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 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.

ObjectiveTo explore the effect of targeted intervention measures based on risk score of venous thromboembolism （VTE）， on the prevention of senile type 2 diabetes inpatients， as well as their influence on the occurrence of venous thromboembolism. MethodsA total of 134 elderly patients with type 2 diabetes mellitus who were hospitalized in geriatrics department of Peking university third hospital during June 1， 2018 to September 30， 2018 were selected as the research subjects. All the patients were divided into control group and observation group according to random number table method， with 67 patients in each group. Patients in the control group were treated with conventional intervention methods， and patients in the observation group were treated with targeted intervention measures based on VTE risk score. After one month of intervention， the Padua score， blood glucose level and coagulation indexes of the two groups were compared. The incidence of thrombosis during the intervention period was also recorded. ResultsThe Padua score in observation group （2.09±2.17） points was significantly lower than that （3.19±2.37） points in control group （P<0.05）. The indexes of fasting blood glucose， 2h postprandial blood glucose and HbA1c in observation group were significantly lower than those in control group （P<0.05）. The fibrinogen， D-dimer， activated partial thromboplastin time and prothrombin time in observation group were significantly lower than those in control group （P<0.05）. The incidence of DVT， PVT， lower limb swelling， pain and abnormal skin color in the observation group were 4.00%， 2.00%， 2.00%， 2.00%， and 0， respectively， and in the control group were 12.00%， 10.00%， 10.00%， 12.00%， and 8.00%， respectively. The incidence of adverse events in observation group was significantly lower than that in control group （P<0.05）. ConclusionTargeted intervention based on VTE risk score can significantly reduce the risk of VTE occurrence， improve blood clotting function and blood glucose level in elderly patients with type 2 diabetes mellitus. This nursing measure has important clinical application value.

OBJECTIVE: To investigate the effectiveness of one-stage total knee arthroplasty (TKA) in the treatment of advanced active knee tuberculosis. METHODS: The clinical data of 38 patients with advanced active knee tuberculosis who received one-stage TKA between January 2011 and December 2020 were retrospectively analyzed. There were 20 males and 18 females. The age ranged from 20 to 84 years, with an average of 52.8 years. The body mass index ranged from 17 to 36 kg/m ², with an average of 23.05 kg/m ². The preoperative C reactive protein (CRP) was (23.49±4.72) mg/L, erythrocyte sedimentation rate (ESR) was (45.95±8.82) mm/1 h. The Hospital for Special Surgery (HSS) score was 48.8±9.1. During the operation, the infected lesions of the knee joint were completely removed, and the operative area was repeatedly soaked with 3% hydrogen peroxide solution and 0.5% povidone iodine solution. The intraoperative pathological examination confirmed the tuberculosis of the knee joint, and systemic anti-tuberculosis treatment was performed. The operation time, postoperative hospitalization stay, postoperative anti-tuberculosis chemotherapy time, and complications were recorded. CRP and ESR were recorded and compared before and after operation. Anteroposterior and lateral X-ray films of the knee joint were taken to evaluate whether the prosthesis had signs of loosening and sinking, and to determine whether there was recurrence of tuberculosis. The knee joint function was evaluated by HSS score. With treatment failure due to any reason as the end event, the survival time of prosthesis was analyzed by Kaplan-Meier survival curve. RESULTS: All operations were successfully completed without fracture, vascular and nerve injury, deep vein thrombosis, and other complications. All incisions healed by first intention after operation. The operation time ranged from 80 to 135 minutes, with an average of 102.76 minutes; postoperative hospitalization stay was 5-16 days, with an average of 9.7 days; the duration of postoperative anti-tuberculosis chemotherapy ranged from 1 to 18 months, and the median duration was 12 months. All 38 cases were followed up 3-133 months (mean, 63.7 months). At last follow-up, CRP was (4.88±1.24) mg/L and ESR was (13.00±2.97) mm/1 h, both of which were significantly lower than those before operation ( t=20.647, P<0.001; t=20.886, P<0.001). During the follow-up, 3 patients (7.89%) had tuberculosis recurrence. Two patients had tuberculosis recurrence due to withdrawal of anti-tuberculosis chemotherapy at 1 and 2 months after operation, respectively. One patient was cured after debridement, preservation of prosthesis and anti-tuberculosis chemotherapy for 12 months, and 1 patient was cured after oral administration of anti-tuberculosis drugs for 12 months. Another 1 patient had recurrent tuberculosis and mixed infection ( Corynebacterium gehreni) at 2 months after operation, and the infection was not controlled after debridement, and finally the thigh was amputated. Except for the patients with recurrent infection, no complications such as prosthesis loosening, periprosthetic fracture, and periprosthetic infection were found. At last follow-up, the HSS score of the knee joint was 86.8±4.8, and the knee joint function significantly improved when compared with that before operation ( t=-31.198, P<0.001). Prosthesis survival time was (122.57±5.77) months [95% CI (111.25, 133.88) months], and the 10-year survival rate was 92.1%. CONCLUSION One-stage TKA combined with postoperative antituberculous chemotherapy in the treatment of advanced active knee tuberculosis can achieve satisfactory infection control and joint function.
