Clinical research on rare diseases has always faced multiple challenges in clinical research design and implementation due to small sample sizes of patients,high heterogeneity,and limited research resources.The rapid development of digital intelligence technology has provided innovative solutions for rare disease research.This article systematically explores the current status and response strategies of clinical research on rare diseases in the digital intelligence age.On the one hand,the efficiency of rare disease research has been optimized through adaptive design,mixed trial mode,and precision medicine stratification methods.On the other hand,solutions based on digital technology have been proposed to address the practical challenges of recruitment difficulties and underrepresentation of rare disease clinical research patients,data management and technical barriers,and insufficient coverage of natural medical history and baseline databases through digital intelligence technology.By combining international collaboration,intelligent screening,and remote experiments,a multidisciplinary collaboration and international cooperation,adaptive design,digital data platform,and patient-centered remote research model have been constructed as the core implementation strategies.Typical cases demonstrate that digital intelligence technology not only effectively shortens the drug development cycle,but also significantly enhances patient benefits,providing a replicable practical paradigm for global rare disease research.The practice of digital platforms represented by the International Rare Disease Research Alliance and the China Rare Disease Diagnosis and Treatment Collaboration Network has further verified the feasibility and promotional value of the digitalization path.In summary,digital intelligence technology has shown considerable promise in overcoming the clinical research challenges of rare diseases and accelerating the development of treatment plans,providing systematic references for researchers,regulatory agencies,and patient organizations.It is expected to drive the clinical research of rare diseases towards a more efficient and accurate future.

Objective To investigate the effects of circular RNA APLP2(circAPLP2)on the proliferation,migra-tion,and invasion of human colorectal cancer(CRC)cell lines by regulating microRNA-455-3p(miR-455-3p)/Stathmin1(STMN1)axis.Methods RT-qPCR was used to detect the expression of circAPLP2,miR-455-3p and STMN1 in CRC and normal colorectal cell lines and the optimal cell line was screened.Proliferation,migra-tion and invasion were detected by MTT assay,scratch assay and Transwell assay,respectively.The relationship between circAPLP2 and miR-455-3p,between miR-455-3p and STMN1 was confirmed by dual Lucifer's reporter gene assay.Results CircAPLP2 and STMN1 were highly expressed in CRC cells,miR-455-3p showed a low ex-pression.Knocking down circAPLP2 resulted in a decrease in rate of survival and of scratch healing rate and in-vasion of SW620 cells,An up regulation of miR-455-3p expression,a down regulation of STMN1,cyclin D1,N-cadherin protein expression and an up regulation of E-cadherin protein expression were also found(P<0.05).Inhibition of miR-455-3p expression reversed inhibitory effect of knocking down circAPLP2 on SW620 cell prolif-eration,migration,and invasion,up-regulated the STMN1,cyclin D1 and N-cadherin protein expression,and down-regulation of E-cadherin protein expression(P<0.05).Dual luciferase reporter gene assay showed that circAPLP2 targeted at negative regulation of miR-455-3p expression,while miR-455-3p targeted at negative reg-ulation of STMN1 expression.Nude mouse transplantation experiment found that knocking down circAPLP2 affect-ed the growth of transplanted tumors,while miR-455-3p expression was up-regulated and STMN1 expression was down-regulated(P<0.05).Conclusions CircAPLP2 inhibits the proliferation,migration and invasion of colorectal cancer cell lines by regulating the miR-455-3p/STMN1 axis.

Colorectal cancer is one of the common malignant tumor in China. However, cases of colorectal cancer with synchronous bone marrow metastasis are extremely rare in clinical practice, and there are few reports on its treatment worldwide. Due to the destructed hematopoietic function caused by tumor cells occupying the bone marrow, the efficacy of chemotherapy, targeted therapy and immunotherapy is very poor. As a result, colorectal cancer with bone marrow metastasis has a very high mortality and very short survival, resulting in a very poor prognosis. The authors review the epidemiology, etiology, pathogenesis, clinical features, diagnosis methods, treatment options and prognosis of this disease.

Clinical research on rare diseases has always faced multiple challenges in clinical research design and implementation due to small sample sizes of patients,high heterogeneity,and limited research resources.The rapid development of digital intelligence technology has provided innovative solutions for rare disease research.This article systematically explores the current status and response strategies of clinical research on rare diseases in the digital intelligence age.On the one hand,the efficiency of rare disease research has been optimized through adaptive design,mixed trial mode,and precision medicine stratification methods.On the other hand,solutions based on digital technology have been proposed to address the practical challenges of recruitment difficulties and underrepresentation of rare disease clinical research patients,data management and technical barriers,and insufficient coverage of natural medical history and baseline databases through digital intelligence technology.By combining international collaboration,intelligent screening,and remote experiments,a multidisciplinary collaboration and international cooperation,adaptive design,digital data platform,and patient-centered remote research model have been constructed as the core implementation strategies.Typical cases demonstrate that digital intelligence technology not only effectively shortens the drug development cycle,but also significantly enhances patient benefits,providing a replicable practical paradigm for global rare disease research.The practice of digital platforms represented by the International Rare Disease Research Alliance and the China Rare Disease Diagnosis and Treatment Collaboration Network has further verified the feasibility and promotional value of the digitalization path.In summary,digital intelligence technology has shown considerable promise in overcoming the clinical research challenges of rare diseases and accelerating the development of treatment plans,providing systematic references for researchers,regulatory agencies,and patient organizations.It is expected to drive the clinical research of rare diseases towards a more efficient and accurate future.

