Intentional tooth replantation (ITR) is an advanced treatment modality and the procedure of last resort for preserving teeth with inaccessible endodontic or resorptive lesions. ITR is defined as the deliberate extraction of a tooth; evaluation of the root surface, endodontic manipulation, and repair; and placement of the tooth back into its original socket. Case reports, case series, cohort studies, and randomized controlled trials have demonstrated the efficacy of ITR in the retention of natural teeth that are untreatable or difficult to manage with root canal treatment or endodontic microsurgery. However, variations in clinical protocols for ITR exist due to the empirical nature of the original protocols and rapid advancements in the field of oral biology and dental materials. This heterogeneity in protocols may cause confusion among dental practitioners; therefore, guidelines and considerations for ITR should be explicated. This expert consensus discusses the biological foundation of ITR, the available clinical protocols and current status of ITR in treating teeth with refractory apical periodontitis or anatomical aberration, and the main complications of this treatment, aiming to refine the clinical management of ITR in accordance with the progress of basic research and clinical studies; the findings suggest that ITR may become a more consistent evidence-based option in dental treatment.
Humans ; Tooth Replantation/methods* ; Consensus ; Periapical Periodontitis/surgery*

Objective:To establish a standard colorectal neoplasm tissue biobank with complete clinical information to provide high quality samples for fundamental and clinical research of colorectal neoplasm.Methods:Based on Affiliated Jinhua Hospital, Zhejiang University School of Medicine, to conduct structural design of colorectal neoplasm tissues, normal tissues and related information. Establish standard operating procedures from the collection and storage of tissue samples, standardize the entry of basic information, medical history, pathology and other relevant clinical information of the patients, and conduct random quality inspections on the pathological morphology and molecular level on a regular basis.Results:A tissue biobank of colorectal neoplasm was successfully constructed. During the establishment and improvement of this tissue biobank, standardized quality control was implemented during the whole-process including sample collection, warehousing, storage and delivery. According to the random sampling quality inspection, the RNA preservation effect was good, the rates of neoplasms in cancer tissue was >80%, and the clinical data of samples were complete.Conclusions:The preliminary construction of colorectal neoplasm tissue biobank not only improves the utilization value of tissue samples, but also provides a guarantee for realizing the bidirectional transformation of fundamental research and clinical application.

OBJECTIVE：To pro vide reference f or resolving structural imbalance of “supply and demand dislocation ”in each stage of new drug R&D funds in China. METHODS ：Through analyzing the fund demand in each stage of new drug R&D and the problem of “supply and demand dislocation ”in detail ，a financing scheme matching the fund demand of each stage was designed ， and analyzed with the financing process of “Wanke”. RESULTS & CONCLUSIONS ：In the basic stage of new drug R&D ，there was a large demand for funds ，but there were great technical risks ，transformation risks and investment risks ，little attention and support from investors ，resulting in the lack of R&D funds in this stage. It is suggested to increase the investment of R&D enterprises themselves. In the stage of new drug discovery ，the risks of R&D and investment were still high ，more funds were needed and funds were in short supply. It is suggested to attract more venture capital into this stage. From preclinical stage to clinical stage Ⅱ，there was a greater demand for funds. It is suggested that this stage should mainly rely on venture capital and pledge financing with patents. From the clinical stage Ⅲ to pre-marketing ，R&D had entered the mature stage with less investment risk. Therefore ，more venture capital could be obtained in this stage ，and there was a situation of excess capital. At this time ，in addition to venture capital ，R&D enterprises can also choose listing financing. In the post-marketing stage ，the sales right of a certain region in the product sales link could be transferred to provide new reserve funds for the next round of new drug R&D ，so as to achieve a virtuous circle of R&D activities. One of the reasons for the success of “Wanke”R&D financing lied in the combination of various financing methods in the financing process. It is suggested that China should improve the financial financing system and patent value evaluation system at the national level ，so as to promote the drug patent pledge financing in China as soon as possible. Finally ，new drug R&D institute must establish the concept of independent innovation ，speed up the output of technological innovation results ，so as to achieve the improvement of China ’s independent R&D capability.

