effects. Controversy remains regarding the effect of macrophages, especially M1 macrophages, on tumor promotion and suppression. We aimed to investigate the role of M1 macrophages in the occurrence and progression of esophageal squamous cell carcinoma (ESCC). Analyzing the data in Gene Expression Omnibus database by the CIBERSORT algorithm found that M1 macrophages were one of the important components of many immune cells in ESCCs, and the increase in their number was obviously negatively correlated with tumor T staging. This result was verified by our experimental data: the density of CD68/HLA-DR double-stained M1 macrophages in ESCC tumor nest and tumor stroma was significantly higher than that in cancer-adjacent normal (CAN) tissues. The density of M1 macrophages in ESCC tumor nest was negatively correlated with the patient’s lymph node metastasis and clinical stage (P < 0.05), and the negative tendency was more obvious for M1 macrophages in ESCC tumor stroma (P < 0.001). Exposure to M1 macrophage-conditioned medium inhibited ESCC cell migration and invasion ability significantly (P < 0.05). Moreover, the increased M1 macrophage density in ESCC tumor stroma correlated positively with good prognosis of ESCC. M1 macrophages were involved in inhibiting ESCC cell migration and invasion, which could serve as a good prognostic factor in patients with ESCC.

The aim of this study was to estimate the burden of ischemic heart disease (IHD) and type 2 diabetes mellitus (T2DM) attributable to a diet high in sugar-sweetened beverages (SSBs) in China from 1990 to 2017.Data from the Global Burden of Disease Study 2017 were used to assess all-age and age-standardized, risk-attributable mortality, years of life lost (YLL), years of life with disability (YLD), and disability-adjusted life years (DALYs) by age, sex, year, province, and sociodemographic index (SDI).For total noncommunicable diseases (NCDs), 12 523 (95% uncertainty interval 776-27 631) deaths, 305 288 (18 611-661 847) YLL, 142 051 (64 530-257 468) YLD, and 447 339 (132 677-858 838) DALYs were attributable to diet high in SSBs in 2017, particularly among males. Age-standardized, risk-attributable mortality, YLL, YLD, and DALY rates increased distinctly by 507.3%, 410.3%, 571.0%, and 453.3% from 1990 to 2017 respectively. Age-sex-specific, risk-attributable mortality and YLL rates for IHD in older adults (over 65 years) were higher than in young (between 25 and 39 years) and middle-aged adults (between 40 and 64 years) in 2017; however, the YLD and DALY rates for T2DM were higher in young and middle-aged males than in older males. The age-standardized, risk-attributable DALY rates for total NCDs increased substantially in high-SDI and high-middle-SDI provinces during the period.China has a huge and growing burden of IHD and T2DM attributable to diet high in SSBs, particularly among young and middle-aged male adults in wealthier provinces. Evidence-based public health policies at the provincial levels to reduce the consumption of SSBs should be prioritized in China.目的: 估计中国1990年至2017年高糖饮料所导致的缺血性心脏病和2型糖尿病的疾病负担。 方法: 使用2017年全球疾病负担研究的数据; 按年龄、性别、年份、省份和社会人口指数评估归因于高糖饮料的缺血性心脏病和2型糖尿病的死亡率、早死所致寿命损失(YLL)、伤残所致寿命损失(YLD)和伤残调整寿命年(DALY)数及标化率。 结果: 2017年归因于高糖饮料的慢性病总死亡人数12523人(776-27631); 早死所致寿命损失为305288人年(18611-661847); 伤残所致寿命损失为142051人年(64530-257468); 伤残调整寿命年为447339人年(132677-858838); 以男性为主。1990年至2017年; 年龄标化的死亡率、YLL、 YLD 和DALY率分别增加了507.3%、410.3%、571.0%和453.3%。2017年; 老年人群(65岁以上)缺血性心脏病的死亡率和YLL率高于年轻人(25-39岁)和中年人(40-64岁); 然而; 对2型糖尿病来说; 青年和中年男性的YLD率和DALY率高于老年男性。1990-2017年; 在高SDI和高-中SDI的省份; 慢性病的标化DALY率大大增加。 结论: 中国归因于高糖饮料的缺血性心脏病和2型糖尿病的疾病负担呈现增长趋势; 特别是在较富裕省份的年轻和中年男性人群中。基于这些证据; 应优先考虑减少高糖饮料消费的公共卫生决策。.

