Nasal drug delivery efficiency is highly dependent on the position in which the drug is deposited in the nasal cavity. However, no reliable method is currently available to assess its impact on delivery performance. In this study, a biomimetic nasal model based on three-dimensional (3D) reconstruction and three-dimensional printing (3DP) technology was developed for visualizing the deposition of drug powders in the nasal cavity. The results showed significant differences in cavity area and volume and powder distribution in the anterior part of the biomimetic nasal model of Chinese males and females. The nasal cavity model was modified with dimethicone and validated to be suitable for the deposition test. The experimental device produced the most satisfactory results with five spray times. Furthermore, particle sizes and spray angles were found to significantly affect the experimental device's performance and alter drug distribution, respectively. Additionally, mometasone furoate (MF) nasal spray (NS) distribution patterns were investigated in a goat nasal cavity model and three male goat noses, confirming the in vitro and in vivo correlation. In conclusion, the developed human nasal structure biomimetic device has the potential to be a valuable tool for assessing nasal drug delivery system deposition and distribution.

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.

Objective:To compare the differences in the prevalence of mild micro-hepatic encephalopathy (MHE) among patients with cirrhosis by using the psychometric hepatic encephalopathy score (PHES) and the Stroop smartphone application (Encephal App) test.Methods:This prospective, multi-center, real-world study was initiated by the National Clinical Medical Research Center for Infectious Diseases and the Portal Hypertension Alliance and registered with International ClinicalTrials.gov (NCT05140837). 354 cases of cirrhosis were enrolled in 19 hospitals across the country. PHES (including digital connection tests A and B, digital symbol tests, trajectory drawing tests, and serial management tests) and the Stroop test were conducted in all of them. PHES was differentiated using standard diagnostic criteria established by the two studies in China and South Korea. The Stroop test was evaluated based on the criteria of the research and development team. The impact of different diagnostic standards or methods on the incidence of MHE in patients with cirrhosis was analyzed. Data between groups were differentiated using the t-test, Mann-Whitney U test, and χ2 test. A kappa test was used to compare the consistency between groups. Results:After PHES, the prevalence of MHE among 354 cases of cirrhosis was 78.53% and 15.25%, respectively, based on Chinese research standards and Korean research normal value standards. However, the prevalence of MHE was 56.78% based on the Stroop test, and the differences in pairwise comparisons among the three groups were statistically significant (kappa = -0.064, P < 0.001). Stratified analysis revealed that the MHE prevalence in three groups of patients with Child-Pugh classes A, B, and C was 74.14%, 83.33%, and 88.24%, respectively, according to the normal value standards of Chinese researchers, while the MHE prevalence rates in three groups of patients with Child-Pugh classes A, B, and C were 8.29%, 23.53%, and 38.24%, respectively, according to the normal value standards of Korean researchers. Furthermore, the prevalence rates of MHE in the three groups of patients with Child-Pugh grades A, B, and C were 52.68%, 58.82%, and 73.53%, respectively, according to the Stroop test standard. However, among the results of each diagnostic standard, the prevalence of MHE showed an increasing trend with an increasing Child-Pugh grade. Further comparison demonstrated that the scores obtained by the number connection test A and the number symbol test were consistent according to the normal value standards of the two studies in China and South Korea ( Z = -0.982, -1.702; P = 0.326, 0.089), while the other three sub-tests had significant differences ( P < 0.001). Conclusion:The prevalence rate of MHE in the cirrhotic population is high, but the prevalence of MHE obtained by using different diagnostic criteria or methods varies greatly. Therefore, in line with the current changes in demographics and disease spectrum, it is necessary to enroll a larger sample size of a healthy population as a control. Moreover, the establishment of more reliable diagnostic scoring criteria will serve as a basis for obtaining accurate MHE incidence and formulating diagnosis and treatment strategies in cirrhotic populations.