OBJECTIVE：To analyze the application of health technology as sessment（HTA）for the selection of essential medicine in Thailand ，and to provide reference for optimizing the selection system of essential medicine in China. METHODS ：By retrieving related literatures and official websites ，the situation （selection mode ，institution and HTA institution ），process（main selection process of selection for essential medcine ，HTA process ） and supporting measures （HTA guideline ，HTA research database，standard cost list ）in the selection of essential medicine in Thailand were analyzed comprehensively. Suggestions to essential medicine selection in China were put forward. RESULTS & CONCLUSIONS ：The current selection model of essential medicines in Thailand is based on the application of stakeholders （pharmaceutical manufacturers ，healthcare providers ，patients or patient organizations ，etc.）through expert selection combined with HTA ，which is charged by essential medicine list subcommittee. The Health Intervention and Technology Assessment Program Center of its health economics working group is responsible for the specific work of essential medicine HTA. Its main process include the submission of applications by pharmaceutical manufacturers ， screening by essential medicine list committee ，expert selection ，and the coordination working group of essential medicine list to form the proposed list ，which is then examined and approved by the subcommittee ，minister of Health and National Drug System Development Committee ；finally the list was released. The high-price but necessary drugs are selected by the subcommittee and then the priority is assessed by the health economics working group. Non-profit organization or other interested organizations conduct HTA ；health economics working group and external audit experts evaluate the research quality ，and the health economics working group forms policy recommendations ； NLEMcommittee will carry out list access or price negotiation which then were considered by the subcommittee. In HTA supporting measures of Thailand ， HTA guidelines include HTA methodology guidelines （ensuring high quality economic evaluation and prom oting standardization of research fr amework）and HTA process guidelines （HTA is strictly regulated from transparency，accountability，inclusiveness，timeliness，quality，consistency，competitiveness）. HTA database include 4 kinds of economic evaluation researches （cost minimization analysis ，cost-benefit analysis ，cost-effectiveness analysis and cost-utility analysis），result evaluation ，quantitative research of life quality ，which supplied reference for research staff. The standard cost list makes the economical evaluation process more accurate and convenient. The selection of essential medicine in China can refer to the relevant experience of Thailand ，gradually establish health technology assessment system ，strengthen international cooperation and personnel training ；introduce the concept of priority ，and reasonably allocate evaluation resources ；formulate HTA guidelines ， improve supporting measures ；emphasize the participation of stakeholders to ensure the standard and transparent selection process ， so as to continuously improve corresponding selection system in China from aspects of the system construction ，resource allocation，supporting measures ，program optimization ，etc.

OBJECTIVE：To provide refe rence for improving the moni toring system of simplified registration system of Chinese classical formulas. METHODS ：A comparative study was conducted on the simplified registration system of traditional herbal medicines in the European Union and Chinese classical formulas from the aspects of regulatory agencies ，regulatory systems ， simplified registration conditions ，simplified registration catalogs and registration data. On the basis of the experience of the simplified registration system of traditional herbal medicines in the European Union ，some suggestions were put forward to improve the simplified registration system of Chinese classical formulas. RESULTS & CONCLUSIONS ：The European Union establishes special committee on traditional herbal medicine for registration and supervision ；has established a complete regulatory system from directives to specific guidelines ；focuses on the history and conditions of the use of traditional herbal medicine ；has published the European Union monographs and European Union list ，which are used as a basis for safety and effectiveness to further reduce or exempt registration data. In China ，National Medical Products Administration and the National Administration of Traditional Chinese Medicine are jointly responsible for the registration and supervision of classical formulas. At present ，the relevant documents to simplify the registration and approval have been issued ，but there is no corresponding implementation rules and guidelines. China also attaches great importance to the clinical experience of classical formulas ，and emphasizes the consistency of preparation methods and dosage forms with ancient classics. Recently ，China has published the Catalogue of Ancient Classic Formula（the First Batch ），including 100 classical formulas ，and the classic formulas in the catalogue can be exempted from relevant registration materials when applying for registration. Our country can learn from the experience of the European Union and combine the actual situation of classic formulas supervision to establish an expert committee ，focus on quality control and risk control to improve registration and supervision system ，optimize the selection conditions of classic formulas ，and explore the classic formulas monographs ， to further stimulate the innovation vitality of traditional Chinese medicine industry.

