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Provision of mental health services through digital technologies (e-mental health) can potentially expand access to treatments for personality disorders (PDs). We evaluated studies on e-mental health for PDs published over the last 3 years (2019-2022).Studies published in English that used e-mental health to treat people with PDs or PD-related symptoms were identified. We identified 19 studies, including four randomized controlled trials and one meta-analysis. Most interventions were based on Dialectical Behavior Therapy and delivered through smartphone applications for adults with Borderline Personality Disorder [BPD] or related symptoms. User experiences of the interventions were generally positive. Evidence for efficacy was limited. The current literature on e-mental health for PDs is limited in scope. Research in understudied populations and randomized controlled trials designed to establish efficacy are warranted. It is not yet clear whether e-mental health may be helpful for the treatment of PDs.

Choledocholithiasis is a severe disorder that affects a significant portion of the world's population. Treatment using endoscopic sphincterotomy (EST) has become widespread; however, recurrence post-EST is relatively common. The bile microbiome has a profound influence on the recurrence of choledocholithiasis in patients after EST; however, the key pathogens and their functions in the biliary tract remain unclear.To investigate the biliary microbial characteristics of patients with recurrent choledocholithiasis post-EST, using next-generation sequencing.This cohort study included 43 patients, who presented with choledocholithiasis at the Guangdong Second Provincial General Hospital between May and June 2020. The patients had undergone EST or endoscopic papillary balloon dilation and were followed up for over a year. They were divided into either the stable or recurrent groups. We collected bile samples and extracted microbial DNA for analysis through next-generation sequencing. Resulting sequences were analyzed for core microbiome and statistical differences between the diagnosis groups; they were examined using the Kyoto Encyclopedia of Genes and Genomes pathway hierarchy level using analysis of variance. Correlation between the key genera and metabolic pathways in bile, were analyzed using Pearson's correlation test.The results revealed distinct clustering of biliary microbiota in recurrent choledocholithiasis. Higher relative abundances (RAs) ofWe demonstrated differences in the bile microbiome of patients with recurrent choledocholithiasis compared to that in patients with stable disease, thereby adding to the current knowledge on its microbiologic etiology.

Oral squamous cell carcinoma (OSCC) is one of the most common malignant tumors worldwide and there are few crucial regulators and druggable targets for early diagnosis. Therefore, the identification of biomarkers for the early diagnosis and druggable targets of OSCC is imminent. In this study, we integrated gene set enrichment analysis, differential gene expression analysis based on the negative binomial distribution, weighted correlation network analysis, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes into analyzing the OSCC cohort downloaded from The Cancer Genome Atlas, and found that cell cycle and related biologic processes are significantly enriched. Then, we constructed the core gene network of OSCC, which showed the connection of encode human Cyclin-A2 protein, encode RAD51-associated protein 1, encode human centromere-associated protein E (CENPE), encode humans centromere protein I (CENPI) and encode polo-like kinase 1 (PLK1) to several cell cycle-related genes. Survival analysis further showed that low expression of these genes was associated with a better prognosis. Furthermore, we utilized a high-throughput virtual screening to find new CENPE and PLK1 inhibitors, and one of the CENPE inhibitor DB04517 suppressed the proliferation of OSCC cells by cell cycle arrest of cell cycle. Taken together, these candidate regulators could serve as the candidate diagnostic and prognostic biomarkers for OSCC, and specific suppression of these genes may be a potential approach to prevent and treat OSCC with the candidate inhibitors.

Blood-based biomarkers have been considered as a promising method for the diagnosis of Alzheimer's disease (AD). The reliability and accuracy of plasma core AD biomarkers, including phosphorylated tau (P-tau181), total tau (T-tau), Aβ42, and Aβ40, have also been confirmed in diagnosing AD and predicting cerebral β-amyloid (Aβ) deposition in Western populations, while fewer research studies have ever been conducted in China's Han population. In this study, we investigated the capability of plasma core AD biomarkers in predicting cerebral Aβ deposition burden among the China Aging and Neurodegenerative Disorder Initiative (CANDI) cohort consisting of cognitively normal (CN), mild cognitive impairment (MCI), AD dementia, and non-Alzheimer's dementia disease (Non-ADD). Body fluid (plasma and CSF) AD core biomarkers were measured via single-molecule array (Simoa) immunoassay. The global standard uptake value ratio (SUVR) was then calculated by

Background Glucagon-like peptide-1(GLP-1) mimetics are widely used for treating type 2 diabetes(T2D) with pleiotropic effects on heart and kidneys. The safety/tolerability and pharmacokinetics/pharmacodynamics((PK/PD) of CJC-1134-PC(a long-acting GLP-1) were investigated in Chinese subjects. Method Two randomized, double-blind, placebo-controlled phase I studies were conducted. Study A: 30 healthy subjects received (subcutaneously injected) a single dose(2mg) or titrate doses(2+3 and 2+3+4mg at weekly intervals) of CJC-1134-PC. Study B: 49 T2D subjects received 10 weekly doses(1, 2, 3, and 4mg). Result CJC-1134-PC was well tolerated with gastrointestinal(GI) side effects. Higher doses increased the adverse events risk. CJC-1134-PC was steadily absorbed, with maximum plasma concentrations(Cmax) occurring at 36-72h and 48h after administration in healthy and T2D subjects, respectively. The steady state exposures in T2D subjects increased more than the dose-proportionally(1-3mg). The mean t1/2 time ranged from 111.6 to 127.6h. After four or five weeks of targeting doses, steady state was reached in T2D subjects with apparent accumulation effect. At week 11 for T2D subjects, HbA1c mean baseline change was significantly different than that of the placebo, and the fasting plasma glucose(FPG) was not significantly altered. Conclusion The safety and PK/PD profiles of weekly CJC-1134-PC doses support Phase II studies with guidance on optimal dose selection. Trial registration The clinical trial registration number for this work is ChiCTR-IPC-15007190.

Background Secretory phospholipase A2 group IIA (sPLA2-IIA) is an independent risk factor for cardiovascular disease, but its role on high-density lipoprotein cholesterol (HDL-C) level has not been clarified. The aim of the present study was to explore the association between circulating sPLA2-IIA and HDL-C, and to evaluate if sPLA2-IIA enhances cholesterol efflux capacity through regulation of peroxisome proliferator-activated receptor γ (PPAR-γ), liver X receptor α (LXR-α), and ATP-binding cassette A1 (ABCA1). Methods 131 patients with coronary artery disease were enrolled. The plasma level of sPLA2-IIA was tested with enzyme-linked immunosorbent assay kit, and serum lipids were assessed by biochemical analyzer. Human monocyte-macrophage cell line THP-1 was co-incubated with sPLA2-IIA in the presence/absence of selective PPAR-γ antagonist GW9662 in vitro. Real-time PCR and Western-blot were employed to measure the mRNA and protein expressions of PPAR-γ, LXR-α, and ABCA1, respectively. The cholesterol efflux was evaluated by using an assay kit. Results In subjects, circulating level of sPLA2-IIA was positively related with that of HDL-C (r = 0.196, p = 0.024). The plasma level of sPLA2-IIA was significantly higher in the high HDL-C (≥ 1.04 mmol/L) group (7477.828 pg/mL) than that in low HDL-C (p = 0.004). For each increase of 1 pg/μl in sPLA2-IIA level, the adjusted odds ratio for HDL-C ≥ 1.04 mmol/L was 1.143. Co-incubation of THP-1 cells with sPLA2-IIA resulted in increased expressions of PPAR-γ, LXR-α, and ABCA1, as well as enhanced cholesterol efflux capacity, that were all reversed by administration of GW9662. Conclusions Circulating sPLA2-IIA was positively associated with HDL-C. PPAR-γ/LXR-α/ABCA1 might be responsible for sPLA2-IIA-regulated cholesterol efflux in macrophages.

This retrospective study was conducted to explore the effects of anlotinib as first-line treatment for patients with advanced lung adenocarcinoma. We retrospectively reviewed medical records of 60 patients with advanced lung adenocarcinoma, admitted to the Fuzhou Pulmonary Hospital between August 2018 and December 2019. We calculated and recorded the objective remission rate (ORR), disease control rate (DCR), adverse reactions, quality of life assessment, progression-free survival (PFS) and overall survival (OS) for each group. We applied χ2, Mann-Whitney U test, Kaplan-Meier and log-rank statistical methods as appropriate to analyze the data. We found no statistically significant differences in either ORR (17.5 vs. 15%) or DCR (67.5 vs. 65.5%) between the anlotinib and pemetrexed groups (P0.05). The adverse reactions graded ≥3 in the anlotinib group were fatigue and diarrhea and they accounted for 5% of all the adverse reactions in the group. The patients in the anlotinib group presented better physical, role, cognitive, emotional, and social functions than those in the pemetrexed group (P0.05). The symptoms of fatigue, nausea and vomiting, loss of appetite and constipation in the anlotinib group were significantly less frequent than those in the pemetrexed group (P0.05). We found similar median PFSs (3.0 vs. 2.8 months) and median OSs (7.0 vs. 7.0 months) in both treatment groups (P0.05). The choice of anlotinib as first-line chemotherapy for treating elderly patients with advanced lung adenocarcinoma was effective, safe; the treatment was better than other drugs at improving the patients' quality of life.

