Biomarkers of malignant transformation in oral leukoplakia: from bench to bedside / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Oral leukoplakia is a common precursor lesion of oral squamous cell carcinoma, which indicates a high potential of malignancy. The malignant transformation of oral leukoplakia seriously affects patient survival and quality of life; however, it is difficult to identify oral leukoplakia patients who will develop carcinoma because no biomarker exists to predict malignant transformation for effective clinical management. As a major problem in the field of head and neck pathologies, it is imperative to identify biomarkers of malignant transformation in oral leukoplakia. In this review, we discuss the potential biomarkers of malignant transformation reported in the literature and explore the translational probabilities from bench to bedside. Although no single biomarker has yet been applied in the clinical setting, profiling for genomic instability might be a promising adjunct.

Analysis on monitoring results of toxicological indexes of drinking water in rural schools of Yunnan Province from 2017 to 2020 / 中国学校卫生

Objective@#To understand the toxicological indexes and indexes factors of drinking water in rural schools in Yunnan Province during 2017-2020, so as to provide scientific basis for ensuring drinking water safety, and targeted intervention in rural schools. @*Methods@#The end water of 456，399，391，387 rural primary and secondary school drinking water supply projects in 129 counties in Yunnan Province was collected from 2017 to 2020, 11 toxicological indexes were analyzed and evaluated.@*Results@#The overall compliance rate of drinking water toxicological indexes in rural primary and secondary schools in Yunnan Province was 99.32 %; The top three indexes exceeding the standard were nitrate nitrogen(0.31%), chloroform (0.15%) and cadmium(0.09%). The difference of compliance rate by year was statistically significant( χ 2=11.04, P <0.05); No difference in compliance rate was found between dry and wet seasons( χ 2=0.05, P >0.05); The rate of the surface water meeting the standard was higher than that of the groundwater( χ 2=9.62, P <0.05). There was no significant difference in the compliance rate between the treated and untreated projects( χ 2=1.55, P >0.05); The daily water supply scale was less than 500 m 3, and the rate of reaching the standard was lower than that of daily water supply is greater than 500 m 3( χ 2=4.27, P <0.05).@*Conclusion@#The overall percentage of the toxicological indexes in drinking water exceeding the standard in rural primary and secondary schools in Yunnan Province is low. Nitrate nitrogen, chloroform and cadmium should be considered as the prioritirized pollutants of drinking water in rural schools of Yunnan Province.

Copy number alteration profiling facilitates differential diagnosis between ossifying fibroma and fibrous dysplasia of the jaws / 国际口腔科学杂志·英文版

Ossifying fibroma (OF) and fibrous dysplasia (FD) are two fibro-osseous lesions with overlapping clinicopathological features, making diagnosis challenging. In this study, we applied a whole-genome shallow sequencing approach to facilitate differential diagnosis via precise profiling of copy number alterations (CNAs) using minute amounts of DNA extracted from morphologically correlated microdissected tissue samples. Freshly frozen tissue specimens from OF (n = 29) and FD (n = 28) patients were obtained for analysis. Lesion fibrous tissues and surrounding normal tissues were obtained by laser capture microdissection (LCM), with ~30-50 cells (5 000-10 000 µm

Effect of the sonic hedgehog inhibitor GDC-0449 on an in vitro isogenic cellular model simulating odontogenic keratocysts / 国际口腔科学杂志·英文版

Odontogenic keratocysts (OKCs) are common cystic lesions of odontogenic epithelial origin that can occur sporadically or in association with naevoid basal cell carcinoma syndrome (NBCCS). OKCs are locally aggressive, cause marked destruction of the jaw bones and have a propensity to recur. PTCH1 mutations (at ∼80%) are frequently detected in the epithelia of both NBCCS-related and sporadic OKCs, suggesting that PTCH1 inactivation might constitutively activate sonic hedgehog (SHH) signalling and play a major role in disease pathogenesis. Thus, small molecule inhibitors of SHH signalling might represent a new treatment strategy for OKCs. However, studies on the molecular mechanisms associated with OKCs have been hampered by limited epithelial cell yields during OKC explant culture. Here, we constructed an isogenic PTCH1 cellular model of PTCH1 inactivation by introducing a heterozygous mutation, namely, c.403C>T (p.R135X), which has been identified in OKC patients, into a human embryonic stem cell line using the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) system. This was followed by the induction of epithelial differentiation. Using this in vitro isogenic cellular model, we verified that the PTCH1 heterozygous mutation causes ligand-independent activation of SHH signalling due to PTCH1 haploinsufficiency. This activation was found to be downregulated in a dose-dependent manner by the SHH pathway inhibitor GDC-0449. In addition, through inhibition of activated SHH signalling, the enhanced proliferation observed in these induced cells was suppressed, suggesting that GDC-0449 might represent an effective inhibitor of the SHH pathway for use during OKC treatment.

Medicine reference price system in Germany and its implication for healthcare payment stand-ard in China / 中国卫生政策研究

It is significantly important but difficult to establish healthcare payment standard system in case our country has cancelled government and government guidance prices. In 1989, Germany was the first country to intro-duce the medicine reference price system in Statutory Health Insurance. It does not only aim to regulate the medicine prices, but also defines a reimbursement level for a cluster of products considered to be therapeutically equivalent, and has a good influence on lowering the price of medicine. This paper systematically reviews the medicine reference price system in Germany, including four aspects:the reference price system overview, the reference price groups’ de-termination procedure, the reference prices calculation and the co-payment mechanisms. Based on the Germany refer-ence price system, we can establish healthcare payment standard in over-the-counter or chronic market first, then sci-entifically divide the reference price groups, formulate and adjust payment standard based on the market price, and perfect the co-payment mechanism to avoid moral hazard.