OBJECTIVES: To develop an E-selectin-targeting nanomedicine delivery system that competitively inhibits E-selectin-neutrophil ligand binding to block neutrophil adhesion to vessels and suppress their recruitment to the lesion sites. METHODS: Doxorubicin hydrochloride (DOX)-loaded liposomes (IEL-Lip/DOX) conjugated with E-selectin-affinity peptide IELLQARC were developed using a post-insertion method. Two formulations [2-1P: Mol(PC): Mol(DPI)=100:1; 2-3P: 100:3] were prepared and their modification density and in vitro release characteristics were determined. Their targeting efficacy was assessed in a cell model of LPS-induced inflammation, a mouse model of acute lung injury (ALI), a rat femoral artery model of physical injury-induced inflammation, and a zebrafish model of local inflammation. RESULTS: The prepared IEL-Lip/DOX 2-1P and 2-3P had peptide modification densities of 4.76 and 7.57 pmoL/cm², respectively. Compared with unmodified liposomes, IEL-Lip/DOX exhibited significantly reduced 48-h cumulative release rates at pH 5.5. In the inflammation cell model, IEL-Lip/DOX showed increased uptake by activated inflammatory endothelial cells, and 2-1P exhibited a higher trans-endothelial ability. In ALI mice, the fluorescence intensity of IEL-Lip/Cy5.5 increased significantly in lung tissues by 53.71% [Z-(2-1P)] and 93.41% [Z-(2-3P)], and 2-1P had an increased distribution by 24.19% in the inflammatory lung tissue compared to normal mouse lung tissue. In rat femoral artery models, 2-1P had greater injured/normal vessel fluorescence intensity contrast. In the zebrafish models, both 2-1P and 2-3P showed increased aggregation at the site of inflammation. CONCLUSIONS This E-selectin-targeting nanomedicine delivery system efficiently targets activated inflammatory endothelial cells to increase drug concentration at the inflammatory site, which sheds light on new strategies for treating neutrophil-mediated inflammatory diseases and practicing the concept of "one drug for multiple diseases".
Animals ; Liposomes ; Rats ; Nanomedicine ; E-Selectin ; Drug Delivery Systems ; Inflammation/drug therapy* ; Mice ; Doxorubicin/analogs & derivatives* ; Zebrafish ; Acute Lung Injury/drug therapy*

OBJECTIVE To evaluate the efficacy of oral and facial muscle functional training in treating adult obstructive sleep apnea(OSA)and to identify clinical indicators influencing treatment outcomes.METHODS Through a prospective cohort study,patients diagnosed with OSA in the study unit were recruited to undergo a 3-month myofunctional therapy,including soft palate-related muscles,tongue muscles,buccal muscles,and labial muscles in multiple muscle groups,once a day,five times a week,with the use of offline clinic guidance,and the APP program video follow up training for effective training.Data were collected on multiple dimensions including physical signs,sleep breathing monitoring parameters,and airway measurements from imaging studies.Treatment efficacy was assessed by comparing subjective and objective sleep indicators before and after training.Patients were categorized into effective and ineffective groups based on treatment outcomes.Differences in baseline clinical indicators between these groups were analyzed using univariate and multivariate regression analyses.RESULTS The study finally included 58 people,51 males and 7 females,age(38.36±8.96)years,BMI(27.14±3.68)kg/m2,AHI of the enrolled patients was reduced from(31.27±22.28)times/h pre-training to(26.27±21.38)times/h post-training,the minimum oxygen saturation was increased from(78.43±10.07)%to(80.50±10.06)%,snoring index decreased from(62.80±75.20)times/h to(36.40±43.19)times/h,and ESS score decreased from 7.00±5.31 pre-training to 5.50±3.17.By comparing the effective and ineffective groups,it was found that there was a statistically significant difference in the tongue position and ESS scores between the two groups(both P<0.05),while no significant differences were found in gender,age,neck circumference,posterior soft palate area,uvula area,posterior tongue area,or posterior epiglottic area(all P>0.05).Univariate logistic regression analysis indicated that tongue position,AHI,and ESS scores were factors affecting the efficacy of oral and facial muscle function training.Multivariate regression analysis revealed that AHI was an independent prognostic factor for this training in OSA patients.CONCLUSION Oral and facial muscle function training can improve both subjective and objective sleep breathing indices in OSA patients.Tongue position,AHI,and ESS scores may serve as prognostic factors for OSA treatment,aiding in guiding subsequent individualized intervention therapies.

