To promote the development of extracellular vesicles of herbal medicine especially the establishment of standardization, led by the National Expert Committee on Research and Application of Chinese Herbal Vesicles, research experts in the field of herbal medicine and extracellular vesicles were invited nationwide with the support of the Expert Committee on Research and Application of Chinese Herbal Vesicles, Professional Committee on Extracellular Vesicle Research and Application, Chinese Society of Research Hospitals and the Guangdong Engineering Research Center of Chinese Herbal Vesicles. Based on the collation of relevant literature, we have adopted the Delphi method, the consensus meeting method combined with the nominal group method to form a discussion draft of "Consensus statement on research and application of Chinese herbal medicine derived extracellular vesicles-like particles (2023)". The first draft was discussed in online and offline meetings on October 12, 14, November 2, 2022 and April and May 2023 on the current status of research, nomenclature, isolation methods, quality standards and research applications of extracellular vesicles of Chinese herbal medicines, and 13 consensus opinions were finally formed. At the Third Academic Conference on Research and Application of Chinese Herbal Vesicles, held on May 26, 2023, Kewei Zhao, convenor of the consensus, presented and read the consensus to the experts of the Expert Committee on Research and Application of Chinese Herbal Vesicles. The consensus highlights the characteristics and advantages of Chinese medicine, inherits the essence, and keeps the righteousness and innovation, aiming to provide a reference for colleagues engaged in research and application of Chinese herbal vesicles at home and abroad, decode the mystery behind Chinese herbal vesicles together, establish a safe, effective and controllable accurate Chinese herbal vesicle prevention and treatment system, and build a bridge for Chinese medicine to the world.

Background::Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography (ERCP), the benefits and safety of high-carbohydrate fluid diet (CFD) intake 2 h before ERCP remain unclear. This study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients’ recovery.Methods::This prospective, multicenter, randomized controlled trial involved 15 tertiary ERCP centers. A total of 1330 patients were randomized into CFD group ( n = 665) and fasting group ( n = 665). The CFD group received 400 mL of maltodextrin orally 2 h before ERCP, while the control group abstained from food/water overnight (>6 h) before ERCP. All ERCP procedures were performed using deep sedation with intravenous propofol. The investigators were blinded but not the patients. The primary outcomes included postoperative fatigue and abdominal pain score, and the secondary outcomes included complications and changes in metabolic indicators. The outcomes were analyzed according to a modified intention-to-treat principle. Results::The post-ERCP fatigue scores were significantly lower at 4 h (4.1 ± 2.6 vs. 4.8 ± 2.8, t = 4.23, P <0.001) and 20 h (2.4 ± 2.1 vs. 3.4 ± 2.4, t= 7.94, P <0.001) in the CFD group, with least-squares mean differences of 0.48 (95% confidence interval [CI]: 0.26–0.71, P <0.001) and 0.76 (95% CI: 0.57–0.95, P <0.001), respectively. The 4-h pain scores (2.1 ± 1.7 vs. 2.2 ± 1.7, t = 2.60, P = 0.009, with a least-squares mean difference of 0.21 [95% CI: 0.05–0.37]) and positive urine ketone levels (7.7% [39/509] vs. 15.4% [82/533], χ2 = 15.13, P <0.001) were lower in the CFD group. The CFD group had significantly less cholangitis (2.1% [13/634] vs. 4.0% [26/658], χ2 = 3.99, P = 0.046) but not pancreatitis (5.5% [35/634] vs. 6.5% [43/658], χ2 = 0.59, P = 0.444). Subgroup analysis revealed that CFD reduced the incidence of complications in patients with native papilla (odds ratio [OR]: 0.61, 95% CI: 0.39–0.95, P = 0.028) in the multivariable models. Conclusion::Ingesting 400 mL of CFD 2 h before ERCP is safe, with a reduction in post-ERCP fatigue, abdominal pain, and cholangitis during recovery.Trail Registration::ClinicalTrials.gov, No. NCT03075280.