Objective:To summarize and discuss the concept and clinical manifestations of complex fracture-dislocations of the elbow in children, and compare its injury characteristics, treatment and clinical effect with adults.Methods:From September 2015 to January 2020, 34 patients seen and treated at our institution for complex fracture-dislocations of the elbow were identified, and their medical records and radiographs were reviewed retrospectively. The inclusion criteria were elbow dislocation combined with one or more fractures at the proximal ulna and radius. There were 25 boys and 9 girls, with an average age of 8.3±3.2 years. The left arm was involved in 27 cases, and the right arm was involved in 7 cases. The causes of injury included falling from a scooter in 16 cases, falling from height in 10 cases, cycling in 5 cases and traffic accident in 3 cases. All patients were treated with closed reduction and the application of plaster under local anaesthesia in the emergency room. Then, X-ray, CT and MRI were performed to evaluate the fracture-dislocation and ligament injury. The following treatment plan was comprehensively evaluated according to the size and displacement of the combined fracture block and the stability of the elbow, for example, open reduction with K-wires and tension band or plate fixation for olecranon fracture, open reduction with loop plate fixation for coronal process fracture, closed reduction or open reduction with K-wires or elasticstable intramedullary nail for radial neck fracture.Results:Among the 34 patients, there were 16 cases of transolecranon fracture-dislocation, 1 case of varus posteromedial rotational instability, 4 cases of valgus posterolateral rotatory instability and 13 cases of divergent dislocation of elbow. All patients were followed up for 13(8, 15) months, and the average fracture healing time was 3.5±0.8 weeks, with no failure of internal fixation. In 2 cases of elbow dislocation combined radial neck fracture, one case had ischemic necrosis of the radial head and one case had early closure of epiphyseal plate of the proximal radius. At the last follow-up, all patients had no subluxation, dislocation or instability of the elbow. The therapeutic efficacy was evaluated at the final follow-up by the Mayo elbow performance score (MEPS) as excellent in 25 cases, good in 5 cases, fair in 3 cases, and poor in one case, with excellent and good rate 88%.Conclusion:The complex fracture-dislocations of the elbow is rare in children. We have the opinion that the clinical characteristics are dislocation combined with one or more fractures of the proximal ulna and radius. Compared with adults, its pathological characteristics and the scope of injury are similar, but most of the injuries are mild. The clinical manifestations are mainly transolecranon fracture-dislocation and divergent dislocation of elbow. Good results can be achieved in most cases through open reduction with internal fixation for fractures.

Aging-induced changes in the immune system are associated with a higher incidence of infection and vaccination failure. Lymph nodes, which filter the lymph to identify and fight infections, play a central role in this process. However, careful characterization of the impact of aging on lymph nodes and associated autoimmune diseases is lacking. We combined single-cell RNA sequencing (scRNA-seq) with flow cytometry to delineate the immune cell atlas of cervical draining lymph nodes (CDLNs) of both young and old mice with or without experimental autoimmune uveitis (EAU). We found extensive and complicated changes in the cellular constituents of CDLNs during aging. When confronted with autoimmune challenges, old mice developed milder EAU compared to young mice. Within this EAU process, we highlighted that the pathogenicity of T helper 17 cells (Th17) was dampened, as shown by reduced GM-CSF secretion in old mice. The mitigated secretion of GM-CSF contributed to alleviation of IL-23 secretion by antigen-presenting cells (APCs) and may, in turn, weaken APCs' effects on facilitating the pathogenicity of Th17 cells. Meanwhile, our study further unveiled that aging downregulated GM-CSF secretion through reducing both the transcript and protein levels of IL-23R in Th17 cells from CDLNs. Overall, aging altered immune cell responses, especially through toning down Th17 cells, counteracting EAU challenge in old mice.
Aging ; Animals ; Autoimmune Diseases ; Disease Models, Animal ; Granulocyte-Macrophage Colony-Stimulating Factor/metabolism* ; Mice ; Mice, Inbred C57BL ; Th17 Cells/metabolism* ; Uveitis/pathology* ; Virulence

