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Abstract To investigate the correlation of cervical central lymph node metastasis (CLNM) in stage T1a unifocal papillary thyroid carcinoma (PTC) with the clinicopathological characteristics, ultrasonography features and the number of lymph node dissection, and to analyze the risk factors of CLNM. Data from 493 unifocal PTC patients (T1a) who underwent partial or total thyroidectomy and pCLND at the Guizhou Provincial People’s Hospital were collected and retrospectively analyzed. They were divided into two groups in accordance with cervical CLNM or not. Their information, including clinical characteristics, ultrasound (US) features, pathological results, and other characteristics of the groups, was analyzed and compared using univariate and multivariate logistic regression analyses. A total of 493 patients were eligible in this study. Among them, 33.7% (166/493) of PTC patients had cervical CLNM, and 66.3% (327/493) did not. The two groups were compared using a univariate analyses, and there were no significant differences between the two groups in age, maximum tumor size, tumor location, aspect ratio, boundary, morphology, echogenicity, BRAFV600E and HT (P > 0.05), and there were significant differences between gender, capsule contact, microcalcifications, rich vascularity, and number of lymph node dissection (P

Objective To investigate the regulatory effect of tRNA-derived small RNA (tsRNA) on ferroptosis in mouse cardiomyocytes and its mechanism. Methods RT-qPCR was used to measure the relative expression level of 5'tRF-LysCTT in the heart, liver, spleen, kidney, brain, and muscle of C57BL/6J mice aged 8 weeks. Primary cultured cardiomyocytes were divi-ded into groups A, B, C, and D: the cardiomyocytes in group A were cultured in a complete medium for 60 h; those in group B were cultured in a complete medium for 24 h, followed by starvation treatment for 12 h and H/R treatment for 24 h; those in groups C and D were transfected with antagomir-NC and antagomir-5'tRF-LysCTT, respectively, and were given starvation treatment (12 h) and H/R treatment (12 h) after 24 h of transfection. Primary cultured cardiomyocytes were divided into groups E, F, and G: the cardiomyocytes in group E were cultured in a complete medium for 24 h; those in group F were transfected with agomir-NC for 24 h; those in group G were transfected with agomir-5'tRF-LysCTT for 24 h. RT-qPCR was used to measure the relative expression levels of 5'tRF-LysCTT, Ptgs2, Gpx4, and Slc7a11 in mouse cardiomyocytes of groups A-G; ferrous ion colorimetric test kit, lipid reactive oxygen species (ROS) staining, and CCK8 assay kit were used to measure the relative content of ferrous ions, ROS level, and the survival rate of cardiomyocytes in groups A-G; Prussian blue staining was used to observe iron ion deposition in cardiomyocytes. Results RT-qPCR showed that the expression level of 5'tRF-LysCTT in heart was significantly higher than that in the liver, spleen, kidney, brain, and muscle (F=16.21,t=3.81-7.93,P0.05). Compared with group E, group G had significant increases in the relative expression levels of 5'tRF-LysCTT and Ptgs2, significant reductions in the relative expression levels of Gpx4 and Slc7a11, significant increases in the relative content of ferrous ions and ROS level, and a significant reduction in the survival rate of cardiomyocytes (t=3.57-91.84,P0.05). Conclusion 5'tRF-LysCTT can regulate ferroptosis in mouse cardiomyocytes, and knockdown of 5'tRF-LysCTT can inhibit cardiomyocyte ferroptosis induced by H/R, while overexpression of 5'tRF-LysCTT can promote cardiomyocyte ferroptosis.

Objective To investigate the regulatory effect of 3'-tRF-PheGAA on angiotensin Ⅱ (Ang Ⅱ)-induced cardiomyocyte hypertrophy and its mechanism. Methods Primary cardiomyocytes of neonatal mice were obtained and cultured for 24 h, and were then divided into groups A to G. The cardiomyocytes in group A were cultured with DMEM/F12 complete culture medium for 36 h. The cardiomyocytes in group B were transfected with negative control (NC) for 36 h. The cardiomyocytes in group C were transfected with agomir-3'-tRF-PheGAA for 36 h. The cardiomyocytes in group D were cultured with DMEM/F12 complete culture medium for 84 h. The cardiomyocytes in group E were treated with Ang Ⅱ at a final concentration of 1 μmol/L for 48 h. The cardiomyocytes in group F were transfected with anta-NC for 36 h and then treated with Ang Ⅱ at a final concentration of 1 μmol/L for 48 h. The cardiomyocytes in group G were transfected with anta-3'-tRF-PheGAA for 36 h and then treated with Ang Ⅱ at a final concentration of 1 μmol/L for 48 h. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to determine the gene expression levels of 3'-tRF-PheGAA, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and β-myosin heavy chain (β-MHC) in the cardiomyocytes in each group. Rhodamine-labeled phalloidin was used to stain F-actin in the cardiomyocytes in each group and calculate the skeletal surface area of cardiomyocytes. Results The RT-qPCR results showed significant differences between groups A to C in the gene expression levels of 3'-tRF-PheGAA, ANP, BNP, and β-MHC in cardiomyocytes (F=137.10-1 061.00,P