Objective:There are significant differences in the distribution of gut microbiota among different populations in different regions.This study mainly explores the structure and distribution of gut microbiota between cow's milk protein allergy（CMPA）children and healthy children in Xiamen,Fujian,and further explores the correlation between gut microbiota and the occurrence and development of CMPA.Methods:Fecal samples have been collected from 30 children with CMPA diagnosed at Xiamen Children’s Hospital from June 2022 to March 2023,and fecal samples from 30 healthy children of the same age have also been collected.The structure and distribution of gut microbiota between the two groups were analyzed using 16S rDNA gene sequencing and bioinformatics analysis.Results:The structure and distribution of gut microbiota between CMPA children and healthy children were quite different.There were no significant differences in α diversity index between groups（ P>0.05）.The analysis of similarities test results showed that there was a significant difference in the distribution of gut microbiota between two groups（ R=0.037, P<0.05）.The β diversity index from PCA showed that there was a significant difference in bacterial community structure between two groups（ P<0.05）.Compared with healthy children,the abundance of Akkermansia in CMPA children was significantly decreased and the abundance of Corynebacterium was significantly increased in CMPA children.LEfSe showed that Proteobacteria were mainly enriched in CMPA children,while Lachnospiraceae were mainly enriched in healthy children.In addition,KEGG analysis showed that the top enrichment of 20 pathways,such as Fructose and mannose metabolism,was significantly decreased in CMPA children（ P<0.05）.COG analysis showed that the enrichment of pathways such as Galactose mutarotase and related enzymes was significantly decreased in CMPA children（ P<0.05）,while the enrichment of pathways including Predicted metal-sulfur cluster biosynthetic enzyme and other two pathways was significantly increased（ P<0.05）. Conclusion:There are significant differences in the structure and distribution of gut microbiota between CMPA children and healthy children,suggesting that a strong correlation between the occurrence and development of CMPA and the gut microbiota.

Objective:An ICP-MS method was established for the determination of arsenic(As),cadmium(Cd),mercury(Hg),lead(Pb),cobalt(Co),nickel(Ni),vanadium(V),lithium(Li),antimony(Sb),copper(Cu)and other 10 elements in pharmaceutical excipients sucrose to assess their risks.Methods:The pharmaceuti-cal excipient sucrose was dissolved in 0.1％HN03 solution directly,and the contents of 75 As,111Cd,202Hg,208Pb,59 Co,60 Ni,51V,7 Li,121 Sb,and 63 Cu in sucrose were determined by the ICP-MS method with the optimized instru-mental parameters in the STD mode.Results:The results showed that the linearity of the method was great in the range of 0-100 ng·mL-1 for As,Cd,Pd,Co,Ni,V,Li,Sb and Cu(the correlation coefficient r was not less than 0.99),and the linearity of the method was good in the range of 0-2 ng·mL-1 for Hg(r=0.999 1).The average recoveries for the 10 elements were in the range of 99.8％-100.0％,and the RSDs were less than 5％(n=6).Conclusion:The method is easy to operate and has high accuracy.It can be used for the determination of 10 elemental impurities in pharmaceutical excipient sucrose.It can be seen that the content of the above ten elements in sucrose is much lower than the specified value in ICH Q3D,and the risk is small.The heavy metal item can no longer be considered separately when revising the standard.

Objective:To analyze food intolerance status in children in Qingdao by detecting the serum levels of food-specific IgG (sIgG).Methods:In this cross-sectional study, a total of 4 249 children aged 0 to 14 years (all were permanent residents of Qingdao City) admitted to Women and Children′s Hospital Affiliated to Qingdao University from May 2017 to December 2020 for suspected food intolerance were selected as the study objects with the whole sampling method. According to the age, the objects were divided into 4 groups: 0-<1 year group (440 cases), 1-<3 years group (1 761 cases), 3-<6 years group (1 193 cases), and ≥6 years group (855 cases). Positive condition of serum sIgG antibodies of 14 kinds of food in the children were detected by enzyme-linked immunosorbent assay. Chi-square test was used to compare the positive rate of the antibodies among different foods, gender and age groups.Results:The total positive rate of food sIgG antibody in 4 249 children was 95.32% (4 050/4 249), the highest positive rate was found in eggs (81.50%) and the lowest positive rate was found in pork (1.15%). The positive rates of sIgG antibody in milk (54.98% vs 49.69%, χ2=11.627), crab (5.59% vs 3.71%, χ2=8.049) and shrimp (4.62% vs 2.75%, χ2=9.784) in boys were significantly higher than those in girls, and the positive rates of sIgG antibody in tomato (49.19% vs 45.54%, χ2=5.510), cod (8.53% vs 5.96%, χ2=10.512) and beef (2.58% vs 1.70%, χ2=3.959) in girls were significantly higher than those in boys (all P<0.05). The total positive rate of sIgG antibody in 14 foods was the lowest in 0-<1 year group (89.09%), and it was the highest in 3-<6 years group (96.98%) ( χ2=63.950, P<0.001). The highest positive rate in 0-<1 year group was found in tomato (56.36%), and it was eggs (85.29%, 88.94%, 85.50%) in all the other 3 groups. The positive rates of corn and beef decreased with age ( χ2=44.098, 20.106, P<0.001), while those of cod and mushroom increased with age ( χ2=32.315, 40.338, P<0.001). The positive rate of wheat (57.13%, χ2=42.273), tomato (57.01%, χ2=209.862), soybean (24.99%, χ2=92.580), crab (6.81%, χ2=33.201), shrimp (6.25%, χ2=47.863) were all the highest in 1-<3 years group among the 4 groups (all P<0.001), and the positive rate of chicken was the highest in 3-<6 years group (7.88%, χ2=29.875; P<0.001). Conclusions:Children in Qingdao have a high level of food intolerance, and the highest positive rate is for eggs. Milk, crab and shrimp should be focused on for boys, while tomatoes, cod and beef shoud be paid more attention to for girls. Children of different ages have different kinds of food intolerance, and their diets should be adjusted reasonably according to the characteristics.