OBJECTIVE: To determine the prevalence of GJB2 gene c.109G>A (p.V37I) variant among infants with congenital hearing loss and analyze the initial audiological characteristics of children harboring the variant, compare the audiometric difference among individuals with various genotypes, and explore genetic and audiological manifestations of the affected families. METHODS: One hundred twenty six infants diagnosed with congenital hearing loss at the Neonate Screening Center of Ningbo City from June 2021 to December 2024 were selected as the study subjects. The neonates, in addition with members from 16 of their families, had undergone genetic screening for variants of 208 hotspot sites within 24 deafness-associated genes. For cases identified with monoallelic variants and concurrent hearing loss, the full GJB2 gene was sequenced. Meanwhile, a retrospective analysis was carried out on 23 children whom were confirmed to have hearing loss and the c.109G>A variant by whole exome sequencing from March 2022 to December 2024. And 102 children who were excluded to have hearing loss and pathogenic variants by whole exome sequencing were selected as normal controls. Audiological features of individuals harboring the c.109G>A variant were compared. This study has been approved by the Medical Ethics Committee of The Affiliated Women and Children's Hospital of Ningbo University (Ethics No.: EC2023-009). RESULTS: For the 126 infants with congenital hearing loss, prospective screening has identified 58 (46.03%) to harbor the c.109G>A variant. These included 38 homozygotes and 16 compound heterozygotes. Retrospective review of the 23 c.109G>A positive children has identified 15 as homozygotes and 8 as compound heterozygotes. Genetic testing of the 16 pedigrees has identified 7 homozygotes and 1 compound heterozygote. For the homozygotes combined (n = 53), 96.2% exhibited bilateral symmetric hearing loss, with 78.3% showing high-frequency sloping patterns, and 98.1% having a hearing threshold ranging from 20 to 65 dB. For the compound heterozygotes combined (n = 24), 95.8% showed symmetric loss, with 59.4% having high-frequency sloping, and 97.9% had a hearing threshold ranging from 20 to 65 dB. Both groups showed significantly elevated ABR/PTA thresholds compared with the normal controls (P = 0.000). The compound heterozygous group had higher ABR thresholds (43.3 ± 15.0 dB nHL) compared with the homozygous group (39.1 ± 12.0 dB nHL, P = 0.005). CONCLUSION Infants harboring the GJB2 c.109G>A variant primarily manifest as mild-to-moderate, symmetric, high-frequency sloping hearing loss. Nearly one-third of affected children have thresholds between 20 to 35 dB nHL, suggesting that ABR > 35 dB nHL alone may underestimate the hearing impairment in this population. Compared with homozygotes, compound heterozygotes with the the GJB2 c.109G>A variant can confer a more severe hearing loss.
Humans ; Connexin 26/genetics* ; Female ; Male ; Infant, Newborn ; Infant ; Hearing Loss/genetics* ; Retrospective Studies ; Child, Preschool ; Child ; Genotype ; Connexins/genetics* ; Mutation

Objective: This study aimed to explore the psychiatric symptoms and associated risk and protective factors among religious adolescents after 2-month home confinement against coronavirus disease-2019 (COVID-19) in China. Methods: 11,603 Chinese adolescents in grades 7–9 were recruited in this survey. An online survey was designed to collect the data. Participants were measured using the Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7 Scale. Results: Religious adolescents showed significantly more severe depressive and anxiety symptoms compared to non-religious. 249 (2.2%) reported COVID-19 exposure. Logistic regression analysis revealed that religiosity was a risk factor for the symptoms of depression (p=0.001) and anxiety (p<0.001). Moreover, among those adolescents with religious beliefs, psychological resilience was protective in preventing depressive and anxiety symptoms. At the same time, emotional abuse, emotional neglect, and a poor parent-child relationship were risk factors. Conclusion Our finding indicates that religious adolescents easily develop depressive and anxiety symptoms, compared to non-religious adolescents. Moreover, those with emotional abuse, emotional abuse, and poor parent-child relationships are more likely to suffer from mental distress and should pay more attention to cope with their mental health.

