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This study aims to investigate the relationship between carbon emissions (CO2) and economic policy uncertainty for East Asian countries. During recent decades, climate change has become a severe issue globally. To our understanding, the impact of economic policy uncertainty (EPU) on CO2 emissions has not been thoroughly studied in the environment-energy literature. To overcome this research gap, this study explores the link between EPU, CO2 emissions, foreign direct investment (FDI), and renewable energy for the panel of four East Asian economies, namely, China, Japan, South Korea, and Singapore, from 1997 to 2020. We used second-generation econometric estimations to confirm cross-sectional dependence, cointegration, and stationarity among the selected variables. This study finds that economic policy uncertanity (EPU), trade, and GDP have a positive correlation with carbon emissions. However, FDI and renewable energy consumption boost the quality of the environment of East Asian economies. The outcomes of the Dumitrescu–Hurlin panel causality estimation revealed two-way association between CO2 and economic policy uncertainty, CO2 and energy consumption, CO2 and economic growth, and CO2 and trade. Afterward, we use the FMOLS estimations for robustness check. Based on the inclusive outcomes, we draw substantial suggestions for decision-makers and urge them to consider the potential negative effects of EPU on CO2 emissions policies. In addition to this, if policymakers seek to simultaneously control EPU and CO2 emissions, they should work out for alternate ways such as the use of green technology related to energy, foreign capital investment, and renewable energy consumption to mitigate CO2 emissions.

Intercellular cross-talk plays important roles in cancer progression and metastasis. Yet how these cancer cells interact with each other is still largely unknown. Exosomes released by tumor cells have been proved to be effective cell-to-cell signal mediators. We explored the functional roles of exosomes in metastasis and the potential prognostic values for hepatocellular carcinoma (HCC). Exosomes were extracted from HCC cells of different metastatic potentials. The metastatic effects of exosomes derived from highly metastatic HCC cells (HMH) were evaluated both in vitro and in vivo. Exosomal proteins were identified with iTRAQ mass spectrum and verified in cell lines, xenograft tumor samples, and functional analyses. Exosomes released by HMH significantly enhanced the in vitro invasion and in vivo metastasis of low metastatic HCC cells (LMH). S100 calcium-binding protein A4 (S100A4) was identified as a functional factor in exosomes derived from HMH. S100A4rich exosomes significantly promoted tumor metastasis both in vitro and in vivo compared with S100A4low exosomes or controls. Moreover, exosomal S100A4 could induce expression of osteopontin (OPN), along with other tumor metastasis/stemness-related genes. Exosomal S100A4 activated OPN transcription via STAT3 phosphorylation. HCC patients with high exosomal S100A4 in plasma also had a poorer prognosis. In conclusion, exosomes from HMH could promote the metastatic potential of LMH, and exosomal S100A4 is a key enhancer for HCC metastasis, activating STAT3 phosphorylation and up-regulating OPN expression. This suggested exosomal S100A4 to be a novel prognostic marker and therapeutic target for HCC metastasis.

Wei-Guo Zhang,1,* Jia-Ping Liu,2,* Xiu-Qin Jia,1 Ji-Yang Zhang,1 Xiang-Nan Li,1 Qi Yang1 1Department of Radiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of China; 2Department of Radiology, Beijing Xiongke Hospital, Capital Medical University, Beijing, 100049, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qi YangDepartment of Radiology, Beijing Chaoyang Hospital, Capital Medical University, No. 8 Gongti South Road, Chaoyang District, Beijing, 100020, People’s Republic of ChinaTel/Fax +86-85231928Email qiyang856@163.comObjective: This study aimed to investigate the effects of the Sn100 kVp tube voltage mode on the image quality and radiation dose of computed tomography pulmonary angiography (CTPA).Methods: A total of 145 patients who underwent CTPA were randomly divided into five groups: control group (120 kVp, 150 mAs), test group A (Sn100 kVp, 270 mAs), test group B (120 kVp, 30 mAs), test group C (70 kVp, 150 mAs), and test group D (80 kVp, 70 mAs). After image post-processing, the image quality and radiation dose of each group were analyzed.Results: The computed tomography values of images in the four test groups were more than 250 HU, which met the criteria for diagnosis. The signal-to-noise ratio and contrast-to-noise ratio of the images in the four test groups were lower than those in the control group. The radiation dose in each test group was lower than in the control group. The radiation dose was lowest in test group A.Conclusion: The Sn100 kVp energy spectrum purification protocol can meet the requirements for clinical diagnosis, ensure image quality, and reduce the dose of radiation that patients receive.Keywords: Sn100 kVp, CTPA, radiation dose, pulmonary embolism, dual-source CT

BACKGROUND Pregnancy and childbirth are the main causes of pelvic floor dysfunction (PFD). Although pelvic floor muscle tension is typically measured at 42 days postpartum to assess the severity of PFD and provide timely rehabilitation, it is still impossible to predict PFD and take targeted preventive measures in clinical practice. A PFD prediction model based on big data obtained in prenatal check-ups was established in this study to allow the formulation of personalized preventive strategies to reduce the incidence of PFD. METHODS A total of 1,500 women who underwent regular prenatal checkups and examinations for PFD at 42 days postpartum at the Zhuji Maternal and Child Health Hospital between May 2015 and May 2020 were selected. The data from 1,000 of them were selected as the training cohort, and the data from 500 of them were used as the validation cohort. The women were divided into a PFD group and a non-PFD group according to whether PFD was diagnosed at 42 days postpartum. A nomogram prediction model was created using the influencing factors that lead to PFD, and the discrimination and calibration of the nomogram were evaluated through internal and external validation. RESULTS A total of 389 cases (38.9%) of PFD were included in the training cohort. Multivariate analysis showed that age (odds ratio (OR) =1.896, P

Antimony Selenide (Sb2Se3) is a promising candidate for thin-film solar cells; however, its low intrinsic doping density, which reduces its power convention efficiency, has limited its further application. In this study, the MoO3 thin films prepared by electron beam (EB) evaporation were used as the back contact layer in an Sb2Se3 thin-film solar cell to compensate for the low intrinsic doping density (insufficient carrier collection) of Sb2Se3 as well as to optimize the back contact issues of Sb2Se3 thin-film solar cell. To achieve this, solar cells with an FTO/CdS/Sb2Se3/MoO3/Au structure were prepared. The thickness and deposition temperature of the MoO3 thin film were optimized, and the device achieved an efficiency of 6.3%, which was approximately 24% higher than that of the solar cells without MoO3. In addition, the material characterization revealed that the EB evaporation-prepared MoO3 thin film was amorphous and exhibited an n-type conductivity with a high work function and deep valence band edge, which facilitated the hole-selective transport. Furthermore, the device performance characterization and analysis revealed that the MoO3 thin film enhanced the efficient charge collection, improved the built-in voltage, and suppressed the carrier recombination at the back contact interface.

How to control the dipole orientation of organic emitters is a challenge in the field of organic light-emitting diodes (OLEDs). Herein, a linear thermally activated delayed fluorescence (TADF) molecule, PhNAI-PMSBA, bearing a 1,8-naphthalimide-acridine framework was designed by a double-site long-axis extension strategy to actively control the dipole orientation. The horizontal ratio of emitting dipole orientation of PhNAI-PMSBA reaches 95%, substantially higher than that of isotropic emitters (67%). This unique feature is associated with the intrinsically horizontal molecular orientation of PhNAI-PMSBA and the good agreement between its transition dipole moment direction and molecular long axis. The PhNAI-PMSBA-based OLED achieves an ultrahigh optical outcoupling efficiency of 43.2% and thus affords one of the highest red electroluminescence with an external quantum efficiency of 22.3% and the Commission International de l’Eclairage 1931 coordinates at around (0.60, 0.40).