Female ; Male ; Humans ; Young Adult ; Adult ; Middle Aged ; Aged ; Aged, 80 and over ; Arthroplasty, Replacement, Knee ; Retrospective Studies ; Knee Joint ; Tuberculosis ; Antitubercular Agents/therapeutic use*

Objective:To investigate the diagnostic value of erythrocyte sedimentation rate/C-reactive protein (ECR), fibrinogen and D-dimer in periprosthetic infection after artificial knee replacement.Methods:A total of 205 patients, including 62 males and 143 females, aged 66.9±9.5 years (range 26-84 years), who underwent revision of artificial knee joint at Department of Joint Surgery, The First Affiliated Hospital of Xinjiang Medical University from January 2017 to December 2021 were retrospectively collected.122 cases of periprosthetic joint infection (PJI), including 43 cases of acute infection; 79 cases of chronic infection (13 cases of chronic infection combined with rheumatoid arthritis were analyzed separately); there were 83 cases without PJI, including 73 cases of aseptic loosening, 8 cases of prosthesis dislocation and 2 cases of joint stiffness. Erythrocyte sedimentation rate, C-reactive protein, white blood cell count, fibrinogen and D-dimer levels were examined before surgery, and the sensitivity and specificity of the indicators were calculated using the receiver operating characteristic (ROC) curve. The diagnostic value of different inflammatory markers was compared according to the area under curve (AUC).Results:The levels of ECR, erythrocyte sedimentation rate, C-reactive protein, fibrinogen, and D-dimer in acute PJI group were 2.47±2.91, 50 (38, 62) mm/1 h, 31.6 (13.9, 79.3) mg/L, 4.25±0.94 g/L, 763 (453, 1 157) ng/ml, respectively. The chronic PJI group was 3.06±2.95, 50 (34, 64) mm/1 h, 20.4(12.7, 43.3) mg/L, 4.19±0.91 g/L, 586 (317, 1 122) ng/ml, and the non-PJI group was 6.20±4.64, 22 (15, 34) mm/1 h, 4.6 (2.7, 7.74) mg/L, 3.10±0.59 g/L and 363 (181, 591)ng/ml were statistically significant ( P<0.05). The AUC of ECR, erythrocyte sedimentation rate, C-reactive protein, fibrinogen, and D-dimer in the acute PJI group were 0.82, 0.85, 0.90, 0.88, and 0.76, respectively.The optimal critical values were 2.89, 37.00 mm/1 h, 13.6 mg/L, 3.86 g/L, and 443.0 ng/ml, respectively, with sensitivity of 76.7%, 79.1%, 76.7%, 69.8%, and 82.4%, and specificity of 79.5%, 78.3%, 94.0%, 94.0%, 90.4%, and 63.8%, respectively. The AUC of ECR, erythrocyte sedimentation rate, C-reactive protein, fibrinogen, D-dimer, and white blood cell count in the chronic PJI group were 0.77, 0.82, 0.87, 0.85, 0.67, and 0.63, respectively. The optimal critical values are 2.91, 33.00 mm/1 h, 10.9 mg/L, 4.01 g/L, 558.5 ng/ml, and 5.575×10 9 /L, respectively, with sensitivity of 68.2%, 78.8%, 81.8%, 63.6%, 57.9%, and 75.8%, and specificity of 79.5%, 73.5%, 88.0%, 95.2%, 72.5%, and 49.4%, respectively. Conclusion:Fibrinogen has a higher diagnostic value for knee joint PJI, followed by ECR, and D-dimer has the lowest diagnostic value for knee joint PJI.