ObjectiveTo study the characteristics of animal models of acute lung injury caused by non-physical factors， so as to provide a reference for the standardization of the preparation of such animal models and lay a foundation for the research on the pathogenesis and the diagnosis and treatment of acute lung injury. MethodThe articles about the animal experiments of acute lung injury published in the last decade were retrieved from China National Knowledge Infrastructure （CNKI）， Wanfang， SinoMed， VIP， and PubMed with the theme terms of "acute lung injury" and "animal model". The animal species， drugs used in modeling， modeling period， methods used in molding， model standards， and model evaluation indicators were summarized， and Excel was used for the frequency analysis. ResultA total of 338 articles were included in this study. The results of the frequency analysis showed that SD rats/C57BL/6 mice were mainly used to establish the animal models of acute lung injury. Male mice were mostly used for modeling， and the commonly used modeling agent was lipopolysaccharides （LPS）. In most cases， the modeling lasted for 6 h after drug administration. Hematoxylin-eosin staining was mainly used for the observation of histological changes in the lungs， which were taken as the criteria for modeling. The established models were mainly evaluated based on lung dry/wet weight ratio， lung index， morphological changes in the lung tissue， myeloperoxidase （MPO）， superoxide dismutase （SOD）， and levels of inflammatory cytokines in the serum and bronchoalveolar lavage fluid （BALF）. ConclusionThe models of acute lung injury were mostly prepared by intraperitoneal injection of LPS （5 mg·kg^-1） in SD rats and tracheal instillation of LPS （5 mg·kg^-1） in C57BL/6 mice， which were praised for the simple operation， high success rate， and consistent with the pathogenesis of acute lung injury. This study provides a reference for the basic research on acute lung injury by animal experiments.

Clinical data of 655 patients with acute ST-elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI) in Luoyang Central Hospital during January 2017 to March 2020 were analyzed retrospectively. There were 425 cases who first visited PCI-capable hospital (PCI hospital group) and 230 cases who were transferred to PCI-capable hospital (transfer group). Compared with PCI hospital group, STEMI patients in the transfer group had a shorter first diagnosis time [2.0 (0.8, 4.2)h vs. 2.5(1.2, 4.1)h, Z=3.66, P<0.01], longer time from first medical contact to the balloon through (FMC2B) [175 (113, 344) min vs. 75 (57, 112) min, Z=-8.92, P<0.01], longer total ischemic time [5.4 (3.5, 9.8) h vs. 3.9 (2.4, 6.0) h, Z=-5.43, P<0.01]. There was no significant difference in the time from PCI hospital entry to balloon passage (DTB) between the two groups [43(29, 103) min vs. 46 (61, 94) min, Z=-0.56, P=0.573]. The compliance rate of FMC2B time<120 min in the transfer group was only 25.9% (50/193). However, the different first-visit hospital had no significant effect on the risk of heart failure ( OR=0.54, 95 %CI:0.16-1.79, P=0.311) and risk of death ( OR=1.14, 95 %CI:0.20-6.36, P=0.885). The results suggest that STEMI patients referred to PCI hospitals have considerable time delay, and the rate of compliance with FMC2B time<120 min is low.

Objective:To observe any effect of repeated unilateral high frequency transcranial magnetic stimulation (rTMS) on the swallowing function and functional magnetic resonance images of dysphagic stroke survivors.Methods:Twenty stroke survivors with dysphagia were randomly divided into a treatment group ( n=10) and a control group ( n=10). Both groups received traditional swallowing rehabilitation training, while the treatment group was additionally provided with high frequency rTMS over the cortical area of the suprahyoid muscle group of the healthy contralateral cerebral hemisphere. The stimulation frequency was 5Hz and the stimulation intensity was 80% of the resting movement threshold. During the 20-minute treatment, there was a 20-second interval between each 2-second dose of stimulation. Before and after the treatment, both groups were evaluated using the Eating Assessment Tool-10 (EAT-10), a swallowing functional communication measurement (FCM) and the modified Mann Assessment of Swallowing Ability (MMASA). In addition, functional magnetic resonance imaging was used to observe any changes in the relevant brain regions. Results:After the treatment the average EAT-10, FCM and MMASA scores of both groups were significantly better than those before the treatment, with the treatment group′s averages significantly superior to those of the control group. After the treatment, the activation range of the parietal lobe, the superior parietal lobule, the BA7 region and the BA40 area in the treatment group was significantly larger than before the treatment and larger than the control group′s ranges.Conclusions:Repeated high-frequency transcranial magnetic stimulation of the cortical area of the suprahyoid muscles in the contralateral cerebral hemisphere can improve dysphagia and promote the activation of brain areas related to swallowing after a stroke.

