Preliminary exploration of deep learning-assisted recognition of superior labrum anterior and posterior lesions in shoulder MR arthrography.

PURPOSE: MR arthrography (MRA) is the most accurate method for preoperatively diagnosing superior labrum anterior-posterior (SLAP) lesions, but diagnostic results can vary considerably due to factors such as experience. In this study, deep learning was used to facilitate the preliminary identification of SLAP lesions and compared with radiologists of different seniority. METHODS: MRA data from 636 patients were retrospectively collected, and all patients were classified as having/not having SLAP lesions according to shoulder arthroscopy. The SLAP-Net model was built and tested on 514 patients (dataset 1) and independently tested on data from two other MRI devices (122 patients, dataset 2). Manual diagnosis was performed by three radiologists with different seniority levels and compared with SLAP-Net outputs. Model performance was evaluated by the receiver operating characteristic (ROC) curve, area under the ROC curve (AUC), etc. McNemar's test was used to compare performance among models and between radiologists' models. The intraclass correlation coefficient (ICC) was used to assess the radiologists' reliability. p < 0.05 was considered statistically significant. RESULTS: SLAP-Net had AUC = 0.98 and accuracy = 0.96 for classification in dataset 1 and AUC = 0.92 and accuracy = 0.85 in dataset 2. In dataset 1, SLAP-Net had diagnostic performance similar to that of senior radiologists (p = 0.055) but higher than that of early- and mid-career radiologists (p = 0.025 and 0.011). In dataset 2, SLAP-Net had similar diagnostic performance to radiologists of all three seniority levels (p = 0.468, 0.289, and 0.495, respectively). CONCLUSIONS: Deep learning can be used to identify SLAP lesions upon initial MR arthrography examination. SLAP-Net performs comparably to senior radiologists.

Application research of AI-assisted compressed sensing technology in MRI scanning of the knee joint: 3D-MRI perspective.

OBJECTIVE: To investigate the potential applicability of AI-assisted compressed sensing (ACS) in knee MRI to enhance and optimize the scanning process. METHODS: Volunteers and patients with sports-related injuries underwent prospective MRI scans with a range of acceleration techniques. The volunteers were subjected to varied ACS acceleration levels to ascertain the most effective level. Patients underwent scans at the determined optimal 3D-ACS acceleration level, and 3D compressed sensing (CS) and 2D parallel acquisition technology (PAT) scans were performed. The resultant 3D-ACS images underwent 3.5 mm/2.0 mm multiplanar reconstruction (MPR). Experienced radiologists evaluated and compared the quality of images obtained by 3D-ACS-MRI and 3D-CS-MRI, 3.5 mm/2.0 mm MPR and 2D-PAT-MRI, diagnosed diseases, and compared the results with the arthroscopic findings. The diagnostic agreement was evaluated using Cohen's kappa correlation coefficient, and both absolute and relative evaluation methods were utilized for objective assessment. RESULTS: The study involved 15 volunteers and 53 patients. An acceleration factor of 10.69 × was identified as optimal. The quality evaluation showed that 3D-ACS provided poorer bone structure visualization, and improved cartilage visualization and less satisfactory axial images with 3.5 mm/2.0 mm MPR than 2D-PAT. In terms of objective evaluation, the relative evaluation yielded satisfactory results across different groups, while the absolute evaluation revealed significant variances in most features. Nevertheless, high levels of diagnostic agreement (κ: 0.81-0.94) and accuracy (0.83-0.98) were observed across all diagnoses. CONCLUSION: ACS technology presents significant potential as a replacement for traditional CS in 3D-MRI knee scans, allowing thinner MPRs and markedly faster scans without sacrificing diagnostic accuracy. CLINICAL RELEVANCE STATEMENT: 3D-ACS-MRI of the knee can be completed in the 160 s with good diagnostic consistency and image quality. 3D-MRI-MPR can replace 2D-MRI and reconstruct images with thinner slices, which helps to optimize the current MRI examination process and shorten scanning time. KEY POINTS: • AI-assisted compressed sensing technology can reduce knee MRI scan time by over 50%. • 3D AI-assisted compressed sensing MRI and related multiplanar reconstruction can replace traditional accelerated MRI and yield thinner 2D multiplanar reconstructions. • Successful application of 3D AI-assisted compressed sensing MRI can help optimize the current knee MRI process.

