The aim of the present study was to explore the role of group II and III metabotropic glutamate receptors (mGluRs) in carotid body plasticity induced by chronic intermittent hypoxia (CIH) in rats. Sprague Dawley (SD) rats were treated with CIH in Oxycycler A84 hypoxic chamber for 4 weeks, and the tail artery blood pressure was measured at the end of model preparation. RT-qPCR was performed to examine the mRNA expression levels of mGluR2/3/8 in rat carotid body. Carotid sinus nerve activity was detected by ex vivo carotid sinus nerve discharge recording technique, and acute intermittent hypoxia (AIH) was administered to induce carotid body sensory long-term facilitation (sLTF), in order to observe the role of group II and group III mGluRs in carotid body plasticity induced by CIH. The results showed that: 1) After 4 weeks of CIH exposure, the blood pressure of rats increased significantly; 2) CIH down-regulated the mRNA levels of mGluR2/3, and up-regulated the mRNA level of mGluR8 in the carotid body; 3) AIH induced sLTF in carotid body of CIH group. In the CIH group, activation of group II mGluRs had no effect on sLTF of carotid body, while activation of group III mGluRs completely inhibited sLTF. These results suggest that CIH increases blood pressure in rats, and group III mGluRs play an inhibitory role in CIH-induced carotid body plasticity in rats.
Rats ; Animals ; Carotid Body/metabolism* ; Rats, Sprague-Dawley ; Hypoxia ; Receptors, Metabotropic Glutamate/metabolism* ; RNA, Messenger/metabolism*

The purpose of this study was to investigate the effect of glutamate and its ionotropic receptor agonists on the response to acute hypoxia in rat carotid body in vitro. Briefly, after SD rats were anesthetized and decapitated, the bilateral carotid bifurcations were rapidly isolated. Then bifurcation was placed into a recording chamber perfused with 95% O₂-5% CO₂ saturated Kreb's solution. The carotid body-sinus nerve complex was dissected, and the carotid sinus nerve discharge was recorded using a suction electrode. To detect the response of carotid body to acute hypoxia, the chamber was perfused with 5% O₂-5% CO₂-90% N₂ saturated Kreb's solution for a period of 100 s at an interval of 15 min. To observe the effect of glutamate, ionotropic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor agonist AMPA or N-methyl-D-aspartate (NMDA) receptor agonist NMDA on the response to acute hypoxia in rat carotid body, the chamber was perfused with 5% O₂-5% CO₂-90% N₂ saturated Kreb's solution containing the corresponding reagent. The results showed that glutamate (20 μmol/L), AMPA (5 μmol/L) or NMDA (10 μmol/L) inhibited the acute hypoxia-induced enhancement of carotid sinus nerve activity, and these inhibitory effects were dose-dependent. In summary, the activation of glutamate ionotropic receptors appears to exert an inhibitory effect on the response to acute hypoxia in carotid body of rats.
Rats ; Animals ; Glutamic Acid/pharmacology* ; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid/pharmacology* ; N-Methylaspartate/pharmacology* ; Carotid Body ; Rats, Sprague-Dawley ; Carbon Dioxide ; Receptors, N-Methyl-D-Aspartate ; Receptors, AMPA ; Hypoxia

The purpose of the present study was to explore the role of carotid body metabotropic glutamate receptor 1 (mGluR1) in chronic intermittent hypoxia (CIH)-induced carotid body plasticity. Sprague Dawley (SD) rats were exposed to CIH (6%-21% O₂, 4 min/cycle, 8 h/day) for 4 weeks. The blood pressure of rats was monitored non-invasively by tail-cuff method under consciousness. RT-qPCR was used to examine the mRNA expression level of mGluR1 in rat carotid body. Western blot was used to detect the protein expression level of mGluR1 in rat carotid body. The role of mGluR1 in CIH-induced carotid body sensory long-term facilitation (sLTF) was investigated by ex vivo carotid sinus nerve discharge recording, and the carotid body sLTF was evoked by a 10-episode of repetitive acute intermittent hypoxia (AIH: 1 min of 5% O₂ interspersed with 5 min of 95% O₂). The results showed that: 1) CIH increased the systolic blood pressure (P < 0.001), diastolic blood pressure (P < 0.005) and mean arterial blood pressure (P < 0.001) of rats; 2) CIH decreased the mRNA and protein levels of mGluR1 in the rat carotid body (P < 0.01); 3) 4 weeks of CIH induced carotid body sLTF significantly, exhibiting as an increasing baseline sensory activity during post-AIH, which was inhibited by application of an agonist of group I metabotropic glutamate receptors, (S)-3,5-dihydroxyphenylglycine (DHPG), during sLTF induction (P < 0.005). In summary, these results suggest that activation of mGluR1 inhibits CIH-induced carotid body plasticity in rats.
Rats ; Animals ; Carotid Body/metabolism* ; Rats, Sprague-Dawley ; Hypoxia ; Receptors, Metabotropic Glutamate/metabolism* ; RNA, Messenger/metabolism*

