AIM To analyze the metabolites of nobiletin in rats in vivo based on characteristic ions.METHODS Ten rats were assigned into administration group and control group,and given intragastric administration of the 0.5％CMC-Na suspension of nobiletin(250 mg/kg)and 0.5％CMC-Na solution,respectively,after which plasma,urine and feces were collected,solid phase extraction method was adopted in pretreatment,UHPLC-HRMS analysis was performed.The candidate metabolites were systematically described according to diagnostic product ions,chromatographic retention time,accurate molecular weight and neutral loss fragments,after which accurate metabolites were obtained in the established metabolite data set with-CH3(m/z 15)characteristic ions as a baits.RESULTS A total of 64 metabolites were identified,whose main metabolic pathways were glucuronidation,sulfation,hydrogenation and their compound reactions.CONCLUSION This experiment elucidates the metabolites of nobiletin in rats in vivo,which provides a new reference for its further development.

In the research on cancer theranostics, most environment-sensitive drug delivery systems can only achieve unidirectional and irreversible responsive changes under pathological conditions, thereby improving the targeting effect and drug release performance of the delivery system. However, such irreversible changes pose potential safety hazards when the dynamically distributed delivery system returns to the blood circulation or transports to the normal physiological environment. Intelligent reversible drug delivery systems can respond to normal physiological and pathological microenvironments to achieve bidirectional and reversible structural changes. This feature will help to precisely control the drug release of the delivery system, prolong the blood circulation time, improve the targeting efficiency, and avoid the potential safety hazards of the irreversible drug delivery system. In this review, we describe the research progress of intelligent reversible drug delivery system from two main aspects: controlled drug release and prolonged blood circulation time/enhanced cellular internalization of drug.

Aim To investigate the potential protein post-translational modifications of psychedelic-induced Head-twith response and underling mechanism. Methods Psychedelics LSD, DOM, or Psilocin was administered to rats by intraperitoneal injection to induce head-twitch response, then the most effective dosage was identified to create animal models of head-twitch behavior. Western blot was performed in detecting the protein phosphorylation, acetylation, and ubiquitination in prefrontal cortex of SD rats after 10 min or 30 min injection. Results LSD (0.025 mg • kg~, i. p.), DOM (3 mg•kg

Small interfering RNA (siRNA) is the initiator of RNA interference and inhibits gene expression by targeted degradation of specific messenger RNA. siRNA-mediated gene regulation has high efficiency and specificity and exhibits great significance in the treatment of diseases. However, the naked or unmodified siRNA has poor stability, easy to degrade by nuclease, short half-life, and low intracellular delivery. As an emerging non-viral nucleic acid delivery system, ionizable lipid nanoparticles play an important role in improving the druggability of siRNA. At present, one siRNA drug based on ionizable lipid nanoparticles has been approved for the treatment of rare disease. This review introduces the research progress in ionizable lipid nanoparticles for siRNA delivery, focusing on the effect of each component of lipid nanoparticles on the efficiency of siRNA-mediated gene silencing, which provides new references for the studies on ionizable lipid nanocarriers for siRNA delivery.

To propose a new student-guided teaching method, in which students carried out the clustering of different diseases with the same pathological characteristics, and differentiated diagnosis of these diseases. This method was named pathological feature clustering (PFC). Seventy-seven undergraduates of School of Stomatology, Wuhan University were enrolled. Stratified random sampling method was adopted to divide the students into 4 groups with 18-20 students in each group. Each group of students selected a disease from the following four topics as the theme and summarize the histological characteristics of the disease: ①oral mucosal disease;②odontogenic tumors and tumor-like lesions, oral and maxillofacial cysts; ③salivary gland diseases;④epithelial-derived tumors and tumor-like lesions (referred to as topics 1, 2, 3, and 4, respectively). When discussing a specific type of disease, the group which select the topic was the summary group (SG), and the other groups were the non-summary group (NSG). After summarizing, students shared the summary results through PPTs, and teachers made comments and supplements. The teaching effect was evaluated by comparing the results of the pre-class test and the final examination. Students' acceptance of PFC teaching method was evaluated through a questionnaire, which included 8 objective questions and 1 subjective question. Likert-scale was used to design the questionnaire, with 1 to 5 points for each question. Students rated each question according to their own situation. Differences among groups were compared by Mann-Whitney U nonparametric test. The pre-class test results showed that the scores of students in SG group in subjects 1, 2, 3 [(5.6±0.8), 5.0(1.0) and (2.9±1.0) points for subjects 1, 2 and 3, respectively] were higher than those in NSG group [(5.1±1.0), 4.0(2.5) and 1.5(2.5) points] (U=402.50, P=0.047; U=392.00, P=0.026; U=295.00, P=0.003). The final examination results showed that there was no significant difference between the scores of the SG group and the NSG group in subjects 1, 2, 3 and 4 (P>0.05). These results showed that the differences between SG and NSG groups were reduced after the summarizing and share between groups, further demonstrating the effectiveness of the PFC teaching method. The results of questionnaire showed that 81.8%(63/77) students were completely satisfied with PFC teaching method, 13.0%(10/77) students were satisfied and 5.2%(4/77) students were basically satisfied. According to the feedback of Likert scale objective evaluation questionnaire, the mean score of each question ranged from 4.19 to 4.77, indicating that students believed that PFC teaching method had a positive impact on the learning of oral pathology. The PFC teaching method proposed in this study could improve the ability of pathological differential diagnosis of undergraduates.