Background:. Psoriasis is a chronic inflammatory skin disease, affecting about 0.6% of the Chinese population. Many patients are not well controlled by conventional treatments, thus there is need for new treatment regimens. In this study, we assessed the efficacy and safety of secukinumab in Chinese patients with moderate to severe plaque psoriasis. Methods:. This study was a 52-week, multicentre, randomized, double-blind, placebo-controlled, parallel-group, Phase 3 trial. A sub-population of study participants (≥18 years) of Chinese ethnicity were randomized to receive subcutaneous injections of 300 or 150 mg secukinumab, or placebo. The co-primary endpoints were psoriasis area severity index (PASI) 75 and Investigator's Global Assessment (IGA) 0/1 at Week 12. Results:. A total of 441 Chinese patients were enrolled in this study. Co-primary outcomes were achieved; 300 and 150 mg secukinumab were superior to placebo as shown in the proportion of patients that achieved PASI 75 (97.7% and 87.2% vs. 3.7%, respectively; P

Metastasis and metabolism reprogramming are two major hallmarks of cancer. In the initiation and progression of cancer, tumor cells are known to undergo fundamental metabolic changes to sustain their development and progression. In recent years, much more attentions have been drawn to their important roles in facilitating cancer metastasis through regulating the biological properties. In this review, we summarized the recent progresses in the studies of metabolism reprogramming of cancer metastasis, particularly of primary liver cancer, and highlight their potential applications.

Background Hepatocellular carcinoma (HCC) is an aggressive form of human liver cancer and the fifth most common malignancy worldwide. Novel effective treatment strategies for HCC are urgently in clinical because of its poor response to conventional therapies. G protein-coupled receptor kinases (GRKs), including GRK2 and GRK3, are known that involves in various essential cellular processes and regulates numerous signaling pathways. However, the role of GRK2/3 in invasion and metastasis of HCC still remains unclear. Materials and methods Immunohistochemistry, Western blot, laser confocal microscopy and qRT-PCR were used to detect the expression of GRK2/3 and EP2 in liver tissues of HCC patients and DEN-induced HCC mice. Wound healing and transwell assay were applied to measure the migration and invasion of HCC cells after transfected with GRK2 siRNA. The downstream pathway of Akt and ERK was verified by Western blot. Results The expression of GRK2 was significantly decreased, while GRK3 was not significantly changed in HCC tissues compared with noncancerous tissues of HCC patients. Moreover, GRK2 expression was reduced during liver tumorigenesis in diethylnitrosamine-induced liver tumor model. In addition, our in vitro study showed that GRK2 expression was gradually decreased with increasing HCC cell line metastatic potential, and GRK2 knockdown significantly promoted the migration and invasion of HCC cells. Furthermore, low GRK2 expression was associated with increased expression of EP2 receptor translocation to HCC cell membrane, and the activation of Akt pathway. Conclusion These data suggest that GRK2 inhibits HCC metastasis and invasion may be through regulating EP2 receptor translocation, and this effect appears to be mediated by Akt pathway.

We assess the safety and feasibility of the left hepatic vein preferential approach (LHVPA) based on left hepatic vein (LHV) anatomy for living donor laparoscopic left lateral sectionectomy (LLLS). Data from 50 donors who underwent LLLS in Huashan Hospital from October 2016 to November 2019 were analyzed retrospectively. On the basis of the classification of the LHV anatomy, the vein was defined as the direct import type, upper branch type, or indirect import type. A subgroup analysis was performed to compare the outcomes between the LHVPA and non-LHVPA groups. All 50 patients underwent pure LLLS. The mean operative duration was 157.5 ± 29.7 minutes. The intraoperative blood loss was 160.4 ± 97.5 mL. No complications more severe than grade 3 occurred. LHVPA was applied in 13 patients, whereas non-LHVPA was applied in 10 patients with the direct import type and upper branch type anatomy. The operative duration was shorter in the LHVPA group than the non-LHVPA group (142.7 ± 22.0 versus 173.0 ± 22.8 minutes; P = 0.01). Intraoperative blood loss was reduced in the LHVPA group compared with the non-LHVPA group (116.2 ± 45.6 versus 170.0 ± 63.3 mL; P = 0.02). The length of the LHV reserved extrahepatically in the LHVPA group was longer than in the non-LHVPA group (4.3 ± 0.2 versus 3.3 ± 0.3 mm; P = 0.01). Fewer reconstructions of the LHV in the direct import type anatomy were required for the LHVPA group than for the non-LHVPA group (0/8 versus 4/6). LHVPA based on the LHV anatomy is recommended in LLLS because it can further increase the safety and the efficiency of surgery for suitable donors.

Epidemiological studies have investigated the relationship between infertility and the risk of ovarian cancer (OC); however, the results have been inconsistent. We therefore conducted the first meta-analysis to update and quantify the aforementioned association based on prospective cohort studies. Studies were identified by searching PubMed, EMBASE and Web of Science databases up to January 8, 2020. We extracted data from the studies and performed quality assessments. Summary relative risks (RRs) with 95% confidence intervals (CIs) were calculated using a random-effects model. Publication bias, and subgroup, meta-regression and sensitivity analyses were also conducted. Nine prospective cohort studies with a total of 10 383 OC cases and 6 278 830 participants were included in the present study. The summary RR of the association between infertility and the risk of OC was 1.51 (95% CI: 1.35-1.69), with low heterogeneity. Positive associations were observed in most subgroup analyses stratified by predefined factors, including region, duration of follow-up, study quality, causes of infertility, invasiveness of OC, infertility treatment status and adjustment of potential confounding parameters. No significant publication bias was detected. Our findings suggest that infertility in women were associated with an increased risk of OC.

Chili peppers are loved by people all over the world and have been indispensable vegetable for three meals a day. However, reports about the association between chili consumption and gastric cancer (GC) risk have been conflicting. So, we carried out this meta-analysis to evaluate the effect of chili consumption on the risk of GC. Medline, PubMed, Web of science, Embase, Cochrane Library databases were systematically searched until May 2019. Heterogeneity among studies was examined using Q and I2 statistics. Combined odds ratio (OR) with their 95% confidence interval (CI) were calculated using a random- or fixed-effects model. All data were analyzed using STATA 15.1 software. 13 studies (3,095 cases and 4,761 controls) were included in the meta-analysis. A 1.96-fold increased risk of GC was shown for the moderate-high chili consumption (OR = 1.96, 95%CI =1.59-2.42). Dose-response analysis showed a significant nonlinear association of GC risk with capsaicin intake (pnon-linearity

Purpose: The rat cervicitis model was established with 20% phenol glue to explore the therapeutic effect of Kangfuxiaomi shuan II on rat cervicitis and its mechanism. Methods: After modeling, the rats were treated with Shuangzuotai suppository (37.84 mg/kg), Kangfuxiaoyan shuan (205.6 mg/kg) and Kangfuxiaomi shuan II (40, 80, 160 mg/kg). The histopathological changes and injury degree of cervix in rats were evaluated by vulvar inflammation score and organ index. The therapeutic effect of Kangfuxiaomi shuan II on cervicitis was evaluated by detecting the levels of copper-protein (CP), C-reactive protein (CRP), Rat interleukin 6 (IL-6), superoxide dismutase (SOD) and malondialdehyde (MDA) in serum and epidermal growth factor (EGF), cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in cervical tissue. Results: Compared with the model group, the vulvar inflammation score and cervical index of rats in other groups decreased significantly (P