OBJECTIVE：To improve the willin gness of chinese pharmaceutical enterprises to participate in drug patient assistance programs ，improve the level of drug use and access to innovative drugs in China and fully evaporate the supplementary role of the medical security system. METHODS ：Through grounded theoretical analysis of the interview results ，the theoretical framework of the factors affecting the implementation of drug patient assistance programs by pharmaceutical companies was proposed. The above theoretical framework was empirically studied through questionnaire survey on the personnel who understood or participated in drug patient assistance program in Chinese pharmaceutical enterprises. Based on partial least squares structural equation model ，Smart PLS 3.0 software was used for data processing to analyze the influence of different factors on the willingness of pharmaceutical companies to participate in drug patient assistance programs ，and the relevant suggestions were put forward. RESULTS & CONCLUSIONS ：Economic benefits ，market competition ，social benefits and policy environment have significants impacts on the willingness of pharmaceutical enterprises to implement drug patient assistance programs. The path coefficients were 0.244 （P＜0.01），0.236 （P＜0.01），0.235 （P＜0.05），0.228 （P＜0.01）. Human resource efficiency and cooperation unit have no significant effects on the willingness of pharmaceutical enterprises to implement drug patient assistance programs（P＞0.05）. Economic benefits are in line with the nature of enterprises ’profit-making and have the most close influence. Therefore，the pricing strategy of drugs and the tax policies of government departments are very important for enterprises. Participation in market competition is also an important factor for enterprises to participate in patient assistance programs. The earlier the implementation of patient assistance ，the more opportunities of relevant drugs will be to seize more markets. The social benefits manifest as reducing the economic burden of patients ，improving the quality of life ，and promoting the social and economic development. At the same time ，enterprises have set up good social image and forms a word-of-mouth effect. The policy environment generally includes the legal environment and medical insurance policies. The legal provisions restrict the donations of pharmaceutical enterprises to a certain extent ，but corresponding regulatory measures are still essential. Medical insurance policies are closely related to the establishment and adjustment of patient assistance programs ，and the connection between medical insurance access and patient assistance programs needs to be further improved. Therefore ，from the perspective of enterprises ，it is recommended to establish a cost and benefit calculation system for drug patient assistance programs ，and broaden the publicity channels and increase the publicity intensity of patient assistance programs. From the perspective of the government ，it is recommended that tax incentives for donations should be increased，the patient assistance supervision system should be improved ，the access and adjustment rules for the drugs of patient assistance programs in medical insurance list should be clarified ，so as to promote pharmaceutical enterprises to actively participate in patient assistance programs and improve the drug use level and drug accessibility of patients.

The oral microbiota is associated with oral diseases and digestive systemic diseases. Nevertheless, the causal relationship between them has not been completely elucidated, and colonisation of the gut by oral bacteria is not clear due to the limitations of existing research models. The aim of this study was to develop a human oral microbiota-associated (HOMA) mouse model and to investigate the ecological invasion into the gut. By transplanting human saliva into germ-free (GF) mice, a HOMA mouse model was first constructed. 16S rRNA gene sequencing was used to reveal the biogeography of oral bacteria along the cephalocaudal axis of the digestive tract. In the HOMA mice, 84.78% of the detected genus-level taxa were specific to the donor. Principal component analysis (PCA) revealed that the donor oral microbiota clustered with those of the HOMA mice and were distinct from those of specific pathogen-free (SPF) mice. In HOMA mice, OTU counts decreased from the stomach and small intestine to the distal gut. The distal gut was dominated by Streptococcus, Veillonella, Haemophilus, Fusobacterium, Trichococcus and Actinomyces. HOMA mice and human microbiota-associated (HMA) mice along with the GF mice were then cohoused. Microbial communities of cohoused mice clustered together and were significantly separated from those of HOMA mice and HMA mice. The Source Tracker analysis and network analysis revealed more significant ecological invasion from oral bacteria in the small intestines, compared to the distal gut, of cohoused mice. In conclusion, a HOMA mouse model was successfully established. By overcoming the physical and microbial barrier, oral bacteria colonised the gut and profiled the gut microbiota, especially in the small intestine.
Animals ; Bacteria ; Gastrointestinal Microbiome ; Germ-Free Life ; Humans ; Mice ; Microbiota ; RNA, Ribosomal, 16S

