Since its establishment in 2016, the National Rare Diseases Registry System of China (NRDRS) has accumulated valuable case data and bio-specimen for basic and clinical research on rare diseases in China. However, the emerging challenges in clinical diagnosis and treatment of rare diseases make it unable for data and resource platform to fully meet the diversified needs. Under this backdrop, we have developed a protocol to optimize and upgrade the system based on the core functions of the NRDRS platform. The goal is to leverage intelligent digital technologies to transform NRDRS into a new platform integrating multimodal data and auxiliary diagnostic and treatment functions. It is specified as the development and construction of "one platform and four intelligent tools." Currently, we have upgraded and developed NRDRS platform, intelligent tool for genotype-phenotype analysis of rare diseases, AI-assisted diagnostic tool for rare diseases, remote multidisciplinary diagnosis and teaching tool for rare diseases, drug screening and validation tool for rare diseases. The next step will focus on the promotion of the application of these tools in clinical settings in order to address the issue of severe imbalance in the allocation of resources for the diagnosis and treatment of rare diseases. This article provides an overview of the digital and intelligent upgrades of the NRDRS, the trials in applications in clinical settings, and direction in the future.

OBJECTIVE: To analyze the effectiveness of single three-dimensional (3D)-printed microporous titanium prostheses and flap combined prostheses implantation in the treatment of large segmental infectious bone defects in limbs. METHODS: A retrospective analysis was conducted on the clinical data of 76 patients with large segmental infectious bone defects in limbs who were treated between January 2019 and February 2024 and met the selection criteria. Among them, 51 were male and 25 were female, with an age of (47.7±9.4) years. Of the 76 patients, 51 had no soft tissue defects (single prostheses group), while 25 had associated soft tissue defects (flap combined group). The single prostheses group included 28 cases of tibial bone defects, 11 cases of femoral defects, 5 cases of humeral defects, 4 cases of radial bone defects, and 3 cases of metacarpal, or carpal bone defects, with bone defect length ranging from 3.5 to 28.0 cm. The flap combined group included 3 cases of extensive dorsum of foot soft tissue defects combined with large segmental metatarsal bone defects, 19 cases of lower leg soft tissue defects combined with large segmental tibial bone defects, and 3 cases of hand and forearm soft tissue defects combined with metacarpal, carpal, or radial bone defects, with bone defect length ranging from 3.8 to 32.0 cm and soft tissue defect areas ranging from 8 cm×5 cm to 33 cm×10 cm. In the first stage, vancomycin-loaded bone cement was used to control infection, and flap repair was performed in the flap combined group. In the second stage, 3D-printed microporous titanium prostheses were implanted. Postoperative assessments were performed to evaluate infection control and bone integration, and pain release was evaluated using the visual analogue scale (VAS) score. RESULTS: All patients were followed up postoperatively, with an average follow-up time of (35.2±13.4) months. In the 61 lower limb injury patients, the time of standing, walk with crutches, and fully bear weight were (2.2±0.6), (3.9±1.1), and (5.4±1.1) months, respectively. The VAS score at 1 year postoperatively was significantly lower than preoperative one ( t=-10.678, P<0.001). At 1 year postoperatively, 69 patients (90.8%) showed no complication such as infection, fracture, prosthesis displacement, or breakage, and X-ray films indicated good integration at the prosthesis-bone interface. According to the Paley scoring system for the healing of infectious bone defects, the results were excellent in 37 cases, good in 29 cases, fair in 3 cases, and poor in 7 cases. In the single prostheses group, during the follow-up, there was 1 case each of femoral prostheses fracture, femoral infection, and tibial infection, with a treatment success rate of 94.1% (48/51). In lower limb injury patients, the time of fully bear weight was (5.0±1.0) months. In the flap combined group, during the follow-up, 1 case of tibial fixation prostheses screw fracture occurred, along with 2 cases of recurrent foot infection in diabetic patients and 1 case of tibial infection. The treatment success rate was 84.0% (21/25). The time of fully bear weight in lower limb injury patients was (5.8±1.2) months. The overall infection eradication rate for all patients was 93.4% (71/76). CONCLUSION The use of 3D-printed microporous titanium prostheses, either alone or in combination with flaps, for the treatment of large segmental infectious bone defects in the limbs results in good effectiveness with a low incidence of complications. It is a feasible strategy for the reconstruction of infectious bone defects.
Humans ; Male ; Female ; Middle Aged ; Printing, Three-Dimensional ; Titanium ; Retrospective Studies ; Surgical Flaps ; Adult ; Prosthesis Implantation/methods* ; Plastic Surgery Procedures/methods* ; Treatment Outcome ; Prostheses and Implants ; Bone Diseases, Infectious/surgery* ; Extremities/surgery* ; Prosthesis Design