Background: The associations of the consumption of cruciferous vegetables (CVs) and their bioactive components, isothiocyanates (ITCs), with ovarian cancer (OC) mortality have been unclear, owing to limited studies and inconsistent findings. To date, no studies have evaluated these associations among Chinese patients with OC. This study aims to provide more evidence indicating the relationships of pre-diagnosis CVs and ITC intake with OC survival.Methods: We examined the associations of pre-diagnosis CV and ITC intake with OC mortality in a hospital-based cohort (n = 853) of Chinese patients with epithelial OC between 2015 and 2020. Pre-diagnosis dietary information was evaluated with a validated food frequency questionnaire. Deaths were ascertained until March 31, 2021 via medical records and active follow-up. The associations were examined with the Cox proportional hazards model, adjusted for potential confounders, and stratified by menopausal status, residual lesions, histological type, and body mass index (BMI).Results: During a median follow-up of 37.2 months (interquartile: 24.7–50.2 months), we observed 130 deaths. The highest tertile of total CV intake was associated with better survival than the lowest tertile intake [hazard ratio (HR) = 0.57, 95% confidence interval (CI) = 0.33–0.98, p trend < 0.05]. In addition, higher intake of ITCs from CVs was associated with better survival (HRT3VS.T1 = 0.59, 95% CI = 0.36–0.99, p trend = 0.06). Significant inverse associations were also observed for subgroup analyses stratified by menopausal status, residual lesions, histological type, and BMI, although not all associations showed statistical significance.Conclusion: Increasing pre-diagnosis consumption of CVs and ITCs was strongly associated with better survival in patients with OC.

Background: Dairy product consumption is associated with ovarian cancer (OC) incidence. However, limited evidence is available on its influence on OC mortality.Methods: The association between pre-diagnostic dairy product intake and OC mortality was investigated in the OC follow-up study, which included a hospital-based cohort (n = 853) of women diagnosed with epithelial OC between 2015 and 2020. Pre-diagnosis diet information was collected using a validated food frequency questionnaire. Deaths were ascertained up to March 31, 2021 via death registry linkage. Cox proportional hazards model was used to estimate the adjusted hazard ratio (HR) and 95% confidence interval (CI) for the aforementioned association.Results: A total of 130 women died during the median follow-up of 37.2 months (interquartile: 24.7–50.2 months). Comparisons of highest to lowest tertile intake showed that pre-diagnosis dairy product use was associated with total OC mortality (HR = 2.03, 95% CI = 1.21–3.40, p trend = 0.06). In addition, short survival was separately associated with protein (HR = 2.09, 95% CI = 1.25–3.49, p trend < 0.05), fat (HR = 2.16, 95% CI = 1.30–3.61, p trend < 0.05), and calcium (HR = 2.03, 95% CI = 1.21–3.4, p trend = 0.06) from dairy intake. Similar positive magnitudes were observed for menopausal status, residual lesions, histological type, and body mass index, although not all of these factors showed statistical significance.Conclusion: Pre-diagnosis dairy product consumption, including protein, fat, and calcium from dairy intake, was associated with higher mortality among OC survivors.

Transarterial chemoembolization (TACE) is a commonly used treatment modality in hepatocellular carcinoma (HCC). The ability to identify patients who will respond to TACE represents an important clinical need, and tumor gene expression patterns may be associated with TACE response. We investigated whether tumor transcriptome is associated with TACE response in patients with HCC. We analyzed transcriptome data of treatment-naive tumor tissues from a Chinese cohort of 191 HCC patients, including 105 patients who underwent TACE following resection with curative intent. We then developed a gene signature, TACE Navigator, which was associated with improved survival in patients that received either adjuvant or post-relapse TACE. To validate our findings, we applied our signature in a blinded manner to three independent cohorts comprising an additional 130 patients with diverse ethnic backgrounds enrolled in three different hospitals who received either adjuvant TACE or palliative TACE. TACE Navigator stratified patients into Responders and Non-Responders which was associated with improved survival following TACE in our test cohort (Responders: 67 months vs Non-Responders: 39.5 months, p

Purpose Gentamicin is a promising antimicrobial for the treatment of gonorrhea. The study aimed to evaluate gentamicin minimum inhibitory concentrations (MICs) of Neisseria gonorrhoeae isolates in China. Methods In this study, the agar dilution method was used to determine the MICs of 470 isolates collected in 2016 to four effective antimicrobials (gentamicin, azithromycin, ceftriaxone, and spectinomycin). Results Gentamicin MICs ranged from 1 to 8 mg/L. No isolate was resistant to gentamicin. Of seven isolates simultaneously resistant to azithromycin and ceftriaxone, 6 isolates demonstrated MICs of 4 mg/L or less to gentamicin. No cross relationships were found between MICs of gentamicinand susceptibility profiles of azithromycin, ceftriaxone, and spectinomycin. Conclusion The in vitro results suggest that gentamicin can be a promising treatment option for gonococcal infections in China. Clinical trials to evaluate the therapeutic efficacy of gentamicin are required.

BACKGROUND As an important aspect of tumor heterogeneity, genetic variation may influence susceptibility and prognosis in different types of cancer. By exploring the prognostic value of genetic variation, this study aimed to establish a model for predicting postoperative survival and assessing the impact of variation on clinical outcomes in patients with hepatocellular carcinoma (HCC). MATERIAL AND METHODS A genome-wide association study of 367 patients with HCC was conducted to identify single nucleotide polymorphisms (SNPs) associated with prognosis. Identified predictors were further evaluated in 758 patients. Two prognostic models were established using Cox proportional hazards regression and Nomogram strategy, and validated in another 316 patients. The effect of the SNP rs2431 was analyzed in detail. RESULTS A prognostic model including 5 SNPs (rs10893585, rs2431, rs34675408, rs6078460, and rs6766361) was established and exhibited high predictive accuracy for HCC prognosis. The panel combined with tumor node metastasis (TNM) stage resulted in a significantly higher c-index (0.723) than the individual c-index values. Stratified by the Nomogram prediction model, the median overall survival for the low-risk and high-risk groups were 100.1 versus 30.8 months (P

Ovarian cancer (OC) is one of the deadliest gynecological cancers worldwide. Previous observational epidemiological studies have revealed associations between modifiable environmental risk factors and OC risk. However, these studies are prone to confounding, measurement error, and reverse causation, undermining robust causal inference. Mendelian randomization (MR) analysis has been established as a reliable method to investigate the causal relationship between risk factors and diseases using genetic variants to proxy modifiable exposures. Over recent years, MR analysis in OC research has received extensive attention, providing valuable insights into the etiology of OC as well as holding promise for identifying potential therapeutic interventions. This review provides a comprehensive overview of the key principles and assumptions of MR analysis. Published MR studies focusing on the causality between different risk factors and OC risk are summarized, along with comprehensive analysis of the method and its future applications. The results of MR studies on OC showed that higher BMI and height, earlier age at menarche, endometriosis, schizophrenia, and higher circulating β-carotene and circulating zinc levels are associated with an increased risk of OC. In contrast, polycystic ovary syndrome; vitiligo; higher circulating vitamin D, magnesium, and testosterone levels; and HMG-CoA reductase inhibition are associated with a reduced risk of OC. MR analysis presents a2 valuable approach to understanding the causality between different risk factors and OC after full consideration of its inherent assumptions and limitations.