With unknown etiology and limited treatment options, unexplained recurrent pregnancy loss (URPL) remains a thorny problem. Ferroptosis, a newly identified type of cell death, has been shown to be crucial in the development in reproductive disorders. This study aims to explore the specific mechanism of ferroptosis in URPL and to uncover whether alpha-lipoic acid (ALA) can inhibit ferroptosis, and then exert a protective effect in URPL.

Objective To detect the expression changes of interleukin-10 （IL-10） and transforming growth factor-β1 （TGF-β1） during the development of deep vein thrombosis in mice, and to explore the application value of them in thrombus age estimation. Methods The mice in the experimental group were subjected to ligation of inferior vena cava. The mice were sacrificed by excessive anesthesia at 1 d, 3 d, 5 d, 7 d, 10 d, 14 d and 21 d after ligation, respectively. The inferior vena cava segment with thrombosis was extracted below the ligation point. The mice in the control group were not ligated, and the inferior vena cava segment at the same position as the experimental group was extracted. The expression changes of IL-10 and TGF-β1 were detected by immunohistochemistry （IHC）, Western blotting and real-time qPCR. Results IHC results revealed that IL-10 was mainly expressed in monocytes in thrombosis and TGF-β1 was mainly expressed in monocytes and fibroblast-like cells in thrombosis. Western blotting and real-time qPCR showed that the relative expression levels of IL-10 and TGF-β1 in each experimental group were higher than those in the control group. The mRNA and protein levels of IL-10 reached the peak at 7 d and 10 d after ligation, respectively. The mRNA expression level at 7 d after ligation was 4.72±0.15 times that of the control group, and the protein expression level at 10 d after ligation was 7.15±0.28 times that of the control group. The mRNA and protein levels of TGF-β1 reached the peak at 10 d and 14 d after ligation, respectively. The mRNA expression level at 10 d after ligation was 2.58±0.14 times that of the control group, and the protein expression level at 14 d after ligation was 4.34±0.19 times that of the control group. Conclusion The expressions of IL-10 and TGF-β1 during the evolution of deep vein thrombosis present time-dependent sequential changes, and the expression levels of IL-10 and TGF-β1 can provide a reference basis for thrombus age estimation.

Objective To investigate the serum levels of 25-hydroxyvitamin D3 [25-(OH)D3] in children and adolescents with type 1 diabetes mellitus (T1DM), and to investigate the relationship between 25-(OH)D3 levels and glycosylated hemoglobin (HbA1c) levels. Methods We included 129 children and adolescents with T1DM who visited the Department of Pediatric Endocrinology, Metabolism & Gastroenterology of The Affiliated Hospital of Qingdao University from January 2016 to December 2021 (T1DM group). They were divided into two subgroups according to HbA1c levels: patients with good glycemic control (group A, HbA1c

Spondyloarthritis (SpA) is a group of chronic inflammatory diseases which predominantly involve spine and/or peripheral joints. SpA can be disabling and seriously affect the quality of life and function of patients. With the increasing clinical use of targeted drug therapy, precise and standardized use becomes the focus. China's first Consensus on Targeted Drug Therapy for Spondyloarthritis was developed by National Clinical Research Center for Dermatologic and Immunologic Diseases using international norms for consensus development. The consensus addresses 13 important clinical questions, ranging from principles, patient eligibility, pre-treatment screening, treatment initiation, drug selection and switch, co-medication, to adverse event monitoring of targeted drug therapy in SpA, and recommends treatment for specific patients, playing a key role in guiding clinical practices.