Background Spermine is frequently elevated in tumor tissues and body fluids of cancer patients and is critical for cancer cell proliferation, migration and invasion. However, the immune functions of spermine in hepatocellular carcinoma progression remains unknown. In the present study, we aimed to elucidate immunosuppressive role of spermine in hepatocellular carcinoma and to explore the underlying mechanism. Methods Whole-blood spermine concentration was measured using HPLC. Human primary HCC tissues were collected to examine the expression of CaSR, p-Akt, β-catenin, STT3A, PD-L1, and CD8. Mouse model of tumorigenesis and lung metastasis were established to evaluate the effects of spermine on hepatocellular carcinoma. Western blotting, immunofluorescence, real time PCR, digital Ca2+ imaging, and chromatin immunoprecipitation assay were used to investigate the underlying mechanisms by which spermine regulates PD-L1 expression and glycosylation in hepatocellular carcinoma cells. Results Blood spermine concentration in the HCC patient group was significantly higher than that in the normal population group. Spermine could facilitate tumor progression through inducing PD-L1 expression and decreasing the CD8+ T cell infiltration in HCC. Mechanistically, spermine activates calcium-sensing receptor (CaSR) to trigger Ca2+ entry and thereby promote Akt-dependent β-catenin stabilization and nuclear translocation. Nuclear β-catenin induced by spermine then activates transcriptional expression of PD-L1 and N-glycosyltransferase STT3A, while STT3A in turn increases the stability of PD-L1 through inducing PD-L1 protein N-glycosylation in HCC cells. Conclusions This study reveals the crucial function of spermine in establishing immune privilege by increasing the expression and N-glycosylation of PD-L1, providing a potential strategy for the treatment of hepatocellular carcinoma.

OBJECTIVE: To study the clinical features of severe meconium aspiration syndrome (MAS) and early predicting factors for the development of severe MAS in neonates with meconium-stained amniotic fluid (MSAF). METHODS: A total of 295 neonates who were hospitalized due to Ⅲ° MSAF from January 2018 to December 2019 were enrolled as subjects. The neonates were classified to a non-MAS group (n=199), a mild/moderate MAS group (n=77), and a severe MAS group (n=19). A retrospective analysis was performed for general clinical data, blood gas parameters, infection indicators, and perinatal clinical data of the mother. The respiratory support regimens after birth were compared among the three groups. The receiver operating characteristic (ROC) curve and multivariate logistic regression analysis were used to investigate predicting factors for the development of severe MAS in neonates with MSAF. RESULTS: Among the 295 neonates with MSAF, 32.5% (96/295) experienced MAS, among whom 20% (19/96) had severe MAS. Compared with the mild/moderate MAS group and the non-MAS group, the severe MAS group had a significantly lower 5-minute Apgar score (P39.02 pg/mL and white blood cell count (WBC) >30.345×10(9)/L at 1 hour after birth were early predicting indicators for severe MAS in neonates with MSAF (P

This study sought to compare the efficacy and clinical safety of the LONGTY drug-coated balloon (DCB) with those of SeQuent Please DCB in patients with in-stent restenosis (ISR).Although DCB technologies have evolved, little is known about the clinical efficacy of the new-generation LONGTY DCB.This was a prospective, multicenter, randomized, noninferiority trial comparing LONGTY DCB with SeQuent Please DCB in patients with ISR. The primary endpoint was target lesion late lumen loss at 9 months' follow-up.A total of 211 patients with ISR from 13 Chinese sites were included (LONGTY DCB, n = 105; SeQuent Please DCB, n = 106). Device success was achieved in all patients. At the 9 month angiographic follow-up, target lesion late lumen loss was 0.35 ± 0.42 mm with LONGTY and 0.38 ± 0.45 mm with SeQuent Please (p for noninferiority.001). The target lesion revascularization rates at 1 year were similar in both DCB groups (15.24 vs. 13.21%; p = .673). Over an extended follow-up of 2 years, the clinical endpoints, including cardiac death, myocardial infarction, and thrombus rate, were extremely low and similar in both groups.In this multicenter, head-to-head, randomized trial, the new-generation LONGTY DCB was noninferior to the SeQuent Please DCB for the primary endpoint of target lesion late lumen loss at 9 months.

The current diagnoses of Alzheimer's disease (AD) mainly rely on such measures as amyloid-β (Aβ) and tau neuropathology biomarkers in vivo via cerebrospinal fluid (CSF) and positron emission tomography (PET) imaging, which had been systematically studied in Caucasian individuals, whereas diagnostic performances of these approaches in Chinese dementia population still remain unclear. This study investigated the associations between the levels of CSF core AD biomarkers, including phosphorylated tau (p-Tau181), total tau (t-Tau), Aβ42, and Aβ40 measured by the single-molecule array (Simoa) and cerebral Aβ deposition status assessed by

Background: There are few studies on postoperative complications after colonoscopic perforation. We aimed to study clinical characteristics and treatment after colonoscopic perforation, and to dete...

BACKGROUND Mounting studies have emerged indicating that patients with peptic ulcer disease (PUD) are at a high risk of developing osteoporosis, but the evidence has not been previously synthesized. The present study aims to examine whether patients with PUD have a significantly higher prevalence of osteoporosis than the healthy normal subjects. METHODS Four electronic databases were systematically searched for eligible studies up to February 2020. The association between PUD and osteoporosis was evaluated by calculating the relative risk (RR) with a 95% confidence interval (CI). RESULTS Six observational studies were finally included, enrolling a total of 216 122 individuals. Synthetic results from the six included studies providing the number of cases for both sexes demonstrated that PUD was significantly associated with an increased risk of osteoporosis (95% CI, 1.37-1.89; P

Background Dysfunction in the late Endothelial Progenitor Cells (EPCs) is responsible for endothelial repair in patients with Coronary Artery Disease (CAD), and the shear stress is beneficial for EPCs function. However, the impact of shear stress on the capacity of EPCs in CAD patients has not been elucidated yet. The C-X-C chemokine receptor 7/extracellular signal-regulated kinase (CXCR7)/(ERK) pathways are identified to regulate EPCs function in CAD patients. Here, we hypothesize that shear stress upregulates the CXCR7/ERK pathways, which restore the EPCs function in CAD patients. Methods The human Peripheral Blood Mononuclear Cells (PBMCs) were collected from healthy adults and CAD patients and then used for EPCs cultivation. The Lv-siRNA for human CXCR7 was transfected into induced EPCs isolated from the CAD patients. Meanwhile, the EPCs from CAD patients were subjected to shear stress generated by a biomimetic device. Next, the cell viability, migration, tube formation, and apoptosis were detected by CCK-8, Transwell assay, Matrigel, and flow cytometry, respectively. Also, the CXCR7/ERK pathways in human EPCs were analyzed by Western blotting and qRT-PCR. Result Compared to the EPCs collected from normal adults, the CAD patient-derived EPCs showed reduced in vitro vasculogenic capacity. Also, the level of CXCR7 in CAD patient-derived EPCs was significantly reduced compared to the EPCs of healthy subjects. Meanwhile, the extracellular signal-regulated kinase (ERK), which represents a CXCR7 downstream signaling pathway, had decreased phosphorylation level. The shear stress treatment augmented the CXCR7 expression and also elevated ERK phosphorylation, which is comparable to the up-regulation of CAD patient-derived EPCs function. Further, the small interfering RNA (siRNA)-mediated CXCR7 knockdown diminished the enhanced migration, adhesion, and tube formation capacity of shear stress treated CAD patient-derived EPCs. Conclusion Up-regulation of the CXCR7/ERK pathways by shear stress can be a promising new target in enhancing the vasculogenic ability of CAD patient-derived EPCs.

