This article combs and summarizes the entire process of rare disease selection and priority theme determination,including the application and preliminary review of rare diseases,standardization of disease theme information,the evaluation methods of evidence sorting and disease selection for priority se-lection of disease themes,and other aspects of the content were analyzed in depth.It is expected to provide reference for the subsequent selection of rare diseases,improve the fairness,rationality and scientificity of rare disease selection,and further promote research and decision-making in China's rare disease-related fields.

Objective To prepare an ophthalmic solution of dihydromyricetin(DMY)based on dipotassium glycyr-rhizinate(DG)nanomicelle solubilization(DG-DMY)and evaluate its effect on dry eyes of mice.Methods DG-DMY was prepared using the thin-film hydration method,and its micelle size,potential,encapsulation efficiency and storage sta-bility at room temperature were tested.The ocular safety of DG-DMY was tested on mice.Dry eye models were built in mice,which were divided into normal control group(normal mice without intervention),PBS control group(dry eye mouse models,intervened by PBS),HA treatment group[dry eye mouse models,intervened by 1 g·L-1 hyaluronic acid(HA)]and DG-DMY treatment group(dry eye mouse models,intervened by DG-DMY),with 10 mice in each group.The fluorescein sodium staining of corneal epithelium and surface tear secretion were recorded after 10 days of intervention.Morphological changes in corneal epithelium,corneal stroma and endothelial cells were monitored by hematoxylin & eosin staining.The enzyme-linked immunosorbent assay(ELISA)was adopted to measure the expression levels of interleukin-6(IL-6)and interleukin-1β(IL-1β).Results DG-DMY is a light yellow,transparent solution with a nanomicelle size of(208.8±3.9)nm,polydispersity index of 0.277,Zeta potential of-(17.6±1.42)mV,encapsulation efficiency of 76.72％,and drug loading efficiency of 10.21％.It is stable at room temperature(25℃)and storage temperature(4 ℃).The mouse studies showed that DG-DMY displayed good in vivo tolerance in mice eyes.The therapeutic results showed that mice in the PBS treatment group still had extensive corneal staining,mice in the HA treatment group had reduced corneal staining,and mice in the DG-DMY treatment group had almost no corneal staining.The tear secretion of mice in the normal control group,PBS control group,HA treatment group and DG-DMY treatment group was(5.15±0.47)mm,(2.26±0.41)mm,(4.02±0.53)mm,and(4.11±0.54)mm.The histopathological results showed that the corneal epithelium,loose collagen structure and basal layer were damaged in the PBS control group;the corneal histopathological injury of mice in the HA treatment group and DG-DMY treatment group were mitigated,with normal corneal epithelium,corneal stroma and endothelial tissues.ELISA results showed that the expression level of IL-6 in the normal control group,PBS control group,HA treatment group and DG-DMY treatment group was(22.98±0.69)ng·g-1,(108.1±6.06)ng·g-1,(56.79±4.87)ng·g-1 and(44.01±0.99)ng·g-1,respectively,and the expression level of IL-1β was(27.97±2.74)ng·g-1,(115.70±5.16)ng·g-1,(50.36±1.56)ng·g-1 and(42.21±1.46)ng·g-1,respectively.Compared with the HA treatment group,the expression levels of IL-6 and IL-1β in the cornea of mice in the DG-DMY treatment group were lower,and the differences were statistically significant(both P＜0.05).Conclusion DG-DMY nano-preparation successfully prepared in this study is verified to act on benzalkonium chloride-induced dry eye effectively and control the inflammatory response of dry eye mouse models by inhibiting the expressions of IL-6 and IL-1β with high safety.

