In recent years, the rapid development of digital intelligence has provided a new path for rare disease data sharing and injected new power into the progress of research of rare diseases. This research is aimed at summarizing and consolidating relevant literatures on data sharing driven by digital intelligence (DI) in China and abroad, and constructing a local theoretical framework of DI-driven data sharing for rare diseases based on the status of rare diseases in China. Searching PubMed, EMbase, Cochrane, CNKI, Wanfang, and VIP database, we obtain a total of 214 representative literatures. Through literature review, we find that DI technologies have played important roles in different aspects of rare disease data sharing. China, the United States, and Europe have formed their own DI-driven data sharing systems for rare disease. From the theory of " Information Commons", we analyze the gap between China′s current situation and the goal of a " Rare Disease Data Commons". Based on the analysis, we put forward the idea of framework of " DI-STARS". China should develop the Data Sharing system making DI as the core of the system. Meanwhile, China should strengthen the data standardization system, create an innovation-encouraging environment, and build a bridge between different platforms. Using the DI-STARS theory, China will be able to build the " Rare Disease Data Commons" so that the diagnosis and treatment of rare diseases will be enhanced in China to meet the patients′ needs.

The diagnosis and treatment resources for rare diseases in China are highly imbalanced. The basic diagnosis and treatment capabilities are weak, the diagnosis period for patients is long, and the rates of missed diagnosis and misdiagnosis are relatively high. The establishment of a hierarchical diagnosis and treatment system is the inevitable approach to enhancing the diagnosis and treatment standards of rare diseases. Currently, the implementation of the domestic hierarchical diagnosis and treatment system for rare diseases still confronts numerous challenges, such as ambiguous referral standards and processes of primary medical institutions, and ineffective information interaction among institutions at all levels. Thus, it is essential to facilitate high-level information construction for the hierarchical diagnosis and treatment of rare diseases. This paper explores the process of constructing a multidisciplinary joint remote diagnosis and treatment platform and a health management platform through informatization, with the hope of establishing two closed loops of digital diagnosis and treatment services and health follow-up management for patients with rare diseases, as well as achieving timely diagnosis and lifelong health management for patients. It integrates and optimizes auxiliary diagnostic tools, promotes the rapid dissemination of rare disease diagnosis and treatment experiences to the grassroots, enhances the information construction level of the hierarchical diagnosis and treatment system, and endeavors to address the practical predicament of weak diagnosis and treatment capabilities of rare diseases in grassroots medical institutions. Additionally, this paper proposes an essential approach for multi-dimensional independent innovation to guide the popularization of efficient and high-quality rare disease diagnosis and treatment services. By encompassing innovating the rare disease diagnosis and treatment collaboration network and multidisciplinary diagnosis and treatment model, facilitating the application of the latest biomedical and informatics technologies to the grassroots, and constructing a national intelligent data platform for rare disease innovation, a new model for rare disease services with Chinese characteristics will be established. This will significantly enhance the medical treatment level of rare diseases in China and strive for more benefits for patients.

With completing a baseline survey of a large natural population cohort, conducting regular follow-up has become a key factor in further improving the quality of cohort construction and ensuring its sustainable development. Typical cohort follow-up methods include repeat surveys, routine monitoring, and community-oriented surveillance. However, in practical applications, there are often issues such as high costs, difficulty, and high error rates. Telephone follow-up is an important supplementary method to the methods mentioned above, as it has the characteristics of low cost, fast response, and high quality. However, the with difficult organization, quality control is challenging, response rates are low, and management levels vary widely, which limits its widespread use in large-scale population cohort studies. Given the above problems, this study draws on customer relationship management based on the actual needs of the China Northwest Cohort follow-up. It relies on the REDCap electronic data collection platform to build a telephone follow-up management and quality control system. Targeted solutions are provided for key issues in telephone follow-up implementation, including organizational structure, project management, data collection, and process quality control, to improve the quality control level of telephone follow-up comprehensively and thereby enhance the quality and efficiency of follow-up. We hope to provide standardized follow-up programs and efficient quality control tools for newly established and existing cohort studies.