The significance of the polypeptide N-acetyl-galactosaminyl transferase-3 (GalNAc-T3) and mucin 1 (MUC1) in solitary pulmonary adenocarcinoma (SPA) initially diagnosed as malignant solitary pulmonary nodule (≤ 3 cm), especially as a combined predictor of prognosis and recurrence, was explored in this study. A retrospective analysis of 83 patients with SPA (≤ 3 cm), which revealed postoperative pathological diagnosis was lung adenocarcinoma after complete resection. Immunohistochemical staining was used to detect the expression of GalNAc-T3 and MUC1 in primary tumor specimens. The relationship between expression and various clinicopathological factors was analyzed, as well as the effects of patients' overall survival (OS) and disease-free survival (DFS). In all patients, GalNAc-T3 was highly expressed in 53 (63.9%) cases; MUC1 was highly expressed in 31 (37.3%) cases. The GalNAc-T3 expression was correlated with differentiation, pathological risk group, N stage, and TNM stage. The group with high GalNAc-T3 expression and low MUC1 expression (GalNAc-T3Hig/MUC1Low) is correlated to pathological differentiation and has a trend related to the TNM stage. The patients with better differentiation, lower pathological risk group, lower N stage, and GalNAc-T3 high expression had better overall survival, especially the GalNAc-T3Hig/MUC1Low group. Moreover, the moderate differentiation, N3 stage, and GalNAc-T3Hig/MUC1Low group were independent predictive factors for OS. Besides, patients with lower N stage, lower TNM stage, higher GalNAc-T3 expression got better disease-free survival (DFS), especially the GalNAc-T3Hig/MUC1Low group. The GalNAc-T3Hig/MUC1Low group was an independent predictive factor for DFS. In conclusion, GalNAc-T3 and MUC1 were combined predictors of prognosis and recurrence in SPA (≤ 3 cm).

Y-box binding protein 1 (YBX1) is involved in the development of multiple types of tumors. However, the relationship between YBX1 and autophagy in non-small cell lung cancer (NSCLC) remains unclear. In this study, we analyzed the expression and clinical significance of YBX1 and markers of autophagy (LC3I/II) in NSCLC and examined their roles in regulating sensitivity to cisplatin in NSCLC. The retrospective analysis of patients with NSCLC indicated that YBX1 was positively correlated with autophagy. Increased levels of YBX1 or autophagy also observed in NSCLC cells compared with those in 16HBE cells. Compared to the controls, the knockdown of YBX1 expression suppressed autophagy, increased drug sensitivity and promoted apoptosis in response to cisplatin in NSCLC cells by targeting the p110β promoter and inhibiting p110β/Vps34/beclin1 signaling pathways. We also demonstrated in an in vivo study that the overexpressed YBX1 effectively increased NSCLC growth and progression and decreased the sensitivity to cisplatin by inducing autophagy in a xenograft tumor model, and these effects were concomitant with the increasing of p110β and beclin1 expression. Collectively, these results show that YBX1 plays an essential role in autophagy in NSCLC.

Angiogenesis is a necessary process for solid tumor growth. Cellular markers for endothelial cell proliferation are potential targets for identifying the vasculature of tumors in homeostasis. Here we customize the behaviors of engineered cells to recognize Apj, a surface marker of the neovascular endothelium, using synthetic Notch (synNotch) receptors. We designed apelin-based synNotch receptors (AsNRs) that can specifically interact with Apj and then stimulate synNotch pathways. Cells engineered with AsNRs have the ability to sense the proliferation of endothelial cells (ECs). Designed for different synNotch pathways, engineered cells express different proteins to respond to angiogenic signals; therefore, angiogenesis can be detected by cells engineered with AsNRs. Furthermore, T cells customized with AsNRs can sense the proliferation of vascular endothelial cells. As solid tumors generally require vascular support, AsNRs are potential tools for the detection and therapy of a variety of solid tumors in adults., Cellular markers of endothelial cell proliferation help identify the vasculature of tumours in homeostasis. Here, the authors report Apelin-based synthetic Notch (synNotch) receptors that can target Apj expressed on endothelium and stimulate the synNotch pathways upon Apj binding, and suggest this as a strategy to treat solid tumours.

Background/Purpose This study aimed to determine the potential effects of angiopoietin-2 (Ang-2), von Willebrand factor (vWF), and extravascular lung water index (EVLWI) on the risk of mortality in sepsis patients with concomitant acute respiratory distress syndrome (ARDS). Methods This retrospective study recruited 41 sepsis patients with concomitant ARDS from January 2015 to June 2018. Data of Ang-2 and vWF levels, EVLWI, and sequential organ failure assessment scores were collected at 0, 24, and 48 h after admission to the hospital. Results The length of intensive care unit stay (P = 0.041) and Acute Physiology and Chronic Health Evaluation-2 (APACHE II) score (P = 0.003) were associated with the risk of mortality. Furthermore, increased Ang-2 levels and EVLWI at 24 h and 48 h were associated with an increased risk of mortality. Moreover, the APACHE II score at hospital admission significantly predicted the risk of mortality (area under the curve [AUC], 0.834; 95% confidence interval [CI], 0.665–0.983). Finally, the models containing a combination of Ang-2 level and EVLWI at 24 h (AUC, 0.908; 95% CI, 0.774–0.996) and Ang-2 level and EVLWI at 48 h (AUC, 0.981; 95% CI, 0.817–1.000) had high diagnostic values for predicting risk of mortality. Conclusion The study findings indicate that Ang-2 levels and EVLWI at 24 h and 48 h after admission are significantly associated with the risk of mortality.

Regulated cell death is a widely attractive subject among the topics of cancer therapy and has gained some advances for discovery of targeted anticancer drugs. In the past decade, nonapoptotic regulated cell death has been implicated in the development and therapeutic responses of a variety of human cancers. Hitherto, targeting autophagy-dependent cell death (ADCD), ferroptosis, and necroptosis with small molecules has been emerging as a hopeful strategy for the improvement of potential cancer therapy, which may have an advantage to bypass the apoptosis-resistance machinery. Thus, in this perspective, we concentrate on the key molecular insights into ADCD, ferroptosis, and necroptosis and summarize the corresponding small molecules in potential cancer therapy. Moreover, the relationships between the three subroutines and small molecules modulating the crosstalk are discussed. We believe that these inspiring findings would be advantageous to exploiting more potential targets and pharmacological small molecules in future cancer treatment.

To investigate the characteristics ofTwenty-one patients with multiple myeloma secondary extramedullary infiltration confirmed by pathology or follow-up from January 2012 to October 2020 in the First Affiliated Hospital of University of Science and Technology of China were retrospectively analyzed. All the patients underwentTwenty-one patients included 12 males and 9 females, aged from 41 to 77 years old, with an average of 58.3±10.0; 9 cases of extramedullary infiltration involving lymph nodes; lung, stomach, spleen, and kidney were involved respectively in 2 cases; retroperitoneal, right auricle, subcutaneous nodule, and spinal meninges involvement were reported in each one case respectively. The maximum SUVmax value of extra-medullary lesions was 21.2, the minimum value was 2.1, and mean was 7.7±5.3. The maximum SUVmax value of bone marrow was 33.5, the minimum was 2.4, and mean was 6.6±3.6. There was no statistically significant difference in SUVmax value between extra-medullary lesions and bone marrow (Z=-1.195, P=0.232).探讨多发性骨髓瘤继发髓外浸润的回顾性分析2012年1月至2020年10月中国科学技术大学附属第一医院21例为穿刺病理或随访证实的多发性骨髓瘤继发髓外浸润患者，所有患者治疗前均行21例患者中，男12例，女9例，年龄41-77岁，平均（58.3±10.0）岁；骨髓外浸润累及淋巴结9例，肺、胃、脾脏及肾脏各2例，腹膜后、右心耳、皮下结节及脊膜受累及各1例；髓外浸润SUVmax最大值21.2，最小值2.1，平均值7.7±5.3，骨髓病变最大值33.5，最小值2.4，平均值6.6±3.6，髓外浸润与骨髓病变SUVmax比较，二者之间差异无统计学意义（Z=-1.195，P=0.232）.