Objective To explore the relationship between Helicobacter pylori (Hp) type, positive expression rate of gastric mucosal occludin and degree of gastric mucosal inflammation in children with Hp-associated gastritis. Methods Ninety children who received gastroscopy and were diagnosed with Hp-associated gastritis in our hospital from June 2018 to December 2021 were selected as the research object. The expression of serum Hp antibody in children was measured by Western blot. The strains of Hp were serotyped. The pathological changes of gastric mucosa in children were observed. The positive expression rate of gastric mucosal occludin was determined by quantitative immunohistochemistry method. The relationship between Hp strain type, positive expression rate of gastric mucosal occludin and degree of gastric mucosal inflammation was analyzed. Results The positive expression rate of gastric mucosal occludin in children infected with type Ⅰ strain was significantly lower than that in children infected with type Ⅱ strain or intermediate type strain (P0.05). There were significant differences in the degree of gastric mucosal inflammation among children infected with different Hp strains (H=18.013,P0.05). The positive expression rates of occludin in children with mild, moderate, and severe gastric mucosal inflammation were 80.0%, 35.1%, and 11.6%, respectively (χ2=19.655,P

Objective·To study the prevalence of mouth opening restriction in oral cancer patients by meta-analysis.Methods·China National Knowledge Infrastructure (CNKI), Chinese Science and Technology Journal Database (VIP), Wanfang Data (Wanfang), Chinese BioMedical Literature Database (CBM), PubMed, Ovid, EMbase, Cochrane Library, Web of Science/SciSearch, and ClinicalTrials.gov were searched for observational studies about the prevalence rate of restricted mouth opening in oral cancer patients (including prospective, retrospective, and cross-sectional studies). The time limit for retrieval was from the database establishment to April 30th, 2022. The obtained documents were independently screened and extracted according to the inclusion and exclusion criteria, and the literature quality evaluation was performed by using methodological index for non-randomized studies (MINORS). The data were combined with the mouth-opening-restricted prevalence rate as the outcome indicator, the meta-analysis was performed by using Stata 15.0 software, and the subgroup analysis was performed based on the detection time, tumor site, and tumor stage. The evidence quality of outcome indicators was evaluated by using GRADE profiler 3.6 software according to GRADE (Grading of Recommendations Assessment, Development, and Evaluation) system.Results·A total of 3 719 documents were obtained during the initial examination, and 18 documents were finally included, including 2 701 objects. The meta-analysis results showed that the total prevalence rate of mouth opening restriction in oral cancer patients was 42.7% (95%CI 27.0%‒59.1%). The results of subgroup analysis showed that the prevalence rates of mouth opening restriction in patients with oral cancer before surgery, and 3 months, 6 months and 1 year or more after surgery were 29.6% (95%CI 9.0%‒55.8%), 75.2% (95%CI 68.3%‒81.5%), 59.1% (95%CI 38.8%‒77.9%) and 22.3% (95%CI 2.0%‒54.3%), respectively. The prevalence rates of mouth opening restriction in patients with oral cancer at T1‒T2 stage and T3‒T4 stage were 38.6% (95%CI 26.0%‒52.0%) and 99.6% (95%CI 93.9%‒100.0%) respectively. The prevalence rates of mouth opening restriction in patients with oral cancer in the retromolar triangle, the gingiva, the tongue, the salivary gland, the floor of mouth and the lip were 93.1% (95%CI 68.5%‒100.0%), 68.1% (95%CI 52.9%‒81.7%), 46.1% (95%CI 11.6%‒82.7%), 26.1% (95%CI 15.9%‒37.5%), 21.9% (95%CI 0.7%‒54.0%), and 3.1% (95%CI 0‒9.3%), respectively. The GRADE system for evidence quality grading indicated that the quality of evidence for outcome indicator was extremely low.Conclusion·The total prevalence rate of mouth opening restriction in patients with oral cancer is high, nearly 50%; the patients at 3 months after surgery, at 6 months after surgery, at T3‒T4 stage or whose tumor located in the retromolar triangle have higher prevalence rates.

Objective To explore the effect and mechanism of pinocembrin on the proliferation, migration and invasion of gastric cancer cell line AGS. Methods AGS cells were divided into different test groups according to concentrations of pinocembrin(50, 100, 200, 400 μmol/L), NC group, 200 μmol/L pinocembrin + anti-miR-NC group, 200 μmol/L pinocembrin + anti-miR-34a-5p group. The proliferation, apoptosis, migration, invasion ability and protein expression of AGS cells were detected by CCK-8 assay, flow cytometry, Transwell chamber assay and Western blot. The expression of miR-34a-5p was detected by real-time fluorescent quantitative PCR (RT-qPCR). Results Different concentrations of pinocembrin reduced the proliferation activity of AGS cells (P＜0.05) and the proportion of in G0/G1 phase cells was increased while the proportion of S phase cells decreased. The expressions of MMP2, MMP9, p-PI3K and p-AKT protein decreased. The cell migration and invasion were inhibited. The expression of miR-34a-5p was increased (P＜0.05), which reduced the inhibitory effect of pinocembrin on the prolifera- tion, migration and invasion of AGS cells. Conclusions Pinocembrin can inhibit the proliferation, migration and invasion of AGS cells by improving the expression of miR-34a-5p.