It is noteworthy that only 5% of more than 7000 described rare diseases are treated. In the era of big data, there is ever-increasing data for understanding biomedicine. The need for efficient and rapid data collection, analyses and characterization methods is pressing. Rare diseases can particularly benefit from artificial intelligence (AI) application. AI, with an emphasis on machine learning, creates a path for such efforts and is being applied to diagnosis and treatment. AI has demonstrated its potential to learn and analyze data from different sources with results in prediction。Presently, there are AI-driven technologies applied for rare diseases and this review aims to summarize these advances. Moreover, this review scrutinizes the limitation and identifies the pitfalls of AI applications in the diagnosis and treatment of rare diseases.

Objective:To compare the therapeutic outcomes between use of antibiotic cement versus non-use of antibiotic cement in the treatment of tibial osteomyelitis after radical debridement.Methods:A retrospective analysis was made of the 68 patients with local tibial osteomyelitis of Cierny-Mader Type Ⅳ who had been treated at Department of Orthopaedic Trauma, The Second People’s Hospital of Shenzhen from January 2010 to June 2015. The dead space was filled with antibiotic-impregnated bone cement beans after radical debridement of the infected bone in 32 of them (cement group) but was not in 36 of them (no-cement group). The operations for both groups were performed by the same surgical team who filled the bone defects after excision of infected bone using Ilizarov bone transport. The 2 groups were compared in terms of Paley functional scores of bone and limb, external fixation index (EFI), infection recurrence rate, total hospital costs and other complications.Results:The 2 groups were comparable because there was no significant difference between them in the preoperative general data ( P>0.05). The cement group was followed up for (71.2±8.9) months and the no-cement group for (71.6±9.7) months, showing no significant difference ( P>0.05). By the Paley functional scores, the good to excellent rate for bone was 100% for both groups (32/32 versus 36/36) while the good to excellent rate for limb was 93.8% (30/32) for the cement group and 94.4% (34/36) for the no-cement group, showing no significant differences between them ( P>0.05). The EFI was (49.0±10.5) d/cm for the cement group and (49.5±11.4) d/cm for the no-cement group, showing no significant differences between them ( P>0.05). The infection recurrence rate at the final follow-up was 3.12% (1/32) for the cement group and 2.78% (1/36) for the no-cement group, showing no significant differences between them ( P>0.05). The total hospital cost was (70,944.1 ± 1,135.5) Yuan RMB for the cement group and (55,205.2 ± 897.3) Yuan RMB for the no-cement group, showing a significant difference ( P<0.05). No serious complications with sequelae were found in either of the 2 groups. Conclusion:In the treatment of local tibial osteomyelitis of Cierny-Mader Type Ⅳ, it is not necessary to fill the dead space with antibiotic cement when radical debridement is achieved.

Objective The aim of this study was to investigate the effect of Ca2+ /calmodulin - dependent kinase II (CaMKII)γ RNA interference on the expression of nuclear factor of activated T-cells cytoplasmic 1(NFATc1),tyrosine kinase(c-Src)and tartrate resistant acid phosphatase(TRAP)genes,and its role and molecular mechanism in osteoclast differentiation. Methods The CaMKII γ RNA interference vector was constructed by lentivirus and transfected into RAW264. 7 cells. The experiment was di-vided into three groups:A,B and C,which were the control group,negative vector group and interference vector group. After transfec-tion for 12 hours,osteoclasts induced by 50 ng/mL RANKL and the cells were harvested after induction for 5 days. Real-time quanti-tative PCR,Western blot and immunofluorescence were used to detect the expression of NFATc1,TRAP and c-Src genes in three groups. Results The mRNA levels of NFATc1,TRAP and c-Src in the group C decreased by 49. 86% ,43. 65% and 53. 57% ,re-spectively(P<0. 001),and the protein levels decreased by 54. 22% ,46. 75% and 45. 86% ,respectively(P<0. 001). There was no significant difference between the A and the B groups(P>0. 05). The fluorescence intensity of the above genes in the group C was significantly weaker than that in the A and B groups,and the formation of osteoclasts was significantly less than that in the A and B groups. Conclusion CaMKIIγ RNA interference significantly inhibited the expression of NFATc1,TRAP and c-Src genes,sugges-ting that CaMKIIγ plays a key regulatory role in osteoclast differentiation.