Pancreatic cancer is an increasingly common cause of cancer mortality with a tight correspondence between disease mortality and incidence. Furthermore, it is usually diagnosed at an advanced stage with a very dismal prognosis. Due to the high heterogeneity, metabolic reprogramming, and dense stromal environment associated with pancreatic cancer, patients benefit little from current conventional therapy. Recent insight into the biology and genetics of pancreatic cancer has supported its molecular classification, thus expanding clinical therapeutic options. In this review, we summarize how the biological features of pancreatic cancer and its metabolic reprogramming as well as the tumor microenvironment regulate its development and progression. We further discuss potential biomarkers for pancreatic cancer diagnosis, prediction, and surveillance based on novel liquid biopsies. We also outline recent advances in defining pancreatic cancer subtypes and subtype-specific therapeutic responses and current preclinical therapeutic models. Finally, we discuss prospects and challenges in the clinical development of pancreatic cancer therapeutics.

BackgroundFibroblast activation protein (FAP) is commonly expressed in activated stromal fibroblasts in various epithelial tumours. Recently, 68Ga-FAPI-04 has been used for tumour imaging in positron emission tomography/computed tomography (PET/CT). This study aimed to compare the diagnostic performances of 68Ga-FAPI-04 PET/CT and 18F-FDG PET/CT in hepatocellular carcinoma (HCC), and to assess factors associated with 68Ga-FAPI-04 uptake in HCC.Materials and MethodsTwenty-nine patients with suspiciously HCC who received both 18F-FDG and 68Ga-FAPI-04 PET/CT were included in this retrospective study. The results were interpreted by two experienced nuclear medicine physicians independently. The maximum and mean standardized uptake values (SUVmax and SUVmean) were measured in the lesions and liver background, respectively. The tumour-to-background ratio (TBR) was then calculated as lesion’s SUVmax divided by background SUVmean.ResultsA total of 35 intrahepatic lesions in 25 patients with HCC were finally involved in the statistical analysis. 68Ga-FAPI-04 PET/CT showed a higher sensitivity than 18F-FDG PET/CT in detecting intrahepatic HCC lesions (85.7% vs. 57.1%, P = 0.002), including in small (≤ 2 cm in diameter; 68.8% vs. 18.8%, P = 0.008) and well- or moderately-differentiated (83.3% vs. 33.3%, P = 0.031) tumors. SUVmax was comparable between 68Ga-FAPI-04 and 18F-FDG (6.96 ± 5.01 vs. 5.89 ± 3.38, P > 0.05), but the TBR was significantly higher in the 68Ga-FAPI-04 group compared with the 18F-FDG group (11.90 ± 8.35 vs. 3.14 ± 1.59, P < 0.001). SUVmax and the TBR in 68Ga-FAPI-04 positive lesions were associated with tumour size (both P < 0.05), but not the remaining clinical and pathological features (all P > 0.05).Conclusions68Ga-FAPI-04 PET/CT is more sensitive than 18F-FDG PET/CT in detecting HCC lesions, and 68Ga-FAPI-04 uptake is correlated mainly with tumour size.

Bcackground There is still a lack of predictive models for early identification of intestinal flora imbalance in stable Chronic Obstructive Pulmonary Disease (COPD) patients. We assessed the risk factors related to intestinal flora imbalance in COPD patients, and established a simple predictive model and scoring rules suitable for clinical medical staff in the respiratory department.Methods From January 1, 2018 to December 31, 2019, COPD patients (195 cases), who attended the Outpatient Department of Respiratory and Critical Care of Yixing Hospital of Jiangsu University, were collected for a cross-sectional study. The patients were divided into the experimental groups (41 cases) and the control group (154 cases) based on the results of stool examination. By single-factor analysis and logistic regression analysis, the baseline data of two groups were performed to obtain a new prediction model, and then simplified it.Results The five predictive factors including body mass index(BMI), serum albumin(ALB), charlson comorbidity index(CCI), gastrointestinal symptom score(GSRs), and Global Initiative for Chronic Obstructive Lung Disease(GOLD) classification entered the model. The area under the ROC curve of the model for predicting intestinal flora imbalance in patients with stable COPD is 0.953 [95%CI (0.924, 0.982)], further simplifying the scoring rules, and the area under the ROC curve is 0.767 [95%CI (0.676, 0.858)]. Conclusions In the study, the prediction model can scientifically and effectively predict the risk of intestinal flora imbalance in patients with stable COPD, and then implement early treatment to improve the prognosis. Furthermore, all indicators can be obtained easily and simply.

Background & aim Recently, the clinical trials of lenvatinib plus pembrolizumab in hepatocellular carcinoma (HCC) displayed an impressive objective response rate (ORR). This study aimed to clarify the mechanism for optimal patient selection. Approach & results First, in patients with HCC, lenvatinib-treated recurrent tumors had lower programmed death ligand 1 (PD-L1) expression and regulatory T cell (Treg) infiltration compared with matched primary tumors. Consistently, in C57BL/6 wild-type mice receiving anti-PD-1 therapy, PD-L1 expression and Treg infiltration in subcutaneous tumors reduced when adding lenvatinib to the scheme. Mechanistically, on one hand, fibroblast growth factor receptor 4 (FGFR4) was the most pivotal target in PD-L1 down-regulation by lenvatinib in vitro. Furthermore, lenvatinib reinforced the proteasomal degradation of PD-L1 by blocking the FGFR4-GSK3β axis and rescued the sensitivity of interferon-γ-pretreated HCC cells to T-cell killing by targeting FGFR4. On the other hand, the level of interleukin 2 (IL-2) increased after anti-PD-1 treatment, but IL-2-mediated Treg differentiation was blocked by lenvatinib through targeting FGFR4 to restrain signal transducer and activator of transcription 5 (STAT5) phosphorylation. By regulating the variations in the number of Tregs and tumor FGFR4 level in C57BL/6-Foxp3DTR (DEREG) mice, we found that high levels of FGFR4 and Tregs infiltration sensitized tumor to the combination treatment. Finally, high levels of FGFR4 and forkhead box protein P3 (Foxp3) conferred immune tolerance but better response to the combined therapy in patient cohorts. Conclusions Lenvatinib reduced tumor PD-L1 level and Treg differentiation to improve anti-PD-1 efficacy by blocking FGFR4. Levels of FGFR4 expression and Tregs infiltration in tumor could serve as biomarkers for screening HCC patients with lenvatinib plus anti-PD-1 combination therapy.

Local activity metrics of resting-state functional MRI (RS-fMRI), such as the amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF), regional homogeneity (ReHo), and degree centrality (DC), are widely used to detect brain abnormalities based on signal fluctuations. Although signal changes with echo time (TE) have been widely studied, the effect of TE on local activity metrics has not been investigated. RS-fMRI datasets from 12 healthy subjects with eyes open (EO) and eyes closed (EC) were obtained with a four-echo gradient-echo-planar imaging pulse sequence with the following parameters: repetition time/TE1/TE2/TE3/TE4 = 2,000/13/30.93/48.86/66.79 ms. Six representative regions were selected for simulating the spatial feature of TE dependency of local activity metrics. Moreover, whole-brain local activity metrics were calculated from each echo dataset and compared between EO and EC conditions. Dice overlap coefficient (DOC) was then employed to calculate the overlap between the T maps. We found that all the local activity metrics displayed different TE dependency characteristics, while their overall change patterns were similar: an initial large change followed by a slow variation. The T maps for local activity metrics also varied greatly with TE. For ALFF, fALFF, ReHo, and DC, the DOCs for voxels in four TE datasets were 6.87, 0.73, 5.08, and 0.93%, respectively. Collectively, these findings demonstrate that local metrics are greatly dependent on TE. Therefore, TE should be carefully considered for the optimization of data acquisition and multi-center data analysis in RS-fMRI.