Fabrication of hollow microtube arrays based on a femtosecond laser double-pulse multiphoton polymerization.

Microtubes with widely varied dimensions and materials have great prospects in functional devices applied in microoptics, microrobot, and biomedicine. However, the fabrication of vertically protruding hollow microtubes with high diameter-to-thickness ratio is challenging and few reported. Femtosecond laser two-photon polymerization can solve this problem via point-by-point scanning or SLM-based parallel processing, but the low efficiency limits its high throughput fabrication. Here, we report a novel, to the best of our knowledge, femtosecond laser double-pulse multiphoton polymerization approach for high efficiency fabrication of hollow microtube arrays. We established a two-aperture laser beam reshaping system to generate a circular beam via two rounds of Fresnel diffraction. Based on the unique laser energy distribution, hollow microtubes with high diameter-to-thickness ratio can be generated by two successively laser pulses exposure, which can improve the fabrication efficiency significantly. With the optimized parameters, we can achieve repeatable and uniform microtube array fabrication in large scale, and the yield can be 94.9%. Defocus testing showed that the proposed approach has a high range of focusing tolerance. The proposed microtube fabrication approach is meaningful in providing some enlightenment for researchers in the field of microfabrication.

Clinicopathological significance and prognostic implications of Ube2v1 expression in colorectal cancer.

The present study aimed to investigate the expression of ubiquitin-conjugating enzyme E2 variant 1 (Ube2v1) in colorectal cancer (CRC) and its clinical significance. The differential expression of Ube2v1 in CRC tissues and normal intestinal tissues, as well as the association between Ube2v1 expression and the prognosis of patients with CRC were analyzed using bioinformatics analyses. TIMER database analysis revealed higher Ube2v1 expression in CRC tissues than in normal intestinal tissues. Cancerous and normal tissues collected retrospectively from 37 cases of CRC between July, 2022 and June, 2023 were analyzed for Ube2v1 expression using immunohistochemistry, and the associations between Ube2v1 expression and the clinical pathological features of patients with CRC were analyzed. Ube2v1 expression was associated with lymph node metastasis in patients with CRC (P<0.05). However, bioinformatics analysis using the GEPIA2 and HPA database revealed that Ube2v1 was not associated with the overall survival of patients with CRC. On the whole, the present study demonstrates that due to its high expression and association with lymph node metastasis, Ube2v1 may serve as a potential target for the treatment of CRC.

Glioblastoma with a primitive neuronal component: A case report.

The present study describes a rare case of glioblastoma with a primitive neuronal component (GBM-PNC), and provides an in-depth analysis of the clinical, pathological and differential diagnostic findings. A comprehensive literature review was conducted to enhance the understanding of GBM-PNC, revealing its distinct characteristics and prognostic implications. A 57-year-old woman presented with acute onset headache, nausea and vomiting, leading to the identification of an intracranial mass through magnetic resonance imaging. Surgical resection revealed the coexistence of a glial component and a PNC within the tumor. Immunohistochemical analysis detected the expression of glial fibrillary acidic protein in the glial component and synaptin in the PNC. The pathological diagnosis confirmed the presence of GBM-PNC. Gene detection analysis revealed no mutations in isocitrate dehydrogenase (IDH)1 and IDH2, and neurotrophic tyrosine kinase receptor-1 (NTRK1), NTRK2 and NTRK3 genes. GBM-PNC is characterized by a propensity for recurrence and metastasis, with a low 5-year survival rate. The present case report highlights the importance of accurate diagnosis and comprehensive characterization of GBM-PNC to guide treatment decisions and improve patient outcomes.

Customer satisfaction evaluation for drugs: A research based on online reviews and PROMETHEE-â ¡ method.