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Female ; Humans ; Adolescent ; SARS-CoV-2 ; Smell ; COVID-19/complications* ; Cross-Sectional Studies ; COVID-19 Vaccines ; Incidence ; Olfaction Disorders/etiology* ; Taste Disorders/etiology* ; Prognosis

Humans ; Consensus ; Hypersensitivity ; Desensitization, Immunologic/adverse effects* ; Immunotherapy/adverse effects* ; Injections, Subcutaneous ; Allergens

Objective: miR-663a has been reported to be downregulated by X-ray irradiation and participates in radiation-induced bystander effect via TGF-β1. The goal of this study was to explore the role of miR-663a during radiation-induced Epithelium-to-mesenchymal transition (EMT). Methods: TGF-β1 or IR was used to induce EMT. After miR-663a transfection, cell migration and cell morphological changes were detected and the expression levels of miR-663a, TGF-β1, and EMT-related factors were quantified. Results: Enhancement of cell migration and promotion of mesenchymal changes induced by either TGF-β1 or radiation were suppressed by miR-663a. Furthermore, both X-ray and carbon ion irradiation resulted in the upregulation of TGF-β1 and downregulation of miR-663a, while the silencing of TGF-β1 by miR-663a reversed the EMT process after radiation. Conclusion Our findings demonstrate an EMT-suppressing effect by miR-663a via TGF-β1 in radiation-induced EMT.
Down-Regulation ; Epithelial-Mesenchymal Transition ; Epithelium/metabolism* ; MicroRNAs/metabolism* ; Transforming Growth Factor beta1/pharmacology*

OBJECTIVES: To investigate the incidence of extrauterine growth retardation (EUGR) and its risk factors in very preterm infants (VPIs) during hospitalization in China. METHODS: A prospective multicenter study was performed on the medical data of 2 514 VPIs who were hospitalized in the department of neonatology in 28 hospitals from 7 areas of China between September 2019 and December 2020. According to the presence or absence of EUGR based on the evaluation of body weight at the corrected gestational age of 36 weeks or at discharge, the VPIs were classified to two groups: EUGR group (n=1 189) and non-EUGR (n=1 325). The clinical features were compared between the two groups, and the incidence of EUGR and risk factors for EUGR were examined. RESULTS: The incidence of EUGR was 47.30% (1 189/2 514) evaluated by weight. The multivariate logistic regression analysis showed that higher weight growth velocity after regaining birth weight and higher cumulative calorie intake during the first week of hospitalization were protective factors against EUGR (P<0.05), while small-for-gestational-age birth, prolonged time to the initiation of total enteral feeding, prolonged cumulative fasting time, lower breast milk intake before starting human milk fortifiers, prolonged time to the initiation of full fortified feeding, and moderate-to-severe bronchopulmonary dysplasia were risk factors for EUGR (P<0.05). CONCLUSIONS It is crucial to reduce the incidence of EUGR by achieving total enteral feeding as early as possible, strengthening breastfeeding, increasing calorie intake in the first week after birth, improving the velocity of weight gain, and preventing moderate-severe bronchopulmonary dysplasia in VPIs.
Female ; Fetal Growth Retardation ; Gestational Age ; Hospitalization ; Humans ; Incidence ; Infant ; Infant, Newborn ; Infant, Premature ; Infant, Very Low Birth Weight ; Prospective Studies ; Risk Factors

OBJECTIVE: To observe the effect of transcutaneous auricular vagus nerve stimulation (taVNS) on the sleep quality and nocturnal heart rate variability (HRV) in patients with primary insomnia. METHODS: Twenty-one patients with primary insomnia were included. Using SDZ-ⅡB electric acupuncture apparatus, Xin (CO₁₅) and Shen (CO₁₀) were stimulated with disperse-dense wave, 4 Hz/ 20 Hz in frequency, (0.2±30%) ms of pulse width and tolerable intensity. Electric stimulation was given once every morning and evening of a day, 30 min each time, for 4 weeks totally. Before and after treatment, the score of Pittsburgh sleep quality index (PSQI), objective sleep structure (total sleep time [TST], sleep latency [SL], wake after sleep onset [WASO], sleep efficiency [SE], the percentages of non-rapid eye movement period 1, 2, 3, and the percentage of rapid eye movement period to TST [N1%, N2%, N3%, REM%] ) and nocturnal HRV (high frequency [HF], low frequency [LF], the ratio of LF to HF [LF/HF], standard deviation for the normal RR intervals [SDNN], squared root of the mean sum of squares of differences between adjacent intervals RR [RMSSD], the percentage of adjacent RR intervals with differences larger than 50 ms in the entire recording [PNN50%], the mean of sinus RR intervals [NNMean] ) were compared in the patients separately. RESULTS: After treatment, the score of each item and the total score of PSQI and SL were all reduced as compared with those before treatment (P<0.01, P<0.001); SE, N3%, LF, HF, LF/HF, SDNN, NNMean and RMSSD were all increased compared with those before treatment (P<0.001, P<0.01). CONCLUSION The taVNS improves the sleep quality and objective sleep structure in patients with primary insomnia, which is probably related to the regulation of autonomic nervous functions.
Heart Rate/physiology* ; Humans ; Sleep/physiology* ; Sleep Initiation and Maintenance Disorders/therapy* ; Vagus Nerve ; Vagus Nerve Stimulation