OBJECTIVE: To investigate the expression and localization of metabotropic glutamate receptors 7 and 8 (mGluR7/8) in rat superior cervical ganglion (SCG) and their changes in response to chronic intermittent hypoxia (CIH). METHODS: We detected the expressions of mGluR7 and mGluR8 in the SCG of 8-week-old male SD rats using immunohistochemistry and characterized their distribution with immunofluorescence staining. The expression of mGluR7 and mGluR8 in the cytoplasm and nucleus was detected using Western blotting. A 6-week CIH rat model was established by exposure to intermittent hypoxia (6% oxygen for 30 s followed by normoxia for 4 min) for 8 h daily, and the changes in systolic blood pressure, diastolic blood pressure and mean arterial pressure were measured. The effect of CIH on expression levels of mGluR7 and mGluR8 in the SCG was analyzed using Western blotting. RESULTS: Positive expressions of mGluR7 and mGluR8 were detected in rat SCG. mGluR7 was distributed in the neurons and small fluorescent (SIF) cells with positive staining in both the cytoplasm and nuclei, but not expressed in satellite glial cells (SGCs), nerve fibers or blood vessels; mGluR8 was localized in the cytoplasm of neurons and SIF cells, but not expressed in SGCs, nerve fibers, or blood vessels. Western blotting of the nuclear and cytoplasmic fractions of rat SCG further confirmed that mGluR7 was expressed in both the cytoplasm and the nucleus, while mGluR8 exists only in the cytoplasm. Exposure to CIH significantly increased systolic blood pressure, diastolic blood pressure and mean arterial pressure of the rats (all P < 0.001) and augmented the protein expressions of mGluR7 and mGluR8 in the SCG (P < 0.05). CONCLUSION mGluR7 and mGluR8 are present in rat SCG but with different localization patterns. CIH increases blood pressure of rats and enhanced protein expressions of mGluR7 and mGluR8 in rat SCG.
Male ; Animals ; Rats ; Rats, Sprague-Dawley ; Superior Cervical Ganglion ; Receptors, Metabotropic Glutamate ; Hypoxia

Background/Aims: The accuracy of endosonographers in diagnosing gastric subepithelial lesions (SELs) using endoscopic ultrasonography (EUS) is influenced by experience and subjectivity. Artificial intelligence (AI) has achieved remarkable development in this field. This study aimed to develop an AI-based EUS diagnostic model for the diagnosis of SELs, and evaluated its efficacy with external validation. Methods: We developed the EUS-AI model with ResNeSt50 using EUS images from two hospitals to predict the histopathology of the gastric SELs originating from muscularis propria. The diagnostic performance of the model was also validated using EUS images obtained from four other hospitals. Results: A total of 2,057 images from 367 patients (375 SELs) were chosen to build the models, and 914 images from 106 patients (108 SELs) were chosen for external validation. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the model for differentiating gastrointestinal stromal tumors (GISTs) and non-GISTs in the external validation sets by images were 82.01%, 68.22%, 86.77%, 59.86%, and 78.12%, respectively. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy in the external validation set by tumors were 83.75%, 71.43%, 89.33%, 60.61%, and 80.56%, respectively. The EUS-AI model showed better performance (especially specificity) than some endosonographers.The model helped improve the sensitivity, specificity, and accuracy of certain endosonographers. Conclusions We developed an EUS-AI model to classify gastric SELs originating from muscularis propria into GISTs and non-GISTs with good accuracy. The model may help improve the diagnostic performance of endosonographers. Further work is required to develop a multi-modal EUS-AI system.

