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 the significance of small intestinal manometry in clinical diagnosis and treatment of patients with gastrointestinal motility disorders.Methods:The clinical data of 20 suspected patients with gastrointestinal motility disorders from February 2019 to January 2020 in Shanghai Jiaotong University Affiliated Ninth People′s Hospital were retrospectively analyzed. All patients were performed small intestinal manometry, and the influence on diagnosis and treatment as well as the clinical value of this technique were analyzed.Results:Among the 20 patients, 18 patients successfully accepted small intestinal manometry. Among the 18 patients, 14 patients showed significant motility abnormalities, among which 9 patients showed significant nutritional improvement after treatment and 5 patients were treated with maintaining nutritional support. In 10 patients, small intestinal manometry served as a deciding diagnostic tool, and in 12 patients, major modifications of treatment strategy were made according to results of small intestinal manometry.Conclusions:The small intestinal manometry significantly improves diagnosis and treatment decision in the patients with gastrointestinal motility disorders and shows great value on the clinical practice on this group of patients.

Objective:To investigate the clinical characters of enteric dysmotility (ED), in order to improve clinical diagnosis and treatment capabilities.Methods:The clinical data of 13 ED patients underwent small intestinal manometry from August 2019 to July 2022 in the Shanghai Jiaotong University Affiliated Ninth People′s Hospital and the Fourth Affiliated Hospital of Nanjing Medical University were retrospectively analyzed, including the clinical manifestation, small intestinal manometry result, treatment and prognosis.Results:Among 13 patients, 1 abnormality was presented in 9 cases, 2 abnormalities presented in 2 cases and 3 abnormalities presented in 2 cases. All 13 cases presented a history of constipation, 5 cases started with constipation and underwent subtotal colectomy. Three patients showed severe chronic abdominal pain with one of them opiate dependence. Eight patients underwent surgical treatment, all of which achieved nutritional improvement and symptom relief.Conclusions:ED is a concisely defined disease with clear diagnostic criteria. The surgery can increase the symptoms of some patients.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of national bloodstream infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:During the study period，9 035 strains of Gram-negative bacteria were collected from 51 hospitals，of which 7 895（87.4%）were Enterobacteriaceae and 1 140（12.6%）were non-fermenting bacteria. The top 5 bacterial species were Escherichia coli（ n=4 510，49.9%）， Klebsiella pneumoniae（ n=2 340，25.9%）， Pseudomonas aeruginosa（ n=534，5.9%）， Acinetobacter baumannii complex（ n=405，4.5%）and Enterobacter cloacae（ n=327，3.6%）. The ESBLs-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus spp. were 47.1%（2 095/4 452），21.0%（427/2 033）and 41.1%（58/141），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（58/4 510）and 13.1%（307/2 340）；62.1%（36/58）and 9.8%（30/307）of CREC and CRKP were resistant to ceftazidime/avibactam combination，respectively. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 59.5%（241/405），while less than 5% of Acinetobacter baumannii complex was resistant to tigecycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 18.4%（98/534）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of main Gram-negative bacteria resistance among different regions，with statistically significant differences in the prevalence of CRKP and CRPA（ χ2=20.489 and 20.252， P<0.001）. The prevalence of CREC，CRKP，CRPA，CRAB，ESBLs-producing Escherichia coli and Klebsiella pneumoniae were higher in provinicial hospitals than those in municipal hospitals（ χ2=11.953，81.183，10.404，5.915，12.415 and 6.459， P<0.01 or <0.05），while the prevalence of CRPA was higher in economically developed regions（per capita GDP ≥ 92 059 Yuan）than that in economically less-developed regions（per capita GDP <92 059 Yuan）（ χ2=6.240， P=0.012）. Conclusions:The proportion of Gram-negative bacteria in bloodstream infections shows an increasing trend，and Escherichia coli is ranked in the top，while the trend of CRKP decreases continuously with time. Decreasing trends are noted in ESBLs-producing Escherichia coli and Klebsiella pneumoniae. Low prevalence of carbapenem resistance in Escherichia coli and high prevalence in CRAB complex have been observed. The composition ratio and antibacterial spectrum of bloodstream infections in different regions of China are slightly different，and the proportion of main drug resistant bacteria in provincial hospitals is higher than those in municipal hospitals.