Online reviews of consumers after purchasing drugs online reflect the factors affecting their satisfaction. How to understand customer satisfaction through online reviews and tapping their needs to improve satisfaction has become an urgent issue facing pharmaceutical e-commerce companies. Based on the online reviews of Alibaba Health Pharmacy, six representative OTC online medicines were selected for this study, including the following categories: tonics, anti-cold drugs, rheumatism and orthopaedic drugs, skin drugs, gastrointestinal drugs, vitamins, and calcium. By training and testing the LDA topic model, five potential topics are extracted as factors affecting customer satisfaction, including drug efficacy, drug cost performance, online customer service, logistics and transportation, and packaging. In this paper, Sentiment Analysis is used to process the review text to quantify the sentiment tendency of the review, and determine the evaluation scale value. Then, the random dominance among various drug factors is determined based on the Stochastic Dominance Rules. Finally, the PROMETHEE-Ⅱ method is used to determine the ranking value of the importance of each factor. The results suggest that the factors in different types of OTC drugs rank differently, which is also rationalized in this paper. This study provides a significant reference for improving customer satisfaction with pharmaceutical e-commerce.

A comparative study on in vitro and in vivo stomach-small intestinal and large intestinal digestion of plant protein meals in growing pigs.

This experiment evaluated the difference between computer-controlled simulated digestion and in vivo stomach-small intestinal or large intestinal digestion for growing pigs. Five diets including a corn-soybean meal basal diet and four experimental diets with rapeseed meal (RSM), cottonseed meal (CSM), sunflower meal (SFM), or peanut meal (PNM) were assigned to each group of five barrows installed terminal ileal cannula or distal cecal cannula in a 5 × 5 Latin square design. Ileal digesta and feces were collected for the determination of digestibility of dry matter (DM) and gross energy (GE) as well as digestible energy (DE) at terminal ileum and total tract. The large intestinal digestibility and DE were calculated by the difference between measurements obtained at the terminal ileum and those obtained from total tract. In vitro stomach-small intestinal digestibility and DE for diets and plant protein meals were determined by stomach-small intestinal digestion in a computer-controlled simulated digestion system (CCSDS). The in vitro large intestinal digestibility and DE of diets were determined in a CCSDS using ileal digesta and enzymes extracted from cecal digesta of pigs. The in vitro large intestinal digestibility and DE of four plant protein meals were determined by the difference between stomach-small intestinal and total tract digestion in the CCSDS. For the experimental diets, the in vitro ileal digestibility and DE were not different from corresponding in vivo values in basal diet and PNM diet, but greater than corresponding in vivo values for diets with RSM, CSM, and SFM (P < 0.05). No difference was observed between in vitro and in vivo large intestinal digestibility and DE in five diets. For the feed ingredients, the in vitro ileal digestibility and DE did not differ from corresponding in vivo ileal values in RSM and PNM but were greater than the in vivo ileal values in CSM and SFM (P < 0.05). The in vitro large intestinal GE digestibility and DE were not different from in vivo large intestinal values in RSM, CSM, and PNM, but lower than in vivo large intestinal values in SFM. This finding may relate to the higher fiber content of plant protein meals resulting in shorter digestion time of in vivo stomach-small intestine thus lower digestibility compared to in vitro, indicating it is necessary to optimize in vitro stomach-small intestinal digestion time.

Comparable in vitro and in vivo values are crucial to develop a novel in vitro digestion technique for growing pigs. The current study evaluated the difference between computer-controlled simulated digestion and in vivo stomach­small intestinal or large intestinal digestion for growing pigs. Five diets including a corn­soybean meal basal diet and four experimental diets with rapeseed meal (RSM), cottonseed meal (CSM), sunflower meal (SFM), or peanut meal (PNM) were used to compare the in vitro and in vivo digestion. Our study demonstrated that the in vitro ileal digestibility of energy was not different from corresponding in vivo values in basal diet and PNM diet, but greater than corresponding in vivo values for diets with RSM, CSM, and SFM. The in vitro stomach­small intestinal digestibility was greater than in vivo digestibility, resulting in less digestible substrates hydrolyzed by in vitro large intestinal fluid, whereas more digestible substrates can be digested by in vivo large intestine in plant protein meals. This difference may relate to the higher fiber content of plant protein meals resulting in shorter digestion time of in vivo stomach­small intestine thus lower digestibility compared to in vitro. Therefore, it is necessary to optimize in vitro stomach­small intestinal digestion time.

Gastric inverted hyperplastic polyp: A case report.