Objective To construct and validate a risk prediction model for poor inhalation in chronic obstructive pulmonary disease(COPD)patients receiving inhaler therapy,providing a decision support tool for personalized prevention of poor inhalation.Methods A cross-sectional study was conducted to collect data related to COPD patients receiving inhaler therapy,forming a dataset.The dataset was randomly divided into a training set and a test set in a ratio of 4∶1.Four different methods for missing value imputation,3 methods for variable feature selection,and 18 machine learning algorithms were employed to successfully construct 216 models on the training set.The monte carlo simulation method was used for resampling in the test set to validate the models,with the area under curve(AUC),accuracy,precision,recall,and F1 score used to evaluate model performance.The optimal model was selected to build the poor inhalation prediction platform.Results A study involving 308 patients with COPD found that 135(43.8%)were at risk of adverse inhalation.Using 33 predictor variables,216 risk prediction models were developed.Of these models,the ensemble learning algorithm yielded the highest average AUC of 0.844,with a standard deviation of 0.058[95%CI=(0.843,0.845)].The differences in predictive performance among the 216 models were statistically significant(P＜0.01).Under the ensemble learning algorithm,adherence to inhaler use(38.087 4%),inhaler satisfaction(25.680 1%),literacy(24.031 3%),number of inhalers(5.482 3%),age(4.204 5%)and number of acute exacerbations in the past year(2.184 7%)contributed most to the predictive model.The model exhibited superior performance,with an AUC of 0.869 3,an accuracy of 83.87%,a precision of 86.96%,a recall of 74.07%,and an F1 score of 0.8.Conclusion This study has developed a predictive model for poor inhalation risk in COPD inhaler therapy patients using machine learning algorithms,which exhibits strong predictive capabilities and holds potential clinical application value.

Objective:To observe and analyze the rate of visual acuity progression and binocular symmetry in patients with choroideremia (CHM).Methods:A single-center retrospective longitudinal cohort study. From April 2009 to August 2022, 38 eyes of 19 patients diagnosed with CHM through clinical and genetic testing at the Department of Ophthalmology, Peking Union Medical College Hospital, were included in this study. All patients underwent at least 2 follow-up visits with a minimum interval of 1 year between visits, and binocular best-corrected visual acuity (BCVA) results were recorded at each follow-up visit. Decimal visual acuity was converted into logarithm of the minimum angle of resolution (logMAR) for analysis. The patient group consisted of 19 males from 16 unrelated families. The age at initial visit was (39.52±13.24) years, with a (2.63±1.61) follow-up visits over a duration of (4.95±2.68) years. A total of 50 binocular BCVA data were included. Annual progression rate of visual acuity was calculated based on longitudinal and cross-sectional data. Spearman correlation coefficient and Bland-Altman method were used to evaluate the binocular symmetry.Results:The rate of visual acuity progression was (0.095±0.148) logMAR units/year based on longitudinal data and (0.018±0.009) logMAR units/year based on cross-sectional data. The binocular symmetry for BCVA of the baseline values was strong; however, the binocular symmetry of progression rates for BCVA was moderate. Spearman correlation analysis showed that binocular symmetry in baseline BCVA was high ( r=0.881, P<0.001). The symmetry of binocular vision progression rates based on longitudinal data was moderately symmetric ( r=0.528, P=0.020). Bland-Altman analysis showed that 94.7% of binocular baseline BCVA differences were within 95% confidence interval ( CI) of 95% limit difference (LOA), indicating good symmetry of binocular baseline BCVA. The number of binocular BCVA progression rate differences within 95% CI of 95%LOA was 89.5%, suggesting moderate symmetry in binocular BCVA progression rate. The results of Spearman correlation coefficient and Bland-Altman analysis of binocular symmetry were basically consistent. Conclusions:The rate of visual acuity progression of patients with CHM based on longitudinal and cross-sectional data is (0.095±0.148) and (0.018±0.009) logMAR units/year, respectively. Cross-sectional data from patients of different ages should not be used to infer the progression rate of the natural history. Binocular eyes with highly symmetrical baseline visual acuity may differ in the rate of visual acuity progression.

Objective:To investigate the Chinese anesthesiologist′s proficiency, training experience and needs of flexible bronchoscope-guided awake flexible bronchoscopy intubation (AFBI) using a questionnaire method.Methods:The cluster sampling was used, and self-designed questionnaires that addressed 54 questions in 5 categories were distributed through WeChat and online platforms. The survey took one month, and the answers were automatically recorded by the WeChat server.Results:A total of 1 250 anesthesiologists participated in the survey in 30 provinces of China, 9 of them were not anesthesiologists, and 1 241 (99.28%) questionnaires were validated. In the valid questionnaires, 52.70% (654) of the anesthesiologists were from tertiary hospitals, and 74.78% (928) of the anesthesiologists were attending physicians or above, only 7.57% (94) of the anesthesiologists had sufficient confidence in AFBI. Twenty-five point two two percent (313) of the anesthesiologists preferred fiberoptic intubation as the first tool when dealing with the anticipated difficult airway. Forty-eight point one one percent (597) of the anesthesiologists had implemented AFBI. Among them, 80.74% (482) had experienced unsuccessful AFBI practices. Eight hundred and ninety-four anesthesiologists had received AFBI training, and the most common AFBI training strategy was theoretical lectures. In addition, the degree of satisfaction regarding the theoretical lectures quality, technical training, clinical practice relativity and non-technical skills training was 21.47% (192), 14.32% (128), 12.3% (110) and 17.90% (160), respectively. The degree of satisfaction with all the 4 training elements mentioned above was 7.27% (65).Conclusions:The awareness and practice of Chinese anesthesiologists in terms of clinical application of AFBI to treat difficult airways need to be strengthened at present, and the lack of high-quality AFBI training may be the key.