Objective:To analyze the value of the modified 5-factor frailty index in assessing postoperative complications and mortality in elderly hip fracture patients.Methods:In this retrospective study, clinical data were collected of hip fracture patients aged 60 years and above surgically treated at Beijing Luhe Hospital affiliated to Capital Medical University between January 2015 and December 2019.Patients' group assignment was based on whether the modified frailty index score was ≤1 or ≥2, and a post-surgery follow-up was conducted for survival at 30 days, 1 year, 2 years, and 4 years, which was analyzed by the Kaplan-Meier method.Multivariate Cox regression analysis was used to identify factors affecting death in elderly patients.Results:A total of 1 208 patients were included, with 890 in the group with the index score ≤1 and 318 in the group with the index score ≥2.There was no difference in mortality at 30 days(1.6% or 14/890 vs.1.9% or 6/318, P=0.707), 1-year(11.3% or 99/874 vs.11.6% or 36/310, P=0.917), 2-years(19.7% or 168/852 vs.24.3% or 73/300, P=0.099)and 4-years(44.0% or 238/541 vs.51.5% or 106/206, P=0.071). The incidence of postoperative complications in the group with the score ≥2 was higher(14.8% or 47/318 vs.9.7% or 86/890, P=0.012), including the incidence of stroke(6.3% or 20/318 vs.1.8% or 16/890, P<0.001)and the incidence of postoperative pneumonia(6.0% or 19/318 vs.3.1% or 28/890, P=0.029), and the differences were statistically significant.Multivariate Cox regression analysis showed that age, being female, the Charlson comorbidity index score and low hemoglobin at admission were risk factors for 1-year, 2-year and 4-year mortality post-surgery(all P<0.05), while the modified frailty index score had no correlation with postoperative mortality. Conclusions:A modified frailty index ≥2 is predictive of increased risk of postoperative pneumonia and stroke in patients with hip fractures, but is not correlated with the risk of postoperative mortality.

AIM To determine the contents of aspartic acid,glutamic acid,serine,glycine,threonine,citrulline,arginine,alanine,γ-amino-butyric acid,tyrosine,valine,phenlalanine,isoleucine,ornithine,leucine,lysine and proline in Gualoupi Injection and its intermediates,and to analyze their change laws.METHODS The OPA-FMOC online derivatization analysis was performed on a 45℃ thermostatic Waters XBridge C18 column(4.6 mm×100 mm,3.5 μm),with the mobile phase comprising of phosphate buffer solution-[methanol-acetonitrile-water(45 : 45 : 10)]flowing at 1 mL/min in a gradient elution manner,and the detection wavelengths were set at 262,338 nm.Principal component analysis and heatmap analysis were adopted in chemical pattern recognition for the corresponding intermediates in ten processes of six batches of samples.RESULTS Seventeen amino acids showed good linear relationships within their own ranges(R2>0.998 0),whose average recoveries were 83.4％-119.5％with the RSDs of 0.91％-7.94％.Different batches of samples in the same process were clustered,and the corresponding intermediates in different processed were clustered into three groups.Alcohol precipitation and cation exchange column demonstrated the biggest influences on amino acid composition.CONCLUSION This experiment can provide important references for the critical factors on quality control of Gualoupi Injection,thus ensure the stability and uniformity of final product.

Rhino-orbito-cerebral mucormycosis (ROCM) is an acute, rapidly progressive, and lethal opportunistic fungal disease. Due to the atypical clinical manifestations, the disease is easily misdiagnosed in the early stage. The patients with ROCM associated cerebrovascular complications generally have a high mortality rate. This article reports a 47-year-old female patient with diabetic ketoacidosis and COVID-19 admitted to Central Hospital Affiliated to Shandong First Medical University. The results of radiological examinations and cerebrospinal fluid metagenomic next-generation sequencing confirmed as Rhizopus oryzae associated ROCM. In spite of receiving amphotericin B colloidal dispersion and isavuconazole treatments, the patient died of ROCM complicated with severe cerebral infarctions and pulmonary infection. The purpose of this case report is to summarize the clinical characteristics of ROCM with cerebrovascular ischemic events and the rare condition of bilateral anterior circulation involvements, and introduce recent diagnostic and therapeutic approaches for this disease.

