Overexpression of ABCG2 transporter in cancer cells has been linked to the development of multidrug resistance (MDR), an obstacle to cancer therapy. Our recent study uncovered that the MET inhibitor, tepotinib, is a potent reversal agent for ABCB1-mediated MDR. In the present study, we reported for the first time that the MET inhibitor tepotinib can also reverse ABCG2-mediated MDR in vitro and in vivo by directly binding to the drug-binding site of ABCG2 and reversibly inhibiting ABCG2 drug efflux activity, therefore enhancing the cytotoxicity of substrate drugs in drug-resistant cancer cells. Furthermore, the ABCB1/ABCG2 double-transfected cell model and ABCG2 gene knockout cell model demonstrated that tepotinib specifically inhibits the two MDR transporters. In mice bearing drug-resistant tumors, tepotinib increased the intratumoral accumulation of ABCG2 substrate drug topotecan and enhanced its antitumor effect. Therefore, our study provides a new potential of repositioning tepotinib as an ABCG2 inhibitor and combining tepotinib with substrate drugs to antagonize ABCG2-mediated MDR.

Objective: To compare the application effect of the colonoscopy, fecal immunochemical test (FIT) and novel risk-adapted screening approach in colorectal cancer screening in Xuzhou population. Methods: From May 2018 to April 2019, 4 280 subjects aged 50-74 were recruited from Gulou district, Yunlong district and Quanshan district of Xuzhou. They were randomly assigned to the colonoscopy group (n=863), FIT group (n=1 723) and novel risk-adapted screening approach group (n=1 694) according to the ratio of 1∶2∶2. For the novel risk-adapted screening approach group, after the risk assessment, high-risk subjects were invited to undergo colonoscopy and low-risk subjects were invited to undergo FIT examination. All FIT positive subjects were invited to undergo colonoscopy. Colonoscopy participation rate [(the number of colonoscopies completed/the number of colonoscopies invited to participate)×100%], detection rate of colorectal lesions [(the number of diagnosed patients/the number of colonoscopies completed)×100%], colonoscopy resource load (the number of colonoscopies completed/the number of diagnosed advanced tumors) and FIT resource load in each group were calculated and compared. Results: The age of all subjects was (61±6) years old, including 1 816 males (42.43%). There was no statistically significant difference in the socio-demographic characteristics of the subjects in different screening groups. The colonoscopy participation rate was 22.60% (195/863) in the colonoscopy group, 57.04% (77/135) in the FIT group, and 33.94% (149/439) in the novel risk-adapted screening approach group, respectively. The colonoscopy participation rate was higher in the FIT group than in the colonoscopy group and the novel risk-adapted screening approach group (P<0.001). The colonoscopy participation rate of novel risk-adapted screening group was significantly higher than the colonoscopy group (P<0.001). The detection rates of advanced tumors were 6.67% (13/195), 9.09% (7/77) and 8.72% (13/149), respectively, and the difference was not statistically significant (P>0.05). The colonoscopy resource load (95%CI) was 15 (13-17) in the colonoscopy group, 11 (9-14) in the FIT group and 11 (10-13) in the novel risk-adapted screening approach group, respectively. Among them, the colonoscopy resource load of high-risk individuals in the novel risk-adapted screening approach group was 12 (9-15). FIT resource loads (95%CI) were 207 (196-218) and 88 (83-94) in the FIT group and the novel risk-adapted screening approach group. Conclusion: The combined application of risk-adapted screening approach and FIT may have a good application effect in colorectal cancer screening.
Aged ; Colonoscopy ; Colorectal Neoplasms/pathology* ; Early Detection of Cancer ; Feces ; Female ; Humans ; Male ; Mass Screening ; Middle Aged ; Occult Blood

Objective To investigate the neutralized antibody level of poliomyelitis among healthy children before and after implementation of the new immunization strategy in Shanghai. Methods The poliomyelitis levels of healthy children were detected by neutralization test of the micro cells. Results The neutralizing antibody positive rates were 100% for polioⅠand polioⅢ before and after implementation of the new immunization strategy.GMTs (geometric mean titers) for polioⅠwere 1:1 047.46 before it, and 1:254.70 after it; those for polio Ⅲ were 1:513.52 before it and 1:185.49 after it. Conclusion The neutralized antibody levels of the poliomyelitis among healthy infants maintain a high level before and after implementing the new immunization strategy in Shanghai.