Objective:To investigate the etiology, clinical features and treatment of familial exudative vitreoretinopathy (FEVR) secondary glaucoma.Methods:A retrospective clinical study. From January 1, 2016 to January 1, 2022, 15 patients (17 eyes) were diagnosed with FEVR secondary glaucoma in Beijing Tongren Hospital, Capital Medical University were included in the study. All patients underwent systematic ophthalmological evaluation. According to the patient's age, visual acuity, intraocular pressure, anterior segment, vitreous body and retina condition, the choice of translimbal lensectomy combined with vitrectomy, goniectomy, cyclophotocoagulation, intravitreal injection of anti-vascular endothelial growth factor (VEGF) treatment were chosen. The follow-up time was 3 to 37 months. The clinical characteristics of the affected eye, and the changes of intraocular pressure, anterior chamber depth and complications after surgery were observed.Results:Among the 15 patients, there were 11 males with 13 eyes, and 4 females with 4 eyes. Age was 6.14±7.37 years old. FEVR stages 2B, 3B, 4A, 4B, 5A, and 5B were 1, 1, 5, 6, 3, and 1 eye, respectively. The intraocular pressure of the affected eye was 42.74±9.06 mm Hg (1 mm Hg=0.133 kPa). All eyes had shallow anterior chamber and angle closure, anterior or posterior iris adhesions, lens opacity, retinal detachment, iris neovascularization in 4 eyes, and vitreous hemorrhage in 2 eyes. Sixteen eyes were treated with translimbal lensectomy combined with vitrectomy and goniotomy, of which 8 eyes were treated with anti-VEGF treatment; 1 eye was treated with cyclophotocoagulation combined with anti-VEGF treatment. After operation, the intraocular pressure of 16 eyes returned to normal range, and the depth of anterior chamber of 16 eyes returned to normal, and no obvious complications occurred.Conclusions:The main etiology of secondary glaucoma in FEVR is the structural and functional abnormalities of the anterior chamber and angle, which are found in the 2B and above stages of FEVR. The lensectomy and vitrectomy via limbal approach can effectively control the intraocular pressure and restore the anterior chamber, with no serious complications.