Objective Compare the tip perfusion index(TPI)with the disappearance of eyelash reflex in guiding the timing of intubation for painless gastroscopy,in order to find the optimal timing for painless gastroscopy.Methods 362 patients who underwent painless gastroscopy from January to June 2024 were selected.According to the random number table method,they were divided into group N(122 cases,direct endoscopic examination after the disappearance of eyelash reflex),group NS(121 cases,endoscopic examination 30 seconds after the disappearance of eyelash reflex),and group E[119 cases,endoscopic examination after continuous increase of TPI(newly measured value>previous measured value more than 3 times)].The changes in heart rate(HR),mean arterial pressure(MAP),and percutaneous arterial oxygen saturation(SpO2)before anesthesia induction(T0),before intubation(T1),through the throat(T2),and after examination(T3)were recorded and compared among the three groups.The intubation waiting time(from the completion of general anesthesia induction to the moment of intubation)and the incidence of adverse reaction were compared among the three groups.Results The waiting time for endoscopy in group N was(5.52±2.17)s,which was significantly shorter than that in group E[(18.60±3.89)s]and group NS[(35.74±2.17)s],and the differences were statistically significant(P<0.01).At T1 time point,the SpO2 of the group E was significantly higher than that of group N and group NS,the differences were statistically significant(P<0.01).There were no statistical difference of SpO2 at T0,T2 and T3 time points among the three groups(P>0.05).There were no statistical differences in HR and MAP at the T0,T1,T2 and T3 time points among the three groups(P>0.05);The MAP and HR of the three groups of patients at time point T0 were significantly higher than those at time points T1,T2 and T3,and the differences were statistically significant(P<0.05).The incidence of lower jaw support in group E was significantly lower than that in group NS and group N,the incidence of body movement and the rate of additional propofol administration were significantly lower than those in group N,the incidence of coughing was significantly lower than that in group NS,and the differences were statistically significant(P<0.05).Conclusion The TPI is a simple,non-invasive,objective,and real-time predictor of the timing of intubation for painless gastroscopy,which is significantly better than guiding the timing of intubation through the eyelash reflex.When the TPI continuously increases from a low point,it is a good time for painless gastroscopy intubation.