Objective:To explore systematic implementation of World Health Organization Family International Classifications (WHO-FICs) in the field of rehabilitation: the theoretical and policy framework at macro level, governance and management mechanism at meso level, and implementation modules at micro levels, respectively. Methods:The policy and theoretical framework of rehabilitation development was discussed based on the international rehabilitation policy documents of WHO, mainly as World Report on Disability, Global Action Plan on Disability and Rehabilitation in Health Service System. Protocol and roadmap of systematic implementation of WHO-FICs, including International Classification of Diseases (ICD-11), International Classification of Functioning, Disability and Health (ICF), and International Classification of Health Intervention (ICHIβ-2) was proposed. Results:With the use of WHO-FICs, the theoretical and policy framework of rehabilitation was constructed, and the contents and principles of modern rehabilitation services were clarified at macro-level. Rehabilitation is an important part of health service, there are six building blocks: i.e. leadership and governance, financing, human resources for health, service providing, medical technology and health information system. It proposed to use knowledge management system of WHO-FICs, including the classification, nomenclature, definitions, descriptions, terminology and coding systems, to standardize rehabilitation evaluation and statistics. The management and governance system of rehabilitation should be implemented using WHO-FICs. Rehabilitation services are based on the bio-psycho-social model and implemented the principles of people-centered and functioning-oriented. The systematic implementation of WHO-FICs in rehabilitation abide by the model of "Evaluation (ICHI)－Evaluation, Description, Classification and Coding of Functioning (ICF)－Disease Classification, Diagnosis and Coding (ICD)－Rehabilitation Intervention (ICHI)", and with the standardized process of "Evaluation (Functioning and unmet needs)－Diagnose (Disease and Functioning)－Planning of Rehabilitation－Intervention－Evaluation of Outcome". The mic-modules of implementation of WHO-FICs in rehabilitation had been constructed. There were 28 categories of diseases, 7 categories of functioning and 6 categories of rehabilitation interventions in rehabilitation proposed by International Society of Physical and Rehabilitation Medicine. According to ICD-11 and ICF, it proposed to use WHO Disability Assessment Schedule 2.0 (WHODAS 2.0), Brief Model Disability Survey (MDS-B) and VB40 Generic Functioning Domains (VB40), and the ICF core-sets in evaluation of functioning and rehabilitation outcome. The implementation of WHO-FICs in management of medical records and reporting realized the standardized management of medical record, encoding of diseases, functioning and intervention, reporting of performance, and provided tools for billing, reimbursement and payment management of rehabilitation. It proposed to develop WHO-FICs based clinical data sets and big data to implement functioning-related Diagnosis Related Groups and case-mix statistics. Conclusion:With the systematic implementation of WHO-FICs in rehabilitation, the policy and theoretical framework at macro level had been developed. The mechanism of management and governance at meso level had been explored. The application modules and approaches at micro level had been established. A scientific and effective overall solution had been proposed to enhance the scientific, standardized, refined and informatization level, strengthen the level and governance capacity, and improve the quality, safety and the coverage of rehabilitation services.