Objective To evaluate clinical significance and application outcomes of using the neutrophil-to-lymphocyte count ratio (NLR) and C-reactive protein to albumin ratio (CRP/ALB) in the aged patients hospitalized with acute exacerbation of chronic obstructive pulmonary disease(AECOPD). Methods 172 aged patients with AECOPD who were hospitalized in the Department of Geriatrics and Department of Respiratory Medicine of the Second People's Hospital of Hefei from January 2016 to January 2020 were recruited. According to clinical outcomes, they were divided into survival group (n=155) and death group (n=17). Survival group was divided into groups according to hospitalization days of more or less than ten days. Parameters were got through contrast of clinical and laboratory test indexes of patients in each group. Logistic regression and receiver operating characteristic curve (ROC) were used to analyze the risk factors and their correlation with in-hospital mortality. Results Among 172 aged AECOPD in-patients, 17 patients died during hospitalization with mortality as 9.88%. There were differences between the death group and the survival group in NLR, CRP, CRP/ALB, red blood cell distribution width (RDW), cigarette consumption, community acquired pneumonia (CAP) and various comorbidities. Parameters above mentioned in the death group was higher than the survival group(P＜0.01). At the same time, 155 aged patients with AECOPD who survived and discharged were divided into two subgroups according to the hospitalization ≥10 days and ＜10 days. It was found that NLR, CRP, CRP/ALB, RDW, smoking and CAP in group with hospitalization longer than ten days were significantly more common than those in group of less than ten days hospitalization(P＜0.01). The Logistic regression analysis of NLR, CRP, CRP/ALB and RDW showed that NLR and CRP/ALB might be independent risk factors for in-hospital death. From the analysis of the ROC, the cut-off value of NLR was 11.04, the area under the curve was 77%, and the cut-off value of CRP/ALB was 1.12, and the area under the curve was 65%. Conclusions NLR and CRP/ALB may be the risk factors for in-hospital death of aged patients with AECOPD, which are associated with poor prognosis.

Abstract Background Adopting healthy lifestyles and staying mentally health are two cost-effective modifiable strategies that cancer survivors can implement in self-management. We aimed to evaluate the independent, mediation, interaction, and joint associations of combined lifestyle and mental health with mortality in cancer survivors. Methods We performed a cohort study including 3145 cancer survivors from National Health and Nutrition Examination Survey (2005–2018). A healthy lifestyle score was constructed based on post-diagnosis body mass index, physical activity, diet, smoking, and drinking. Post-diagnosis mental health was assessed by Patient Health Questionnaire (PHQ-9). Hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause, cancer, and non-cancer mortality were computed using Cox proportional hazards regression models. Results After 20,900 person-years of follow-up (median, 6.3 years), cancer survivors with higher lifestyle score had decreased mortality, independent of mental health. Compared to participants with lower lifestyle score (0–1), HRs (95% CIs) for all-cause and non-cancer mortality among those with higher lifestyle score (3–5) were 0.68 (0.52–0.89) and 0.69 (0.56–0.85), respectively. 6.2–10.3% of the associations were mediated by mental health. Similar trends were observed among participants categorized by mental health, those with better mental health had lower mortality, independent of lifestyle. Participants with better mental health benefited more from adopting healthy lifestyles, and vice versa. Combinations of higher healthy lifestyle score and better mental health were associated with significant decreased mortality, the lowest mortality was seen in participants with highest healthy lifestyle score and concurrently with best mental health. Conclusions For the first time, in this cohort study with a nationally representative sample of US cancer survivors, we comprehensively explored the complex associations of lifestyle, mental health, and mortality. Evidence derived from this study may give much confidence to cancer survivors and healthcare providers that, changing one’s lifestyle and/or staying mentally healthy after cancer diagnosis can improve survival.