Objective Compare the tip perfusion index(TPI)with the disappearance of eyelash reflex in guiding the timing of intubation for painless gastroscopy,in order to find the optimal timing for painless gastroscopy.Methods 362 patients who underwent painless gastroscopy from January to June 2024 were selected.According to the random number table method,they were divided into group N(122 cases,direct endoscopic examination after the disappearance of eyelash reflex),group NS(121 cases,endoscopic examination 30 seconds after the disappearance of eyelash reflex),and group E[119 cases,endoscopic examination after continuous increase of TPI(newly measured value>previous measured value more than 3 times)].The changes in heart rate(HR),mean arterial pressure(MAP),and percutaneous arterial oxygen saturation(SpO2)before anesthesia induction(T0),before intubation(T1),through the throat(T2),and after examination(T3)were recorded and compared among the three groups.The intubation waiting time(from the completion of general anesthesia induction to the moment of intubation)and the incidence of adverse reaction were compared among the three groups.Results The waiting time for endoscopy in group N was(5.52±2.17)s,which was significantly shorter than that in group E[(18.60±3.89)s]and group NS[(35.74±2.17)s],and the differences were statistically significant(P<0.01).At T1 time point,the SpO2 of the group E was significantly higher than that of group N and group NS,the differences were statistically significant(P<0.01).There were no statistical difference of SpO2 at T0,T2 and T3 time points among the three groups(P>0.05).There were no statistical differences in HR and MAP at the T0,T1,T2 and T3 time points among the three groups(P>0.05);The MAP and HR of the three groups of patients at time point T0 were significantly higher than those at time points T1,T2 and T3,and the differences were statistically significant(P<0.05).The incidence of lower jaw support in group E was significantly lower than that in group NS and group N,the incidence of body movement and the rate of additional propofol administration were significantly lower than those in group N,the incidence of coughing was significantly lower than that in group NS,and the differences were statistically significant(P<0.05).Conclusion The TPI is a simple,non-invasive,objective,and real-time predictor of the timing of intubation for painless gastroscopy,which is significantly better than guiding the timing of intubation through the eyelash reflex.When the TPI continuously increases from a low point,it is a good time for painless gastroscopy intubation.

Objective To investigate independent risk factors for unintended initial dissection of the posterior plane(UIDPP)during small incision lenticule extraction(SMILE)by surgeons with different qualifications.Methods A total of 1 600 patients(3 003 eyes)who underwent SMILE performed by three surgeons with different qualifications from April to September 2021 were selected as the research subjects,including 911 males and 689 females,with an average age of(21.82±3.55)years.The incidence of UIDPP in patients was recorded,along with a comprehensive summary of the age,gender,eyes,surgeons,surgical proficiency,subjective refraction,central corneal thickness,lenticule thickness,side cut angle,and peripheral lenticule thickness of the patients.Independent risk factors of UIDPP were analyzed using the binary logistic regression.Test level:α=0.05.Results In this study,the incidence of UIDPP was 6.56％(197/3 003),and the lenticule was successfully removed in all eyes.Multivariate logistic regression analysis demonstrated that surgeon(P=0.035),surgical proficiency(P=0.026),eyes(P=0.007),lenticule thickness(P＜0.001),and peripheral lenticule thick-ness(P＜0.001)were independent risk factors associated with the UIDPP during SMILE surgery.No significant differences were observed in other parameters(all P＞0.05).Conclusion Surgeons,surgical proficiency,eyes,lenticule thick-ness,and peripheral lenticule thickness are independent risk factors of UIDPP.

This review aims to summarize the current evidence on the risk and impact of coronavirus disease 2019 (COVID-19) in patients with inflammatory bowel disease (IBD), and to discuss optimal management of IBD during this outbreak. IBD patients did not have a higher incidence of COVID-19 or more severe disease progression. Multiple factors are associated with an increased risk of COVID-19 infection, increased hospitalization rate, and increased risk of severe COVID-19. Treatment of IBD is not associated with more severe COVID-19, and the association of 5-aminosalicylic acid and thiopurine with increased risk of COVID-19 is controversial. Treatment regiments for IBD patients with different categories and levels of disease need to be adjusted during the epidemic. COVID-19 vaccine is effective and safe for patients with IBD.

This review aims to summarize the current evidence on the risk and impact of coronavirus disease 2019 (COVID-19) in patients with inflammatory bowel disease (IBD), and to discuss optimal management of IBD during this outbreak. IBD patients did not have a higher incidence of COVID-19 or more severe disease progression. Multiple factors are associated with an increased risk of COVID-19 infection, increased hospitalization rate, and increased risk of severe COVID-19. Treatment of IBD is not associated with more severe COVID-19, and the association of 5-aminosalicylic acid and thiopurine with increased risk of COVID-19 is controversial. Treatment regiments for IBD patients with different categories and levels of disease need to be adjusted during the epidemic. COVID-19 vaccine is effective and safe for patients with IBD.