Objective: To translate the English version of the Pressure Ulcer Risk Primary or Secondary Evaluation Tool (PURPOSE T) into Chinese and evaluate its reliability and validity. Methods: Firstly, PURPOSE T was translated and revised, cross-cultural debugging, and then 213 inpatients from Jiangsu University Affiliated Hospital from November 2017 to May 2018 were selected for investigation. Choosing the total item content validity index (S-CVI/Ave) and the content validity of the item level content validity index (I-CVI) to evaluate content validity, using the Chinese version of the Braden scale as the criterion to measure the validity-related validity of the Chinese version of PURPOSE T. The internal consistency reliability Cronbach α coefficient, the assessor reliability, and the test-retest reliability measure the reliability. Results: The Chinese version of PURPOSET S-CVI was 0.967; I-CVI was 0.6-1.0, The coefficients between PURPOSET and Braden scale in mobility, activity ability, perception status, nutritional status and humidity were 0.600, 0.661, 0.699, 0.519, and 0.783. The PURPOSET and Braden scales had a correlation coefficient of 0.407 in predicting the risk of pressure injury. The Cronbach α=0.859 of the evaluation tool, the assessor reliability were 0.87 and the correlation coefficient of the 2 measurements of the test-retest reliability were 0.91. Conclusions The Chinese version of PURPOSET has good reliability and validity and can be used as a risk assessment tool for pressure injury in hospitalized patients in China.

Tooth preparation is the primary and core operation technique for dental esthetic restoration treatment, due to its effect of providing restoration space, bonding interfaces and marginal lines for dental rehabilitation after tooth tissue reduction. The concept of microscopic minimal invasive dentistry put forward the issue of conducting high-quality tooth preparation, conserve tooth-structure, protect vital pulp and periodontal tissue simultaneously. This study reviewed the concepts, physiology background, design and minimal invasive microscopic tooth preparation, and in the meantime, individualized strategies and the two core elements of tooth preparation (quantity and shape) are listed.
Dental Porcelain ; Dental Restoration, Permanent ; Esthetics, Dental ; Tooth Preparation

Objective:This paper reviewed the current development of education of physical therapy and discussed the growing demand for physical therapists and gaps of their professional education. It is crucial to reconstruct a framework and system of sciences and specialty in physical therapy at the undergraduate level using WHO International Classification of Functioning, Disability and Health (ICF) to meet the requirement of core competency of physiotherapist developed by World Confederation of Physical Therapy. The core curricula should be integrated into the conceptual framework and approaches of functioning and rehabilitation. Methods:Using ICF, the construction framework, system of specialty and development of curricula of physical therapy at undergraduate education had been proposed and reconstructed. Results:With the theories and approaches of modern pedology and curriculum theory and ICF, referenced by competency requirements for physical therapists from World Confederation of Physical Therapy, three core courses had been proposed and their content had been reconstructed, involving the theories, methods and practical skills in the fields of physical therapy. These courses include functional diagnosis, intervention and evaluation based on ICF. Conclusion:It is implicated from the theory and approaches of ICF that the education and professional training of physical therapy should be tailored to the needs of health-related services.

OBJECTIVE: To investigate the impact of preoperative diagnostic ureteroscopy and biopsy (UB) on radical nephroureterectomy (RNU) and the prognosis of upper tract urothelial carcinoma (UTUC). METHODS: The clinical data of UTUC patients receiving RNU between Jan. 2007 and Dec. 2016 were retrospectively collected. The median follow up time was 40 months. The operation time and blood loss of RNU were compared between UB group and non-UB group. Subgroup analyses were conducted according to the time interval between UB and RNU, and surgery methods of lower ureter. The linear regression model was used to adjust for other common factors that impacted operation time. RESULTS: A total of 163 UTUC patients were included in the final analysis. For the lower ureter, open ureterectomies were performed in 91 patients (55.9%), while retroperitoneal laparoscopic ureterectomies were performed in 72 patients (44.1%). A total of 110 (67.5%) patients received preoperative UB. Compared with non-UB group, the average operation time of UB group was significantly longer [(252.5±79.8) min vs. (221.3±79.8) min, P=0.019], but no difference of blood loss was found (median, 50 mL vs. 50 mL, P=0.143). In subgroup analysis, the average operation time of RNU was significantly prolonged when RNU was performed after 1 week of UB (P=0.023). Meanwhile, the median blood loss of RNU increased significantly when it was done after 2 weeks of UB compared with non-UB group (100 mL vs. 50 mL, P=0.012). UB was also significantly prolonged the operation time of RNU in retroperitoneal laparoscopic ureterectomy group (P=0.012). In multivariable analysis, UB (P=0.049), ≥pT3 (P=0.039), pN+ (P=0.018) and ureterectomy method (P=0.005) were independent risk factors of prolonged operation time. The 3-year cancer specific survival (CSS) rate was 87.2% in our cohort. UB had no significant impact on cancer specific survival (P=0.435). CONCLUSION UB was an independent risk factor of prolonged RNU time, but did not significantly influence cancer specific survival of upper tract urothelial carcinoma patients.
Biopsy ; Carcinoma, Transitional Cell/diagnostic imaging* ; Humans ; Nephrectomy ; Nephroureterectomy ; Retrospective Studies ; Ureter ; Ureteral Neoplasms/diagnostic imaging* ; Ureteroscopy

