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To test the hypothesis that β -glucan enhances protective qi (PQi), an important Chinese medicine (CM) concept which stipulates that a protective force circulates throughout the body surface and works as the first line of defense against “external pernicious influences”. A total of 138 participants with PQi deficiency (PQD) were randomized to receive β -glucan (200 mg daily) or placebo for 12 weeks. Participants’ PQi status was assessed every 2 weeks via conventional diagnosis and a standardized protocol from which a PQD severity and risk score was derived. Indices of participants’ immune and general health status were also monitored, including upper respiratory tract infection (URTI), saliva secretory IgA (sIgA), and self-reported measures of physical and mental health (PROMIS). PQi status was not significantly different between the β -glucan and placebo treatment groups at baseline but improved significantly in the β -glucan (vs. placebo) group in a time-dependent manner. The intergroup differences [95% confidence interval (CI)] in severity score (scale: 1–5), risk score (scale: 0–1), and proportion of PQD participants (%) at finish line was 0.49 (0.35–0.62), 0.48 (0.35–0.61), and 0.36 (0.25–0.47), respectively. Additionally, β -glucan improved URTI symptom (scale: 1–9) and PROMIS physical (scale: 16.2–67.7) and mental (scale: 21.2–67.6) scores by a magnitude (95% CI) of 1.0 (0.21–1.86), 5.7 (2.33–9.07), and 3.0 (20.37–6.37), respectively, over placebo. β -glucan ameliorates PQi in PQD individuals. By using stringent evidence-based methodologies, our study demonstrated that Western medicine-derived remedies, such as β -glucan, can be employed to advance CM therapeutics. (ClinicalTrial.Gov registry: NCT03782974)

To preliminarily explore the potential effect of β-glucan on Chinese medicine (CM) concept protective qi deficiency (PQD), and the methodology for future definitive studies. To have a standardized assessment of PQD, a list of 13 potentially PQD-relevant parameters were firstly created, each with defined quantitative or categorial scales. Using the data from 37 participants with (21 cases) or without (16 cases) PQD, multivariate logistic modeling was conducted to create a preliminary diagnostic PQD risk score. Subsequently, 21 participants diagnosed with PQD were treated with β-glucan in a dose of 200 mg/day for 8 weeks. Data were collected for trial acceptability measures (rate of recruitment, withdrawal, and compliance), and the participants were assessed for PQD status at baseline and every 2 weeks thereafter. The preliminary logistic model consisted of 3 parameters (low voice and apathy, aversion to wind and cold, and Cun pulse). The resulting risk score demonstrated a degree of PQD-predicting accuracy that, as evaluated by statistical (discrimination and classification) methods, was higher than those obtained from any of the individual candidate parameters. The 21 PQD participants treated with β-glucan demonstrated good receptibility and a time-dependent improvement in PQD status as evidenced by the decrease of PQD participant to 9.5% at the end of study. This study demonstrated the effect of proof-of-concept of β-glucan on improving PQD and the proof-of-concept of a multivariate-model-derived diagnostic PQD risk score. It also indicated feasibility for future definitive studies. Studies like this embody an innovative approach that uses therapies derived from the mainstream biomedicine to enrich therapeutics guided by CM principle. (Trial registration No. NCT03829228)

This paper presents an extremely rare case of testicular metastasis arising from renal pelvis carcinoma. The testicle is a rare site of clinically detectable tumor metastasis, originating rarely from upper tract urothelial carcinoma (UTUC). There are only two cases concerning UTUC metastasis to the testis available in the literature. In this report, we presented a patient who developed serial testicle, lung, liver and retroperitoneal lymph node metastasis from primary urothelial carcinoma of the renal pelvis within one year after surgery and chemotherapy. In conclusion, for patients with a history of UTUC who present with testicular symptoms, clinicians should be highly alert for the possibility of malignant involvement at this site.