Objective To explore the effect of reducing bladder TGF-β1 expression with RNA interference(RNAi) on neurogenic bladder(NB). Methods Forty-eight female rats were evenly divided into sham, T10 transaction, LV-vector and LV-shTGF-β1 groups. The sham group underwent sham operation of T10 spinal cord transection, and the other three groups underwent spinal cord transection. The bladder wall was injected immediately after the operation. The first two groups were injected with 0.9% NaCl, the LV-vector group was the control lentivirus, and the LV-shTGF-β1 group was TGF-β1 RNAi lentivirus. On the 28th day after operation, cystometry and bladder weighing were performed, the bladder tissue was stained with HE and Masson, and the expression of detrusor TGF-β1 was detected by immunohistochemistry, RT-qPCR and Western blot. Results In the three groups with spinal cord transection compared with the sham group, the frequency and amplitude of detrusor over activity were significantly increased (P＜0.01), the bladder capacity was significantly reduced (P＜0.05), and the bladder weight, the detrusor interstitial percentage and TGF-β1 expression were significantly increased (P＜0.05). The T10 transection group had no significant difference compared with the LV-vector group. In the LV-shTGF-β1 group compared with the T10 transection group, the frequency and amplitude of detrusor over activity were significantly reduced (P＜0.01), the bladder capacity was significantly increased (P＜0.01), and the bladder weight, the detrusor interstitial percentage and TGF- β1 expression were significantly reduced (P＜0.05). Conclusions Reducing bladder TGF-β1 expression with RNAi can improve detrusor over activity and bladder fibrosis in rats with spinal cord injury.

Objective To investigate the incidence and related risk factors of aspirin resistance (AR) in elderly patients. Methods Clincal data of ninety elderly patients who were treated in the Second People's Hospital of Hefei from December 2016 to July 2020 were collected. They took aspirin orally for more than one year with daily dose of 100 mg. The inhibition rate of aspirin on platelet was detected by thromboelastography(TEG), and the general biochemical indexes of all patients were tested. The results were analyzed, and the inhibition rate ＜50% was recorded as AR. Chi square test was used to evaluate the relationship between AR and related factors of patients' general condition. Multivariate logistic analysis was used to analyze the independent risk factors of aspirin resistance in elderly patients. Results A total of 90 patients were included, the average age was (74.06±7.90)years old, AR was 17.78% (16/90); AR had no significant difference in age, gender, smoking, creatinine, uric acid and other factors between groups, but there were significant differences in fasting blood glucose, platelet count, low density lipoprotein (LDL) between groups (P＜0.05). Logistic analysis showed that fasting blood glucose and LDL were closely related to the occurrence of AR in elderly patients (P＜0.01, OR=3.97, 95% CI=0.889-9.714), (P＜0.05, OR=3.11, 95% CI=2.42-4.01). Conclusions Fasting blood glucose and LDL seem to be the independent risk factors of AR in elderly patients. Active intervention is necessary to implement.

The purpose of this study was to investigate the role of voltage-dependent anion channel (VDAC) in mitochondria-mediated apoptosis of neurons in refractory epilepsy. Western blot analyses were carried out to detect the changes in cytochrome C, caspase 9, Bax, and Bcl-2. TUNEL assays were also carried out to investigate cell apoptosis under the upregulation and downregulation of VDAC1 with or without Bax or Bcl-2. VDAC1 induced Bax, Bcl-2, and caspase 9, increasing the release of cytochrome C. VDAC1 played an essential role in the apoptotic cell death of refractory epilepsy. It is concluded that VDAC1 plays an important role in refractory epilepsy and could be a possible therapeutic target of anti-epileptic drugs. The current study provides a new understanding of the possible mechanisms of refractory epilepsy.

Objective To investigate the apoptosis and drug resistance mechanism of Src homolog and collagen homolog 3 (Shc3) in human hepatocellular carcinoma (HCC). Methods Human hepatocellular carcinoma cell lines HCCLM3 and HepG2 with stable Shc3 downregulation and their scramble cell control groups were selected, Huh7 and HepG2 cells with stable Shc3 up-regulation and their pCDH control groups were selected. Protein expression levels of Shc3,MEK,p-MEK,ERK and p-ERK were determined by Western blot analysis. The mRNA level of Shc3 were determined by real-time PCR. Apoptotic experiment was used to observe cell apoptosis. CCK-8 assays were used to observe cell proliferation. Results Shc3 down-regulation and up-regulation cell lines were proved. Compared with scramble cells, Shc3 down-regulation significantly decreased activity of MEK/ERK pathway (P＜0.05), promoted cell apoptosis significantly (P＜0.05). Compared with pCDH cells, Shc3 up-regulation increased cell tolerance to sorafenib (P＜0.05), Moreover, significantly enhanced activity of MEK/ERK pathway (P＜0.05). Conclusions Shc3 may increase the resistance of HCC cells to sorafenib by interfering with apoptosis of HCC cells and activating MEK/ERK pathway. The results of this study provide theoretical basis and laboratory basis for targeting at Shc3 in the treatment of hepatocellular carcinoma.