Background Colorectal cancer (CRC) has emerged as a major public health concern. However, little is known about the burden attributable to specific risk factors. The present study aimed to estimate the temporal trends and geographical variation of CRC burden attributable to a diet low in milk in China. Methods Following the general analytic strategy used in the 2017 Global Burden of Disease study, we assessed the age-, sex-, and province-specific mortality and disability-adjusted life-years (DALYs) of CRC caused by a diet low in milk in China from 1990 to 2017. Results In 2017, a diet low in milk contributed 32 032 [95% uncertainty interval (UI) = 11 350-53 806] deaths and 726 710 (95% UI = 256 651-1 218 153) DALYs for CRC with a population attributable fraction of 17.1%. The age-standardised mortality and DALY rates per 100 000 were 1.7 (95% UI = 0.6-2.9) and 36.8 (95% UI = 13.0-61.7), respectively. An upward trend with age in rates of mortality and DALYs was observed. Males had higher age-standardised rates than females. The number of deaths and DALYs increased significantly from 1990 to 2017, whereas the corresponding age-standardised rates showed relatively stable trends. In 2017, Hunan and Liaoning were ranked as the top two provinces in terms of disease burden. Socio-demographic index had a weak correlation with the age-standardised mortality (r = 0.348, P = 0.047). Conclusions The present study shows a substantial increase in the CRC burden attributable to a diet low in milk over the past three decades. Greater priority in CRC prevention should be given to males and the elderly population throughout China, particularly in less-developed provinces.

ObjectivesA noveltp0548sequence-type was identified in one clinical isolate (X-4) from a patient diagnosed with primary syphilis in Xiamen, China. To precisely define and characterise a new clinical isolate, we performed further genome-scale molecular analysis.MethodsThe pooled segment genome sequencing method followed by Illumina sequencing was performed.ResultsThis novel sequence-type contained a unique nucleotide substitution ‘T’ at position 167 and belonged to the SS14-like clade of TPA strains, as determined by phylogenetic analysis. Multi-locus sequence analysis of nine chromosomal loci demonstrated that the X-4 isolate was clustered within a monophyletic group of TPA strains. Whole-genome phylogenetic analysis subsequently corroborated the TPA strain classification of the X-4 isolate and revealed that the isolate was closely related to the SS14 strain, with 42 single-nucleotide variations and 12 insertions/deletions. In addition, high intrastrain heterogeneity in the length of the poly G/C tracts was found in the TPAChi_0347 locus, which might indicate that this gene of the X-4 isolate is likely involved in phase variation events. The length heterogeneity of the poly A/T tracts was lower than the genetic variability of the poly G/C tracts, and all the observed intrastrain variations fell within coding regions.ConclusionThe noveltp0548sequence-type was determined to belong to a new TPA isolate, X-4. The identification of variable length in homopolymetic tracts (G/C and A/T) could provide a snapshot of the genes that potentially involved in genotype–phenotype variations. These findings provide an unequivocal characterisation for better understanding the molecular variation of this emerging isolate.

BACKGROUND To investigate the feasibility of a freehand transperineal (TP) systematic prostate biopsy protocol under local anaesthesia (LA) and the value of different sectors in diagnosing prostate cancer (PCa). METHODS A total of 611 consecutive freehand TP biopsies under LA in 2 hospitals were prospectively evaluated. Cancer detection rate in each of the four different sectors (anterior, mid, posterior, basal) was recorded to evaluate the value of each sector. Procedure tolerability was assessed by pain score and complications were documented. RESULTS Systematic biopsies were performed in 556 out of 611 men with a median of 20 (IQR 12-24) biopsy cores taken. The median PSA was 9.9 (Inter-quartile range[IQR] 6.4-16.2) ng/mL, and 89.0% were first biopsies. All PCa and ISUP grade group (GG) ≥ 2 PCa (HGPCa) were diagnosed in 41.4% (230/556) and 28.2% (157/556) biopsies respectively. 77.0% HGPCa was diagnosed in ≥2 sectors. Single-sector HGPCa was predominantly found in anterior or posterior sector. Omitting base sector would have missed 1.5% (1/65) HGPCa out of the 219 cases with ≥24-core biopsies performed. Further omission of mid sector would have missed 3.1% (2/65) HGPCa and 7.4% (7/94) ISUP GG1 PCa (in which 3/7 involved 2 sectors). LA TP biopsy was well tolerated and the mean pain scores of the different steps of the procedure were between 1.9-3.1 (out of 10). Post-biopsy fever occurred in 0.3% of patients (2/611) and no sepsis was reported. The risk of urinary retention in men with ≥20 cores in ≥60 ml prostate was 7.8% (14/179), compared with 1.7% (7/423) in other groups (p

With the growing popularity of social network in sport, it expresses the social relationships between individuals and facilitates realistic applications, e.g., social event mining and discovery. Sport network as a specific social network has been widely studied in research and commercial fields. However, most of the existing works utilize a simplex strategy to improve certain indicators in the team and do not consider the effect of strategy adjustment based on the current situation. In this paper, we study the problem of efficient strategy mining in football social network. To address this problem, we propose a quantitative way to combine the aspects of coordination, adaptability, flexibility, and tempo into a passing network, which notably improves the timeliness and information content of the existing network. On this basis, we design a suppression function to express the impact of strategy. Then, we propose a novel passing network and group cooperation scheme based on quantified team performance to obtain the efficient strategies. At last, the experimental results show that, based on the performance of the same team, our optimized passing network has a higher winning rate in practice.