【Objective】 To analyze the hepatitis B virus (HBV) infection data of blood donors from 18 domestic blood stations, so as to investigate the HBV infection situation of blood donors. 【Methods】 The positive rate of HBV and its distribution characteristics of regions, the percentage of HBsAg+ ELISA in first-time vs repeated blood donors, and the percentage of HBsAg-/HBV DNA+ blood donors of 18 domestic blood stations during 2017 to 2020 were collected from the Working Platform for Practice Comparison of Blood Centers, and the HBV infection among blood donors were statistically analyzed. 【Results】 From 2017 to 2020, the positive rate of HBV in blood donors among 18 domestic blood stations was 13.48/10 000-144.02/10 000, with the average HBV positive rate in eastern, central and western region at 26.14/10 000, 51.98/10 000 and 41.00/10 000, respectively. The HBsAg+ rate by ELISA among first-time and repeated blood donors was 14.55/10 000-305.39/10 000 vs 1.04/10 000-87.43/10 000 The HBsAg-/HBV DNA+ yield was 1.80/10 000-35.31/10 000. 【Conclusion】 The distribution of HBV infection in blood donors has regional characteristics, and HBV prevalence was low in repeated blood donors. HBsAg ELISA combined with HBV DNA detection can better ensure blood safety.

OBJECTIVE To determ ine the contents of main active constituents in Gynura divaricata leaf with different drying methods and at different harvesting time ，so as to confirm the best drying method and harvesting time. METHODS G. divaricata leaf with different drying methods [drying in the shade ，drying in the sun ，oven drying （60℃，70℃，80℃），microwave drying and freeze drying] and different harvesting time （March to October ）were prepared. The content of water-soluble extract was determined by hot dip method. The contents of total flavonoids and polysaccharides were determined by ultraviolet-visible spectrophotometry. The content of astragalin was determined by HPLC. Analytic hierarchy process was used for comprehensive analysis. RESULTS The time of drying in the shade ，drying in the sun ，drying at 60 ℃，drying at 70 ℃，drying at 80 ℃， microwave drying and freeze drying were 7 d，5 d，8 h，5 h，3.5 h，6 min and 1 d respectively. The average contents of water-soluble extract in G. divaricata leaf were 55.98％，60.78％，52.33％，49.54％，46.87％，59.70％ and 58.24％；those of total flavonoids were 3.27％，3.22％，1.99％，1.70％，1.31％，3.92％ and 2.28％；those of polysaccharides were 4.70％，6.09％， 6.48％，5.45％，5.74％，5.76％ and 7.15％；those of astragalin were 0.48％，0.46％，0.24％，0.23％，0.20％，0.48％，0.29％. The comprehensive score of microwave drying was the highest ，being 0.996 3. The average contents of water-soluble extract from March to October were 41.50％，40.57％，39.16％，40.65％，40.68％，43.30％，45.19％ and 40.12％；those of total flavonoids were 2.24％，2.81％，3.87％，3.92％，3.82％，3.93％，3.66％ and 3.25％；those of polysaccharides were 4.41％，4.61％， 4.98％，5.26％，5.75％，5.94％，5.32％ and 4.47％；those of astragalin were 0.20％，0.21％，0.25％，0.26％，0.25％，0.24％， 0.25％ and 0.21％，respectively. The comprehensive scores of samples collected from May to September exceeded 0.92，and the comprehensive score in August was the highest （0.988 6）. CONCLUSIONS Microwave-dried Gynura divaricata leaf has the best quality ，and the best harvesting time is from May to September.