Objective: To analyze the clinical epidemiological characteristics including composition of pathogens , clinical characteristics, and disease prognosis acute bacterial meningitis (ABM) in Chinese children. Methods: A retrospective analysis was performed on the clinical and laboratory data of 1 610 children <15 years of age with ABM in 33 tertiary hospitals in China from January 2019 to December 2020. Patients were divided into different groups according to age,<28 days group, 28 days to <3 months group, 3 months to <1 year group, 1-<5 years of age group, 5-<15 years of age group; etiology confirmed group and clinically diagnosed group according to etiology diagnosis. Non-numeric variables were analyzed with the Chi-square test or Fisher's exact test, while non-normal distrituction numeric variables were compared with nonparametric test. Results: Among 1 610 children with ABM, 955 were male and 650 were female (5 cases were not provided with gender information), and the age of onset was 1.5 (0.5, 5.5) months. There were 588 cases age from <28 days, 462 cases age from 28 days to <3 months, 302 cases age from 3 months to <1 year of age group, 156 cases in the 1-<5 years of age and 101 cases in the 5-<15 years of age. The detection rates were 38.8% (95/245) and 31.5% (70/222) of Escherichia coli and 27.8% (68/245) and 35.1% (78/222) of Streptococcus agalactiae in infants younger than 28 days of age and 28 days to 3 months of age; the detection rates of Streptococcus pneumonia, Escherichia coli, and Streptococcus agalactiae were 34.3% (61/178), 14.0% (25/178) and 13.5% (24/178) in the 3 months of age to <1 year of age group; the dominant pathogens were Streptococcus pneumoniae and the detection rate were 67.9% (74/109) and 44.4% (16/36) in the 1-<5 years of age and 5-<15 years of age . There were 9.7% (19/195) strains of Escherichia coli producing ultra-broad-spectrum β-lactamases. The positive rates of cerebrospinal fluid (CSF) culture and blood culture were 32.2% (515/1 598) and 25.0% (400/1 598), while 38.2% (126/330)and 25.3% (21/83) in CSF metagenomics next generation sequencing and Streptococcus pneumoniae antigen detection. There were 4.3% (32/790) cases of which CSF white blood cell counts were normal in etiology confirmed group. Among 1 610 children with ABM, main intracranial imaging complications were subdural effusion and (or) empyema in 349 cases (21.7%), hydrocephalus in 233 cases (14.5%), brain abscess in 178 cases (11.1%), and other cerebrovascular diseases, including encephalomalacia, cerebral infarction, and encephalatrophy, in 174 cases (10.8%). Among the 166 cases (10.3%) with unfavorable outcome, 32 cases (2.0%) died among whom 24 cases died before 1 year of age, and 37 cases (2.3%) had recurrence among whom 25 cases had recurrence within 3 weeks. The incidences of subdural effusion and (or) empyema, brain abscess and ependymitis in the etiology confirmed group were significantly higher than those in the clinically diagnosed group (26.2% (207/790) vs. 17.3% (142/820), 13.0% (103/790) vs. 9.1% (75/820), 4.6% (36/790) vs. 2.7% (22/820), χ²=18.71, 6.20, 4.07, all P<0.05), but there was no significant difference in the unfavorable outcomes, mortility, and recurrence between these 2 groups (all P>0.05). Conclusions: The onset age of ABM in children is usually within 1 year of age, especially <3 months. The common pathogens in infants <3 months of age are Escherichia coli and Streptococcus agalactiae, and the dominant pathogen in infant ≥3 months is Streptococcus pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. ABM should not be excluded even if CSF white blood cell counts is within normal range. Standardized bacteriological examination should be paid more attention to increase the pathogenic detection rate. Non-culture CSF detection methods may facilitate the pathogenic diagnosis.
Adolescent ; Brain Abscess ; Child ; Child, Preschool ; Escherichia coli ; Female ; Humans ; Hydrocephalus ; Infant ; Infant, Newborn ; Male ; Meningitis, Bacterial/epidemiology* ; Retrospective Studies ; Streptococcus agalactiae ; Streptococcus pneumoniae ; Subdural Effusion ; beta-Lactamases

Objective:To discuss the pathological characteristics and strategy for diagnosis and treatment of the transolecranon fracture-dislocation of the elbow in children.Methods:Retrospectively reviewed were the 15 patients who had been treated at Hospital of Pediatric Orthopedics, Xi'an Honghui Hospital from October 2016 to March 2019 for transolecranon fracture-dislocation of the elbow. They were 11 boys and 4 girls, with an average age of 8.3 years (from 5 to 14 years) and 10 left and 5 right arms injured. Type Ⅰ (simple fracture) was found in 11 cases and type Ⅱ (comminuted fracture) in 4 cases in 3 of which the coronoid process was affected. Of them, 14 were treated successfully with closed reduction and plaster fixation under local anesthesia in emergency but one was unsuccessfully. Of the 11 simple fractures, 10 received tension band fixation with Kirschner wire and a short oblique one underwent bone plate fixation; the 4 comminuted fractures were treated by fixation with a combination of Kirschner wire and bone plate.Results:The 15 patients obtained follow-up for 8 to 15 months (average, 11 months). The final follow-up observed fine anatomical relationship of the elbow in all patients, and no such complications as relapse of radial head dislocation, avascular necrosis of the trochlea or early closure of the epiphyseal plate. The transolecranon fracture-dislocation of the elbow obtained bony union in all patients after 5 to 7 weeks (average, 5.6 weeks). The therapeutic efficacy was evaluated at the final follow-up by the Mayo elbow performance score as excellent in 11 cases, as good in 3 and as fair in one.Conclusions:As a type of complicated fracture-dislocation of the elbow, the transolecranon fracture-dislocation of the elbow is rare in children, mainly manifested as simple ones. Treatment options depend on the type of fracture-dislocation. Only anatomical reduction of the olecranon fracture and restoration of a normal trochlear notch can lead to a stable humeroradial joint and thus fine clinical efficacy.

