Prospective Clinical Application of Thioredoxin Reductase as a Novel Diagnostic Tumor Marker

Background: Developing a novel, efficient biomarker for detecting malignant tumors is essential for the early diagnosis of cancers. Our aim was to assess the diagnostic value of a potential plasma tumor marker, thioredoxin reductase (TR), which is expressed in many types of malignant tumor, for the non-invasive detection of cancers. Methods: The plasma activities of TR were measured in 1513 patients with common clinical diseases, 59 patients with benign tumors, and 154 patients with cancers and 586 healthy controls. The area under the ROC curve (AUC) of TR and logistic regression results of different groups were compared by sensitivity, specificity and Youden’s index. Diagnostic cut-offs and clinical reference intervals were established via ROC curve analysis. Results: The logistic regression indicated that TR activity can discriminate between cancers and benign tumors or other common diseases very well (p < 0.0001), with an area under the curve from the receiver-operator characteristics between 0.91 and 0.96. The positive critical value was 2.51 and the cancer critical value was 9.90. The diagnostic gray zone (2.51 - 9.90) may be associated with benign tumors and some common clinical diseases. Conclusions: As a novel potential marker of malignant tumors with quantitative evaluation of proliferation, TR activity detection has an excellent diagnostic potential for early-stage malignant tumors. Impact: The convenient, economical, relatively non-invasive, and reproducible detection method of TR activity makes it suitable for routine clinical practice.

An analysis of the Long-term Therapeutic Effect of the Integrated Therapy of Traditional Chinese Medicine and Radiotherapy on Abdominal Malignant Tumor

To observe the long-term therapeutic effect of the integrated therapy of radiotherapy and Chinese herbal drugs for treatment of abdominal malignant tumor and explore the applied value of differential treatment during radiotherapy. Sixty cases of abdominal malignant tumor with hyperactivity of fire due to yin deficiency or deficiency of both qi and blood were randomly divided into an integrated treatment group of 30 cases and a control group of 30 cases. The integrated treatment group was treated by combination of radiotherapy and Chinese herbal drugs and the control group by simple radiotherapy. The results shows that in the integrated treatment group, the score of physical state was 23.17 ± 7.18, score of psychological quality 21.23 ± 4.53 and total score of living quality 44.40 ± 11.22, and survival rate for three years was 67.55%, which were significantly superior to those of the control group (P＜0.01). It is then concluded that differential treatment of TCM could play a valuable role in treating abdominal malignant tumor during radiotherapy, which can improve the long-term living quality and prolong the survival time of the patients.

Application of ^(18) F-FDG PET/CT Imaging in Diagnosing Bladder Tumor Metastasis Lesions

Bladder tumor is the most common malignant tumor in urinary system and always com- panied with lymph node metastasis. The accurate staging plays a significant role in treatment for bladder tumor and prognostic evaluation, and the distant metastasis predicts worse prognosis. The objective of this study was to assess the clinical significance of 18F-FDG PET/CT imaging in diagnosing bladder tumor metastasis lesions. A retrospective analysis of 60 patients with bladder tumor from October 2008 to May 2010 was done. The patients were stratified based on the imaging technique. Among all 60 cases, besides the primary lesion, 81 suspected lesions were spotted and 73 confirmed as metastasis, including 50 lymph node metastases, 22 distant metastases, and 1 bone metastasis. For PET/CT imaging, its sensitivity was 94.5%, specificity 87.5%, positive predictive value 98.6%, negative predictive value 63.6% and accuracy 93.8% respectively. For CT, its sensitivity was 82.2%, specificity 50%, positive predictive value 93.8%, negative predictive value 23.5% and accuracy 79% respectively. PET/CT im- aging was superior to CT in sensitivity, specificity and accuracy. In conclusion, 18F-FDG PET/CT imaging is more significant in diagnosing bladder tumor metastasis lesions.