Background: The resistance rate of carbapenem-resistant Enterobacteriaceae (CRE) is increasing yearly but rarely reported in children. Objectives: This retrospective study analyzed the characteristics of isolated CRE strains in pediatric patients, intending to explore reasonable antimicrobial treatment options. Methods: Some CRE isolates were collected from infected pediatric patients in Liaocheng People’s Hospital from January 2014 to December 2019. The strain identification and antimicrobial susceptibility testing were conducted using Vitek mass spectrometry and the Vitek 2 system, respectively. The carbapenemase genotypes of blaKPC, blaIMP, blaVIM, blaNDM-1, and blaOXA-48 were each detected by polymerase chain reaction and sequencing. The molecular homology analysis of strains was conducted via Pulse-field Gel Electrophoresis (PFGE). The clinical data of CRE-infected pediatric patients were collected from the hospital’s medical data information system. Results: Twenty CRE strains were isolated from 1945 infected pediatric patients with Enterobacteriaceae. All CRE strains showed multiple resistance to commonly used antimicrobials. Twelve strains of imipenemase (IMP)-4 and seven strains of IMP-8 carbapenemase were confirmed. Besides, PFGE revealed that two strains of Escherichia coli and three of Klebsiella pneumoniae had indistinguishable patterns. Sixteen patients were cured, including 10 patients using piperacillin/tazobactam. Conclusions: This study found the major sources of resistance were IMP carbapenemases. Piperacillin/tazobactam is potentially effective for the treatment of CRE infection, despite insensitivity in vitro.

Background An individual prognostic model that includes inflammation caused by the delayed recovery of liver function after surgery for the early recurrence of hepatocellular carcinoma (HCC) following liver transplantation (LT) has not been well determined. Our aim was to develop a nomogram model for predicting individual survival and early recurrence following LT for patients. Methods Retrospective data, including clinical pathology and follow-up data, on HCC patients were collected between October 2016 and October 2019 at Huashan Hospital Affiliated to Fudan University. A nomogram estimating recurrence post-transplantation was constructed using multivariate Cox regression analysis. Results A total of 210 patients were included in the present study. The multivariate estimators of recurrence consisted of age, maximum tumor diameter, tumor thrombus, microvascular invasion (MVI), alanine aminotransferase and alpha-fetoprotein on postoperative day 7. Nomogram of recurrence-free survival was developed. The calibration and discrimination of the novel model were assessed with the calibration curves and concordance index (C-index). Its reliability and advantages were evaluated by comparing it with the conventional American Joint Committee on Cancer (AJCC) 8th edition staging system using integrated discrimination improvement (IDI) and net reclassification improvement (NRI). In comparison to the AJCC 8th edition staging system, the C-index (development set: 0.796 vs. 0.643, validation set: 0.741 vs. 0.563), the area under the receiver operating characteristic curve (AUC) of the validation set (1-year AUC: 0.732 vs. 0.586, 2-year AUC: 0.705 vs. 0.504), the development set (1-year AUC: 0.799 vs. 0.551, 2-year AUC: 0.801 vs. 0.512), and this model's calibration plots all showed improved performance. In addition, NRI and IDI verified that the nomogram is an accurate prognostic tool. Subsequently, a web calculator was generated to assess the risk of tumor recurrence post-LT. Conclusions The nomogram, based on clinical and pathological factors, showed good accuracy in estimating prognostic recurrence and can be used to guide individual patient follow-up and treatment.

This research article planned to investigate the efficacy of edaravone in combination with dihydropyridine calcium ion antagonist on hypertensive intracerebral hemorrhage. Between February 2017 and January 2019, we collected the clinical data from 126 hypertensive intracerebral hemorrhage patients and divided them into the control group and observation group, with 63 patients in each group. Patients in two groups all underwent the regular treatment, while those in the observation group took edaravone in combination with dihydropyridine calcium ion antagonist (nimodipine) for treatment. Following the treatment, we compared the clinical efficacy, plasmin endothelin 1, volume of edema and hematoma and National Institute of Health stroke scale scores. In the control group, the total effectiveness rate of treatment was 71.44 %, significantly lower than that of the observation group (p 0.05), while after 2 and 4 w of treatment, patients in the observation group had scores of (12.43±4.07) and (7.52±1.84) points, significantly higher than those in the control group (p

Background: Spectral-Domain Optical coherence tomography (SD-OCT) provides non-invasive, high speed, high resolution, three-dimensional cross-section imaging of macula. This study was aimed to investigate the diagnostic value of multimodal imaging technique of three-dimension (3D) optical coherence tomography (OCT) (3D-OCT) for diagnosis and characterizing of acute central serous chorioretinopathy (CSC). Methods: The 3D-OCT examinations of 82 cases of acute CSC were performed on the macular area, and the image characteristics were analyzed. Our study included a total of 87 eyes from 82 cases of CSC patients, 67 males and 15 females, aged 27 to 56 years, mean age 42.89±7.80 years old.Results: According to B-scan images, 87 (100%) eyes had ERD, 38 (44%) eyes had bulge of RPE, 36 (41%) eyes had PED, 8 (9%) eyes had membrane -like structure, 2 (2%) eyes had subretinal dot-like precipitates, 1 (1%) eyes had focal choroidal excavation (FCE), and 1 (1%) eye had fluctuation of internal limiting membrane (FI). In ILM-RPE thickness map, all eyes had a round or round like regular uniform domes. Total of 57 (66%) domes were limited in exam area and 30 (44%) domes beyond the scope of this examination and only part of the dome could be observed. In the Shadowgram image, all eyes had a round or round like black figure that correspond with domes In ILM-RPE thickness map. In RPE surface, 76(87%) eyes had a shallow plate depression, 71(82%) had small focal uplift and 1 (1%) eye had a focal concave.Conclusions: In OCT ILM-RPE thickness map, Shadowgram, and RPE surface, acute CSC had special images and can be helpful for diagnosis and difference diagnosis.Trial registration: Not applicable.

Rationale: Metastasis, the development of secondary malignant growth at a distance from a primary tumor, is the main cause of cancer-associated death. However, little is known about how metastatic cancer cells adapt to and colonize in the new organ environment. Here we sought to investigate the functional mechanism of cholesterol metabolic aberration in colorectal carcinoma (CRC) liver metastasis. Methods: The expression of cholesterol metabolism-related genes in primary colorectal tumors (PT) and paired liver metastases (LM) were examined by RT-PCR. The role of SREBP2-dependent cholesterol biosynthesis pathway in cell growth and CRC liver metastasis were determined by SREBP2 silencing in CRC cell lines and experimental metastasis models including, intra-splenic injection models and liver orthotropic injection model. Growth factors treatment and co-culture experiment were performed to reveal the mechanism underlying the up-regulation of SREBP2 in CRC liver metastases. The in vivo efficacy of inhibition of cholesterol biosynthesis pathway by betulin or simvastatin were evaluated in experimental metastasis models. Results: In the present study, we identify a colorectal cancer (CRC) liver metastasis-specific cholesterol metabolic pathway involving the activation of SREBP2-dependent cholesterol biosynthesis, which is required for the colonization and growth of metastatic CRC cells in the liver. Inhibiting this cholesterol biosynthesis pathway suppresses CRC liver metastasis. Mechanically, hepatocyte growth factor (HGF) from liver environment activates SREBP2-dependent cholesterol biosynthesis pathway by activating c-Met/PI3K/AKT/mTOR axis in CRC cells. Conclusion: Our findings support the notion that CRC liver metastases show a specific cholesterol metabolic aberration. Targeting this cholesterol biosynthesis pathway could be a promising treatment for CRC liver metastasis.