Objective To explore the prevalence and risk factors of hyperuricemia(HUA) in patients with chronic kidney disease(CKD) on stages 3-5 and to investigate the effect of uric acid on renal function during the past 15 years.Methods Patients with CKD on stages 3-5 who admitted to the Nephrology Department of Affiliated Hospital of Qingdao University from January 2000 to December 2014 were recruited.The prevalence of HUA in patients with CKD on stages 3-5 were analyzed statistically,the risk factors of HUA and the effect of uric acid on the estimated glomerular filtration rate(eGFR) were analyzed by regression analysis.Results (1)The prevalence of HUA was 55.6%,and there was no significant difference between male and female in the 3 547 patients who met the inclusion criteria(χ2=0.184,P=0.683).The prevalence of HUA for CKD on stage 3,4,5 was 42.6%,59.1%,61.2%,respectively.(2)The independent risk factors of HUA in patients with CKD on stages 3-5 were hypertension(OR:1.209(95%CI:1.002-1.458)),increased BMI(OR:1.039(95%CI:1.015-1.062)),increased total cholesterol(OR:1.411(95%CI:1.274-1.564)),increased CKD stage(OR:1.891(95%CI:1.515-2.359),OR:1.898(95%CI:1.481-2.431)) and decreased HDL-C(OR:0.178(95%CI:0.134-0.238))(P<0.05).(3)In patients with CKD on stages 3-5,multiple regression analysis showed that after adjusting for confounding factors,each 100 mol/L-higher uric acid at baseline led to a change in the rate of the baseline eGFR decline of 1.49 ml.min-1.(1.73 m2)-1[95% CI:-2.20--1.05).(4)In 348 hyperuricemic patients with CKD on stage 3,Logistic regression analysis showed that persistent HUA was associated with a higher risk for eGFR decreasing more than 10 ml/min/(1.73 m2) 1 year later(hazard ratio(HR)=2.645,95%CI:1.388-5.039,P=0.003).Conclusion The prevalence of HUA in patients with CKD stages 3-5 is high.Hypertension,hyperlipidemia and overweight are risk factors of HUA.HUA is an independent risk factor for renal function deterioration.

Objective To study the effect of zoledronate (ZOL) on Ca2+/calmodulin-dependent kinase Ⅱ δ (CaMK Ⅱ δ) and down-stream gene expressions during osteoclast differentiation.Methods Mouse osteoclast precursors RAW264.7 cells were divided into the control group and ZOL group.The cells in both groups were induced with 50μg/L receptor activator of nuclear factor kappa B ligand (RANKL) and were harvested on 5 d,while the cells in ZOL group were also simultaneously treated with 1 × 10-6 mol/L ZOL for 2 d.Five days later,the cells were harvested and examined osteoclastogenesis,as well as gene expressions of CaMK Ⅱ δ,nuclear factor of activated T-cells cytoplasmic 1 (NFATc1),tartrate-resistant acid phosphatase (TRAP) and cell-sarcoma receptor coactivator (c-Src).Results The number of TRAP positive multinuclear osteoclasts,number and size of dentin absorption lacunae and area in the ZOL group were (20.0±3.2),(18.0±4.2) and (6 335.3± 1 043.2)μm2 respectively,which were significantly lower than (36.0 ± 8.4),(37.2 ± 5.0) and (11 636.2 ± 3 661.1) μm2 in the control group and decreased by 44.4 ％,51.6 ％ and 45.6 ％ respectively (P＜0.01).ZOL also significantly inhibited the gene expressions of CaMK Ⅱ δ,NFATc1,TRAP and c-Src,and the mRNA levels of these genes were decreased by 44.1％,49.0％,53.8％ and 49.6％ respectively,the protein level were decreased by 43.5 ％,32.2 ％,45.5 ％ and 48.0 ％ respectively.The immunofluorescent cytochemistry detection results showed the fluorescence intensity of CaMK Ⅱ δ,NFATc1,TRAP and c-Srcin in the ZOL group was significantly weakened when compared with the control group.Conclusion ZOL could significantly inhibit the osteoclast formation and bone absorption function,and down-regulates gene expressions of CaMK Ⅱ δ,NFATc1,TRAP and c-Src in osteoclast differentiation.