Objective:To investigate the gender differences in serum C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), platelet (PLT), fibrinogen (FIB) and D-dimer for the diagnosis of chronic periprosthetic joint infection (PJI).Methods:A total of 470 patients who underwent revision arthroplasty in the Department of Joint Surgery, First Affiliated Hospital of Xinjiang Medical University from January 2013 to December 2021 were retrospectively analyzed. According to gender and diagnosis, they were divided into four groups: 78 cases of male chronic PJI, 108 cases of male aseptic loosening, 95 cases of female chronic PJI, and 189 cases of female aseptic loosening. The serological results of CRP, ESR, PLT, FIB and D-dimer were collected before operation. The receiver operating characteristics (ROC) curves were used to determine the optimal cut-off values of CRP, ESR, PLT, FIB and D-dimer for the diagnosis of chronic PJI in different genders, and to calculate their sensitivity and specificity. The diagnostic efficacy of the index was analyzed by comparing the area under curve (AUC) of different indicators.Results:The levels of ESR, PLT and D-dimer in the male chronic PJI group were 43 (20.0, 52.5) mm/1 h, 249×10 9 (204×10 9, 306×10 9) /L, 449 (219,833) μg/L, respectively, which were lower than those in the female group of 56 (40, 65) mm/1 h, 295×10 9 (228×10 9, 364×10 9) /L, and 645 (345, 1 157) μg/L, with statistically significant differences ( Z=-4.17, P<0.001; Z=-2.17, P=0.030; Z=-2.82, P=0.005). The AUC of CRP in the male chronic PJI group was 0.841, which was higher than the AUC of the other four indicators; CRP was combined with ESR, PLT, FIB and D-dimer to establish a joint prediction model for male chronic PJI. The ROC curve showed that the combination of CRP+FIB had a maximum AUC [0.849, 95% CI (0.79, 0.91)], sensitivity of 80% and specificity of 86%. The AUC of CRP in the female chronic PJI group was 0.866, which was higher than the AUC of the other four indices; CRP was combined with ESR, PLT, FIB and D-dimer to establish a combined prediction model for female chronic PJI. The ROC curve showed that the combination of CRP+PLT had the maximum AUC [0.883, 95% CI (0.84, 0.93)], sensitivity of 87% and specificity of 79%. Conclusion:Serologic indicators in patients with chronic PJI are gender-specific. CRP combined with FIB has the highest diagnostic value for the chronic PJI in males, while CRP combined with PLT has the highest diagnostic value for the chronic PJI in females.

Objective:To investigate the diagnostic value of plasma fibrinogen (FIB) in chronic periprosthetic joint infection (PJI).Methods:A total of 470 patients who underwent revision hip and knee arthroplasty after primary hip and knee arthroplasty in the First Affiliated Hospital of Xinjiang Medical University from January 2013 to December 2021 were retrospectively analyzed. According to the diagnosis of the disease, 173 patients (112 hips and 61 knees) were divided into chronic PJI group, including 78 males and 96 females, aged 65 (53, 72) years; and 297 patients (216 hips and 81 knees) were divided into aseptic loosening group, including 108 males and 189 females, aged 63 (50, 72) years. The preoperative levels of FIB, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), D-dimer and platelet were compared between the two groups, and the sensitivity and specificity of the diagnosis of chronic PJI were calculated. Receiver operating characteristic (ROC) curves were used to determine the optimal cut-off values of FIB, CRP, ESR, platelet and D-dimer for the diagnosis of chronic PJI. The diagnostic efficacy of each indicator was analyzed by comparing the area under curve (AUC) and using a combined diagnostic test.Results:FIB, CRP, ESR, platelets and D-dimer in the chronic PJI group were 4.05 (3.52, 4.72) g/L, 19.5 (10.7, 40.0) mg/L, 50 (28, 60) mm/1 h, 270 (221, 351)×10 9 /L, 514 (261, 873) μg/L, respectively, which were higher than 3.25 (2.80, 3.63) g/L, 3.7 (2.0, 6.7) mg/L, 20 (12, 30) mm/1 h, 225 (182, 269)×10 9 /L, and 310 (167, 569) μg/L in sterile loosening group, with statistically significant differences ( P<0.05). The AUC of FIB, CRP, ESR, platelets and D-dimer in the diagnosis of chronic PJI were 0.78 (95% CI: 0.73, 0.82), 0.86 (95% CI: 0.82, 0.89), 0.80 (95% CI: 0.76, 0.85), 0.68 (95% CI: 0.63, 0.73), 0.64 (95% CI: 0.59, 0.69); the optimal cut-off values were 3.73 g/L, 9.64 mg/L, 39 mm/1 h, 280×10 9 /L, 624 μg/L; the sensitivity was 68%, 79%, 69%, 47%, 43%; the specificity was 81%, 85%, 85%, 81%, 79%, respectively. When CRP, ESR, FIB, platelets and D-dimer were combined sequentially to diagnose patients with chronic PJI, the sensitivity and specificity of the series test were 12.7% and 99.7%, and those of the parallel test were 100% and 37.3%. The combined diagnostic test showed that the maximum AUC of FIB combined with CRP was 0.85 (95% CI: 0.81, 0.89), with a sensitivity of 76% and a specificity of 89%. Conclusion:The clinical value of plasma FIB in the diagnosis of chronic PJI is not superior to that of CRP and ESR, but the combination of FIB and CRP can improve the specificity.