Background The single nucleotide polymorphism of the gene 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T (or rs1801133) is the most established genetic factor that increases plasma total homocysteine (tHcy) and consequently results in hyperhomocysteinemia. Yet, given the limited penetrance of this genetic variant, it is necessary to individually predict the risk of hyperhomocysteinemia for an rs1801133 carrier. Objective We hypothesized that variability in this genetic risk is largely due to the presence of factors (covariates) that serve as effect modifiers, confounders, or both, such as folic acid (FA) intake, and aimed to assess this risk in the complex context of these covariates. Design We systematically extracted from published studies the data on tHcy, rs1801133, and any previously reported rs1801133 covariates. The resulting metadata set was first used to analyze the covariates' modifying effect by meta-regression and other statistical means. Subsequently, we controlled for this modifying effect by genotype-stratifying tHcy data and analyzed the variability in the risk resulting from the confounding of covariates. Results The data set contains data on 36 rs1801133 covariates that were collected from 114,799 participants and 256 qualified studies, among which 6 covariates (sex, age, race, FA intake, smoking, and alcohol consumption) are the most frequently informed and therefore included for statistical analysis. The effect of rs1801133 on tHcy exhibits significant variability that can be attributed to effect modification as well as confounding by these covariates. Via statistical modeling, we predicted the covariate-dependent risk of tHcy elevation and hyperhomocysteinemia in a systematic manner. Conclusions We showed an evidence-based approach that globally assesses the covariate-dependent effect of rs1801133 on tHcy. The results should assist clinicians in interpreting the rs1801133 data from genetic testing for their patients. Such information is also important for the public, who increasingly receive genetic data from commercial services without interpretation of its clinical relevance. This study was registered at Research Registry with the registration number reviewregistry328.

Objective: To study the SDF-1/CXCR4 expression in bladder cancer tissue and the correlation with negative costimulatory molecule PD-L1, cell apoptosis and invasion. Methods: A total of 118 cases of bladder cancer tissue and para-carcinoma tissue surgically removed in our hospital between May 2014 and May 2016 were selected as the research samples, the RNA was extracted and then reverse-transcribed into cDNA, and the expression levels of SDF-1/ CXCR4, PD-L1/PD-1, cell apoptosis-related molecules and cell invasion-related molecules were detected. Results: SDF-1 and CXCR4 mRNA expression in bladder cancer tissue were significantly higher than those in para-carcinoma tissue; PD-L1, PD-1, Rec1, Survivin, MRPS5, Nanog, BCAPP2Ac, TRPM8, TRPV2, ILK, β-catenin and GUGBP1 mRNA expression in bladder cancer tissue were significantly higher than those in para-carcinoma tissue and positively correlated with SDF-1 and CXCR4 mRNA expression. Conclusion: Highly expressed SDF-1/CXCR4 in bladder cancer tissue are closely related to the high expression of negative costimulatory molecule PD-L1, pro-proliferation molecules and proinvasion molecules, and SDF-1/CXCR4 can promote the immune escape, proliferation and invasion of bladder cancer cells.

Introduction Standardized diagnosis is required and therefore advocated for evidence-based research in Traditional Chinese Medicine (TCM). In this study, we aimed to standardize and validate a protocol that assesses Protective Qi Deficiency (PQD), a common TCM condition that predisposes individuals to pathogenic invasion. Methods 3 TCM practitioners evaluated 151 participants for PQD status via conventional TCM methods and a standardized protocol consisting of 13 PQD-related variables identified as potential predictors of a diagnostic algorithm of PQD. The collected data served as the training dataset to determine which predictors that significantly contributed to PQD diagnosis and their coefficients in the resulting algorithm. The algorithm was then reviewed and modified by an independent expert panel following the Delphi method, and subsequently validated using a separate validation dataset (n = 56). Results The Delphi-modified algorithm contained 8 predictor variables and accounted for 73.4 % of the PQD variance in the training dataset. Using the validation dataset, the algorithm predicted a TCM practitioner’s conventional diagnosis of PQD with a high degree of accuracy. The protocol also demonstrated significant precision as demonstrated by a high between-practitioner consistency (0.993) measured by intraclass correlation coefficient. Conclusion Our study provides evidence that, through rigorous standardization, quantitation, and statistical analysis, reliable assessment of a TCM concept can be achieved and applied for researching TCM therapeutics. Nonetheless, the generalizability of these findings need to be tested in future studies with increased numbers of practitioners and participants and in studies conducted at multiple geographical venues.

A series of novel quinazolin-4-amine derivatives containing p-toluenesulfonate moiety have been synthesised through the reaction of 4-chloro-7-methoxyquinazolin-6-yl acetate with substituted anilines in toluene solution at 90 °C. Further treatment of the synthesised compound with ammonium hydroxide gave the corresponding substituted quinazoline derivatives which were subsequently processed through the sulfonyl reaction into quinazolin-4-amines containing p-toluenesulfonate moiety in DMF. Their structures were established by elemental analysis, IR and 1H NMR spectra.