Background To explore the value of alpha fetoprotein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II) in diagnosis of HBV-related hepatocellular carcinoma (HCC) and their relationship with vascular invasion, tumor differentiation and size. Methods A total of 433 participants were enrolled in this study including 266 cases with HBV-related HCC, 87 cases with HBV DNA positive benign liver disease and 80 healthy individuals. Then we explored the correlation between AFP, PIVKA-II serum level and several pathological features such as vascular invasion, tumor differentiation and size. The value of these two markers used singly or jointly in diagnosing HBV-related HCC was evaluated by receiver operating characteristic (ROC) curve. The ROC curve was also plotted to identify AFP, PIVKA-II serum cut-off values that would best distinguish HBV-related HCC patients with and without vascular invasion. Results The level of AFP and PIVKA-II in HBV-related HCC group was significantly higher (Z was 7.428, 11.243 respectively, all P P was 0.007 and 0.014 respectively). The AFP level > 64.4 ng/ml or PIVKA-II level > 957.61mAU/ml was the best critical value to predict the presence of vascular invasion. Conclusion Our results validate that AFP and PIVKA-II play a significant role in the diagnosis of HBV-related HCC. The diagnostic value of AFP and PIVKA-II combined detection or single assay of PIVKA-II is higher than that of separate assay of AFP. Moreover, their concentration has important clinical value in judging tumor size, tumor cell differentiation and vascular invasion.

Background and aims Pyruvate kinase M2 (PKM2) is an essential regulator of the Warburg effect, but its biological function promoting immune escape of hepatocellular carcinoma (HCC) is unclear. Methods GEPIA web tool and immunohistochemistry (IHC) analysis were employed to evaluate the clinical relevance of PKM2 in HCC patients. Both in vitro CCK-8, colony formation, and transwell assays, and in vivo xenografts were performed to evaluate the malignancy of HCC cells. PKM2 and PD-L1 levels were examined by Western blot, qRT-PCR, and IHC. The role of PKM2 on in vivo immune response was also investigated. Results PKM2 was significantly upregulated in HCC and associated with a poor prognosis of HCC patients. Knockdown of PKM2 inhibited in vitro proliferation, migration, and invasion of HCC cells, as well as in vivo tumor growth. Strikingly, PKM2 showed a strong correlation with the expression of immune inhibitory cytokines and lymphocyte infiltration in HCC. The overexpression of PKM2 sensitized HCC to immune checkpoint blockade, which enhanced IFN-γ positive CD8 T cells in HCC mice models. Conclusion PKM2 might be a predictor and a potential therapeutic target for immune checkpoint inhibitors in HCC.

BackgroundAntimicrobial resistance to Neisseria gonorrhoeae has emerged for each of the antibiotics recommended as first-line therapies following their introduction into clinical practice. To improve rational and effective clinical antibiotic treatment, we analyzed the prescription patterns of antibiotics and their therapeutic effect in the treatment of uncomplicated gonorrhea in China.MethodsWe obtained data from a follow-up multicenter surveillance program. Multinomial logistic regression analyses were conducted to explore the associations between demographic/clinical variables with the levels of sensitivity to ceftriaxone and prescription of high-dose ceftriaxone.ResultsIn this study, 1686 patients infected with N. gonorrhoeae were recruited in a surveillance network during 1 January 2013 through 31 December 2017 in 7 hospitals distributed in 5 provinces. The prevalence of isolates with decreased susceptibility to ceftriaxone was 9.8% (131/1333), fluctuating between 5.6% and 12.1%. Injectable ceftriaxone was chosen as the first-line treatment among 83.1% of patients, and most of them (72.7% [1018/1401]) received >1000 mg dosage. Patients who were previously infected with gonorrhea or other sexually transmitted infections (adjusted odds ratio [AOR], 1.618 [95% confidence interval {CI}, 1.11–2.358]; AOR, 2.08 [95% CI, 1.41–3.069]) or who already used antibiotics for this infection (AOR, 1.599 [95% CI, 1.041–2.454]) were associated with a higher prescribed ceftriaxone dosage. All of the patients recruited in this study were cured regardless of the isolates’ susceptibility to ceftriaxone or the dosage of ceftriaxone they received.ConclusionsNo ceftriaxone treatment failure for uncomplicated gonorrhea was reported in China; however, high-dose ceftriaxone was widely used in China. Its impacts need further study.

Background: Coronavirus disease 2019 (COVID-19) is a current global pandemic. However, impact of recent influenza A virus infection on the clinical course and outcomes of severe COVID-19 adult inpatients needs to be further explored.Methods: In this retrospective cohort study, severe, laboratory confirmed COVID-19 adult patients from Wuhan Tongji Hospital were included. Data were obtained from electronic medical records and compared between patients with and without recent influenza A virus infection.Results: 200 patients were included, 51.5% with recent influenza A virus infection. Recent influenza A virus infection group presented with longer persistence of cough and sputum from illness onset (35.0 vs. 27.0 days, P = 0.018) and (33.0 vs. 26.0 days, P = 0.015), respectively. Median time of progression to critical illness from illness onset was shorter (day 11.5 vs. day 16.0, P = 0.034). Time to clinical improvement and length of hospital stay were longer in recent infection group (23.0 vs. 19.0 days, P = 0.044) and (22.0 vs. 18.0 days, P = 0.030), respectively.Conclusions: Patients with recent influenza A virus infection showed a delay in time to clinical improvement and increased length of hospital stay. There is a high clinical need to improve the detection of common respiratory pathogens to identify co-infection during the epidemic of COVID-19.

Passivated emitter and rear cells (PERC) on p-type Cz Si wafers are currently being migrated to mainstream production, applying the ongoing improvements in recent years. For PERC solar cells, the emitter recombination loss becomes the main loss of the entire cell. Currently, two-step diffusion consisting of low temperature phosphosilicate glass (PSG) deposition and high-temperature drive-in has been widely applied in production and can reduce saturation current density (J0) of the emitter in the passivated area. However, a low contact resistance under metal area cannot be guaranteed. Meanwhile, the determination of the saturation current density J0 in the passivated area is dependent on the injection density during the measurement, and exact calculation of J0,metal is not as convenient as J0,diffusion, which could lead to a wrong assessment in cell analysis. In this study, a three-step diffusion (low-temperature PSG deposition–high-temperature drive-in–low temperature PSG deposition) with low J0 and low Ag-Si contact resistance is investigated and combined with a selective emitter by an etch-back process. The results are compared with a conventional two-step POCl3 diffusion. The accuracy of J0 measurement and J0,metal test method is also discussed. With these improvements, the champion cell efficiency of our PERC solar cells fabricated on 156 × 156 mm2 wafers using screen printing technology and industrial-type process has reached 22.61% with Voc of 684.4 mV and a fill factor of 81.49%, as confirmed by Fraunhofer ISE CalLab PV cells. By implementing the diffusion process to mass production, the average cell-efficiency gain is approximately 0.2% with a median efficiency of 21.7%.