To investigate the clinical effects of the L-carnitine-astaxanthin compound nutrients Menglankang (MLK) on idiopathic oligospermia (OS) and asthenospermia (AS).This study included 73 cases of OS and 220 cases of AS treated with MLK once a bag, bid, for 3 successive months. Before and at 1, 2 and 3 months after treatment, we obtained and analyzed the semen parameters and sperm DNA fragmentation index (DFI) of the patients.Compared with the baseline, the OS patients showed remarkable increases after 1 and 2 months of treatment in the semen volume (［3.07 ± 1.47］ vs ［3.26 ± 1.26］ and ［3.30 ± 1.28］ ml), sperm concentration (［10.96 ± 6.09］ vs ［16.74 ± 11.15］ and ［17.56 ± 9.92］ ×10⁶/ml, P0.05), total sperm count (［29.78 ± 17.48］ vs ［52.98 ± 32.07］ and ［57.67 ± 36.98］ ×106, P0.05) and the percentages of progressively motile sperm (PMS) (［39.8 ± 11.66］% vs ［45.3 ± 14.03］% and ［46.42 ± 10.69］%, P0.05) and morphologically normal sperm (MNS) (［1.71 ± 1.07］% vs ［1.79 ± 0.91］% and ［1.84 ± 0.96］%), and so did the AS patients in PMS (［19.23 ± 8.32］% vs ［25.46 ± 13.86］% and ［27.33 ± 12.88］%, P0.05). After 3 months of medication, the OS patients exhibited even more significant increases in the semen volume (［3.63 ± 1.39］ ml) (P0.05), sperm concentration (［20.56 ± 14.7］ ×10⁶/ml) (P0.05), total sperm count (［66.35 ± 55.91］ ×106) (P0.05), PMS (［49.24 ± 13.45］%) (P0.05) and MNS (［2.59 ± 0.93］%) (P0.05), and so did the AS patients in the semen volume (［3.27 ± 1.42］ vs ［3.85 ± 1.59］ ml, P0.05), PMS (［29.11 ± 13.58］%) (P0.05) and NMS (［2.01 ± 1.14］% vs ［2.57 ± 1.15］%, P0.05). In comparison with the baseline, the sperm DFI was not significantly improved at 1 month after treatment, but remarkably decreased at 2 and 3 months in the OS patients (［25.87 ± 13.76］% vs ［18.66 ± 10.83］% and ［16.48 ± 11.46］%, P0.05) and the AS patients as well (［26.40 ± 12.28］% vs ［19.35 ± 11.54］% and ［15.32 ± 10.89］%, P0.05).The L-carnitine-astaxanthin compound nutrients Menglankang can significantly improve the semen quality of the patients with idiopathic oligospermia or asthenospermia.

This paper describes the development and validation of a Monte Carlo (MC) dose computing module dedicated to organ dose calculations of patients undergoing nuclear medicine (NM) internal radiation exposures involving 18F-FDG PET/CT examination. This new module extends the more-than-10-years-long ARCHER project that developed a GPU-accelerated MC dose engine by adding dedicated NM source-definition features. To validate the code, we compared dose distributions from the 0.511-MeV point photon source calculated for a water phantom as well as a patient PET/CT phantom against a well-tested MC code, GATE. The water-phantom results show excellent agreement, suggesting that the radiation physics module in the new NM code is adequate. To demonstrate the clinical utility and advantage of ARCHER-NM, one set of PET/CT data for an adult male NM patient is calculated using the new code. Radiosensitive organs in the CT dataset are segmented using a CNN-based tool called DeepViewer. The PET image intensity maps are converted to radioactivity distributions to allow for MC radiation transport dose calculations at the voxel level. The dose rate maps and corresponding statistical uncertainties were calculated for the duration of PET image acquisition. The dose rate results of the 18F-FDG PET imaging patient show that ARCHER-NM's results agree very well with those of the GATE within 0.58% to 4.11%. Most impressively, ARCHER-NM obtains such results in less than 0.5 minutes while it takes GATE as much as 376 minutes. This is the first study presenting GPU-accelerated patient-specific MC internal radiation dose rate calculations for clinically realistic 18F-FDG PET/CT imaging cases involving auto-segmentation of whole-body PET/CT images. This study suggests that modern computing tools -- ARCHER-NM and DeepViewer -- are accurate and fast enough for routine internal dosimetry in NM clinics., 17 pages, 5 figures, 1 table

Background Osteoporosis (OP) is a well-known chronic degenerative disease, with impaired mesenchymal stem cells (MSCs) function and suppressed osteogenic differentiation. Total glycosides from Eucommia ulmoides seed (TGEUS) was a Chinese medicine and have rich pharmacological effects. This study was designed to explore the mechanism of TGEUS in promoting osteogenic differentiation and bone formation in ovariectomized (OVX) rats. Methods Adipose‐derived mesenchymal stem cells (ADSCs) were isolated and treated with different concentration of TGEUS. Cell viability was assessed using cell counting kit-8 (CCK-8) assay. Osteogenic capacity was identified by ALP staining and ARS staining. Moreover, RNA sequencing between control and TGEUS treated ADSCs were further performed to reveal the mechanism of TGEUS in promoting osteogenic differentiation. The expression of Jag1, Lfng and Hey1 were measured using quantitative real-time polymerase chain reaction (qRTPCR). Osteogenic markers were further assessed by western blot. DAPT and NICD were further used to identify whether Notch signaling pathway involved into TGEUS promoting osteogenic differentiation of ADSCs. Ovariectomy-induced bone loss rats model was established and divided into three groups: sham, OVX and OVX + TGEUS groups. HE staining and immunohistochemical staining were further performed to identify whether TGEUS could promote bone formation. Results TGEUS treatment significantly enhanced the cell viability and ALP activity than control group, the optimal dose of TGEUS was 5 μM. We selected 5 μM TGEUS for further study. TGEUS significantly enhanced ALP activity and calcium deposition than that of control group. Activation of Notch signaling fully blocked TGEUS-induced osteogenic differentiation of ADSCs. Following TGEUS treatment, the trabecular bone of the rats was significantly increased, thickened, and more connected compared to the OVX group. With the treatment of TGEUS, the expression of Osterix (Osx), Osteocalcin (OCN) and RUNX Family Transcription Factor 2 (RUNX2) increased than OVX group. Conclusion TGEUS enhanced osteogenic differentiation of ADSCs and promoted bone formation in ovariectomy-induced bone loss rats. Our study broadened the understanding of TGEUS as a therapeutic target against osteoporosis.

OBJECTIVE: To study the clinical features and prognosis of neonates with severe meconium aspiration syndrome (MAS) and acute respiratory distress syndrome (ARDS). METHODS: A retrospective analysis was performed on the medical data of 60 neonates with severe MAS who were admitted from January 2017 to December 2019. According to the presence or absence of ARDS, they were divided into two groups: ARDS (n=45) and non-ARDS (n=15). Clinical features and prognosis were compared between the two groups. RESULTS: Among the 60 neonates with severe MAS, 45 (75%) developed ARDS. Arterial blood gas analysis showed that the ARDS group had a significantly higher median oxygenation index within 1 hour after birth than the non-ARDS group (4.7 vs 2.1, P0.05). The ARDS group had a significantly higher incidence rate of shock than the non-ARDS group (84% vs 47%, P0.05). The ARDS group required a longer median duration of mechanical ventilation than the non-ARDS group (53 hours vs 3 hours, P

Liuwei Dihuang Pill is widely used to treat tinnitus in China. However, the underlying mechanism of Liuwei Dihuang Pill in treating tinnitus still remains unclear.To explore the potential pharmacological mechanism of Liuwei Dihuang Pill in the treatment of tinnitus based on network pharmacology and molecular docking.The active components of the Liuwei Dihuang Pill were obtained from the traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP) database. Cytoscape software was used to draw the active component-target network diagram of Liuwei Dihuang Pill, and obtain the core components. Then the corresponding targets were also obtained from the TCMSP database. Targets related to tinnitus were obtained from the GeneCards, DisGeNET, TTD and DrugBank databases. The String database was used to construct protein-protein interaction (PPI) network of common targets of drugs and diseases, then the core targets were screened out. The Annotation, Visualization and Integrated Discovery (DAVID) database was used for gene ontology (GO) enrichment and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis of common targets. Finally, the molecular docking between the core component and the core target was carried out by AutoDock.The core components of Liuwei Dihuang Pill in the treatment of tinnitus including quercetin, stigmasterol, kaempferol, β-sitosterol, tetrahydroalstonine, which may act on core targets such as STAT3, transcription factor AP-1 (JUN), tumor necrosis factor (TNF), interleukin-6 and MAPK3. HIF-1 signaling pathway, Influenza A, P53 signaling pathway, and Toll-like receptor signaling pathway play a role in anti-inflammatory, improving microcirculation in the blood-labyrinth barrier, increasing cochlear blood flow, and preventing hair cell damage. The molecular docking results showed that the affinity between core components and core targets was good.The potential mechanism of Liuwei Dihuang Pill in the treatment of tinnitus was preliminarily discussed in this study, which may provide a theoretical basis and evidence for further experimental research.