BackgroundThe single nucleotide polymorphism (SNP) of the gene Methylenetetrahydrofolate Reductase (MTHFR) C677T (or rs1801133) is the most established genetic factor that increases plasma total homocysteine (tHcy) and consequently results in hyperhomocysteinemia. Yet given the limited penetrance of this genetic variant, it is necessary to individually predict the risk of hyperhomocysteinemia for a rs1801133 carrier.ObjectiveWe hypothesized that variability of this genetic risk is largely due to the presence of factors (covariates) that serve as effect modifiers and/or confounders, such as folic acid (FA) intake, and aimed to assess this risk in the complex context of these covariates.DesignWe systematically extracted from published studies the data of tHcy, rs1801133, and any previously reported rs1801133 covariates. The resulting meta-dataset was first used to analyze the covariates’ modifying effect by meta regression and other statistical means. Subsequently, we stratified tHcy data by the rs1801133 genotypes and analyzed under each genotype the variability of the risk resulted from the covariates’ confounding.ResultsThe dataset contains data of 36 rs1801133 covariates that were collected from 114,448 subjects and 249 qualified studies, among which 6 covariates (sex, age, race, FA intake, smoking, and alcohol consumption) are the most frequently informed and therefore included for statistical analysis. The effect of rs1801133 on tHcy exhibits significant variability that can be attributed to effect modification and, to a larger degree, confounding by these covariates. Via statistical modeling, we predicted the covariate-dependent risk of tHcy elevation and hyperhomocysteinemia in a systematic manner.Conclusionswe demonstrated an evidence-based approach that globally assesses the covariate-dependent effect of rs1801133 on tHcy. The results should assist clinicians in interpreting the rs1801133 data from genetic testing for their patients. Such information is also important for the public that increasingly receives genetic data from commercial services without interpretation of its clinical relevance.

Objectives To investigate whether tumor-infiltrating lymphocytes (TILs) transfected with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and interleukin-2 (IL-2) genes are capable of improving the potency and efficacy of propagation and cytotoxicity against renal cell carcinoma (RCC) cells in vitro. Methods A mammal expression vector system was constructed. TILs were transfected by liposome-mediated gene transfection. The degree of cytokine mRNA expression was evaluated with Northern blot. Protein expression was determined with Western blot and enzyme-linked immunosorbent assay. Cytotoxicity of TILs against autologous RCC cells and the human RCC cell line (786-0) were examined by chromium release assay. Flow cytometric analyses were performed to determine the apoptosis of tumor cells. Results A high level of expression of the human TRAIL and IL-2 stable transfected TILs was observed. The mean IL-2 production was 22.6 ± 5.2, 507.7 ± 52.4, and 549.0 ± 74.0 ng/10 6 cells/24 hours in the TIL/parental, TIL/IL-2, and TIL/TRAIL+IL-2 genes, respectively. The mean cytotoxicity (effector/target ratio 20:1) of TIL/parental, TIL/IL-2, TIL/TRAIL, and TIL/TRAIL+IL-2 against autologous RCC cells in the percentage of cytolysis was 21.2% ± 4.8%, 32.1% ± 5.5%, 63.5% ± 6.6%, and 78.1% ± 9.63%, respectively. These four groups showed cytotoxic activity against allogeneic 786-0 RCC cells; the corresponding values were 9.8% ± 3.5%, 12.3% ± 3.4%, 24.1% ± 4.9%, and 30.4% ± 6.2%. The number of apoptotic cells was significantly greater for autologous RCC cells than for 786-0 cells after TIL/TRAIL and TIL/TRAIL+IL-2 treatment. Conclusions TIL/TRAIL+IL-2 and TIL/IL-2 were expanded by autocrine IL-2. TIL/TRAIL+IL-2 and TIL/TRAIL showed significant cytotoxicity that was induced by TRAIL. TILs, including parental TILs and transfected TILs, demonstrated a potent cytotoxicity against RCC cells with remarkable selectivity. Autologous RCC cells seemed more sensitive than allogeneic RCC cells.