Objective:To analyze the risk factors leading to the failure of early periprosthetic joint infection (PJI) treated by debridement, antibiotics and implant retention (DAIR) combined with intra-articular injection of antibiotics.Methods:A total of 100 patients who received DAIR combined with intra-articular injection of antibiotics between January 2010 and October 2020 in the Department of Orthopaedics, First Affiliated Hospital of Xinjiang Medical University, were retrospectively analyzed. There were 47 males and 53 females, with an average age of 62.8±13.0 years (26-84 years). 75 patients were diagnosed as PJI after primary surgery while 25 PJI after revision or debridement, involving 41 hips and 59 knees. According to the clinical outcomes, the patients were divided into the cured group (78 cases) and the uncured group (22 cases). Risk factors were screened by univariate analysis on their gender, age, body mass index, site of infection (hip/knee), synovial white blood cell count, erythrocyte sedimentation rate (ESR), C reactive protein (CRP), time of infection, types of pathogenic bacteria (gram-positive bacteria, gram-negative bacteria or fungi), preoperative sinus tract and previous surgical history. For the factors with P<0.20, multivariate binary logistic regression analysis was performed to determine the independent risk factors. Kaplan-Meier survival curve was drawn and any cause that led to treatment failure was seen as the end point event. Calculate prosthetic survival time and 10-year survival rate. Results:The average follow-up was 59.8±40.6 months (0.3-129.0 months). The infection control rate of DAIR combined with intra-articular injection of antibiotics in the treatment of early PJI was 78% (78/100). The univariate analysis showed that the successful rate of non-fungal infection group (81%, 77/95) was significantly higher than the fungal infection group (20%, 1/5) and the successful rate of the group without previous surgical history (85.3%, 64/75) was significantly higher than that with previous surgical history (56.0%, 14/25, χ 2=7.07, P=0.008; χ 2=9.40, P=0.002). The multivariate binary Logistic regression analysis showed that fungal infection [ OR=0.08, 95% CI(0.01, 0.79), P=0.031] and history of previous surgical intervention [ OR=0.25, 95% CI(0.09, 0.73), P=0.001] were independent risk factors for treatment failure. Kaplan-Meier survival curves showed that the survival time of the prosthesis was 96.83±5.30 months, and the 10-year survival rate was 68.1%. Meanwhile, the survival rate of patients with fungal infection and previous surgical history was significantly lower than that of patients without fungal infection or previous surgical history, the difference was statistically significant (χ 2=15.49, P<0.001; χ 2=8.91, P=0.030). Conclusion:The time of PJI, bacterial virulence and species, and preoperative inflammatory indicators had no effect on the outcome of DAIR combined with intra-articular injection of antibiotics in the treatment of early PJI. However, DAIR was not recommended for patients with a history of surgical intervention and fungal infection.