This study aims to establish a quantitative method of 4 aristolochic acids-DNA adducts in mice kidney and liver based on high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS) for monitoring the content changes of aristolochic acids-DNA adducts. A Shiseido Capcellpak AQ C_(18) column(3 mm×100 mm, 3 μm) was used, with a mixture of 0.2% acetic acid-5 mmol·L~(-1) ammonium acetate as the aqueous phase and methanol as the organic phase for gradient elution. The multiple reaction monitoring(MRM) scanning method under positive mode by electrospray ionization(ESI) was performed for the detection of the aristolochic acids-DNA adducts which formed by combining aristolochic acid Ⅰ/Ⅱ with deoxyadenosine, deoxyguanosine, and deoxycytidine, respectively. Balb/c mice were given Guanmutong extract by gavage, and the relative content of aristolochic acids-DNA adducts in liver and kidney samples were analyzed within 60 days. It was found that the concentration of 4 aristolochic acids-DNA adducts in the kidney was significantly higher than that in the liver, and there were about 15.87 adducts in per 1×10~6 normal deoxynucleosides, which was 4.5-7.5 times than that of the liver. What's more, some adducts can still be detected on the 30 th day after administration. The concentration of the adducts in the liver was highest on the first day after administration, and a second peak appeared during the 7 th to 14 th days. The results indicated that aristolochic acids-DNA adducts are difficult to eliminate in vivo, and it is of great significance to study the mechanism of liver and kidney injury of aristolochic acid.
Animals ; Aristolochic Acids ; Chromatography, High Pressure Liquid ; DNA Adducts ; Liver ; Mice ; Spectrometry, Mass, Electrospray Ionization ; Tandem Mass Spectrometry

Objective:To evaluate the treatment of nonunion of lateral humeral condyle complicated with cubitus valgus with primary fixation in situ and secondary supracondylar varus osteotomy.Methods:A retrospective analysis was made of the 8 children who had been treated for nonunion of lateral humeral condyle complicated with cubitus valgus at Department of Pediatric Orthopedics, Honghui Hospital from January 2016 to March 2018. They were 5 boys and 3 girls with 5 left and 3 right sides involved. Their age at injury ranged from 6 to 14 years (average, 10 years) and the duration from injury to operation from 2 to 6 years (average, 4 years). At the primary stage, the fragments were fixated in situ with compressive cannulated screws after cleaning the nonunion ends, followed by iliac autograft. At the secondary stage, the humeral supracondylar varus osteotomy was performed after the nonunion was healed and the elbow range of motion recovered. The therapeutic effects were assessed by comparing the elbow range of motion, carrying angle and Mayo elbow performance score (MEPS) between preoperation and the final follow-up.Results:All the patients were followed up for an average of 44.5 months (range, from 27 to 64 months). The average healing time for obsolete nonunion of lateral humeral condyle was 81.3 days (range, from 55 to 120 days) after the primary operation and that for supracondylar varus osteotomy 51.1 days (range, from 45 to 60 days) after the secondary operation. The elbow range of motion was 129.0°±4.6° before operation and 138.0°±5.4° at the final follow-up, showing a significant difference ( P<0.001). The average carrying angle at the healthy side in 8 children was 5.4° (range, from 3° to 8°). The carrying angle at the affected side was 31.9°±4.7° (range, from 25° to 42°) before operation and 4.0°±2.2°(range, from 1° to 8°) at the final follow-up, showing a significant difference ( P<0.05). Their preoperative MEPS was 57.5 ± 6.5 (4 good cases and 4 poor ones) but 95.9±3.4 (6 excellent cases and 2 good ones) at the final follow-up, showing a significant difference ( P<0.05). Conclusions:Treatment of nonunion of lateral humeral condyle complicated with cubitus valgus can be effectively carried out by cleaning fibrous tissue in the nonunion gap, iliac autograft and fragments fixation in situ with compressive cannulated screws at the primary stage and supracondylar varus osteotomy at the secondary stage. Intraoperative preservation of the blood supply to the nonunited fragments is the key to successful management.