Traditional electrical displacement sensors usually are big and insensitive, difficult to multiplex, therefore, they are not suitable for model test. In this paper, a novel subminiature multipoint FBG displacement sensor which has overcome the shortages of above displacement sensors is designed especially for the model test based on analysis of displacement detecting principle. It mainly consists of several FBGs, springs, crusts and the bases. FBGs which are sensitive device connect with springs in series. When key point moves, stretching deformation of spring will occur, so that FBG will receive axial force which will make central wavelength of FBG drifts. According to drift of center wavelength of the sensor, displacement of several points can be detected simultaneously. Calibration experiments of several sensors are carried out, in which it could get the conclusions that the sensitivity is about 1.3nm / mm and the linearity is over 0.99. FBG displacement sensors are embedded in the tunnel wall rock symmetrically to monitor precursory information of disaster. In the process of tunnel excavation, displacement increased gradually, and the detecting results had a strong symmetry.

BACKGROUND Bladder cancer accounts for approximately 4.4% of adult malignancies, and approximately 80% of bladder cancer presents initially as transitional cell carcinoma that is confined to the urothelium (stage Ta) or lamina propria (stage T1). Intravesical administration of Bacillus Calmette-Guerin (BCG) and epirubicin (EPI) has been proven to reduce tumour recurrence and prevent or delay progression to muscle invasion and metastases. However, comparison of the effectiveness and safety of intravesical BCG and EPI in bladder cancer has yet to be explored. OBJECTIVES To compare the effectiveness and safety of BCG with EPI in the treatment of Ta and T1 bladder cancer. SEARCH STRATEGY A comprehensive search of MEDLINE (1966 to April 2010), EMBASE (1980 to April 2010), Health Services Technology, Administration, and Research (HealthSTAR), the Cochrane Central Register of Controlled Trials (CENTRAL), CancerLit, and Database of Abstracts of Reviews of Effectiveness (DARE), was performed, and handsearching of relevant journals was undertaken. SELECTION CRITERIA All randomised or quasi-randomised trials (in which allocation was obtained by alternation - e.g., alternate medical records, date of birth, or other predictable methods) in patients with Ta or T1 bladder cancer that compared intravesical BCG with EPI were included. No language restrictions were applied. DATA COLLECTION AND ANALYSIS Trial eligibility, methodological quality and data extraction were assessed independently by two reviewers. We compared dichotomous outcomes (frequency of tumour recurrence, progressive disease by stage, mortality, distant metastases, local and systemic adverse effects, treatment delayed or stopped due to adverse effects) using risk ratios (RR) with 95% confidence intervals (CI). MAIN RESULTS Five trials of 1111 participants were included in this review. For BCG, 549 patients were treated, and 562 with EPI. Of the evaluated patients, 35.5% (195/549) in the BCG group and 51.4% (289/562) in the EPI group had tumour recurrence (P < 0.05). For disease progression (BCG, 44/549; EPI, 58/562) and distant metastases (BCG, 23/487; EPI, 31/495), there were no significant differences (P = 0.19 and P = 0.29, respectively). Only two trials, including 769 patients, had sufficient data for us to analyze disease-specific (BCG, 22/383; EPI, 26/386) and overall mortality (BCG, 125/383; EPI, 147/386). Neither comparison was significant (P = 0.93 and P = 0.12, respectively). In four studies reporting toxicity, BCG was associated with significantly more drug-induced cystitis [BCG, 54.1% (232/429); EPI, 31.7% (140/441)] and haematuria [BCG, 30.8% (132/429); EPI, 16.1% (71/440)]. Similarly, in three studies reporting systemic toxicity, BCG had significantly higher toxicity than the EPI (34.8% (134/385) versus 1.3% (5/393), respectively). In a meta-analysis comparing 'treatment delayed or stopped' (BCG, 40/431; EPI, 33/441), there was no significant difference between BCG and EPI treatments (P = 0.82). AUTHORS' CONCLUSIONS The data from the present meta-analysis indicate that intravesical BCG treatment is more efficacious than EPI in reducing tumour recurrence for Ta and T1 bladder cancer. However, BCG appears to be associated with a higher incidence of adverse effects, such as drug-induced cystitis, haematuria and systemic toxicity, than EPI. The overall quality of the evidence is rather low. Well-designed, high quality randomised controlled trials with good allocation concealment are required.