8-bromo-7-methoxychrysin inhibits properties of liver cancer stem cells via downregulation of β-catenin

AIM:To evaluate whether 8-bromo-7-methoxychrysin(BrMC),a synthetic analogue of chrysin,inhibits the properties of cancer stem cells derived from the human liver cancer MHCC97 cell line and to determine the potential mechanisms.METHODS:CD133+cells were sorted from the MHCC97 cell line by magnetic activated cell sorting,and amplified in stem cell-conditioned medium to obtain the enriched CD133+sphere forming cells(SFCs).The stem cell properties of CD133+SFCs were validated by the tumorsphere formation assay in vitro and the xenograft nude mouse model in vivo,and termed liver cancer stem cells(LCSCs).The effects of BrMC on LCSCs in vitro were evaluated by MTT assay,tumorsphere formation assay and transwell chamber assay.The effects of BrMC on LCSCs in vivo were determined using a primary and secondary xenograft model in Balb/c-nu mice.Expressions of the stem cell markers,epithelialmesenchymal transition(EMT)markers andβ-catenin protein were analyzed by western blotting or immunohistochemical analysis.RESULTS:CD133+SFCs exhibited stem-like cell properties of tumorsphere formation and tumorigenesis capacity in contrast to the parental MHCC97 cells.We found that BrMC preferentially inhibited proliferation and self-renewal of LCSCs(P<0.05).Furthermore,BrMC significantly suppressed EMT and invasion of LCSCs.Moreover,BrMC could efficaciously eliminate LCSCs in vivo.Interestingly,we showed that BrMC decreased the expression ofβ-catenin in LCSCs.Silencing ofβ-catenin by small interfering RNA could synergize the inhibition of self-renewal of LCSCs induced by BrMC,while Wnt3a treatment antagonized the inhibitory effects of BrMC.CONCLUSION:BrMC can inhibit the functions and characteristics of LCSCs derived from the liver cancer MHCC97 cell line through downregulation ofβ-catenin expression.

Gut-lung crosstalk in pulmonary involvement with inflammatory bowel diseases

Pulmonary abnormalities,dysfunction or hyper-reactivity occurs in association with inflammatory bowel disease(IBD) more frequently than previously recognized.Emerging evidence suggests that subtle inflammation exists in the airways among IBD patients even in the absence of any bronchopulmonary symptoms,and with normal pulmonary functions. The pulmonary impairment is more pronounced in IBD patients with active disease than in those in remission. A growing number of case reports show that the IBD patients develop rapidly progressive respiratory symptoms after colectomy,with failure to isolate bacterial pathogens on repeated sputum culture,and often request oral corticosteroid therapy. All the above evidence indicates that the inflammatory changes in both the intestine and lung during IBD. Clinical or subclinical pulmonary inflammation accompanies the main inflammation of the bowel.Although there are clinical and epidemiological reports of chronic inflammation of the pulmonary and intestinal mucosa in IBD,the detailed mechanisms of pulmonaryintestinal crosstalk remain unknown. The lung has no anatomical connection with the main inflammatory site of the bowel. Why does the inflammatory process shift from the gastrointestinal tract to the airways? The clinical and subclinical pulmonary abnormalities,dysfunction,or hyper-reactivity among IBD patients need further evaluation. Here,we give an overview of the concordance between chronic inflammatory reactions in the airways and the gastrointestinal tract. A better understanding of the possible mechanism of the crosstalk among the distant organs will be beneficial in identifying therapeutic strategies for mucosal inflammatory diseases such as IBD and allergy.

Basic transcription factor 3 is involved in gastric cancer development and progression