As a non-essential metal, cadmium (Cd) pollution poses severe threats to plant growth, environment, and human health. Phytoextraction using nursery stocks prior to their transplantation is a potential useful approach for bioremediation of Cd contaminated soil. A greenhouse pot experiment was performed to investigate the growth, Cd accumulation, profiles of transcriptome as well as root-associated microbiomes of Photinia frase in Cd-added soil, upon inoculation of two types of arbuscular mycorrhizal fungi (AMF) Sieverdingia tortuosa and Funneliformis mosseae. Compared with the control, inoculation of F. mosseae increased Cd concentrations in root, stem and leaf by 57.2%, 44.1% and 71.1%, respectively, contributing to a total Cd content of 182 μg/plant. KEGG pathway analysis revealed that hundreds of genes involved in 'Mitogen-activated protein kinase (MAPK) signaling pathway', 'plant hormone signal transduction', 'biosynthesis of secondary metabolites' and 'glycolysis/gluconeogenesis' were enriched upon inoculation of F. mosseae. The relative abundance of Acidobacteria was increased upon inoculation of S. tortuosa, while Chloroflexi and Patescibacteria were increased upon inoculation of F. mosseae, and the abundance of Glomerales increased from 23.0% to above 70%. Correlation analysis indicated that ethylene-responsive transcription factor, alpha-aminoadipic semialdehyde synthase, isoamylase and agmatine deiminase related genes were negatively associated with the relative abundance of Glomerales operational taxonomic units (OTUs) upon inoculation of F. mosseae. In addition, plant cysteine oxidase, heat shock protein, cinnamoyl-CoA reductase and abscisic acid receptor related genes were positively associated with the relative abundance of Patescibacteria OTUs upon inoculation of F. mosseae. These finding suggested that AMF can enhance P. frase Cd uptake by modulating plant gene expression and altering the structure of the soil microbial community. This study provides a theoretical basis for better understanding the relationship between root-associated microbiomes and root transcriptomes of P. frase, from which a cost-effective and environment-friendly strategy for phytoextraction of Cd in Cd-polluted soil might be developed.
Cadmium ; Humans ; Microbiota ; Mycorrhizae ; Photinia ; Soil Pollutants ; Transcriptome

Objective:To investigate the effect of the transcriptional coactivator Mediator 1 (Med1) on mouse hair regeneration, and to explore potential mechanisms.Methods:Med1 flox/flox C57BL/6J mice were mated with K14-Cre mice, and the mice with epidermis-specific knockout of Med1 gene, namely K14-Cre-expressing Med1 flox/flox mice (knockout group) , were obtained by using the Cre-Loxp system, while Med1 flox/flox mice without K14-Cre expression served as control group. Mice in the two groups (3 mice in each group) were raised together for 8 weeks followed by dorsal hair removal. Hair regeneration was observed for 12 consecutive days after hair removal. After 12 days, all mice in the two groups were sacrificed, their depilated and non-depilated dorsal skin tissues were resected, and total RNA was extracted from the tissues. Real-time quantitative PCR was performed to determine the mRNA expression of hair keratin genes, vitamin D receptor/β-catenin pathway-related genes, and genes associated with maintenance of hair follicle stem cell proliferation and quiescence. Paraffin-embedded sections of depilated and non-depilated mouse skin tissues were prepared, and immunofluorescence staining was conducted to determine the number of stem cells in the hair follicle bulge. Two-independent-sample t test was used for comparisons between two groups. Results:From days 0 to 12 after depilation, hair regeneration was delayed in the depilated skin area in the knockout group compared with the control group. Real-time quantitative PCR showed significantly decreased mRNA relative expression levels of hair keratin genes Ha1 and Krt2-16, vitamin D receptor/β-catenin pathway-related genes S100a3, Dlx3 and Tubb3, and genes associated with maintenance of hair follicle stem cell proliferation and quiescence including Lhx2, Sox9 and Nfatc1 in the depilated skin tissues in the knockout group (22.09 ± 12.32, 2.07 ± 0.20, 0.02 ± 0.01, 12.36 ± 2.12, 1.75 ± 0.46, 0.39 ± 0.02, 4.42 ± 0.76, 0.44 ± 0.07, respectively) compared with the control group (70.53 ± 9.46, 7.76 ± 0.49, 0.05 ± 0.01, 26.16 ± 2.96, 2.60 ± 0.14, 0.71 ± 0.09, 11.93 ± 0.42, 0.75 ± 0.04, respectively; t = 5.40, 18.64, 3.89, 6.57, 3.04, 6.10, 15.03, 6.18, respectively, all P < 0.05) . Immunofluorescence staining showed that the number of CD34 +K15 + hair follicle stem cells in the hair follicle bulge in both depilated and non-depilated skin tissues was significantly lower in the knockout group than in the control group. Conclusion:Med1 gene knockout may down-regulate the expression of downstream genes of the vitamin D receptor/β-catenin pathway and genes associated with maintenance of hair follicle stem cell proliferation and quiescence (Sox9, Nfatc1 and Lhx2) , and reduce the number of hair follicle stem cells, leading to hair follicle differentiation disorder and hair regeneration delay.