ObjectiveTo explore the relationship among 14 kinds of intolerant food by using association rules to provide evidence for more reasonable diet intake.Methods A total of 2962 adults who received medical examination at the First Affiliated Hospital of China Medical University during January 2008 and June 2010 were enrolled in this investigation.ELISA was used to detect allergen-specific IgG antibody of 14 kinds of food.An association rules model was established by SPSS Clementinel2.0.In order to find positive intolerance association rules,food frequency was recorded with SPSS 16.0.Results Five most commonly seen food intolerance were eggs,crabs,shrimp,milk,and cod (positive rates were 32.5％,26.0％,19.8％,13.8％ and 12.0％,respectively).Positive association rules were found in crab and shrimp,or milk and eggs.Single order association was found in female,while multi-order association was identified in male.Conclusions Our data show a strong positive association among animal foods.Female may be affected by milk,eggs and seafood,while male may be affected by a variety of foods.

Objective To evaluate food intolerance sensitivity among 2962 health check-up receivers from the First Hospital of China Medical University.Methods Serum samples of 2962 adults were collected from January 2008 to June 2010.Serum allergen-specific IgG antibodies of 14 kinds of food were detected by ELISA.The data were analyzed by using One-way analysis of variance.Results In this study,the rate of food intolerance was 0.4%(mushrooms) to 38.0%(eggs).Higher rates of food intolerance were found in egg,crab,shrimp,milk,and cod fish(Eggs 32.5%,crabs 26.0%,shrimps 19.8%,milk 13.8%,and cod fish 12.0% respectively).However,wheat,pork,and mushroom showed relatively lower rates of food intolerance(Wheat 0.8%,pork 0.4%,and mushrooms1.4% respectively).Positive reaction to food intolerance was even stronger in women(9.4% versus 8.2%).Conclusion It is discovered by study that in general population,the diversity of intolerance among different food is associated with 4 factors: gender; age; feature of food; individual diversity.It is recommended that the status of intolerance to food in the general population be investigated by health management.

Objective To evaluate the efficiency of second trimester screenings for Down syndrome using alpha-fetoprotein and β-human chorionic gonadotropin duplex.MethodsPregnant women of south Zhejiang were screened for Down syndrome fetuses by maternal alpha-fetoprotein and β-human chorionic gonadotropin duplex during second trimester.The high-risk women underwent prenatal diagnosis by amniocentesis,cell culture and chromosome analysis.The newborns followed up by the maternal and child tertiary health care network and suspected to have Down syndrome were diagnosed by peripheral blood chromosome analysis.Statistical analysis was performed using two-sample t test and x2 test.Risk probability of Down Syndrome was calculated by random screening software. Results From Oct.2007 to May 2009,1130 of 32 188 singleton pregnant women in second trimester received prenatal screening were discovered with high risk(≥1 ∶ 270).Prenatal diagnosis was performed in 90.79％ cases (1026/1130) of high risk women and seven fetuses were diagnosed as Down syndrome by amniotic fluid chromosome analysis,and the pregnancies were terminated.Among the other 104 cases without prenatal diagnosis one Down syndrome baby was delivered.Six of 31 058 pregnancy women with low risk delivered Down syndrome babies with the incidence of Down syndrome of 0.19‰ (6/31 058).Detection rate of second trimester screenings for Down syndrome using alpha-fetoprotein and β-human chorionic gonadotropin duplex was 57.14％(8/14).False positive rate was 3.48％ (1122/32 188).Positive predictive value was 7.08‰(8/1130).During the same period,there were 23 813 pregnant women who didn't receive screening and 15 fetuses with Down syndrome were diagnosed after birth.There was no statistical difference in the prevalence rate of Down syndrome between those pregnant women who received prenatal screening or not [0.43‰ (14/32 188) vs 0.63‰ (15/23 813),x2 =1.004,P＞0.05].The prevalence of Down syndrome was 0.52‰ (29/56 001) in this area. ConclusionsThe prenatal screening and diagnosis could reduce the birth rate of Down syndrome patients.However,detection rate,false positive rate and positive predictive value of which were lower than reports in other studies.It's possible that the reference data might be not suitable for Chinese.