AIM: To further analyse cancer involvement of basic transcription factor 3 (BTF3) after detection of its upregulation in gastric tumor samples. METHODS: BTF3 transcription rates in human gastric tumor tissue samples (n = 20) and adjacent normal tissue (n = 18) specimens as well as in the gastric cancer cell lines AGS, SGC-7901, MKN-28, MKN-45 and MGC803 were analyzed via quantitative real-time polymerase chain reaction. The effect of stable BTF3 silencing via infection with a small interfering RNA (siRNA)-BTF3 expressing lentivirus on SGC-7901 cells was measured via Western blotting analysis, proliferation assays, cell cycle and apoptosis profiling by flow cytometry as well as colony forming assays with a Cellomic Assay System. RESULTS: A significant higher expression of BTF3 mRNA was detected in tumors compared to normal gastric tissues (P < 0.01), especially in section tissues from female patients compared to male patients, and all tested gastric cancer cell lines expressed high levels of BTF3. From days 1 to 5, the relative proliferation rates of stable BTF3-siRNA transfected SGC7901 cells were 82%, 70%, 57%, 49% and 44% compared to the control, while the percentage of cells arrested in the G 1 phase was significantly decreased (P = 0.000) and the percentages of cells in the S (P = 0.031) and G 2 /M (P = 0.027) phases were significantly increased. In addition, the colony forming tendency was significantly decreased (P = 0.014) and the apoptosis rate increased from 5.73% to 8.59% (P = 0.014) after BTF3 was silenced in SGC7901 cells. CONCLUSION: BTF3 expression is associated with enhanced cell proliferation, reduced cell cycle regulation and apoptosis and its silencing decreased colony forming and proliferation of gastric cancer cells.

Hepatitis C virus and antiviral innate immunity:Who wins at tug-of-war?

Hepatitis C virus(HCV) is a major human pathogen of chronic hepatitis and related liver diseases. Innate immunity is the first line of defense against invading foreign pathogens, and its activation is dependent on the recognition of these pathogens by several key sensors. The interferon(IFN) system plays an essential role in the restriction of HCV infection via the induction of hundreds of IFN-stimulated genes(ISGs) that inhibit viral replication and spread. However, numerous factors that trigger immune dysregulation, including viral factors and host genetic factors, can help HCV to escape host immune response, facilitating viral persistence. In this review, we aim to summarize recent advances in understanding the innate immune response to HCV infection and the mechanisms of ISGs to suppress viral survival, as well as the immune evasion strategies for chronic HCV infection.

CT characteristics of ovarian dysgerminoma

Objective: To study the CT features of ovarian dysgerminoma. Methods: CT findings of 11 cases with pathologically-proved dysgerminoma of ovary were retrospectively analyzed. Results: All the 11 cases were solitary. The maximum diameter of lesion was averagely 17.1 cm. The tumor presented as a solid (n = 8) or cystic-solid (n = 3) mass. After contrast medium administration, the solid component of the lesions showed prominent enhancement on CT scan. Blood vessels were found in 5 masses. Of the 11 cases with ovarian dysgerminoma, invasion of adjacent structure (n=4), ascites (n=6) and adenopathy in pelvic wall (n=3) were demonstrated. Conclusion: Ovarian dysgerminoma has its CT characteristics. Associated with clinic data, CT is helpful in the diagnosis and differential diagnosis of ovarian dysgerminoma.

REAL-TIME ASSESSMENT OF MICROWAVE ABLATION EFFICACY BY NIR SPECTROSCOPIC TECHNIQUE

Microwave ablation(MWA)status monitoring in real time plays a key role in assessment of therapeutic fectiveness.As a novel realtime assessment method,near infrared spectroscopy(NIRs)was used to evaluate the ablation eficacy.MWA experiments were carried out on in vitroporcine livers.An optical measurement system for biological tissue is developed by our lab tomonitor reduced scattering coefficient(μ')at 690 nm of the coagulation zones.It is noted that p's of liver tissue,which increases as the liver tissue being ablated,is clearly related with the co-agulation status.μ's of normal tissue and coagulated tissue is 3-5 and 17-19 cm-1,respectively.Continuous changes ofμ's demonstrate that optical parameter can be used as an efficacy evaluation factor because it essentially indicates the degree of thermal damage.Compared withtemperat ure,optical parameter is more sensitive and accurate,which is promising for real-timetherapeutic eficacy assessment in MWA.