Background It is uncertain whether long-term use of clopidogrel alone can cause gastric mucosal injury. This study aimed to evaluate the relationship between ABCB1 C3435T polymorphisms, which could affect the intestinal absorption of clopidogrel, and gastric mucosal erosion in elderly Chinese men who used clopidogrel alone. Methods We selected 298 male patients (aged between 68.2 and 89.5 years, average age 78); 201 of them constituted the control group, and 97 constituted the case group. Patients taking clopidogrel alone who had undergone endoscopic screening for gastric erosion were analyzed for ABCB1 C3435T polymorphisms by a TaqMan assay. Results The proportion of people carrying the ABCB1 3435T allele (n = 63, 64.9% vs n = 97, 48.3%, p = 0.007) was significantly higher in the case group than in the control group. After adjustments for significant factors were made, ABCB1 3435T allele carrier (OR 2.14, 95% CI 1.43-3.84, p

Objective To determine the prevalence of masked morning hypertension and investigate its role in target organ damage in nondialysis patients with chronic kidney disease. Methods A total of 1841 patients with chronic kidney disease admitted to our hospital were recruited. According to measurements of clinic blood pressure and ambulatory blood pressure, they were divided into four groups: normotension, white-coat hypertension, masked morning hypertension, and sustained hypertension. Multivariate logistic regression analyses were used to evaluate the association between masked morning hypertension and cardiovascular and renal parameters. Results Overall, 288 (15.6%) patients were diagnosed with masked morning hypertension. Patients with masked morning hypertension had a higher prevalence of left ventricular hypertrophy, abnormal carotid intima-media thickness, and impaired renal function when compared with normotensive patients, although lower than those with sustained hypertension. After adjustment for demographics and clinical characteristics, masked morning hypertension was related to cardiovascular damage and renal dysfunction compared with normotension. The odds ratio for left ventricular hypertrophy, abnormal carotid intima-media thickness and impaired renal function was 1.955 [95% confidence interval (CI), 1.247-3.065], 1.469 (95% CI: 1.011-2.133), and 1.819 (95% CI: 1.112-2.976), respectively. Masked morning hypertension correlated with target organ damage even when patients with a history of cardiovascular disease were excluded. Conclusion The prevalence of masked morning hypertension in nondialysis chronic kidney disease patients was high, and masked morning hypertension was associated with target organ damage in chronic kidney disease patients.

PARP inhibitor monotherapies are effective to treat patients with breast, ovary, prostate, and pancreatic cancer with BRCA1 mutations, but not to the much more frequent BRCA wild-type cancers. Searching for strategies that would extend the use of PARP inhibitors to BRCA1-proficient tumors, we found that the stability of BRCA1 protein following ionizing radiation (IR) is maintained by postphosphorylational prolyl-isomerization adjacent to Ser1191 of BRCA1, catalyzed by prolyl-isomerase Pin1. Extinction of Pin1 decreased homologous recombination (HR) to the level of BRCA1-deficient cells. Pin1 stabilizes BRCA1 by preventing ubiquitination of Lys1037 of BRCA1. Loss of Pin1, or introduction of a BRCA1-mutant refractory to Pin1 binding, decreased the ability of BRCA1 to localize to repair foci and augmented IR-induced DNA damage. In vitro growth of HR-proficient breast, prostate, and pancreatic cancer cells were modestly repressed by olaparib or Pin1 inhibition using all-trans retinoic acid (ATRA), while combination treatment resulted in near-complete block of cell proliferation. In MDA-MB-231 xenografts and triple-negative breast cancer patient-derived xenografts, either loss of Pin1 or ATRA treatment reduced BRCA1 expression and sensitized breast tumors to olaparib. Together, our study reveals that Pin1 inhibition, with clinical widely used ATRA, acts as an effective HR disrupter that sensitizes BRCA1-proficient tumors to PARP inhibition. Significance: PARP inhibitors have been limited to treat homologous recombination–deficient tumors. All-trans retinoic acid, by inhibiting Pin1 and destabilizing BRCA1, extends benefit of PARP inhibitors to patients with homologous recombination–proficient tumors. See related commentary by Cai, p. 2977

Handheld robotic laparoscopic instruments fill the gap between robotic and conventional instruments, combining the advantages of degrees of freedom and low price. The difficulty and value in learning these new instruments require detailed investigation. Forty novice surgeons with no laparoscopic experience were randomly assigned to two groups: conventional instrument group (Group Conv) and robotic instrument group (Group Rob). The same training protocol was used in both groups: after viewing a standard operation film, laparoscopic suture training was administered using the corresponding instruments. After each training period, surgeons were tested using a force-sensing test platform. Maximum force (MF) and impulse (IMP) of operators through each ring were recorded. Learning curves based on MF and IMP for both instruments were compared. Institutional review board approval is not needed for this study. MF and IMP of both groups decreased with increased training time; the learning curve of Group Conv decreased faster than that of Group Rob. When training time reached 13 h, the MF of Group Rob was significantly lower than that of Group Conv (P