To evaluate the effectiveness and safety of transcutaneous electrical acupoint stimulation (TEAS) for improving postoperative cognitive function in senior patients undergoing video-assisted thoracoscopic surgical (VATS).From January to December 2020, 97 participants were randomly assigned to the TEAS group (49 cases) and the control group (48 cases) by a random number table. The patients in the TEAS group received TEAS, at the bilateral Neiguan (PC 6) and Zusanli (ST 36) acupoints. The control group received sham TEAS. The stimulation was started from 30 min before surgery until the end of the operation. The primary outcome was the incidence of pstoperative cognitive dysfunction (POCD), diagnosed based on the changes in the Mini-Mental Status Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores. The secondary outcomes were plasma levels of S100β protein and neuron-specific enolase (NSE).The incidence of POCD on day 1 and 3 after surgery in the TEAS group was significantly lower than that in the control group [day 1 after surgery: 28.3% (13/46) vs. 52.3% (23/44), P=0.028; day 3 after surgery: 21.7% (10/46) vs. 40.9% (18/44), P=0.043]. Compared with baseline, the MMSE and MoCA scores decreased to various extents in both groups. The MMSE scores on day 1, 3, and 5 after surgery and MoCA scores on day 1, 3, 5, and 7 after surgery in the TEAS group were higher than those in the control group (all P0.05) in both groups. Compared with baseline, the plasma levels of S100β and NSE were significantly increased at 4, 8, 12, 24 h after surgery (all P0.05). Compared with the control group, the plasma levels of S100β and NSE were lower in the TEAS group at 4, 8, 12, and 24 h after surgery (all P0.05). No obvious adverse events were found during the trial.Application of TEAS in senior patients after VATS could reduce incidence of POCD and improve postoperative cognitive function.

Long non-coding RNA (lncRNA) small nucleolar RNA host gene 11 (SNHG11) has been shown to play an important role in the development and progression of numerous types of cancer. However, to the best of our knowledge, the role of SNHG11 in prostate cancer (PCa) development and metastasis remains unclear. Thus, the aim of the present study was to investigate the functional role and molecular mechanisms of SNHG11 in PCa progression. It was revealed that the SNHG11 expression levels were significantly upregulated in PCa tissues, in comparison with those in adjacent normal tissues. Functionally, SNHG11 knockdown significantly suppressed PCa cell proliferation, migration, invasion and metastasis in vitro and in vivo. Furthermore, SNHG11 was found to positively regulate insulin-like growth factor 1 receptor (IGF-1R) expression by sponging microRNA (miRNA/miR)-184 in PCa cells. The results of rescue experiments demonstrated that IGF-1R overexpression reversed the suppressive effects of SNHG11 knockdown on the proliferation, migration and invasion of PCa cells. On the whole, the findings of the present study suggest that SNHG11 expression is upregulated in PCa and that it facilitates PCa progression, at least in part, via the modulation of the miR-184/IGF-1R signaling axis.

Background Breast cancer is the most common female cancer worldwide. DNA methylation is a common modification in epigenetics and affects the prognosis of breast cancer by changing gene expression. In the present study, we aim to investigate the role of DNA methylation in TMEM130 gene expression, and the function of TMEM130 in breast cancer cell migration. Methods The transcriptional expression of TMEM130 was detected by qRT-PCR in breast cancer cell lines and tissues. Bisulfite sequencing PCR (BSP) was used to confirm the methylation status of TMEM130 promoter. Then, TMEM130 was transfected in breast cancer cell lines and to explore its role in cell migration by Transwell and western blot. Results TMEM130 mRNA expression was decreased in breast cancer cell lines and tissues, and consistent with the data in The Cancer Genome Atlas (TCGA). The promoter of TMEM130 was hypermethylated in breast cancer and the expression of TMEM130 could be restored by the methyltransferase inhibitor. Overexpression of TMEM130 could inhibit cell migration ability in breast cancer cell lines. Conclusion Taken together, these results indicate TMEM130 downregulation and hypermethylation might contribute to breast cancer migration and TMEM130 might be a promising biomarker for breast cancer.

Background and objective : Computed tomography (CT) examination plays an important role in screening suspected and confirmed patients in pneumocystis carinii pneumonia (PCP), and the efficient acquisition of high-quality medical CT images is essential for the clinical application of computer-aided diagnosis technology. Therefore, improving the resolution of CT images of pneumonia is a very important task. Methods : Aiming at the problem of how to recover the texture details of the reconstructed PCP CT super-resolution image, we propose the image super-resolution reconstruction model based on self-attention generation adversarial network (SAGAN). In the SAGAN algorithm, a generator based on self-attention mechanism and residual module is used to transform a low-resolution image into a super-resolution image. A discriminator based on depth convolution network tries to distinguish the difference between the reconstructed super-resolution image and the real super-resolution image. In terms of loss function construction, on the one hand, the Charbonnier content loss function is used to improve the accuracy of image reconstruction, and on the other hand, the feature value before activation of the pre-trained VGGNet is used to calculate the perceptual loss to achieve accurate texture detail reconstruction of super-resolution images. Results : Experimental results show that our SAGAN algorithm is superior to other state-of-the-art algorithms in both peak signal-to-noise ratio (PSNR) and structural similarity score (SSIM). Specifically, our SAGAN method can obtain 31.94 dB which is 1.53 dB better than SRGAN on Set5 dataset for 4 enlargements. Conclusion : Our SAGAN method can reconstruct more realistic PCP CT images with clear texture, which can help experts diagnose the condition of PCP.

Background Tetranectin is a secreted homotrimeric protein belonging to the C-type lectin family. Our previous studies found that tetranectin was not only related to, but also played a protective role in, Parkinson disease. In this study, we aim to illustrate the molecular mechanism of the secreted tetranectin. Methods We used exogenous tetranectin to investigate the function and molecular mechanism of secreted tetranectin in a 1-methyl-4-phenylpyridine (MPP+)–induced SH-SY5Y cell model. Cell viability and reactive oxygen species were measured to assess the protective effects of tetranectin against MPP+. Apoptosis was measured in several aspects, including Bcl-2/Bax expression, caspase-3/7 activity, annexin V staining, and nuclear morphology. Autophagy was measured as LC3 expression and autophagy flux. Moreover, we used cell immunofluorescence to detect the transport of tetranectin. Western blotting was performed to measure the phosphorylation level of ribosomal protein S6 kinase beta-1 (p70S6K1), and co-immunoprecipitation was applied to confirm the interaction between tetranectin and p70S6K1. Results The data showed exogenous tetranectin alleviated MPP+-induced toxicity, high reactive oxygen species levels, apoptosis, and autophagy and changed the phosphorylation level of p70S6K1. Immunofluorescence images suggested exogenous tetranectin could be taken into SH-SY5Y cells, and the co-immunoprecipitation experiment indicated tetranectin interacted with p70S6K1. Conclusions Exogenous tetranectin protects against MPP+-induced neurotoxicity by promoting p70S6K1 phosphorylation once taken into SH-SY5Y cells.

Purpose Sexual functioning is an important factor influencing quality of life. Mounting evidence suggests that both male and female patients with epilepsy (PWE) have an increased risk of developing sexual dysfunction (SD). The aim of this meta-analysis was to quantify the association between epilepsy and the risk of SD. Methods PubMed, Embase, and Cochrane Library database were systematically searched to identify the pertinent studies focusing on the association between epilepsy and SD. Relative risk (RR) for SD with 95% confidence interval (CI) was calculated. The overall quality of the evidence was generated by applying the GRADE-profiler. This meta-analysis was registered on the PROSPERO (ID: CRD42018103572, http://www.crd.york.ac.uk/PROSPERO ). Results Nine studies (3 cross-sectional, 5 case-control, and 1 cohort) were included in this meta-analysis, for a total of 1556 subjects and 599 cases of epilepsy. Synthetic results demonstrated that epilepsy was associated with an increased risk of female SD (6 studies, pooled RR = 2.69, 95%CI: 1.48–4.89, P = 0.001; heterogeneity: I2 = 88.9%, P Conclusions Epilepsy is significantly associated with an increased risk of SD in both sexes. These findings suggest that both clinicians and patients should recognize that epilepsy has a potential hazardous effect on sexual functioning.