Inverted hyperplastic polyp (IHP) is a rare disease characterized by the downward growth of proliferative mucosal components into the submucosal layer. It is often misdiagnosed as other submucosal tumors and accurate diagnosis requires pathological examination. Most patients with IHP have no clinical symptoms and some have non-specific symptoms, such as abdominal distension, abdominal pain and even anemia. IHP is treated via endoscopic mucosal resection or endoscopic sub-mucosal section. The present study reported a case of IHP and discussed its clinical manifestations, clinicopathological diagnosis, differential diagnosis and treatment to improve our understanding of the disease.

Revisiting students' foreign language learning demotivation: From concepts to themes.

Demotivation is a common psychological phenomenon in foreign language learning. Having a good understanding of learners' foreign language learning demotivation is conducive to enriching the fruits of psychological research on foreign language learning theoretically and practically by exploring effective ways to improve learners' foreign language learning motivation. Therefore, this study entails an analysis of the selected literature from 2001 to 2021 to interpret the concept of foreign language learning demotivation, illustrate the research topics from the classification of demotivators and their relationships with other psychological factors, and fully describe the research methods and participants. Future research should expand theoretical perspectives, include more participants of different grades, and adopt multiple research methods.

An automatically progressed computer-controlled simulated digestion system to predict digestible and metabolizable energy of unconventional plant protein meals for growing pigs.

The objective of this experiment was to develop a new computer-controlled simulated digestion system to predict the digestible energy (DE) and metabolizable energy (ME) of unconventional plant protein meals for growing pigs. Nine meals tested included 1 source of rapeseed meal, 4 sources of cottonseed meal, 2 sources of sunflower meal, and 2 sources of peanut meal. Twenty growing pigs (Duroc × [Landrace × Large White]) with an initial body weight (BW) of 41.7 ± 2.6 kg were allotted to a replicated 10 × 3 incomplete Latin square design to determine the DE and ME of 1 basal diet and 9 experimental diets formulated with 9 unconventional plant protein meals. The DE and ME values of unconventional plant protein meals were calculated by the difference method. The in vitro digestible energy (IVDE) of 1 basal diet, 9 experimental diets, and 9 unconventional plant protein meals were determined with 5 replicates of each sample in a complete randomized arrangement. The IVDE/DE or IVDE/ME ranged from 0.96 to 0.98 or 1.00 to 1.01, and the correlation coefficient between IVDE and DE or ME was 0.97 or 0.98 in 10 experimental diets. Accordingly, the IVDE/DE or IVDE/ME ranged from 0.86 to 1.05 or 0.96 to 1.20, and the correlation coefficient between IVDE and DE or ME was 0.92 or 0.91 in 9 unconventional plant protein meals. The coefficient of variation (CV) of IVDE was less than that of DE and ME in the experimental diets (0.43%, 0.80%, and 0.97% for CV of IVDE, DE and ME, respectively) and unconventional plant protein meals (0.92%, 4.84%, and 6.33% for CV of IVDE, DE and ME, respectively). The regression equations to predict DE from IVDE in 10 experimental diets and 9 unconventional plant protein meals were DE = 0.8851 × IVDE +539 (R 2 = 0.9411, residual standard deviation [RSD] = 23 kcal/kg DM, P < 0.01) and DE = 0.9880 × IVDE + 166 (R 2 = 0.8428, RSD = 182 kcal/kg DM, P < 0.01), respectively. There was no statistical difference in the slopes (P = 0.82) or intercepts (P = 1.00) of these 2 equations. Thus, 10 diets and 9 unconventional plant protein meals were pooled to establish the regression equation of DE on IVDE as: DE = 0.9813 × IVDE +187 (R 2 = 0.9120, RSD = 118 kcal/kg DM, P < 0.01). The regression equations to predict ME from IVDE in 10 experimental diets and 9 unconventional plant protein meals were ME = 0.9559 × IVDE +146 (R 2 = 0.9697, RSD = 18 kcal/kg DM, P < 0.01) and ME = 0.9388 × IVDE + 3 (R 2 = 0.8282, RSD = 182 kcal/kg DM, P < 0.01), respectively. There was no statistical difference in slopes (P = 0.97) but significant difference between the intercepts (P = 0.02) of these 2 equations. Our results indicate IVDE has similar response to the DE but different response to the ME in 10 experimental diets and 9 unconventional plant protein meals. Therefore, IVDE is more suitable to predict DE than ME of diets and unconventional plant protein meals for growing pigs.