To elucidate the mechanism of the multi-target action of Epimedii Folium on Alzheimer’s disease, this study focuses on the analysis of network pharmacology. Based on a bioinformatics approach, this study obtained the effective components of Epimedium through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, predicted the compound targets through the Pharmapper and Swiss target prediction database and then through Gene Expression Omnibus Datasets and Therapeutic Target Database. We collected and analysed of heral and disease targets, constructed the network. Through the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, Gene Ontology enrichment, then the key targets and pathways of Epimedii Folium to cope with Alzheimer’s disease have been identified. Twenty-three bioactive components and 477 potential target genes of Epimedii Folium were identified. A total of 1612 target diseases were identified. Through network module analysis, 30 hub target genes were identified. Through enrichment analysis of the KEGG pathway, hub target genes were largely enriched in the PI3K-AKT signaling pathway. Through the analysis of network pharmacology, it was found that Epimedii Folium might play the role of multi-compound and multi-target therapy through the PI3K-AKT signaling pathway. These findings provide helpful directions for future clinical studies.

Background: This study aimed to investigate the rates and causality of patient-reported adverse events (AEs) associated with concomitant Chinese Herbal Medicine (CHM) and Western Medicine prescription drug (WMPD) consumption through active surveillance in Singapore's Traditional Chinese Medicine (TCM) clinics. Methods: A cross-sectional study was conducted at five TCM clinics across Singapore from 8th May till 8th July 2023. Patients were screened to determine rates of CHM and WMPD consumption, and then interviewed if an AE was reported. An expert committee assessed the AE reports to determine causality. Along with descriptive statistics, odds ratios were calculated to determine AE occurrence likelihoods for patients who consumed both CHM and WMPD compared to CHM consumption alone. Results: 1028 patients were screened and 62.65% of them reported concurrent CHM-WMPD consumption. Patients who consumed CHM and WMPD were 3.65 times more likely to experience an AE as compared to CHM consumption alone. 18 AE reports were adjudicated, with most AEs deemed unlikely due to CHM consumption. Conclusions: A large proportion of patients consumed CHM and WMPD concurrently, thus increasing their risk of experiencing AEs compared to those consuming CHM only. Active surveillance is applicable for detecting AEs, collecting data for causality assessment, and analysis. [ABSTRACT FROM AUTHOR]

Spinal cord injury (SCI) causes severe disability, and the current inability to restore function to the damaged spinal cord leads to lasting detrimental consequences to patients. One strategy to reduce SCI morbidity involves limiting the spread of secondary damage after injury. Previous studies have shown that connexin 43 (Cx43), a gap junction protein richly expressed in spinal cord astrocytes, is a potential mediator of secondary damage. Here, we developed a specific inhibitory antibody, mouse-human chimeric MHC1 antibody (MHC1), that inhibited Cx43 hemichannels, but not gap junctions, and reduced secondary damage in 2 incomplete SCI mouse models. MHC1 inhibited the activation of Cx43 hemichannels in both primary spinal astrocytes and astrocytes in situ. In both SCI mouse models, administration of MHC1 after SCI significantly improved hind limb locomotion function. Remarkably, a single administration of MHC1 30 minutes after injury improved the recovery up to 8 weeks post-SCI. Moreover, MHC1 treatment decreased gliosis and lesion sizes, increased white and gray matter sparing, and improved neuronal survival. Together, these results suggest that inhibition of Cx43 hemichannel function after traumatic SCI reduces secondary damage, limits perilesional gliosis, and improves functional recovery. By targeting hemichannels specifically with an antibody, this study provides a potentially new, innovative therapeutic approach in treating SCI.

Background: One of the main aims of the updated Prostate Imaging Reporting and Data System Version 2 (PI-RADS v2) is to diminish variation in the interpretation and reporting of prostate imaging, especially among readers with varied experience levels. This study aimed to retrospectively analyze diagnostic consistency and accuracy for prostate disease among six radiologists with different experience levels from a single center and to evaluate the diagnostic performance of PI-RADS v2 scores in the detection of clinically significant prostate cancer (PCa). Methods: From December 2014 to March 2016, 84 PCa patients and 99 benign prostatic shyperplasia patients who underwent 3.0T multiparametric magnetic resonance imaging before biopsy were included in our study. All patients received evaluation according to the PI-RADS v2 scale (1–5 scores) from six blinded readers (with 6 months and 2, 3, 4, 5, or 17 years of experience, respectively, the last reader was a reviewer/contributor for the PI-RADS v2). The correlation among the readers' scores and the Gleason score (GS) was determined with the Kendall test. Intra-/inter-observer agreement was evaluated using κ statistics, while receiver operating characteristic curve and area under the curve analyses were performed to evaluate the diagnostic performance of the scores. Results: Based on the PI-RADS v2, the median κ score and standard error among all possible pairs of readers were 0.506 and 0.043, respectively; the average correlation between the six readers' scores and the GS was positive, exhibiting weak-to-moderate strength (r = 0.391, P = 0.006). The AUC values of the six radiologists were 0.883, 0.924, 0.927, 0.932, 0.929, and 0.947, respectively. Conclusion: The inter-reader agreement for the PI-RADS v2 among the six readers with different experience is weak to moderate. Different experience levels affect the interpretation of MRI images.