Epigenetics mainly refers to covalent modifications to DNA or histones without affecting genomes, which ultimately lead to phenotypic changes in cells or organisms. Given the abundance of regulatory targets in epigenetic pathways and their pivotal roles in tumorigenesis and drug resistance, the development of epigenetic drugs holds a great promise for the current cancer therapy. However, lack of potent, selective, and clinically tractable small-molecule compounds makes the strategy to target cancer epigenetic pathways still challenging. Therefore, this review focuses on epigenetic pathways, small molecule inhibitors targeting DNA methyltransferase (DNMT) and small molecule inhibitors targeting histone modification (the main regulatory targets are histone acetyltransferases (HAT), histone deacetylases (HDACs) and histone methyltransferases (HMTS)), as well as the combination strategies of the existing epigenetic therapeutic drugs and more new therapies to improve the efficacy, which will shed light on a new clue on discovery of more small-molecule drugs targeting cancer epigenetic pathways as promising strategies in the future.

Although multiple intracranial aneurysms (MIAs) are frequent and disastrous, determining treatment strategy for them is often complicated, especially in elderly patients (≥60 years old). We evaluated the safety and effectiveness of one-stage coiling versus surgical clipping for MIAs in elderly patients.All elderly patients who underwent one-stage embolization or surgical clipping for more than two aneurysms were identified in our hospital between January 2012 and June 2018. Patient characteristics and clinical outcomes at discharge and follow-up were retrospectively evaluated.A total of 32 patients with 76 IAs underwent one-stage coiling and 21 patients with 46 IAs underwent one-stage clipping were enrolled in this study. Patients who underwent clipping were younger (mean age 64.1 versus 67.2, P = 0.006) and had lower total hospital costs (mean14764 $ versus 24,620 $, P0.001) compared with patients who underwent coiling. Immediate posttreatment angiography showed complete occlusion in 56 aneurysms, near complete in 11 and incomplete in 2 in coiling group. Aneurysms wrapping was performed in 2, incomplete clipping in 1 and complete clipping in 41 aneurysms in clipping group. At discharge, 49 (92.5 %) patients were in a good condition (GOS score 4 and 5), 4 (7.5 %) were disabled. At 12 months after discharge, 25 (92.6 %) and 16 (94.1 %) patients had favorable outcomes in the coiling and clipping groups, respectively.Both one-stage coiling and surgical clipping are safe, effective methods for treating MIAs in elderly patients.

To determine the effect of intravenous injection of recombinant human brain natriuretic peptide (rhBNP) on lowering the incidence of asymptomatic peri-procedural myocardial injury (PMI) in patients who underwent coronary stent implantation. In this retrospective observational study, data pooled from a tertiary hospital electronic medical records were used to quantify the troponin enzyme change after patients with coronary artery disease (CAD) were pretreated with rhBNP infusion one day prior to percutaneous coronary intervention (PCI). The primary end point was to analyze the incidence of the elevated high-sensitivity cardiac troponin I serum levels above the upper normal limit after PCI. A total of 156 CAD patients were enrolled into rhBNP group (n = 76) and control group (n = 80). The incidence of asymptomatic PMI was 33% in the rhBNP group versus 51% in the control group (P = 0.02) after PCI. At eight months, the incidences of composite endpoints were 25.3% in the control group and 13% in the rhBNP group (difference, 12.3 percentage points; 95% confidence interval (CI), 0.197 to 1.048; P = 0.061). There were 7 visits in the rhBNP group and 15 visits in the control group for recurrent angina (difference, 10 percentage points; 95% CI 0.168–1.147; P = 0.087). A time-to-event analysis of the composite clinical endpoints and the recurrent angina between the control group and rhBNP group showed that the hazard ratios were 2.566 (95% CI 1.187–5.551; P = 0.017) and 2.607 (95% CI 1.089–6.244; P = 0.032) respectively. The decreased incidence of asymptomatic PMI after PCI and the reduced episodes of recurrent angina at eight months follow-up were associated with the administration of rhBNP infusion prior to PCI.

Interleukin (IL)-35 is the newest member of the IL-12 family. It is expressed in many immune cells and has been recognized as a novel inflammatory cytokine that may have bifunctional properties. Recent findings have indicated that the expression of IL-35 is abnormal in rheumatoid arthritis (RA) patients. However, the results were inconsistent. In this study, 400 RA patients were recruited to evaluate serum levels of IL-35 in a Chinese Han population by enzyme-linked immunosorbent assay. The association of IL-35 gene polymorphisms and RA genetic susceptibility was investigated in 400 RA patients and 612 healthy controls. The results showed that serum levels of IL-35 were elevated in 100 RA patients compared to 51 healthy controls, relating to disease activity and synovial fluid IL-35 expression in the training cohort. Another independent 300 RA patients and 369 other rheumatic disease patients (98 lupus, 95 osteoarthritis, 95 gout, 42 Sjogren's syndrome and 39 ankylosing spondylitis patients) confirmed that serum levels of IL-35 were elevated in RA patients, and serum IL-35 has good diagnostic ability for differentiating RA from the other rheumatic diseases. The genotyping of 10 IL-35 polymorphisms, including rs2227314, rs2243115, rs2243123, rs2243131, rs568408, rs583911, rs428253, rs4740, rs9807813 and rs4905, revealed that rs2227314, rs2243131, rs9807813, and rs583911 were correlated with RA risk. Different genotypes (rs2227314, rs583911, and rs9807813) exhibited different expression of IL-35. These findings demonstrate that serum levels of IL-35 are increased in RA patients and that IL-35 polymorphisms are correlated with RA risk.

Cow's milk protein allergy, which occurs in approximately 5-10% of the population of infants and children, has become an important public food safety problem. As a major allergen in cow's milk, the most abundant protein casein (CN) is considered to be potent in inducing food allergy. In recent years, ultrasound treatment has played a significant role in the field of colloidal particulate system. In this study, we found that ultrasound treatment dramatically decreased the diameter of a CN particle to less than 100 nm in the presence of Tween 80, producing colloidal casein (c-CN) with high transparency. The electrophoretic and transmission electron microscopy analysis showed that the advanced protein structure of CN changed significantly. In addition, the enzyme-linked immunosorbent assay with allergic sera showed that the immunoglobulin-E-binding capacity of c-CN was significantly decreased. In the meantime, the LAD2 mast cell line degranulation assay demonstrated that ultrasound treatment made CN hypoallergenic. The colloidal and hypoallergenic properties of c-CN were stably maintained for more than 30 days. Likewise, the allergenicity of fresh whole milk also decreased after ultrasound treatment. This work provided an effective way to reduce the allergenicity of milk allergen, which could be beneficial to the production of hypoallergenic cow's milk.

Inflammatory mediators and inflammatory cells in the inflammatory microenvironment promote the transformation of normal cells to cancer cells in the early stage of cancer, promote the growth and development of cancer cells, and induce tumor immune escape. The monomeric active ingredient β-elemene is extracted from the traditional Chinese medicine Curcuma wenyujin and has been proven to have good anti-inflammatory and antitumor activities in clinical applications for more than 20 years in China. Recent studies have found that this traditional Chinese medicine plays a vital role in macrophage infiltration and M2 polarization, as well as in regulating immune disorders, and it even regulates the transcription factors NF-κB and STAT3 to alter inflammation, tumorigenesis, and development. In addition, β-elemene regulates not only different inflammatory factors (such as TNF-α, IFN, TGF-β, and IL-6/10) but also oxidative stress in vivo and in vitro. The excellent anti-inflammatory and antitumor effects of β-elemene and its ability to alter the inflammatory microenvironment of tumors have been gradually elaborated. Although the study of monomeric active ingredients in traditional Chinese medicines is insufficient in terms of quality and quantity, the pharmacological effects of more active ingredients of traditional Chinese medicines will be revealed after β-elemene.

The dysfunction of endothelial progenitor cells (EPCs) is closely associated with diabetic vascular complications. Both glucagonlike peptide-1 receptor (GLP-1R) and silent information regulator 1 (SIRT1) can control systemic glucose homeostasis and protect endothelial cells against hyperglycemia-induced oxidative stress. In this study, we mainly assessed the role played by SIRT1 and GLP-1R and their relationship in regulating the function of late EPCs under hyperglycemia stimulation. Human peripheral blood mononuclear cells (PBMCs) were cultured in EGM-2 medium and induced to differentiate into EPCs and 25 mM glucose was used to stimulate EPCs to obtain a hyperglycemia condition. Subsequently, the expression and location of GLP-1R and SIRT1 in EPCs were detected. After GLP-1R or SIRT1 knockdown, or the treatment by GLP-1R agonist and/or SIRT1 agonist/inhibitor, the effects of SIRT1 and GLP-1R and their relationship in regulating the function of late EPCs under hyperglycemia stimulation was studied by detecting the apoptosis, migration, adhesion and angiogenicity abilities of EPCs. Results demonstrated that, in high-glucose stimulated EPCs, the expression of GLP-1R and SIRT1 was down-regulated. The knockdown of either GLP-1R or SIRT1 could increase EPCs apoptosis and weaken the migration, adhesion and angiogenicity abilities of EPCs. In addition, the improvement effects of Exendin-4 or GLP-1R over-expression on EPCs dysfunction could be weakened to some degree under SIRT1 knockdown. In conclusion, both GLP-1R and SIRT1 expression played important roles in regulating EPCs dysfunction under hyperglycemia and the up-regulation of GLP-1R improved the dysfunction of late EPCs by regulating SIRT1 expression.