【Objective】 To analyze the related factors of emotional and behavioral abnormalities in children with overactive bladder (OAB). 【Methods】 OAB children (aged 6 to 16 years) in a survey of 5 032 children from a county in Henan Province during Sep.2022 and Dec.2022 were identified and surveyed with Overactive Bladder Symptom Score (OABSS), Strength and Difficulties Questionnaire (SDQ) and Pediatric Sleep Questionnaire (PSQ). According to the SDQ score, they were divided into abnormal group (SDQ≥20) and normal group. 【Results】 There were 35.7%(137/385) cases in the abnormal group and 64.3% (248/385) in the normal group. Gender, education level of caregivers, body mass index (BMI), age, constipation, enuresis and severity of OAB were significantly associated with emotional and behavioral abnormalities (P<0.05). Children in the abnormal group showed significant differences in emotional symptoms, conduct problems, hyperactivity symptoms, peer interaction and sleep (P<0.001). Multivariate regression analysis revealed significant differences in gender, educational level of caregi-vers, BMI, age, constipation, enuresis, severity of OAB and PSQI between the two groups (P<0.05). 【Conclusion】 The prevalence of emotional and behavioral abnormalities is high in children with OAB, which is related to female gender, high BMI, puberty, constipation, enuresis and severity of OAB.

Objective: To investigate the effect of acetyl-CoA carboxylase 1 (ACC1) knockdown on the migration of esophageal squamous cell carcinoma (ESCC) KYSE-450 cell and underlying mechanism. Methods: Lentiviral transfection was conducted to establish sh-NC control cell and ACC1 knocking down cell (sh-ACC1). Human siRNA HSP27 and control were transfected by Lipo2000 to get si-HSP27 and si-NC. The selective acetyltransferase P300/CBP inhibitor C646 was used to inhibit histone acetylation and DMSO was used as vehicle control. Transwell assay was performed to detect cell migration. The expression of HSP27 mRNA was examined by reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) and the expressions of ACC1, H3K9ac, HSP27 and epithelial-mesenchymal transition-related proteins E-cadherin and Vimentin were detected by western blot. Results: The expression level of ACC1 in sh-NC group was higher than that in sh-ACC1 group (P<0.01). The number of cell migration in sh-NC group was (159.00±24.38), lower than (361.80±26.81) in sh-ACC1 group (P<0.01). The protein expression levels of E-cadherin and Vimentin in sh-NC group were statistically significant compared with sh-AAC1 group (P<0.05). The migrated cell number in sh-NC+ si-NC group was (189.20±16.02), lower than (371.60±38.40) in sh-ACC1+ si-NC group (P<0.01). The migrated cell number in sh-NC+ si-NC group was higher than that in sh-NC+ si-HSP27 group (152.40±24.30, P<0.01), and the migrated cell number in sh-ACC1+ si-NC group was higher than that in sh-ACC1+ si-HSP27 group (P<0.01). The protein expression levels of E-cadherin and Vimentin in sh-NC+ si-NC group were significantly different from those in sh-ACC1+ si-NC and sh-NC+ si-HSP27 groups (P<0.01). The protein expression levels of E-cadherin and Vimentin in sh-ACC1+ si-NC group were significantly different from those in sh-ACC1+ si-HSP27 group (P<0.01). After 24 h treatment with C646 at 20 μmmo/L, the migrated cell number in sh-NC+ DMSO group was (190.80±11.95), lower than (395.80±17.10) in sh-ACC1+ DMSO group (P<0.01). The migrated cell number in sh-NC+ DMSO group was lower than that in sh-NC+ C646 group (256.20±23.32, P<0.01). The migrated cell number in sh-ACC1+ DMSO group was higher than that in sh-ACC1+ C646 group (87.80±11.23, P<0.01). The protein expressions of H3K9ac, HSP27, E-cadherin and Vimentin in sh-NC+ DMSO group were significantly different from those in sh-ACC1+ DMSO group and sh-NC+ C646 group (P<0.01). The protein expression levels of H3K9ac, HSP27, E-cadherin and Vimentin in sh-ACC1+ DMSO group were significantly different from those in sh-ACC1+ C646 group (P<0.01). Conclusion: Knockdown of ACC1 promotes the migration of KYSE-450 cell by up-regulating HSP27 and increasing histone acetylation.
Humans ; Esophageal Neoplasms/pathology* ; Esophageal Squamous Cell Carcinoma/genetics* ; Vimentin/metabolism* ; Dimethyl Sulfoxide ; HSP27 Heat-Shock Proteins/metabolism* ; Histones/metabolism* ; Cadherins/metabolism* ; Cell Movement ; Cell Line, Tumor ; Cell Proliferation/genetics* ; Epithelial-Mesenchymal Transition/genetics* ; Gene Expression Regulation, Neoplastic