Objective To evaluate the effects of renin-angiotensin system (RAS) blockades [angiotensin-converting enzyme inhibitors (ACEI) and angiotensin Ⅱ type 1 receptor blockers (ARB)]on contrast-induced nephropathy (CIN) in patients undergoing angiography.Methods Pubmed,Embase,Cochrane library,Wanfang database and CNKI were searched.The literature limited range was from their start year to July 2015.Randomized controlled trials (RCTs) and non-randomized controlled trials of renin-angiotensin system blockades in influencing CIN were assessed.Two investigators extracted data and performed quality analysis independently from all trims included.Rev man 5.3 software was used.Results 16 trials with a total of 15 897 patients were identified.There were 7490 patients who received renin-angiotensin system blockades and 8407 patients in control group.The meta analysis revealed a higher CIN incidence in ACEI/ARB group than that in control group (14.35％ vs 12.13％,P=0.04,OR=1.44,95％CI 1.01-2.04).For patients with renal insufficiency,ACEI/ARB group had a higher CIN incidence than control group (12.23％ vs 7.32％,P=0.02,OR=1.80,95％CI 1.10-2.94),and the serum creatinine changes in ACEI/ARB group were higher than those in control group.There was statistical difference in serum creatinine changes between groups (P=0.02,MD=0.08,95％CI 0.02-0.15).Conclusions Renin-angiotensin system blockades can increase theincidence of CIN in patients undergoing angiography.Renin-angiotensin system blockades can contribute to CIN for patients with renal insufficiency.

[ ABSTRACT] AIM:To study the expression profiles and the role of Ca 2+/calmodulin-dependent kinase II delta ( CaMKIIδ) during osteoclast differentiation .METHODS:Mouse RAW264.7 cells were induced by receptor activator of nuclear factor κB ligand ( RANKL) at 50μg/L for osteoclastogenesis .Tartrate-resistant acid phosphatase ( TRAP) staining and bone resorption lacunae examination were performed to verify osteoclast formation .The expression of CaMKIIδat mR-NA and protein levels was also determined by immunofluorescent cytochemistry , RT-qPCR and Western blot at days 0, 1, 3 and 5.RESULTS:TRAP positive multinuclear cells with bone resorption function were formed after 5 d of induction. The mRNA levels of CaMKIIδdetected by RT-qPCR were 1.028 ±0.041, 2.478 ±0.087, 10.524 ±1.284 and 42.914 ± 2.667 at days 0, 1, 3 and 5, respectively, while the protein levels of CaMKIIδ detected by Western blot were 0.762, 0.963, 1.802 and 3.136, respectively.The changes of protein level were also verified by immunofluorescence cytochemis -try, in which the fluorescence intensity increased in a time-dependent manner (P<0.05).CONCLUSION:The expres-sion of CaMKIIδincreases with the differentiation of osteoclasts .CaMKIIδmay play a key role in the osteoclastogenesis .