Exploring Senior High School Students' English Learning Demotivation in Mainland China.

In the last 20 years, much attention has been paid to learners' demotivation. Researchers have conducted many studies on second/foreign language learning demotivation from the perspectives of social culture, social psychology, and so forth. In China, related studies have mainly focused on college students' demotivation; scant attention has been paid to senior high school students. Regarding scale development, although much progress has been made, there remains a need for a scale with high reliability and validity that is suitable for students in the basic education stage. Therefore, based on previous studies and choosing Chinese senior high school students as participants, this research study developed a scale with 55 items, and exploratory factor analysis (EFA) was used to develop a 28-item scale with six dimensions. The six-dimensional construct encompasses teacher knowledge, important others, teacher responsibility, learner-related factors, learning contents, and critical incidents, which are the key factors leading to English learners' demotivation. Among them, the factor of critical incidents is new and has been overlooked by other researchers. Moreover, the descriptive analysis demonstrated the degree to which the demotivators influence learners, and the independent samples t-test found a significant difference in the impact of critical incidents in terms of the students' language proficiency. Ultimately, four suggestions are put forward to remotivate and sustain learners' motivation.

A new classification of talocalcaneal coalitions based on computed tomography for operative planning.

BACKGROUND: Current classifications emphasize the morphology of the coalition, however, subtalar joint facets involved should also be emphasized. OBJECTIVE: The objective of this study was to develop a new classification system based on the articular facets involved to cover all coalitions and guide operative planning. METHODS: Patients were diagnosed with talocalcaneal coalition using a CT scan, between January 2009 and February 2021. The coalition was classified into four main types according to the shape and nature of the coalition: I, inferiorly overgrown talus or superiorly overgrown calcaneus; II, both talus and calcaneus overgrew; III, coalition with an accessory ossicle; IV, complete osseous coalition (I-III types are non-osseous coalition). Then each type was further divided into three subtypes according to the articular facets involved. A, the coalition involving the anterior facets; M, the coalition involving the middle facets, and P, the coalition involving the posterior facets. Interobserver reliability was measured at the main type (based on nature and shape) and subtype (articular facet involved) using weighted Kappa. Results There were 106 patients (108 ft) included in this study. Overall, 8 ft (7.5%) were classified as type I, 75 ft (69.4%) as type II, 7 ft (6.5%) as type III, and 18 ft (16.7%) as type IV. Twenty-nine coalitions (26.9%) involved the posterior facets only (subtype-P), 74 coalitions (68.5%) involved both the middle and posterior facets (subtype-MP), and five coalitions (4.6%) simultaneously involved the anterior, middle, and posterior facets (subtype-AMP). Type II-MP coalition was the most common. The value of weighted Kappa for the main type was 0.93 (95%CI 0.86-0.99) (p<0.001), and the value for the subtype was 0.78 (95%CI 0.66-0.91) (p<0.001). CONCLUSION: A new classification system of the talocalcaneal coalition to facilitate operative planning was developed.

Effects of Optimal Carbohydrase Mixtures on Nutrient Digestibility and Digestible Energy of Corn- and Wheat-Based Diets in Growing Pigs.

This study aimed to evaluate the effects of optimal carbohydrase mixture (OCM) on macronutrients and amino acid digestibility and the digestible energy (DE) in growing pigs fed the corn-soybean meal-based diet (CSM) and the wheat-soybean meal-based diet (WSM). A total of 36 ileal-cannulated pigs (50.9 ± 4.9 kg initial body weight) were allotted to four dietary treatments randomly, which included CSM and WSM diets, and two diets supplied with corresponding OCM. These OCMs were screened using an in vitro method from our previous study. After the five day adaptation period, fecal samples were collected from d six to seven, and ileal digesta samples were collected on d 8 and 10. Chromic oxide was added as an indigestible marker. The results show that the addition of OCM improved the apparent ileal digestibility (AID) of dry matter (DM), ash, carbohydrate (CHO), neutral detergent fiber, and gross energy (GE) and the apparent total tract digestibility (ATTD) of DM, CHO, and GE in CSM diet (p < 0.05), but reduced the apparent hindgut disappearance (AHD) of DM in CSM diet (p < 0.05). The ATTD of DM, crude protein (CP), ether extract (EE), ash, and GE and the AHD of DM, CP, EE, ash, CHO, and GE in WSM diet were improved by the OCM addition (p < 0.05), whereas the AID of DM, CP, ash, CHO, and GE were decreased (p < 0.05). The respective DE contents in CSM and WSM diets were increased from 15.45 to 15.74 MJ/kg and 15.03 to 15.49 MJ/kg under the effects of OCM (p < 0.05). Similar to the trend of AID of CP, the OCM addition increased the AID and standardized ileal digestibility (SID) of Ile, Thr, and Cys in CSM diet, but decreased the AID and SID of Ile, Phe, Thr, Val, Ala, Pro, Ser, and Tyr in WSM diet. In conclusion, the OCMs screened by an in vitro method could improve the total tract nutrient digestibility and DE for pigs fed corn-based diet or wheat-based diet but had inconsistent effects on the ileal digestibility of nutrients and energy.