OBJECTIVES: Shelter hospital was an alternative way to provide large-scale medical isolation and treatment for people with mild coronavirus disease 2019 (COVID-19). Due to various reasons, patients admitted to the large shelter hospital was reported high level of psychological distress, so did the healthcare workers. This study aims to introduce a comprehensive and multifaceted psychosocial crisis intervention model. METHODS: The psychosocial crisis intervention model was provided to 200 patients and 240 healthcare workers in Wuhan Wuchang shelter hospital. Patient volunteers and organized peer support, client-centered culturally sensitive supportive care, timely delivery of scientific information about COVID-19 and its complications, mental health knowledge acquisition of non-psychiatric healthcare workers, group activities, counseling and education, virtualization of psychological intervention, consultation and liaison were exhibited respectively in the model. Pre-service survey was done in 38 patients and 49 healthcare workers using the Generalized Anxiety Disorder 7-item (GAD-7) scale, the Patient Health Questionnaire 2-item (PHQ-2) scale, and the Primary Care PTSD screen for the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (PC-PTSD-5). Forty-eight healthcare workers gave feedback after the intervention. RESULTS: The psychosocial crisis intervention model was successfully implemented by 10 mental health professionals and was well-accepted by both patients and healthcare workers in the shelter hospital. In pre-service survey, 15.8% of 38 patients were with anxiety, 55.3% were with stress, and 15.8% were with depression; 16.3% of 49 healthcare workers were with anxiety, 26.5% were with stress, and 22.4% were with depression. In post-service survey, 62.5% of 48 healthcare workers thought it was very practical, 37.5% thought more practical; 37.5% of them thought it was very helpful to relief anxiety and insomnia, and 27.1% thought much helpful; 37.5% of them thought it was very helpful to recognize patients with anxiety and insomnia, and 29.2% thought much helpful; 35.4% of them thought it was very helpful to deal with patients' anxiety and insomnia, and 37.5% thought much helpful. CONCLUSIONS Psychological crisis intervention is feasible, acceptable, and associated with positive outcomes. Future tastings of this model in larger population and different settings are warranted.
Humans ; COVID-19 ; Sleep Initiation and Maintenance Disorders ; Crisis Intervention ; Psychosocial Intervention ; SARS-CoV-2 ; Mental Health ; Depression/epidemiology* ; Health Personnel/psychology* ; Anxiety/etiology*

Objective:To investigate clinical efficacy of tunneled subcutaneous pedicle flaps in the repair of ipsilateral nasal alar defects.Methods:A total of 20 patients with nasal alar defects after excision of basal cell carcinoma, which were repaired with ipsilateral tunneled subcutaneous pedicle flaps, were retrospectively collected from January 2018 to January 2020. There were 11 male patients and 9 female patients, with an average age of 60.6 years (range, 48 - 76 years) . According to clinical manifestations, the basal cell carcinoma lesions could be classified into 3 types: nodular-ulcerative type (13 cases) , superficial type (4 cases) and pigmented type (3 cases) , and the skin lesions varied from 0.4 cm × 0.5 cm to 0.9 cm × 1.1 cm in size. All the patients received extended surgical resection of basal cell carcinoma, and nasal alar defects were repaired with tunneled subcutaneous pedicle flaps, with the size of flaps ranging from 0.7 cm × 0.8 cm to 1.2 cm × 1.4 cm.Results:All flaps survived successfully, the nasal alar defects were completely repaired, and all wounds healed primarily. During the postoperative follow-up of 6 - 24 months, neither recurrence of tumors nor obvious scar hyperplasia occurred on the nasal ala, and nasal morphology and appearance were favorable.Conclusion:The tunneled subcutaneous pedicle flap can be used for the repair of ipsilateral nasal alar defects following excision of tumors or other lesions, resulting in favorable therapeutic outcomes and aesthetic appearance.

The existing regulations and systems of the Swedish Medical Products Agency (MPA) have clear provisions on the definition, classification and listed on the market procecure of pharmaceutical products, and the supervision strictly follows the EU standards. Traditional Chinese Medicine (TCM) products belong to the category of Swedish Herbal Medicine Products (HMP) or Traditional Herbal Medicine Products (THMP) and are under the supervision of Swedish Pharmaceutical Products Administration (MPA). This paper analyzes the classification, relevant regulations and registration procecures of TCM products in Sweden. It is suggests that TCM enterprises should fully understand the EU regulations and guidance regulations before listed on the market of TCM products. They should also clarify the product category, and provide sufficient and accurate evidence. In the application process, they should pay attention to strengthening communication with the drug administration units of Sweden.