Objective To investigate the feasibility and value of a multi-parametric MRI radiomics-based nomogram model for pretreatment predicting the lymphovascular space invasion(LVSI)of endometrial endometrioid adenocarcinoma(EEA).Methods Preoperative MRI and baseline clinical characteristics of 205 EEA patients were prospectively collected from Oct 2020 to Jan 2022 in the Obstetrics and Gynecology Hospital,Fudan University,and randomly divided into training set(n=123)and validation set(n=82)in a 6∶4 ratio.The whole-tumor region of interest was manually drawn on T2-weighted imaging,diffusion-weighted imaging(apparent diffusion coefficient),and dynamic contrast-enhanced MRI,respectively,for radiomics features extraction.In the training set,univariate and multivariate Logistic regression analysis were used to select independent clinical predictors of LVSI(+)and construct the clinical model.The least absolute shrinkage and selection operator(LASSO)regression and multivariate Logistic regression analysis were used to select optimal radiomics features to form a radiomics signature.A combined nomogram model was established by integrating clinical independent predictors and the radiomics signature,and validated in the validation set.The predicting performance and clinical net benefit were evaluated by using the area under the receiver operating characteristic curve(AUC)and clinical decision curve analysis,respectively.Results Of the 205 EEA cases,144 cases were LVSI(-)and 61 cases were LVSI(+).Menopausal status,CA125,and CA199 were independent clinical predictors for the LVSI(+),and contributing to a clinical model with AUCs of 0.714(training)and 0.731(validation).From 8 240 extracted radiomics features,five were selected to construct a MRI radiomics signature after de-redundancy and LASSO dimensionality reduction,yielding AUCs of 0.860(training)and 0.759(validation).The combined nomogram model showed AUCs of 0.887(training)and 0.807(validation),outperforming others and achieving maximum clinical benefit in a large range of threshold probability in both training and validation sets.Conclusion The multi-parametric MRI-based nomogram model has the potential for pretreatment predicting the LVSI status of EEA,providing valuable information for clinical management decision-making and improving patient's clinical benefits.

Objective To observe the clinical efficacy of Zhenwu Decoction plus Guizhi Fuling Pills in the treatment of patients with chronic heart failure(CHF)of fluid retention due to yang deficiency type,and to explore its therapeutic mechanism by network pharmacology.Methods A total of 64 cases of CHF patients with fluid retention due to yang deficiency type were randomly divided into treatment group and control group,with 32 cases in each group.The control group was given the basic western medicine treatment,and the treatment group was treated with Zhenwu Decoction plus Guizhi Fuling Pills on the basis of treatment for the control group.The course of treatment lasted for 4 weeks.The changes of traditional Chinese medicine(TCM)syndrome scores,echocardiographic parameters,distance of 6-minute walking test(6MWT),Minnesota Living with Heart Failure Questionnaire(MLHFQ)score,and serum levels of N-terminal pro-brain natriuretic peptide(NT-proBNP)and omentin-1 in the two groups were observed before and after treatment.After treatment,the efficacy for TCM syndrome was compared between the two groups.The active components,component targets and CHF disease targets of Zhenwu Decoction plus Guizhi Fuling Pills were obtained from the relevant databases by using the network pharmacological methods.After the intersection targets were obtained,the intersection target protein-protein interaction network was constructed and the enrichment analysis was carried out to predict the therapeutic mechanism of Zhenwu Decoction plus Guizhi Fuling Pills for CHF.Results(1)After 4 weeks of treatment,the total effective rate of the treatment group was 90.62%(29/32),and that of the control group was 71.87%(23/32).The intergroup comparison(tested by chi-square test)showed that the efficacy for TCM syndrome in the treatment group was significantly superior to that in the control group(P＜0.05).(2)After treatment,the scores of TCM syndromes such as shortness of breath/wheezing,palpitation,aversion to cold and cold limbs,facial edema and edema of limbs,fatigue,darkish-purple lip and nails,gloomy complexion,oliguria and cough as well as the total scores in the two groups were decreased when compared with those before treatment(P＜0.01),and the decrease of the scores of shortness of breath/wheezing,aversion to cold and cold limbs,facial edema and edema of limbs,fatigue,darkish-purple lip and nails,gloomy complexion and oliguria as well as the total scores in the treatment group was superior to that in the control group(P＜0.05 or P＜0.01).(3)After treatment,the left ventricular end-diastolic diameter(LVEDD)and left ventricular end-systolic diameter(LVESD)in the two groups were decreased when compared with those before treatment(P＜0.01),and the left ventricular ejection fraction(LVEF)was increased when compared with that before treatment(P＜0.01).Moreover,the decrease in LVEDD and LVESD and the increase in LVEF in the treatment group were superior to those in the control group(P＜0.01).(4)After treatment,the 6MWT distance in the two groups was increased(P＜0.01)and the MLHFQ score was decreased(P＜0.01)when compared with that before treatment,and the increase of 6MWT distance and the decrease of MLHFQ score in the treatment group were significantly superior to those in the control group(P＜0.01).(5)After treatment,the serum NT-proBNP level in the two groups was decreased(P＜0.01)and the serum omentin-1 level was increased when compared with that before treatment(P＜0.01).The intergroup comparison showed that the decrease of NT-proBNP level and the increase of Omentin-1 level in the treatment group were superior to those in the control group(P＜0.01).(6)A total of 106 active components and 818 targets of Zhenwu Decoction plus Guizhi Fuling Pills as well as 10 660 disease genes of CHF were obtained.A total of 21 network core targets such as NOS3,TP53,MMP9,VEGFA,IL6,TNF,and CASP3 were screened.The enriched analysis yielded the therapeutic pathways of renin secretion,cyclic guanosine monophosphate-protein kinase(cGMP-PKG)signaling pathway,hypoxia-inducible factor 1(HIF-1)pathway,calcium signaling pathway,Th17 cell differentiation,advanced glycation end products and their receptors(AGE-RAGE)signaling pathway,insulin resistance and so on.Conclusion Zhenwu Decoction plus Guizhi Fuling Pills exert certain effect on CHF.It is effective on inhibiting the inflammatory response,decreasing cardiac load and improving ventricular remodeling through the multi-component,multi-target and multi-pathway mechanism of Chinese medicine,so as to effectively relieve the clinical symptoms of patients and improve the quality of life and prognosis of the CHF patients.