Clinicopathological significance of chemotactic factor IL-8, MCP-1 and MIP-1α expressions in gallbladder carcinoma

Objective：Gal bladder carcinoma was one of the malignant tumors in the digestive system, characterized by high recurrence and invasion. Recent research indicates that chemotactic factors such as IL-8, MCP-1 and MIP-1αhave played an important role in such aspects as formulation, growth, shifting of the tumor. The aim of this study was to investigate expressions of IL-8, MCP-1 and MIP-1αin gal bladder adenocarcinoma tissues. Methods：Gal bladder adenocarcinoma and noncancerous tissues were routinely formalin-fixed and paraf in-embedded, and in situ hybridization assay for IL-8, MCP-1 and MIP-1αmRNA. Results：（1） The positive rates or the scorings of IL-8, MCP-1 and MIP-1αmRNA were significantly higher in human gal bladder adenocarcinoma than those in human chronic cholecystitis （P〈0.01）. The positive rates or the scorings of three factors were lower in wel-dif erentiatiated gal bladder adenocarcinoma than in poorly-dif erenfiatted ones, whereas there was only one significant dif erence between MCP-1 mRNA （P〈0.05）. The closely positive correlation were found among IL-8, MCP-1 and MIP-1αmRNA. （2） Both the positive rates of IL-8 mRNA and MCP-1 mRNA as wel as their scorings were tightly related to their invasion of the common bile duct and the occurrence of lymph node transfer, moreover, the positive rates of MIP-1αmRNA and its scorings were tightly related to its invasion of liver. （3） Close positive correlation exists not only in IL-8 mRNA and MCP-1 mRNA （r=0.528）, but also in MIP-1αmRNA and IL-8 mRNA （r=0.422）, so does in MCP-1 mRNA and MIP-1αmRNA （r=0.638）. Conclusion：The positive rates or the scorings of IL-8, MCP-1 and MIP-1αmRNA are significantly higher in human gal bladder adenocarcinoma than those in human chronic cholecystitis, and the closely positive correlation are found among them, which suggests that IL-8, MCP-1 and MIP-1αregulate and influence the development and transformation of the gal bladder adencarcinoma together.

FLIM as a Promising Tool for Cancer Diagnosis and Treatment Monitoring

Fluorescence lifetime imaging microscopy(FLIM)has been rapidly developed over the past 30 years and widely applied in biomedical engineering.Recent progress in fluorophore-dyed probe design has widened the application prospects of fluorescence.Because fluorescence lifetime is sensitive to microenvironments and molecule alterations,FLIM is promising for the detection of pathological conditions.Current cancer-related FLIM applications can be divided into three main categories:(i)FLIM with autofluorescence molecules in or out of a cell,especially with reduced form of nicotinamide adenine dinucleotide,and flavin adenine dinucleotide for cellular metabolism research;(ii)FLIM with Förster resonance energy transfer for monitoring protein interactions;and(iii)FLIM with fluorophore-dyed probes for specific aberration detection.Advancements in nanomaterial production and efficient calculation systems,as well as novel cancer biomarker discoveries,have promoted FLIM optimization,offering more opportunities for medical research and applications to cancer diagnosis and treatment monitoring.This review summarizes cutting-edge researches from 2015 to 2020 on cancer-related FLIM applications and the potential of FLIM for future cancer diagnosis methods and anti-cancer therapy development.We also highlight current challenges and provide perspectives for further investigation.

Decreased frontal lobe function in people with Internet addiction disorder

In our previous studies, we showed that frontal lobe and brainstem functions were abnormal in online game addicts. In this study, 14 students with Internet addiction disorder and 14 matched healthy controls underwent proton-magnetic resonance spectroscopy to measure cerebral function. Results demonstrated that the ratio of N-acetylaspartate to creatine decreased, but the ratio of cho- line-containing compounds to creatine increased in the bilateral frontal lobe white matter in people with Internet addiction disorder. However, these ratios were mostly unaltered in the brainstem, suggesting that frontal lobe function decreases in people with Internet addiction disorder.