Background Photodynamic therapy (PDT) is a promising anti-tumor treatment strategy. Photosensitizer is one of the most important components of PDT. In this work, the anticancer activities of PDT mediated by six new ruthenium porphyrin complexes were screened. The mechanisms of the most efficacious candidate were investigated. Methods Photocytotoxicity of the six porphyrins was tested. The most promising complex, Rup-03, was further investigated using Geimsa staining, which indirectly detects reactive oxygen species (ROS) and subcellular localization. Mitochondrial membrane potential (MMP), cell apoptosis, DNA fragmentation, c-Myc gene expression, and telomerase activities were also assayed. Results Rup-03 and Rup-04 had the lowest IC 50 values. Rup-03 had an IC 50 value of 29.5 ± 2.3 μM in HepG2 cells and 59.0 ± 6.1 μM in RAW264.7 cells, while Rup-04 had an IC 50 value of 40.0 ± 3.8 μM in SGC-7901 cells. The complexes also induced cellular morphological changes and impaired cellular ability to scavenge ROS, and accumulated preferentially in mitochondria and endoplasmic reticulum. Rup-03 reduced MMP levels, induced apoptosis, and repressed both c-Myc mRNA expression and telomerase activity in HepG2 cells. Conclusions Among six candidates, Rup-03-mediated PDT is most effective against HepG2 and RAW264.7, with a similar efficacy as that of Rup-04-mediated PDT against SGC-7901 cells. Repression of ROS scavenging activities and c-Myc expression, which mediated DNA damage-induced cell apoptosis and repression of telomerase activity, respectively, were found to be involved in the anticancer mechanisms of Rup-03.

Mortality from hepatitis B virus (HBV)–related acute-on-chronic liver failure (ACLF) is high due to limited treatment options. Preclinical and clinical investigations have proved that treatment with mesenchymal stromal cells (MSCs) is beneficial for recovery from liver injury. We hypothesized that the outcome of HBV-related ACLF would be improved by MSC treatment. From 2010 to 2013, 110 patients with HBV-related ACLF were enrolled in this open-label, nonblinded randomized controlled study. The control group (n = 54) was treated with standard medical therapy (SMT) only. The experimental group (n = 56) was infused weekly for 4 weeks with 1.0 to 10 × 105 cells/kg allogeneic bone marrow–derived MSCs and then followed for 24 weeks. The cumulated survival rate of the MSC group was 73.2% (95% confidence interval 61.6%-84.8%) versus 55.6% (95% confidence interval 42.3%-68.9%) for the SMT group (P = 0.03). There were no infusion-related side effects, but fever was more frequent in MSC compared to SMT patients during weeks 5-24 of follow-up. No carcinoma occurred in any trial patient in either group. Compared with the control group, allogeneic bone marrow–derived MSC treatment markedly improved clinical laboratory measurements, including serum total bilirubin and Model for End-Stage Liver Disease scores. The incidence of severe infection in the MSC group was much lower than that in the SMT group (16.1% versus 33.3%, P = 0.04). Mortality from multiple organ failure and severe infection was higher in the SMT group than in the MSC group (37.0% versus 17.9%, P = 0.02). Conclusion: Peripheral infusion of allogeneic bone marrow–derived MSCs is safe and convenient for patients with HBV-related ACLF and significantly increases the 24-week survival rate by improving liver function and decreasing the incidence of severe infections. (Hepatology 2017;66:209–219).

Background The combination of brain tissue oxygen and standard intracranial pressure (ICP)/cerebral perfusion pressure (CPP)–guided therapy is thought to improve traumatic brain injury (TBI) prognosis compared with standard ICP/CPP-guided therapy. However, related results of previous observational studies and recently published cohort studies and randomized controlled trials (RCTs) remain controversial. The objective of this study was to compare the effect of the combined therapy with that of standard ICP/CPP-guided therapy on mortality rate, favorable outcome, ICP/CPP, and length of stay (LOS). Methods We systematically searched PubMed, Embase, Cochrane Library, ClinicalTrials.gov , and Web of Science in July 2016 for studies comparing the combined therapy and standard ICP/CPP-guided therapy. Random-effect and fixed-effect models were used for pooled analyses. Results After screening 362 studies, 8 cohort studies and 1 RCT were included. Primary outcomes were mortality and favorable outcome. The overall mortality risk ratio showed no obvious advantages between the 2 groups (risk ratio [RR], 0.76; 95% confidence interval [CI], 0.54–1.06) and discharge mortality (RR, 1.01; 95% CI, 0.80–1.26) and 3-month mortality (RR, 0.77; 95% CI, 0.53–1.12). Compared with the ICP/CPP group, the combined group was more likely to achieve better outcome during the 6 months after TBI (RR, 1.26; 95% CI, 1.04–1.52) or exactly at 6 months (RR, 1.34; 95% CI, 1.07–1.68), whereas ICP (standardized mean difference [SMD], −0.19; 95% CI, −0.43 to 0.05), CPP (SMD, 0.13; 95% CI, −0.09 to 0.35), and LOS (SMD, 0.13; 95% CI, −0.11 to 0.37) showed no obvious differences. Conclusions Compared with standard ICP/CPP-guided therapy, brain tissue oxygen combined with ICP/CPP-guided therapy improved long-term outcomes without any effects on mortality, ICP/CPP, or LOS.

The expression of programmed cell death-ligand 1 (PD-L1) and its correlation with the prognosis and clinicopathologic features of renal cell carcinoma (RCC) remain controversial to date. Concerning this issue, we had conducted a meta-analysis of relevant studies searched in the Web of Science, PubMed, EMBASE, and Cochrane Library databases. The Newcastle-Ottawa quality assessment scale was applied to assess the quality of the included studies. The hazard ratio (HR) and its corresponding 95% confidence intervals (CIs) were collected by Stata 12.0 and used for the results of overall survival (OS) and disease-free survival (DFS). A total of 1,644 patients in 8 studies were included in this meta-analysis. Results showed that PD-L1 expression significantly correlated with OS (HR = 1.98, 95% CI: 1.22–3.22, Z = 2.77, p = 0.006) and DFS (HR = 3.70, 95% CI: 2.07–6.62, Z = 4.40, p = 0.0001) in ccRCC. Subgroup analysis indicated that PD-L1 expression significantly correlated with the lymph-gland transfer ratio (HR = 2.45, 95% CI: 1.02–5.92, Z = 1.99, p = 0.05) and tumor necrosis (HR = 6.05, 95% CI: 3.78–9.67, Z = 7.51, p < 0.00001). This meta-analysis suggests that PD-L1 expression is a valuable prognostic tool for patients with ccRCC. Subgroup analyses demonstrated that it was helpful for screening patients with RCC who need anti-PD-1/PD-L1 treatment and support them to benefit from such immune-targeted therapy.