Objective Based on data from the US SEER database,this study investigates the incidence,epidemiological characteristics,treatment modalities,prognosis assessment,and risk stratification of advanced-stage lung adenocarcinoma in young patients.Methods SEER*Stat software was used to collect the incidence rates of lung adenocarcinoma among people under 50 in the US from 2000 to 2020,with annual percentage changes(APCs)calculated using Joinpoint software.Clinical data of 4490 advanced-stage lung adenocarcinoma patients under 50 years old from the SEER database(2010-2018)were retrospectively collected and analyzed.Kaplan-Meier method was used to calculate overall survival,log-rank test to estimate survival rates,and Cox proportional hazards regression model to conduct univariate and multivariate prognostic analyses,and a nomogram model was established to predict the survival of young advanced lung adenocarcinoma patients.The predictive performance of the nomogram was evaluated using ROC curves and calibration curves.X-Tile software was used for risk stratification of the prognosis of young advanced lung adenocarcinoma patients.Results From 2000 to 2020,the incidence rates of young lung adenocarcinoma in men and women in the US decreased from 2.1/100 000 and 2.2/100 000 to 1.1/100 000 and 1.5/100 000 respectively,with APCs of-2.16 and-1.39(P<0.05).Compared to patients aged 40 to<50 years,patients under 40 were more likely to develop bone metastasis,liver metastasis,and lung metastasis,had a higher probability of receiving chemotherapy,tumors were more likely to occur in the lower or middle lobes of the lung,but had a lower probability of receiving radiotherapy,with statistically significant differences(P<0.05).Cox regression analysis showed that gender,age,race,N stage,M stage,subsite,liver metastasis,and bone metastasis were prognostic factors for young advanced lung adenocarcinoma patients(P<0.05);male patients had worse prognosis than female patients(HR=1.17,95%CI 1.09-1.25);African American patients had worse prognosis than Caucasian patients(HR=1.12,95%CI 1.02-1.23),other races had better prognosis than Caucasian patients(HR=0.83,95%CI 0.77-0.97);patients aged 40 to<50 had worse prognosis than those under 40(HR=1.34,95%CI 1.21-1.48);patients with bone metastasis(HR=1.29,95%CI 1.19-1.40)and liver metastasis(HR=1.40,95%CI 1.28-1.54)had worse prognosis,with statistically significant differences(P<0.05).Based on the above prognostic factors,a nomogram model was established to predict 1-year,3-year,and 5-year survival with areas under the curve(AUC)of 0.717,0.692,and 0.699 respectively,and the calibration curve was close to the 45° diagonal.According to the risk scores,patients were divided into low-risk group[1017 cases(22.7%)],medium-risk group[2871 cases(63.9%)],and high-risk group[602 cases(13.4%)].The difference is statistically significant comparing the survival rates among three groups(P<0.0001).Conclusion Gender,age,race,N stage,M stage,subsite,liver metastasis,and bone metastasis are prognostic factors for young advanced lung adenocarcinoma patients,and the nomogram model established based on these factors has high predictive performance.