Effects of intrathecal injection of glial cell inhibitor on spinal cord astrocytes following chronic compression of dorsal root ganglia in rats

BACKGROUND： Astrocytes are considered to provide nutritional support in the central nervous system. However, recent studies have confirmed that astrocytes also play an important role in chronic pain. OBJECTIVE： To investigate the effects of intrathecal injection of fluorocitrate, minocycline or both on astrocyte activation and proliferation in the spinal dorsal horn of compressed dorsal root ganglion in rats. DESIGN, TIME AND SETTING： The neurology randomized controlled animal study was performed at the Jiangsu Institute of Anesthesia Medicine, from September 2006 to April 2007. MATERIALS： A total of 96 male Sprague Dawley rats, aged 6-8 weeks, were selected for this study. Following intrathecal catheterization, 80 rats underwent steel bar insertion into the L4-5 intervertebral foramina to make a stable compression on the L4-5 posterior root ganglion. Thus rat models of ganglion compression were established. Minocycline and fluorocitrate were purchased from Sigma, USA. METHODS： A total of 96 rats were randomly and equally divided into six groups. Rat L4, L5 transverse process and intervertebral foramina were exposed in the sham operation group, but without steel bar insertion. The model group did not receive any manipulations. Rats in the phosphate buffered saline （PBS） group were intrathecally injected with 0.01 mmol/L PBS （20 μL）. Rats in the fluorocitrate group were subjected to 1 μmol/L fluorocitrate （20 μL）. Rats in the minocycline group were intrathecally injected with 5 g/L minocycline （20 μL）. Rats in the minocycline and fluorocitrate group received a mixture （20 μL） of 5 g/L minocycline and 1 μmol/L fluorocitrate. Following model establishment, drugs were administered once a day. MAIN OUTCOME MEASURES： At 7 and 14 days following model induction, glial fibrillary acidic protein expression in the spinal dorsal horn was measured by immunofluorescence microscopy. Six sections with significant glial fibrillary acidic protein -positive expression were obtained to count astrocytes under an inverted microscope. RESULTS： No significant differences in astrocyte count were detected between the fluorocitrate and model groups. Cell bodies were small with a few processes in the fluorocitrate group, compared with the model group. The astrocyte count decreased significantly in the minocycline group and the minocycline and fluorocitrate group compared with the sham operation, model, PBS and fluorocitrate groups （P 〈 0.01）. The decrease in astrocyte count was mainly found in layers Ⅲ–Ⅳ of the spinal dorsal horn. Cell body volume was smaller and process numbers were fewer in the minocycline group and the minocycline and fluorocitrate group, compared with the model and PBS groups. CONCLUSION： Fluorocitrate can inhibit astrocyte activation, but does not affect astrocyte proliferation. However, minocycline can inhibit the activation and proliferation of astrocytes.

Pattern recognition receptors in health and diseases

Pattern recognition receptors(PRRs)are a class of receptors that can directly recognize the specific molecular structures on the surface of pathogens,apoptotic host cells,and damaged senescent cells.PRRs bridge nonspecific immunity and specific immunity.Through the recognition and binding of ligands,PRRs can produce nonspecific anti-infection,antitumor,and other immunoprotective effects.Most PRRs in the innate immune system of vertebrates can be classified into the following five types based on protein domain homology:Toll-like receptors(TLRs),nucleotide oligomerization domain(NOD)-like receptors(NLRs),retinoic acid-inducible gene-1(RIG-1)-like receptors(RLRs),C-type lectin receptors(CLRs),and absent in melanoma-2(AIM2)-like receptors(ALRs).PRRs are basically composed of ligand recognition domains,intermediate domains,and effector domains.PRRs recognize and bind their respective ligands and recruit adaptor molecules with the same structure through their effector domains,initiating downstream signaling pathways to exert effects.In recent years,the increased researches on the recognition and binding of PRRs and their ligands have greatly promoted the understanding of different PRRs signaling pathways and provided ideas for the treatment of immune-related diseases and even tumors.This review describes in detail the history,the structural characteristics,ligand recognition mechanism,the signaling pathway,the related disease,new drugs in clinical trials and clinical therapy of different types of PRRs,and discusses the significance of the research on pattern recognition mechanism for the treatment of PRR-related diseases.

Red blood cell distribution width and ischaemic stroke

The red blood cell distribution width(RDW)is a measure of red blood cell(RBC)size heterogeneity,which is easily calculated by dividing the SD of erythrocyte volumes for the mean corpuscular volume.Recent reporter suggested that,besides haematological diseases and anaemia,many human disorders may be closely associated with the elevated RDW.A literature review has revealed the RDW may be closely related to the development of ischaemic stroke,carotid artery atherosclerosis and cerebral embolism.Higher RDW could independently predict adverse outcomes in patients in these conditions.