The goal of cancer eradication has been overshadowed despite the continuous improvement in research and generation of novel cancer therapeutic drugs. One of the undeniable existing problems is drug resistance due to which the paradigm of killing all cancer cells is ineffective. Tumor microenvironment plays a crucial role in inducing drug resistance besides cancer development and progression. Recently, many efforts have been devoted to understand the role of tumor microenvironment in cancer drug resistance as it provides the shelter, nutrition, and paracrine niche for cancer cells. Cancer-associated fibroblasts (CAFs), one major component of tumor microenvironment, reside in symbiotic relationship with cancer cells, supporting them to survive from cancer drugs. The present review summarizes the recent understandings in the role of CAFs in drug resistance in various tumors. Acknowledging the fact that drug resistance depends not only upon cancer cells but also upon the microenvironment niche could guide us to formulate novel cancer drugs and provide the optimal cancer treatment.

Background: Tracking the spread of the Neisseria gonorrhoeae strains with decreased susceptibility or resistance to cephalosporins is a major priority for global surveillance programmes. Whole-genome sequencing (WGS) has been widely used by increasing countries in North America, Europe, and Pacific to determine the decreased susceptible or resistance determinants of Neisseria gonorrhoeae, track the spread of these determinants throughout the gonococcal population at national or regional level. However, no studies to date have examined the genomic epidemiology of gonorrhea in Asia where the antimicrobial resistant strains of Neisseria gonorrhoeae appears to have emerged before disseminating the strains globally. Methods: We obtained clinical isolates and data from the China Gonococcal Resistance Surveillance Programme (China-GRSP) from 2012 to 2013. We sequenced the genomes of 435 clinical isolates of Neisseria gonorrhoeae, including 112 (25.6%) isolates with decreased susceptibility to ceftriaxone (Cfx-DS). We assessed the association between antimicrobial resistance genotype and phenotype. We also compared our data with the whole genome data of the isolates from the USA and the UK in the GenBank. Findings: The most prevalent MLST STs in our gonococcal population were MLST ST7827 (n = 74), followed by ST7365 (n = 58), ST1600 (n = 38), ST7367 (n = 35), and ST7363 (n = 29). MLST ST1901 which was reported as the predominant ST in the US was not found in our population. A total of 2512 strains, including additional 2077 published NG strains, were further included for phylogenetic analysis. It generated two distinct lineages - lineage 1 and lineage 2. Analysis of MLST ST1901 in the database indicate that most of MLST ST1901 isolates in the lineage2.6 were Cfx-DS isolates while all isolates in the lineage 2.1 were sensitive to ceftriaxone (77/110 vs. 0/13; p

Background DL-3-n-butylphthalide (NBP) has been approved to be effective in improving cognitive deficits. The aim of the current study was to determine whether NBP protects against cognitive deficits in a rat model of vascular dementia (VD) induced by chronic cerebral hypoperfusion (CCH) by regulating the sonic hedgehog (Shh)/patched1 (Ptch1) pathway and endoplasmic reticulum stress (ERS)-related markers. Methods Adult male Sprague-Dawley rats were subjected to permanent bilateral occlusion of the common carotid arteries (2VO) to established the model of VD. These rats were randomly divided into five groups: sham, model, NBP30 (30 mg/kg), NBP 60 (60 mg/kg), and NBP 120 (120 mg/kg) groups. The Morris water maze test was used to assess for cognitive function at 4 weeks after operation. Results NBP significantly alleviated spatial learning and memory impairment, and inhibited the loss of neurons in the CA1 region of the hippocampus. Western blot analysis and real-time quantitative polymerase chain reaction analysis revealed that plasticity-related synaptic markers and the Shh/Ptch1 pathway significantly increased in the NBP treated groups, while ERS-related markers decreased. Conclusion The results of the current study prove that the Shh/Ptch1 pathway plays an essential role in the model of VD. NBP had protective effects on cognitive impairment induced by CCH. This mechanism was associated with ERS and the Shh/Ptch1 pathway. Meanwhile, the Shh/Ptch1 pathway and ERS may interact with each other.

In the hepatocellular carcinoma (HCC) microenvironment, chemokine receptors play a critical role in tumorigenesis and metastasis. Our previous studies have found that osteopontin (OPN) is a promoter for HCC metastasis. However, the role of chemokine receptors in OPN-induced HCC metastasis remains unclear. In this study, we demonstrate that OPN is dramatically elevated in HCC tissues with metastasis and that high expression of OPN correlates with poorer overall survival and higher recurrence rate. OPN upregulates chemokine receptor expression, migration, invasion and pulmonary metastasis in HCC. We find that C-C chemokine receptor type 1 (CCR1) and C-X-C chemokine receptor type 6 (CXCR6) are the most upregulated chemokine receptors induced by OPN. CCR1 knockdown results in reduction of migration, invasion and pulmonary metastasis induced by OPN in vitro and in vivo, whereas CXCR6 knockdown does not reverse OPN-promoted migration and invasion. Moreover, OPN upregulates the expression of CCR1 through activating phosphoinositide 3-kinase (PI3K)/AKT and hypoxia-inducible factor 1α (HIF-1α) in HCC cells. Furthermore, blockade of OPN-CCR1 axis with CCR1 antagonist significantly restrains the promoting effects of OPN on HCC progression and metastasis. In human HCC tissues, OPN expression shows significantly positive correlation with CCR1 expression, and the patients with high levels of both OPN and CCR1 have the most dismal prognosis. Collectively, our results indicate that the OPN-CCR1 axis in HCC is important for accelerating tumor metastasis and that CCR1 is a potential therapeutic target for controlling metastasis in HCC patients with high OPN.

BACKGROUND This study analyzed the macular 3D-OCT images of Vogt-Koyanagi-Harada disease (VKH) in uveitis, explored the characteristics of 3D-OCT images of the macular region of VKH, and assessed which characteristics contribute most to VKH diagnosis. MATERIAL AND METHODS The 3D-OCT examination of 25 cases of VKH was performed on the macular area, and the image characteristics were analyzed. RESULTS Our study included a total of 50 eyes from 25 cases of VKH patients, 10 males and 15 females, aged 17 to 64 years, mean (39.44±11.60) years old. According to OCT B-scan images, 49 (98%) eyes had ERD, 49 (98%) eyes had nerve retinal edema, 36 (72%) eyes had endometrium-like structure (including cysts), 5 (10%) eyes had RPE folds, 35 (70%) eyes had changes in the internal septum, 49 (98%) eyes had RPE monolayer structure outside the ERD region. In ILM-RPE thickness, 49 (98%) eyes had retinal irregular thickening and 31 (62%) eyes had radial stripe changes. In ILM contour figure, 50 eyes (100%) showed exceptional uplift, 5 (10%) eyes had small focal uplift for PED on the RPE surface, and 48 (96%) eyes had wavy ups and downs. CONCLUSIONS In OCT B-scan imaging, the ERT, retinal edema of the retina, and the RPE monolayer structure outside the range are most likely to occur in VKH. The ILM-RPE thickness chart in 3D reconstruction showed irregular thickening of the retina. The ILM contour graph showed abnormal uplift, and RPE surface wavy ups and downs in VKH most likely to occur.