Rare diseases have been a major challenge for clinical medicine and public health challenge in China. One of the effective measures is to conduct proactive research on rare diseases to deal with the disease burden of the diseases. However, low prevalence, disperse distribution of patients, lack of knowledge about the disease course, and phenotype heterogeneity hamper the development of research for rare diseases. Recently, it has been found that patients registry is effective in understanding the course of the disease and accu- mulating the cases and data of clinical research or clinical trial design. At present, most of developed countries or regions in the world have promoted clinical research and clinical trials of new medications on rare diseases by using the registration of rare disease. In 2016, Peking Union Medical College Hospital established China's first registry system at the national level-National Rare Disease Registry System of China(NRDRS). NRDRS has accumulated 68 137 cases data registered by the researchers from China's 101 collaborating hospitals in 29 provinces/municipalities/autonomous regions, covering 171 different, and forming 188 cohorts. To date, NRDRS complete the initial stage of resources buildup.Nex stage will be focused on clinical research and clinical trials related to rare diseases based on NRDRS. This article is on the process of building NRDRS, the potential support for conducting clinical research and clinical trials related to rare diseases, and the challenges will be faced.

Objective:To explore the influencing factors of chronic atrophic gastritis (CAG) with peripheral neuropathy.Methods:Patients with CAG in Zhoupu Hospital Affiliated to Shanghai University of Medical&Health Science from October 2015 to October 2018 were prospectively selected and divided into peripheral neuropathy group (149 cases) and no peripheral neuropathy group (398 cases). Serum creatinine, serum gastrin, vitaminA, vitaminB1, vitaminB6, vitaminB9 (folic acid), vitaminB12, vitaminE, Serum 25 hydroxyvitamin D3(25(OH)D3) and helicobacter pylori (HP) were measured.The peripheral nerve conduction velocity was detected before and after the treatment.The influencing factors of CAG with peripheral neuropathy were analyzed, and the correlation between potential vitamin content and peripheral nerve conduction velocity was analyzed.One way ANOVA was used to assess changes in patients after treatment.Results:Folic acid ( OR=0.412, 95% CI 0.280-0.607, P<0.001), vitamin B12 ( OR=0.974, 95% CI=0.968-0.979, P<0.001) and 25(OH)D3 ( OR=0.759, 95% CI=0.711-0.810, P<0.001) were the independent protection factors of CAG with peripheral neuropathy.The motor nerve conduction velocity of the median nerve was positive related with serum folic acid ( r=0.443, P=0.019), vitamin B12 ( r=0.482, P=0.028) and 25(OH)D3 level ( r=0.331, P=0.020). After treatment, serum folic acid ( F=5.013, P=0.028), vitamin B12 ( F=6.051, P=0.016) and 25(OH)D3 levels ( F=5.630, P=0.020) gradually increased, the motor nerve conduction velocity of median nerve ( F=8.336, P=0.005) also gradually increased. Conclusion:Vitamin B12, folic acid and vitamin D are protective factors for CAG patients with peripheral neuropathy.

Cell death plays important roles in living organisms and is a hallmark of numerous disorders such as cardiovascular diseases, sepsis and acute pancreatitis. Moreover, cell death also plays a pivotal role in the treatment of certain diseases, for example, cancer. Noninvasive visualization of cell death contributes to gained insight into diseases, development of individualized treatment plans, evaluation of treatment responses, and prediction of patient prognosis. On the other hand, cell death can also be targeted for the treatment of diseases. Although there are many ways for a cell to die, only apoptosis and necrosis have been extensively studied in terms of cell death related theranostics. This review mainly focuses on molecular imaging and therapeutic strategies directed against necrosis. Necrosis shares common morphological characteristics including the rupture of cell membrane integrity and release of cellular contents, which provide potential biomarkers for visualization of necrosis and necrosis targeted therapy. In the present review, we summarize the updated joint efforts to develop molecular imaging probes and therapeutic strategies targeting the biomarkers exposed by necrotic cells. Moreover, we also discuss the challenges in developing necrosis imaging probes and propose several biomarkers of necrosis that deserve to be explored in future imaging and therapy research.