Clinical phenotypes and gene characteristics of a patient diagnosed with Mowat-Wilson syndrome (MWS) with Hirschsprung′s disease (HSCR) and vaginal atresia in the Department of Neonatal Surgery, Beijing Children′s Hospital, Capital Medical University in March 2021 were analyzed retrospectively.The eight-month-old girl was admitted to the hospital with symptoms of constipation for nine days and abdominal distension for two days.Lower digestive tract radiography and rectal mucosa biopsy results suggested HSCR.The child also had specific facial features and motor development delay.Whole exome test showed a de novo heterozygous mutation, ZEB2 gene c. 2761C>T (p.R921*). After laparoscopic-assisted Soave procedure, the child had normal bowel movements, and no surgery-related compli-cations occurred during the follow-up period.The child′s motor development improved after rehabilitation treatment.According to literature review, 2 female cases show similar clinical manifestations to this girl, but the genotypes were different.This patient expands the clinical phenotype of ZEB2 gene pathogenicity.

Objective:To understand the use of inhaled corticosteroids (ICS) in patients with chronic obstructive pulmonary disease (COPD) in the real world and analyze its compliance with the guidelines.Methods:This study is a multicenter, cross-sectional study. 1 051 COPD patients who were treated in the Second Xiangya Hospital of Central South University, the First Affiliated Hospital of Shaoyang College and Zhuzhou Central Hospital from January 2020 to March 2022 were collected. The general information, drug use, types of exposure risk factors, acute exacerbation (AE) in the past year, the scores of the modified British Medical Research Council Dyspnea Questionnaire (mMRC), COPD Assessment Test (CAT), pulmonary function, blood routine of patients were collected. The status of ICS use in COPD patients, the clinical characteristics and guideline compliance of non-ICS users and ICS users were analyzed.Results:Among 1 051 patients with COPD, ICS was used in 490 cases (46.6%) and was not used in 561 cases (53.4%). ICS use was associated with relapse, frequent AE, severe AE, Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD) grade 2 or above, GOLD D group, mMRC score, bronchial asthma, and blood eosinophils (EOS) (all P<0.05). Among 1 051 patients, 583(55.5%) were newly treated, 222(38.1%) were newly treated with ICS, and 361(61.9%) were not treated with ICS. ICS use in newly treated patients was associated with frequent AE, severe AE in the past year, GOLD grade 2 to 3, GOLD B and D group, mMRC score, bronchial asthma, and blood EOS (all P<0.05). Conclusions:Nearly half of patients with COPD are treated with ICS, and patients with ICS use had a higher risk of AE, more severe symptoms, higher blood EOS, and higher rates of asthma. However, there still exists the phenomenon of overuse of ICS.

Objective:To observe the clinical characteristics and guideline compliance of chronic obstructive pulmonary disease (COPD) patients with initial triple therapy in real-life world.Methods:This study is a cross-sectional study. The subjects of the study were COPD patients admitted to 13 hospitals in Hunan Province and Guangxi Zhuang Autonomous Region from December 2016 to December 2021. The initial treatment was triple inhaled drugs. The data collected included gender, age, diagnosis, body mass index (BMI), history of acute exacerbation (AE) in the past year, pulmonary function, COPD Assessment Test (CAT) score, modified British Medical Research Council Dyspnea Questionnaire (mMRC), inhaled drugs and other indicators. The characteristics and differences of COPD patients before and after 2020 were analyzed.Results:7 184 patients with COPD were enrolled in this study, including 2 409 COPD patients treated with initial triple therapy, accounting for 33.5%(2 409/7 184). Taking January 1st, 2020 as the cut-off point, 1 825 COPD patients (75.8%) received initial treatment with triple inhaled drugs before 2020 and 584 patients (24.2%) after 2020 were included in this study. Compared with COPD patients before 2020, the COPD patients after 2020 had higher FEV 1% [(40.9±15.5 )% vs (39.3±15.5)%, P=0.040], lower CAT [(15.8±6.5)point vs (17.5±6.2)point, P<0.001], less AE in the past year [1(0, 2)times vs 1(0, 2)times, P=0.001] and higher rate of non-AE [255(43.7%) vs 581(37.1%), P=0.006]. In addition, before 2020, patients with COPD were mainly treated with open triple drugs (1 825/1 825, 100%); after 2020, 306 patients (52.4%) received open triple inhaled drugs, and 278 patients (47.6%) received closed triple inhaled drugs. Conclusions:In real-life world, most of patients with COPD treated with triple therapy have severe lung function, obvious symptoms and high risk of acute exacerbation. The real-world prescribing of triple therapy in patients with COPD does not always reflect recommendations in guidelines and strategies, and overtreatment is common. After 2020, prescribing triple therapy for COPD patients is more positive and worse consistency with guideline.