Abstract The novel pyrazoline derivative, BHX, has recently been shown to exhibit potent anti-tumour activity by blocking the Wnt/β-catenin signalling pathway. However, its effect on breast cancer growth and invasion are unknown. Our results show that BHX suppresses MDA-MB-231 cell viability and colony formation in a dose-dependent manner, and induces apoptosis and G0/G1 phase arrest. BHX-treated breast cancer cells showed morphological characteristics of cells undergoing apoptosis. Furthermore, BHX inhibited cell migration and invasion, which was associated with increased E-cadherin mRNA and protein expression, and down-regulation of SNAIL and vimentin. In addition, BHX induced the generation of intracellular ROS and decreased β-catenin protein and mRNA expression. We used a mouse xenograft model to investigate the effects of BHX in vivo, where the growth of MDA-MB-231 xenografted tumours was suppressed in nude mice treated continuously with BHX for 21 days. Finally, the rat plasma concentration of BHX was measured by ultra-performance liquid-chromatography tandem mass spectrometry and the pharmacokinetic parameters of BHX were processed by non-compartmental analysis. In conclusion, BHX merits further study as a novel therapeutic small molecule for the treatment of breast cancer.

Abstract Aim to evaluate the efficacy and safety of glucocorticoid monotherapy vs combination therapy of cyclophosphamide (CYC) for IgG4 related disease (IgG4-RD). 102 newly diagnosed IgG4-RD patients were enrolled and assigned to 2 groups: Group I was prednisone monotherapy (0.5–1.0 mg/kg.d, tapered gradually) and Group II was glucocorticoid and CYC (50–100 mg per day). Patients were assessed at different periods. Primary end point was relapse rate; secondary end points included response, remission rate and adverse effects. 52 patients were in Group I and 50 in Group II. At 1 month, both groups achieved obvious improvement. Accumulated relapse rate during 1 year was 38.5% in Group 1, including 12 cases with clinical relapse and 8 patients manifesting only serological relapse; whereas there was 12.0% of relapse in Group 2, only 1 with clinical relapse and other 5 patients got serological relapse. The mean flare time in Group II was significantly longer than that in Group I. All relapsing patients in Group I were sensitive to immunosuppressants. Most patients involving more than 6 organs in Group I relapsed during 1 year. IgG4 levels of relapse cases were significantly higher than non-relapsing patients at baseline. Bile duct, lacrimal glands and lymph nodes were commonly relapsed organs in Group I.

Background: Prostate Imaging Reporting and Data System (PI-RADS) is a globally acceptable standardization for multiparametric magnetic resonance imaging (mp-MRI) in prostate cancer (PCa) diagnosis. The American College of Radiology revised the PI-RADS to address the limitations of version 1 in December 2014. This study aimed to determine whether the PI-RADS version 2 (PI-RADS v2) scoring system improves the diagnostic accuracy of mp-MRI of the prostate compared with PI-RADS v1. Methods: This retrospective study was approved by the institutional review board. A total of 401 consecutive patients, with clinically suspicious PCa undergoing 3.0 T mp-MRI (T2-weighted imaging + diffusion-weighted imaging + DCE) before transrectal ultrasound-guided biopsy between June 2013 and July 2015, were included in the study. All patients were scored using the 5-point PI-RADS scoring system based on either PI-RADS v1 or v2. Receiver operating characteristics were calculated for statistical analysis. Sensitivity, specificity, and diagnostic accuracy were compared using McNemar′s test. Results: PCa was present in 150 of 401 (37.41%) patients. When we pooled data from both peripheral zone (PZ) and transition zone (TZ), the areas under the curve were 0.889 for PI-RADS v1 and 0.942 for v2 (P = 0.0001). Maximal accuracy was achieved with a score threshold of 4. At this threshold, in the PZ, similar sensitivity, specificity, and accuracy were achieved with v1 and v2 (all P > 0.05). In the TZ, sensitivity was higher for v2 than for v1 (96.36% vs. 76.36%, P = 0.003), specificity was similar for v2 and v1 (90.24% vs. 84.15%, P = 0.227), and accuracy was higher for v2 than for v1 (92.70% vs. 81.02%, P = 0.002). Conclusions: Both v1 and v2 showed good diagnostic performance for the detection of PCa. However, in the TZ, the performance was better with v2 than with v1.