This study aims to investigate the effect of different local testicular treatments and validate common prognostic factors on primary testicular lymphoma (PTL) patients. We retrospectively reviewed the clinical records of 32 patients from 1993 to 2017 diagnosed with PTL and included 22 patients for analysis. The Kaplan-Meier method, Log-rank test, and multivariate Cox proportional hazard regression analysis were applied to evaluate progression-free survival (PFS), overall survival (OS), and determine prognosis predictors. The median follow-up time was 30 months. Median OS and PFS were 96 months and 49 months, respectively. In univariate analysis, advanced Ann Arbor stage (III/IV) (P < 0.001), B symptoms (P < 0.001), and extranodal involvement other than testis (P = 0.001) were significantly associated with shorter OS and PFS. In multivariate analysis, Ann Arbor stage was significantly associated with OS (OR = 11.58, P = 0.049), whereas B symptom was significantly associated with PFS (OR = 11.79, P= 0.049). In the 10 patients with the systemic usage of rituximab, bilateral intervention could improve median OS from 16 to 96 months (P = 0.032). The study provides preliminary evidence on bilateral intervention in testes in the rituximab era and validates common prognostic factors for Chinese PTL patients.
Aged ; Aged, 80 and over ; Antineoplastic Agents/therapeutic use* ; Asian People ; China/epidemiology* ; Humans ; Kaplan-Meier Estimate ; Lymphoma/mortality* ; Male ; Middle Aged ; Prognosis ; Progression-Free Survival ; Retrospective Studies ; Rituximab/therapeutic use* ; Survival Analysis ; Testicular Neoplasms/mortality* ; Treatment Outcome

OBJECTIVES: To identify the new designer drugs which are totally unknown and not in the routine testing list by the technologies such as high-resolution mass spectrometry in drug facilitated sexual assault, in order to solve the problem in actual cases. METHODS: The milky fluid from an actual case was extracted and analyzed using LC-QE, ¹H-NMR and GC-MS, respectively. The accurate masses and cluster ions isotope patterns of unknown compound were obtained by LC-QE. The molecular formula was confirmed as C₁₆H₁₂C₂N₂O based on the protons number of ¹H-NMR. The isomers diclazepam and 4-chlorodiazepam were separated and detected with GC-MS. RESULTS: The new designer benzodiazepine as diclazepam in the milky fluid was identified. The results provided direct evidence for the investigation and qualitative analysis of such cases. CONCLUSIONS The combined application of various methods, including LC-QE, ¹H-NMR and GC-MS, can be used to detect unknown new psychoactive substances.
Benzodiazepines/chemistry* ; Benzodiazepinones ; Chromatography, Liquid/methods* ; Designer Drugs/chemistry* ; Female ; Gas Chromatography-Mass Spectrometry/methods* ; Humans ; Male ; Mass Spectrometry/methods* ; Sex Offenses ; Substance Abuse Detection/methods* ; Toxicology/methods*