Regulation network and expression profiles of Epstein-Barr virus-encoded microRNAs and their potential target host genes in nasopharyngeal carcinomas

Epstein-Barr virus(EBV)is associated with nasopharyngeal carcinoma(NPC)tumorigenesis.However,the mechanism(s)connecting EBV infection and NPC remain unclear.Recently,a new class of EBV microRNAs(miRNAs)has been described.To determine how EBV miRNAs control the expression of host genes,and to understand their potential role in NPC tumorigenesis,we profiled the expression of 44 mature EBV miRNAs and potential host genes in NPC and non-tumor nasopharyngeal epithelial tissues.We found that 40 EBV miRNAs from the BART transcript were highly expressed in NPC.Analysis of potential BART miRNA target genes revealed that 3140 genes and several important pathways might be involved in the carcinogenesis of NPC.A total of 105 genes with potential EBV miRNA binding sites were significantly downregulated,suggesting that EBV miRNAs may regulate these genes and contribute to NPC carcinogenesis.An EBV miRNA and host gene regulation network was generated to provide useful clues for validating of EBV miRNA functions in NPC tumorigenesis.

Prognostic factors for primary superficial transitional cell carcinoma of the bladder:a retrospective cohort study

Background Previous studies showed that the prognostic factors for superficial transitional cell carcinoma of the bladder varied with the findings of different cohorts. Few multivariate analyses of prognostic factors for superficial bladder tumors have been reported in China and bladder preservation as a prognostic index of superficial bladder tumors is limited and scarce in Chinese patients. This study was conducted to analyze a group of risk factors for prognostic outcomes for patients with primary superficial transitional cell carcinoma of the bladder. Methods Between January 1980 to December 2000, 198 patients [172 men and 26 women; mean age （52.98± 11.28） years] with primary superficial transitional cell carcinoma who were pathologically classified as Ta or T1 in Hunan Provincial Tumor Hospital （Changsha, China） were enrolled in this study. Surgical methods included local resection and electric coagulation of bladder tumors, transurethral resection of bladder tumors and partial cystectomy. After initial surgical treatment, patients were followed through a cystoscopy every three months during the first two years and every six months thereafter in the design of retrospective cohort. Survival analysis was performed to analyze risk factors of the prognostic outcomes for transitional cell carcinoma of the bladder. Canonical correlation analysis was conducted to present and interpret synthetically the multi-correlation between all kinds of prognostic outcomes and risk factor in multiply dimensions. Results The average follow-up period was （6.65±4.74） years. Assessments at three, five, and 10 years showed recurrence rates, respectively, of （28.32±3.45）%, （35.31±3.83）%, and （42.48±4.40）%; progression rates of （8.89±2.14）%, （15.16±2.94）%, and （23.88±4.19）%; bladder-preservation rates of （94.68± 1.74）%, （93.87± 1.91）%, and （91.51±2.49）%; metastasis rates of （8.25＋2.05）%, （11.24±2.47）%, and （28.94±4.93）%; and cancer-related survival rates of （95.02± 1.62）%, （90.70±2.45）%, and （77.14±4.88）%. The main risk factors for recurrence were histological grade, blood transfusion during surgery and the duration of symptoms. Progression was affected by blood transfusion during surgery, histological grade, the number of re-examinations, and the length of the recurrence-free period. Metastasis was associated with tumor multifocality, hydronephrosis, microscopic growth pattern, and the recurrence-free period. Cancer-related survival was influenced by microscopic growth pattern and the recurrence-free period. Bladder preservation involved only the recurrence-free period. The comprehensive results from canonical correlation analysis showed that the main prognostic outcomes were cancer-related survival, metastasis and progression respectively, while the dominate risk factors were histological grade, tumor multifocality and blood transfusion. Conclusions The risk factors were different for each prognostic outcome of transitional cell carcinoma of the bladder. This is helpful for predicting the prognosis of transitional cell carcinoma of the bladder and designing therapeutic and follow-up strategies for this cancer.