Objective:To review the outcome of intravitreous anti-vascular endothelial growth factor (VEGF) treatment in patients with X-linked retinoschisis (XLRS) complicated with vitreous hemorrhage (VH).Methods:A retrospective clinical study. From March 1, 2016 to April 1, 2022, 18 patients (19 eyes) diagnosed with XLRS complicated with vitreous hemorrhage in Beijing Tongren Hospital, Capital Medical University of Eye Center were included. All the patients were male, with a median age of 7.05±3.8 years. Best corrected visual acuity (BCVA) and wide-angle fundus photography were performed in all the patients. BCVA was carried out using international standard visual acuity chart, and converted into logarithm of minimum resolution angle (logMAR) in statistics analysis. According to whether the patients received intravitreal injection of ranibizumab (IVR), the patients were divided into injection group and observation group, with 11 eyes in 10 cases and 8 eyes in 8 cases, respectively. In the injection group, 0.025 ml of 10 mg/ml ranibizumab (including 0.25 mg of ranibizumab) was injected into the vitreous cavity of the affected eye. Follow-up time after treatment was 24.82±20.77 months. The VH absorption time, visual acuity changes and complications were observed in the injection group after treatment. Paired sample t test was used to compare BCVA before and after VH and IVR treatment. Independent sample t test was used to compare the VH absorption time between the injection group and the observation group. Results:LogMAR BCVA before and after VH were 0.73±0.32 and 1.80±0.77, respectively. BCVA decreased significantly after VH ( t=-3.620, P=0.006). LogMAR BCVA after VH and IVR were 1.87±0.55 and 0.62±0.29, respectively. BCVA was significantly improved after IVR treatment ( t=6.684, P<0.001). BCVA records were available in 5 eyes before and after IVR, and the BCVA values after VH and IVR were 0.58±0.31 and 0.48±0.20, respectively, with no statistically significant difference ( t=1.000, P=0.374). BCVA increased in 1 eye and remained unchanged in 4 eyes after treatment. BCVA records were available in 5 eyes before VH and after VH absorption in the 8 eyes of the observation group. LogMAR BCVA before VH and after VH absorption were 0.88±0.28 and 0.90±0.26, respectively, with no significant difference ( t=-1.000, P=0.374). After VH absorption, BCVA remained unchanged in 4 eyes and decreased in 1 eye. The absorption time of VH in the injection group and the observation group were 1.80±1.06 and 7.25±5.04 months, respectively. The absorption time of VH was significantly shorter in the injection group than in the observation group, the difference was statistically significant ( t=-3.005, P=0.018). Multivariate linear regression analysis showed that IVR treatment was significantly correlated with VH absorption time ( B=-6.66, 95% confidence interval -10.93--2.39, t=-3.40, P=0.005). In the injection group, VH recurrence occurred in 1 eye after IVR treatment. Vitrectomy (PPV) was performed in one eye. In the 8 eyes of the observation group, VH recurrence occurred in 2 eyes, subsequent PPV in 1 eye. The rate of VH recurrence and PPV was lower in the injection group, however, the difference was not statistically significant( P=0.576, 1.000). In terms of complications, minor subconjunctival hemorrhage occurred in 2 eyes and minor corneal epithelial injury occurred in 1 eye in the injection group, and all recovered spontaneously within a short time. In the injection group, 9 eyes had wide-angle fundus photography before and after IVR treatment. There was no significant change in the range of peripheral retinoschisis after treatment. No obvious proliferative vitreoretinopathy, infectious endophthalmitis, retinal detachment, macular hole, complicated cataract, secondary glaucoma or other serious complications were found in all the treated eyes, and there were no systemic complications. Conclusion:Intravitreous anti-VEGF treatment may accelerate the absorption of vitreous hemorrhage in patients with XLRS. No impact is found regarding to the peripheral retinoschisis.

Objective:To investigate the efficacy of 532 nm wavelength laser using indirect ophthalmoscope combined with ranibizumab (IVR) in treating stage 2 and greater pediatric Coats disease.Methods:A retrospective, non-controlled clinical study. From February 2018 to August 2020, 21 eyes of 21 patients with Coats disease stage 2 and greater diagnosed by examination in the Eye Center of Beijing Tongren Hospital were included in the study. Among them, 20 patients were males; 1 patient was female. Mean age was 5.00±1.92 years old. Stage 2A, 2B, 3A, 3B, and 4 were 2, 8, 7, 2, and 2 eyes, respectively. All eyes underwent wide-field fundus color photography and fluorescein fundus angiography (FFA). Best corrected visual acuity (BCVA) was performed in 17 eyes. Abnormal dilated retinal blood vessels, interretinal and subretinal exudates were found in all eyes. Abnormally dilated capillaries and aneurysms in the retina was shown in FFA examination. All eyes underwent 532 nm laser photocoagulation using indirect ophthalmoscope combined with IVR. Patients with severe retinal detachment of stage 3B or greater were treated by external drainage of subretinal fluid (SRF). The subsequent treatment was the same as before. The follow-up time was 35.67±6.13 months. Relevant examinations were performed using the same equipment and methods before. The frequency of treatment, visual acuity changes, anatomic prognosis, and complications were observed.Results:The frequency of eye photocoagulation was 2.43±0.98. The number of IVR treatments was 2.00±0.89. Three eyes were treated with SRF drainage in the first time. At the last follow-up, visual acuity improved, no change, and decreased in 5, 11, and 1 eyes after BCVA examination, respectively. In 21 eyes, the retina was in situ in 17 eyes; 5 eyes with retinal cysts. During the follow-up, cataract and vitreous hyperplasia occurred in 1 eye, which was treated by vitrectomy, and mild vitreous hyperplasia occurred in 1 eye.Conclusion:Indirect ophthalmoscope 532 nm wavelength laser combined with IVR is an effective treatment for pediatric Coats disease.