Colorectal cancer is one of the common malignant tumor in China. However, cases of colorectal cancer with synchronous bone marrow metastasis are extremely rare in clinical practice, and there are few reports on its treatment worldwide. Due to the destructed hematopoietic function caused by tumor cells occupying the bone marrow, the efficacy of chemotherapy, targeted therapy and immunotherapy is very poor. As a result, colorectal cancer with bone marrow metastasis has a very high mortality and very short survival, resulting in a very poor prognosis. The authors review the epidemiology, etiology, pathogenesis, clinical features, diagnosis methods, treatment options and prognosis of this disease.

Betacoronavirus ; Coronavirus Infections ; Humans ; Pandemics ; Pneumonia, Viral ; Single-Cell Analysis

OBJECTIVETo study the influence of SGHWJN particles on inflammation and the mediators of inflammation in esophageal tissues of rat with reflux esophagitis.

METHODFifty SD rats were randomly divided into 5 groups, namely, a control group, a sham-operated group, a model group, a SGHWJN particles group and a PPI group. Reflux esophagitis was induced by adopting partial pyloric ligation plus cardiomyotomy. One week later, the rats were orally administered twice daily for 28 days. Pathological changes of esophagus mucous membrane were evaluated by using HE staining and Harry S. Cooper's method in every groups. MDA and SOD contents in esophageal tissues were measured by colorimetric method. Expression of TNF-alpha in esophageal tissues were examined by real-time fluorescent quantitative reverse transcriptase polymerase chain reaction (RT-FQ-PCR) with SYBR Green.

RESULTModel group, esophageal inflammation scores, expression of TNF-alpha in esophageal tissues and MDA contents compared with the normal group and sham operation group were significantly higher (P < 0.05). SOD contents in the esophageal tissues of the model group was significantly lower than that of control group and sham-operated group (P < 0.05). SGHWJN particles group and PPI group of esophageal tissue inflammation scores, expression of TNF-a in esophageal tissues and MDA levels than those in model group decreased significantly (P < 0.05). SOD content was significantly higher than that of model group (P < 0.05), SGHWJN particles group and PPI group showed no statistically significant difference between the above-mentioned indicators. The above-mentioned indicators showed no statistically significant difference between the normal group and sham-operated group. MDA content and expression of TNF-alpha in esophageal tissue was positively correlated with inflammatory scores of model group (r = 0.813). Model group esophageal tissue SOD content and inflammation scores were negatively correlated (r = -0.847). Esophageal tissue SOD levels were negatively correlated with MDA levels (r = -0.863).

CONCLUSIONSGHWJN particles can effectively inhibit inflammation in rat with reflux esophagitis through regulating TNF-alpha, SOD and MDA.

Animals ; Disease Models, Animal ; Drugs, Chinese Herbal ; administration & dosage ; Esophagitis, Peptic ; drug therapy ; genetics ; immunology ; Esophagus ; drug effects ; immunology ; Female ; Gene Expression ; drug effects ; Humans ; Inflammation Mediators ; immunology ; Male ; Rats ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha ; genetics ; immunology

In light of the situations of overseas education in the 21st century,this paper summarizes the general working guidelines for and concrete measures of the overseas education in military universities from four aspects:tapping the full potentials of the university to carry out comprehensive education;renovating training modes to implement individualized teaching;insisting on being human-centered to show the theme of friendship;exerting great efforts to develop a first-rate overseas training base.

Objective To detect the expressions of interleukin-17(IL-17) and interleukin-23(IL-23) in esophageal tissues of rats with reflux esophagitis(RE) and explore the role of IL-23/IL-17 axis in the pathogenesis of RE.Methods Thirty SD rats were randomly divided into 3 groups,namely,control group,sham-operated group and model group.RE was induced by adopting partial pyloric ligation plus cardiomyotomy.Then rats in each group were fasted for 24 h but had free access to water.They were fed 24 h after operation.Four weeks later,rats were killed and pathological changes of esophagus mucous membrane were observed by HE staining in each group.The expressions of IL-23p19 and IL-17 mRNA in esophageal tissues were examined by real-time fluorescent quantitative reverse transcriptase polymerase chain reaction(RT-FQ-PCR).IL-17 protein content in esophageal tissues was measured by ELISA.Results After four weeks,compared with control group,model group had significant pathological changes of esophagus mucous membrane.Expressions of IL-23p19 and IL-17 mRNA in the esophageal tissues of model group were significantly higher than those of the other two groups;the content of IL-17 protein was significant higher in model group than in the other two groups.There were no significant differences between control group and sham-operated group.Conclusion IL-23/IL-17 axis is an important cellular factor involved in the pathogenesis of RE and may be involved in the chronic inflammation of RE.