This paper reviews the currently research on competency of practitioners in the field of nutrition and food hygiene at home and abroad. Through literature review, it's found that the there are few researches on competency in China at present. Furthermore, compared with foreign countries, there are several issues in China, such as the methods and index system setting. However, due to different national conditions, there are significant differences in the demand for nutrition and food hygiene practitioners, related disciplines and characteristics between China and abroad. Therefore, when drawing lessons from foreign models, we should appropriately make adjustments according to China's national conditions. This review will provide references for further research on establishing a set of scientific and standardized competency evaluation indexes for practitioners in the field of nutrition and food hygiene with Chinese characteristics.

Objective:To evaluate the clinical efficacy and safety of endoscopic submucosal dissection (ESD) for treatment of duodenal lesions.Methods:A retrospective analysis was performed on the data of 45 patients with 46 duodenal lesions who underwent ESD at the Second Xiangya Hospital of Central South University from January 2011 to May 2019. The lesion features, en bloc resection rate, complete resection rate, complications, postoperative pathology and recurrence were assessed.Results:Among the 45 patients, 20 were males and 25 were females, with age of 52.0±11.8 years. Of the 46 lesions, 31 (67.4%) were located in the duodenal bulb, 12 (26.1%) in the descending part, and 3 (6.5%) at the junction of bulb and descending part. The diameter of the lesions was 2.4±1.9 cm. There were 14 (30.4%) lesions originated from mucosal layer, 29 (63.1%) from submucosal layer, and 3 (6.5%) from muscularis propria.Postoperative pathology showed 11 (23.9%) cases of Brunner gland tumors, 9 (19.6%) neuroendocrine tumors, 5 (10.9%) ectopic pancreas, 5 (10.9%) lipomas, and 16 (34.8%) other pathological patterns. All 45 patients with 46 lesions underwent ESD successfully, and the en bloc resection rate was 100.0% (46/46), complete resection rate was 91.3% (42/46). Intraoperative bleeding occurred in 1 case (2.2%), which was successfully treated by endoscopy. One (2.2%) delayed perforation occurred and was treated by surgical intervention. Electrocoagulation syndrome occurred in 1 case (2.2%), which was relieved after conservative medical therapy. Two cases received further surgery after ESD. The mean hospital stay was 6.2 days (ranged 2-21 days) and no death occurred. Forty-one cases were followed up for 1-78 months, with mean time of 30 months. During the follow-up period, local recurrence occurred in 1 patient (2.4%).Conclusion:ESD is an effective and safe treatment for duodenal lesions and has a good clinical practical value.

Objective: To explore the relationship between genotype and phenotype of ABCB11 deficiency. Methods: Clinical data of two siblings with ABCB11 deficiency were retrospectively analyzed. Related literature from PubMed, CNKI and Wangfang databases was reviewed to date (up to August 2017) with 'ABCB11 gene’ or 'bile salt export pump’, 'cholestasis’ and 'child’ as key words. Results: The patients were siblings. Both of them presented as jaundice, pruritus and hepatosplenomegaly since 3 days after birth. Significant laboratory findings on admission of the older sister included high total bilirubin, 170 µmol/L;conjugated bilirubin, 115.8 µmol/L;alanine aminotransferase, 168 U/L;total bile acid 186.3 µmol/L and normal gamma-glutamyl transpeptidase. While routine laboratory data of the younger brother were as follows: total bilirubin, 148.8 µmol/L;conjugated bilirubin, 96.3 µmol/L;alanine aminotransferase, 232.8 U/L;total bile acid 226 µmol/L, and normal gamma-glutamyl transpeptidase.Both received ursodeoxycholic acid and fat-soluble vitamins. Liver pathology of the younger brother showed giant hepatocytes with ballooning degeneration, focal necrosis and intrahepatic cholestasis. Both the patients harbor the same compound heterozygous mutations in ABCB11 gene, c.145C>T (p.Q49X) and c.1510G>A (p.E504K). The sister is 9 years old now, with normal liver function. Jaundice faded around 3 months after birth, pruritus relieved at age 5, and medications was stopped since then. The brother progressed to liver failure after an operation on perianal abscess when he was 8-month-old, and received living-related liver transplantation when he was 9 month and 20 days old (from his mother). Now he is 1 year and 5 months old, with normal liver function. Both are under our follow-up. Literature review revealed 18 ABCB11 deficiency patients from 7 families who had apparent different prognoses, within each family the siblings had the same ABCB11 gene mutation. Seven cases relieved after ursodeoxycholic acid therapy and/or partial external biliary diversion, 5 received orthotopic liver transplantation, 2 developed hepatocellular carcinoma and 4 cases died in childhood. Conclusions The clinical manifestations of ABCB11 deficiency may vary greatly in patients carrying the same genotype, even in siblings. Patients should be managed in individualized maner.