Niemann Pick Type C1 Like 1 (NPC1L1) protein plays a key role in intestinal and hepatic cholesterol metabolism in humans. Genetic variation in NPC1L1 has been widely studied in recent years. We analyzed NPC1L1 single nucleotide polymorphisms in Chinese gallstone disease patients to investigate their association with gallstone disease. NPC1L1 mRNA expression was also measured in liver biopsies from patients with cholesterol gallstone disease and compared between genotypes. The G allele of the g1679C>G (rs2072183) polymorphism was significantly more prevalent in patients with gallstones compared with gallstone-free subjects. Moreover, patients carrying the G allele had lower hepatic NPC1L1 mRNA expression and higher biliary cholesterol (molar percentages) and cholesterol saturation index. Our study suggests that the G allele of the NPC1L1 polymorphism g1679C>G may be a positive marker of gallstone formation risk.

Little is known regarding the effects of environmental exposure of chemicals on androgenic system in the general population. We studied 5,107 subjects included in the National Health and Nutrition Examination Survey (2011-2012).Urinary, serum, and blood levels of 15 subclasses comprising 110 individual chemicals were analyzed for their association with serum testosterone levels. The subjects were divided into high and low testosterone groups according to the median testosterone concentration (374.51 ng/dL). Odds ratios (ORs) of individual chemicals in association with testosterone were estimated using logistic regression after adjusting for age, ethnicity, cotinine, body mass index, creatinine, alcohol, and the poverty income ratio.Adjusted ORs for the highest versus lowest quartiles of exposure were 2.12 (95% CI: 1.07, 4.21; Ptrend = 0.044), 1.84 (95% CI: 1.02, 3.34; Ptrend = 0.018) for the association between urinary mandelic acid, and strontium quartiles with low testosterone concentrations in adult men, respectively. However, no association was observed for the remaining chemicals with testosterone.The National Health and Nutrition Examination Survey data suggest that elevations in urinary mandelic acid, and strontium levels are negatively related to low serum testosterone levels in adult men.

The association of the aldehyde dehydrogenases-2 (ALDH2) Glu504Lys polymorphism (also named Glu487Lys, or rs671) and cancers has been investigated. This meta-analysis aims to comprehensively assess the influence of this polymorphism on the overall cancer risk.Eligible publications were retrieved according to inclusion/exclusion criteria and the data were analyzed using the Review Manager software (V5.2).A meta-analysis based on 51 case-control studies consisting of 16774 cases and 32060 controls was performed to evaluate the association between the ALDH2 Glu504Lys polymorphism and cancer risk. The comparison of genotypes Lys+ (Lys/Lys and Lys/Glu) with Glu/Glu yielded a significant 20% increased cancer risk (OR = 1.20, 95%CI: 1.03-1.39, P = 0.02, I2 = 92%). Subgroup analysis by cancer type indicated a significantly increased UADT cancer risk (OR = 1.39, 95%CI: 1.11-1.73, P = 0.004, I2 = 94%) in individuals with the Lys+ genotypes. Subgroup analysis by country indicated that individuals from Japan with the Lys+ genotypes had a significant 38% increased cancer risk (OR = 1.38, 95%CI: 1.12-1.71, P = 0.003, I2 = 93%).Our results indicated that the ALDH2 Glu504Lys polymorphism is a susceptible loci associated with overall cancers, especially esophageal cancer and among Japanese population.

Gastric cancer is a common and highly malignant tumor of the digestive system, which seriously threatens human health. The benefit of surgical treatment is limited. The effect of radiotherapy and chemotherapy is not significant, and the toxic and side effects are large. Although the diagnosis and treatment modes of molecular targeting and multidisciplinary cooperation have also been further developed and applied, a relatively unified comprehensive treatment standard scheme has not been formed. Traditional Chinese medicine (TCM), as complementary and alternative medicine, has unique advantages in the development of diagnosis and treatment of diseases in China. Therefore, the Chinese Association of Integrative Medicine formed "Expert Consensus for Diagnosis and Treatment of Gastric Cancer with Integrated Traditional Chinese and Western Medicine" on the basis of clinical practice and experience. In this article, the consensus is interpreted from the perspective of nursing, focusing on the pathogenesis, high-risk factors, characteristic therapies of TCM, and nursing of integrated traditional Chinese and Western medicine for gastric cancer, to provide a reference for front-line medical personnel in the roots in the future nursing care of gastric cancer. [ABSTRACT FROM AUTHOR]