To explore the changes of serum miR-375 and its target genes in patients with allergic rhinitis (AR) before and after treatment and its significance. Methods: A total of 120 AR patients treated in Wuhan Fourth Hospital were selected as an observation group (AR group), and 120 healthy volunteers served as a control group. Real-time quantitative polymerase chain reaction was used to detect the expression changes of miR-375 and its predicted target genes, such as 3-phosphoinositide-dependent protein kinase-1 (PDK1), protein kinase B (AKT1), Janus kinase 2 (JAK2), and signal transducer and activator of transcription 3 (STAT3), as well as inflammatory factors, such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-10 (IL-10), and interleukin-13 (IL-13) in the AR group before and after treatment. According to the relative expression levels of miR-375 and target genes, the AR patients were also subdivided into a high expression group and a low expression group for comparative analysis. Results: Before treatment, the level of miR-375 in the serum in the AR group was higher than that in the control group (P0.01); the expressions of PDK1, AKT1, JAK2 and STAT3 in the plasma in the AR group were lower than those in the control group (all P0.01); the plasma levels of TNF-α, IL-6, IL-10, and IL-13 in the AR group were higher than those in the control group (all P0.05). After treatment, compared with the control group, the level of miR-375 in the serum was down-regulated (P0.01), while the levels of target genes (PDK1, AKT1, JAK2 and STAT3) were up-regulated (all P0.05), and the levels of TNF-α, IL-6, IL-10, and IL-13 were down-regulated in the AR group (all P0.05). The total effective rate, total nasal symptom score (TNSS), symptom improvement time, and incidence of adverse reactions in the AR groups with high expression of miR-375 and low expression of target genes before treatment were better than those in the correspending groups with low expression of miR-375 and high expression of target genes (all P0.05). Conclusion: MiR-375 might be a potential predictor of treatment response for AR patient, which might be related to the plasma levels of its target genes and inflammatory factors.目的：探讨血清miR-375及其靶基因在过敏性鼻炎(allergic rhinitis，AR)患者治疗前后的表达变化及其意义。方法：选取在武汉市第四医院接受治疗的120例AR患者作为观察组(AR组)，同时选取120名健康志愿者作为对照组。通过real-time PCR检测miR-375及其靶基因3-磷酸肌醇依赖性蛋白激酶1(3-phosphoinositide-dependent protein kinase-1，PDK1)、蛋白激酶 B(protein kinase B，AKT1)、Janus激酶2(Janus kinase 2，JAK2)和信号转导与转录激活因子3(signal transducer and activator of transcription 3，STAT3)，以及肿瘤坏死因子-α(tumor necrosis factor-α，TNF-α)、白介素-6(IL-6)、白介素-10(IL-10)和白介素-13(IL-13)等炎症因子在AR患者治疗前后的表达变化。并根据miR-375和靶基因的相对表达量将AR患者划分为高表达组和低表达组进行对比分析。结果：治疗前AR组血清miR-375的表达量高于对照组(P0.01)；血液中PDK1，AKT1，JAK2和STAT3的表达量均低于对照组(均P0.01)；TNF-α，IL-6，IL-10和IL-13的表达量均高于对照组(均P0.05)。与对照组相比，治疗后AR组血清miR-375的表达下调(P0.01)；血液中靶基因PDK1，AKT1，JAK2和STAT3的表达均上调(均P0.05)；炎症因子TNF-α，IL-6，IL-10和IL-13的表达均下调(均P0.05)。并且，治疗前血清miR-375高表达组和靶基因低表达组患者治疗的总有效率、鼻炎症状评分标准、症状改善时间和不良反应发生率等均优于对应的miR-375低表达组和靶基因高表达组患者(均P0.05)。结论：MiR-375可能通过与PDK1，AKT1，JAK2和STAT3等靶基因的负调控作用而抑制TNF-α，IL-6，IL-10和IL-13等炎症因子的表达。.

Rationale: Transradial access (TRA) is common for cardiac catheterization, but radial artery spasm (RAS) is suggested to be highlighted. Severe radical artery spasm could be solved by a relative novel approach called “sheathless technique,” using a Tiger diagnostic catheter. Patient concerns: A 73-year-old woman presented to our institution with a recurrent feeling of discomfort in her chest. Her electrocardiogram showed ST segment depression. Her medical history indicated arterial hypertension, diabetes, and chronic renal failure. She was on hemodialysis for 5 years for the management of renal problems. Five stents were implanted from femoral access in another hospital via 2 percutaneous coronary interventions. The patient agreed to angiography this time and wanted a more comfortable solution. Diagnosis: Recurrent exertional angina was confirmed based on the chief complaint, electrocardiogram, and history. Interventions: After a successful radial artery puncture, a 6F arterial sheath pipe and a 5F Tiger diagnostic ductus could only advance slightly because of the RAS. Glonoin and verapamil functioned with the help of the radial sheath, and systemic nitroglycerin was applied later but had a negative outcome. Warm covers were positioned on the antebrachium, but no relief was reported. The “homemade sheathless technique” was applied. The 5F tube was held, and the 6F sheath was withdrawn. A blade was used to damage the sheath in reverse, and the excess sheath tube was removed. Outcomes: The diagnostic catheter was successfully advanced to the ascending aorta, enabling left main and right coronary engagement and angiography. No significant coronary lesion was observed. The patient was discharged 3 days after angiography. Moreover, no complications were observed. A follow-up for 1 month after discharge also showed no complications. Lessons: Severe RAS causing failure of TRA is frequent in the transradial catheterization procedure. The sheathless technique may be useful in relieving spasm when other measures fail.

Chiral ruthenium(II) complexes have long been considered as potential anticancer agents. Herein, in vivo inhibitory activity of a chiral ruthenium(II) complex coordinated by ligand 2-(2'-trifluoromethyphenyl) imidazo [4,5-f][1,10]phenanthroline, Δ-[Ru(bpy)

Sirtuin 2 (SIRT2) is a member of NAD+-dependent protein deacetylases involved in a wide range of pathophysiological processes including myocardial injury, Parkinson's disease, and Huntington's disease. However, the direct implication of SIRT2 in ischemic stroke is still unclear. In the present study, we observed that SIRT2 protein was mainly expressed in the cytoplasm of neurons, but not in astrocyte and microglia. SIRT2 was upregulated in ischemic neurons in the oxygen-glucose deprivation cell model and in the transient middle cerebral artery occlusion (tMCAo) mouse model. Moreover, expression of SIRT2 was evaluated by immunohistochemistry in human brains consisting of ischemic penumbra of cerebral stroke, and their age-matched normal controls without diagnosed neurological disorders. The results revealed that SIRT2 was mainly expressed in the cytoplasm and neurites of neurons in the brains of normal subjects, while an elevated expression and nuclear translocation of SIRT2 were detected in the ischemic penumbra of cerebral stroke. Downregulation of SIRT2 using the SIRT2-specific inhibitor AGK2 or SIRT2 knockout had neuroprotective effects in tMCAo model, which could decrease the infract volume and neurological impairment scores. In summary, our findings revealed that SIRT2 was upregulated during neuronal ischemia and translocated into neuronal nuclei, while downregulation of SIRT2 could significantly protect neurons against cerebral ischemia.

Since the withdrawal of cerivastatin, statin-fibrate combination therapy has been questioned in China due to safety concern. The objective of this study was to evaluate the efficacy and safety profile of fenofibrate as an add-on in patients with dyslipidemia despite receiving statin therapy.This was a prospective, multi-center, single-arm, open-label study conducted in Chinese dyslipidemia patients with high CV risk. Fenofibrate (200mg daily) was added to the existing statin treatment for 8weeks. Lipid profile and safety parameters were measured and compared between baseline and after the treatment. Five hundred and six subjects were enrolled from 28 sites from 14 cities nationwide across China.After 8weeks of fenofibrate treatment, the mean blood triglyceride level decreased to 1.77mmol/L (38.1% reduction vs. 3.00mmol/L at the baseline; p0.01). Mean high-density lipoprotein cholesterol (high density lipoprotein cholesterol) was increased to 1.22mmol/L (by 17.4% from 1.07mmol/L at the baseline; p0.01). No case of severe muscle damage (defined as elevated creatine kinase over 5 times of upper limit of normal (ULN) or rhabdomyolysis was observed.In statin-treated patients with high CV risk who had elevated triglyceride, adding fenofibrate could improve lipid profile with acceptable safety profiles.

Background: The long noncoding RNAs (lncRNAs) have gradually been reported to be an important class of RNAs with pivotal roles in regulation of gene expression, and thus are involved in multitudinous human complex diseases. However, the biological functions and precise mechanisms of the majority of lncRNAs are still poorly understood. Methods: In the study, we tested genomic variations in lncRNA-metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) loci, and their potentially functional correlationship with pulmonary arterial hypertension (PAH) susceptibility based on a case-control study with a total of 587 PAH patients and 736 healthy controls in southern Chinese. Results: We found that the rs619586A>G single nucleotide polymorphism (SNP) was significantly associated with PAH risk. The carriers with G variant genotypes had a decreased risk of PAH (odds ratio [OR]=0.69, 95% confidence interval [CI]=0.53–0.90, p=0.007) compared to the rs619586AA genotype. Further functional experiments indicated that the alteration from rs619586A to G in MALAT1 could directly upregulate X box-binding protein 1 (XBP1) expression via functioning as the competing endogenous RNA (ceRNA) for miR-214, and consequentially inhibiting the vascular endothelial cells proliferation and migration in vitro by shortening S-M phase transition. Conclusions: Taken together, our findings propose that functional polymorphism rs619586A>G in MALAT1 gene plays an important role in PAH pathogenesis and may serve as a potential indicator for PAH susceptibility.