Objective:To study the long-term effects and outcomes of adjuvant intravitreal injection of conbercept (IVC) therapy in juvenile Coats disease.Methods:A retrospective case series study. From January 1, 2015 to December 31, 2018, 40 patients (40 eyes) who were diagnosed as juvenile Coats disease at Beijing Tongren Hospital Affiliated to Capital Medical University were included in the study. Among them, there were 37 males (37 eyes) and 3 females (3 eyes). All patients had unilateral Coats disease. The average age was 55.00 (44.75, 81.25) months. Five eyes were in stage 2B, 15 eyes were in stage 3A, 19 eyes were in stage 3B and 1 eye was in stage 4. Idiopathic retinal vascular telangiectasia associated with extensive subretinal fluid (SRF) (stage 3 or above) or massive foveal exudation and edema (stage 2B) were found in fundus examination. All affected eyes underwent wide-field color fundus images and fluorescein fundus angiography. Thirty-one eyes underwent best corrected visual acuity (BCVA) examination. The BCVA was carried out using a standard logarithmic visual acuity chart, which was converted into the logarithmic minimum angle of resolution (logMAR) visual acuity. All cases received adjuvant IVC combined with treatments such as retinal photocoagulation. The average number of injections was 4 (1, 5). The average follow-up after initial treatment was 59.00 (52.50, 63.00) months. The changes in BCVA, occlusion of abnormal blood vessels in fundus, absorption of SRF and ocular and systemic complications were observed.Results:At last follow-up, among 31 affected eyes with the examination of BCVA, 13 (32.5%, 13/40) eyes had an improved vision, 12 eyes(30.0%, 12/40) had a stable vision and 6 eyes (15.0%, 6/40) had a decreased vision. The difference between average logMAR BCVA of the affected eyes in each stage after treatment and that before treatment was not statistically significant ( Z=-0.56, -1.80, -0.84; P>0.05). Abnormal blood vessels in fundus were all partially or completely occluded, and SRF was obviously or completely absorbed in all cases; of which, 28 eyes (70.0%, 28/40) were completely occluded, and 12 eyes (30.0%, 12/40) were partially occluded. No patient underwent eye enucleation. Nineteen eyes (47.5%, 19/40) developed vitreoretinal fibrosis; 8 eyes (20.0%, 8/40) developed tractional retinal detachment; 15 eyes (37.5%, 15/40) developed complicated cataract. None had ocular or systemic complications related to IVC therapy during follow-up. Conclusions:IVC combined with classic treatments such as photocoagulation in juvenile Coats disease can keep or improve the visual acuity in most juvenile patients by reducing SRF. IVC is a long-term safe and effective adjuvant therapy in juvenile Coats disease.

Objective:To investigate the correlation between serum uric acid levels and thyroid hormones in hospitalized elderly gout patients.Methods:A total of 646 hospitalized gout patients, including 616 males and 30 females, aged(68.8±5.1)years, who were hospitalized at the Department of Gout, Chu Hsien-I Memorial Hospital from April 2014 to December 2019, were retrospectively analyzed.Clinical information was collected and relevant biochemical tests were conducted.Serum uric acid (SUA)levels were divided into quartiles and their associations with thyroid hormone levels were analyzed.Results:With the increase of SUA, body mass index, the prevalence of obesity, the prevalence of dyslipidemia, and the prevalence of fatty liver, the number of involved joints, cholesterol, low-density lipoprotein cholesterol, triacylglycerol, and homeostasis model assessment trended upward significantly( P<0.05); FUA showed a downward trend( F=9.42, P>0.05). The prevalence of subclinical hypothyroidism in older patients was 11.3%(73 cases). With the increase of SUA, the prevalence of subclinical hypothyroidism and free triiodothyronine levels showed an upward trend, whereas free thyroxine levels showed a downward trend( P<0.01). Conclusions:In elderly gout patients, the prevalence of subclinical hypothyroidism increases with SUA levels.Hyperuricemia and multiple metabolic disorders are independent risk factors for subclinical hypothyroidism in these patients.