Hepatectomy is currently routinely performed in most hospitals in China. China owns the largest population of liver diseases and the biggest number of liver resection cases. A nationwide multicenter retrospective investigation involving 112 hospitals was performed, and focused on liver resection for patients with hepatocellular carcinoma (HCC). 42,573 cases of hepatectomy were enrolled, and 18,275 valid cases of liver resection for HCC patients were selected for statistical analysis. The epidemiology of HCC, distribution of hepatectomy, postoperative complications and prognosis were finally analyzed. In the 18,275 HCC patients, 81% had hepatitis B virus infection and 10% had hepatitis C virus infection. 38% of the HCC patients had normal Alphafetoprotein (AFP) level, and other 35% had an AFP level lower than 400 ng mL-1. In the study period, 97% of the hepatectomy for HCC were treated with open surgery, and 23.81% had vascular exclusion techniques. The operation time was (191.7±105.6) min, the blood loss was (546.0±562.8) mL, and blood transfusion was (543.0±1,035.2) mL. The median survival for HCC patients was 631 days, with 1-, 3-, and 5-year overall survival of 73.2%, 28.8% and 19.6%, respectively. Liver cirrhosis, multiple nodules, tumor thrombosis and high AFP level were risk factors that affect postoperative survival.

Altered metabolism is one of the hallmarks of cancer cells. Pentose phosphate pathway (PPP) is a fundamental component of cellular metabolism. Glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme of the PPP, is elevated in many cancers and contributes to tumor growth by producing ribose-5-phosphate and NADPH through PPP. However, the role of G6PD in hepatocellular carcinoma (HCC) metastasis and the clinical significance of G6PD in HCC progression and prognosis have not been well determined. In this study, by investigating tissue samples from HCC patients and HCC cell lines, we found that elevated G6PD expression is significantly associated with HCC metastasis and poor prognosis of HCCs, and that knockdown of G6PD inhibits in vitro proliferation, migration and invasion of HCC cell lines. Further studies reveal that G6PD contributes to HCC migration and invasion of hepatocellular carcinoma cells by inducing epithelial-mesenchymal transition through activation of signal transducer and activator of transcription 3 (STAT3) pathway. Our findings suggest that targeting G6PD could open up possibilities for metastasis intervention and improve the patients' outcomes for HCC.

The incidence and mortality of intrahepatic cholangiocarcinoma (ICC) are increasing worldwide in recent decades. Osteopontin (OPN) plays an important role in cancer metastasis, but its functional mechanism in ICC is not clear yet. In this study, we found that OPN level was elevated both in plasma and tumor tissues of ICC patients, which was closely related to a shorter overall survival (OS) and high probability of tumor relapse after curative resection. The gain- and loss-of-function studies determined that OPN could promote ICC growth and metastasis. OPN selectively interacted with β-Catenin and knockdown of β-Catenin abrogated the effects induced by OPN. OPN recruited MAPK1 and activated MEK–MAPK1 pathway to mediate the S675 phosphorylation of β-Catenin and nucleus accumulation, which induced the activation of Wnt signaling. Moreover, a significant correlation between OPN and β-Catenin was found in ICC tissues. OPN, β-Catenin, and their combination were independent prognostic indicator for ICC patients. In conclusion, OPN promotes ICC progression through recruiting MAPK1 and activating the Wnt/β-Catenin pathway and can serve as a novel prognostic marker and therapeutic target for ICC.

Background/Aims: Effective drug treatment for intrahepatic cholangiocarcinoma (ICC) is currently lacking. Therefore, there is an urgent need for new targets and new drugs that can prolong patient survival. Recently targeting the ubiquitin proteasome pathway has become an attractive anti-cancer strategy. In this study, we aimed to evaluate the therapeutic effect of and identify the potential mechanisms involved in targeting the proteasome subunit ADRM1 for ICC. Methods: The expression of ADRM1 and its prognostic value in ICC was analyzed using GEO and TCGA datasets, tumor tissues, and tumor tissue arrays. The effects of RA190 on the proliferation and survival of both established ICC cell lines and primary ICC cells were examined in vitro. Annexin V/propidium iodide staining, western blotting and immunohistochemical staining were performed. The in vivo anti-tumor effect of RA190 on ICC was validated in subcutaneous xenograft and patient-derived xenograft (PDX) models. Results: ADRM1 levels were significantly higher in ICC tissues than in normal bile duct tissues. ICC patients with high ADRM1 levels had worse overall survival (hazard ratio [HR] = 2.383, 95% confidence interval [CI] =1.357 to 4.188) and recurrence-free survival (HR = 1.710, 95% CI =1.045 to 2.796). ADRM1 knockdown significantly inhibited ICC growth in vitro and in vivo. The specific inhibitor RA190 targeting ADRM1 suppressed proliferation and reduced cell vitality of ICC cell lines and primary ICC cells significantly in vitro. Furthermore, RA190 significantly inhibited the proteasome by inactivating ADRM1, and the consequent accumulation of ADRM1 substrates decreased the activating levels of NF-κB to aggravate cell apoptosis. The therapeutic benefits of RA190 treatment were further demonstrated in both subcutaneous implantation and PDX models. Conclusions: Our findings indicate that up-regulated ADRM1 was involved in ICC progression and suggest the potential clinical application of ADRM1 inhibitors (e.g., RA190 and KDT-11) for ICC treatment.

// Yinlong Kong 1 , Lin Sun 1 , Zhenyu Hou 1 , Yongqiang Zhang 1 , Ping Chen 1 , Yunlong Cui 1 , Xiaolin Zhu 1 , Tianqiang Song 1 , Qiang Li 1 , Huikai Li 1 , Ti Zhang 1 and Lunxiu Qin 2, 3 1 Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin 300060, China 2 Department of General Surgery, Huashan Hospital & Cancer Metastasis Institute, Fudan University, Shanghai 200040, China 3 Cancer Research Center, Institute of Biomedical Science, Fudan University, Shanghai 200032, China Correspondence to: Ti Zhang, email: zhangti@tjmuch.com Huikai Li, email: tjchlhk@126.com Lunxiu Qin, email: qinlx99@vip.163.com Keywords: apatinib; hepatocellular carcinoma; vascular endothelial growth factor receptor Received: May 24, 2017 Accepted: September 21, 2017 Published: November 06, 2017 ABSTRACT As treatment options for hepatocellular carcinoma (HCC) are currently limited, we evaluated the efficacy and safety of oral apatinib, a VEGFR-2 inhibitor, on patients with advanced HCC. Twenty-two patients from Tianjin Medical University Cancer Institute and Hospital were enrolled for evaluation. Apatinib was administered at 500 mg/day or 250 mg/day continuously. Clinical endpoints were time to disease progression (TTP), overall survival (OS), and safety. The median TTP of treated patients was 10.4 months (95% CI 3.4 -17.5). At the last follow-up, 50% patients had survived longer than 11.4 months from the first dose. Complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) rates were 0%, 40.9%, 40.9%, and 18.2%, respectively. The most common apatinib-related adverse events were hand-foot skin reaction (HFSR) (81.8%) and diarrhea (77.3%). Hypertension (27.3%) and HFSR (13.6%) were the most frequent grade 3/4 adverse events. In summary, results of this small study indicate that apatinib is well tolerated and extremely effective for the treatment of advanced HCC. It is therefore imperative to design and carry out well-controlled clinical trials to confirm its efficacy.