Both Magnetic Resonance Imaging and Computed Tomography Are Reliable and Valid in Evaluating Cystic Osteochondral Lesions of the Talus.

BACKGROUND: Compared with computed tomography (CT), magnetic resonance imaging (MRI) might overestimate the condition of osteochondral lesions of the talus (OLTs) owing to subchondral bone marrow edema and the overlying cartilage defect. However, no study has compared MRI and CT directly in evaluating OLTs with subchondral cysts. PURPOSE: To compare the reliability and validity of MRI and CT in evaluating OLTs with subchondral cysts. STUDY DESIGN: Cohort study (diagnosis); Level of evidence, 2. METHODS: An institutional radiology database was queried for inpatients diagnosed with OLTs with subchondral cysts who had undergone surgical treatment between May 2015 and October 2019. A total of 48 patients met the inclusion criteria. Based on our measurement method, 2 experienced observers who were blinded to the study independently measured the length, width, and depth of the cysts using MRI and CT. The classification of cystic lesions was also performed based on MRI and CT findings. RESULTS: Interobserver reliability was almost perfect, with intraclass correlation coefficients (ICCs) ranging from 0.935 to 0.999. ICCs for intraobserver reliability ranged from 0.944 to 0.976. The mean size of cysts measured on MRI (length, 13.38 ± 4.23 mm; width, 9.28 ± 2.28 mm; depth, 11.54 ± 3.69 mm) was not significantly different to that evaluated on CT (length, 13.40 ± 4.08 mm; width, 9.25 ± 2.34 mm; depth, 11.32 ± 3.54 mm). The size of subchondral cysts was precisely estimated on both MRI and CT. The MRI classification and CT classification revealed almost perfect agreement (kappa = 0.831). CONCLUSION: With our measurement method, both MRI and CT were deemed to be reliable and valid in evaluating the size of subchondral cysts of OLTs, and the MRI classification was well-correlated with the CT classification. The presented measurement method and classification systems could provide more accurate information before surgery.

Hearing Improvement in A/J Mice via the Mouse Nerve Growth Factor.

OBJECTIVES: To investigate the otoprotective effects of mouse nerve growth factor (mNGF) in A/J mice. METHODS: The mice at postnatal day 7 (P7) were randomly separated into a mNGF treated group (mNGF group) and a distilled water (for injection) treated group (control group). The mNGF dissolved in distilled water or distilled water alone was given to the mice once every other day from P7 by intramuscular injection in the hips. The otoprotective effects of mNGF in A/J mice were observed in a time course manner. The thresholds of auditory-evoked brainstem response (ABR) were tested from the age of the 3rd to the 8th week. Sections of the inner ears were stained by hematoxylin and eosin, and spiral ganglion neurons (SGNs) were observed at the age of the 3rd, the 6th,and the 8th week. Counts of whole mount outer hair cells (OHCs) in the cochleae were made at the age of 8 weeks. Expression of apoptosis related genes was determined by quantitative real-time polymerase chain reaction and Western blotting. RESULTS: ABR thresholds of the mNGF group were significantly lower than those of the control group at the age of the 6th and the 8th week. Moreover, the mNGF preserved OHC and SGN in the mouse cochleae in this period. Further experiments showed that the expression of caspase genes (including caspase-3) was inhibited in the mouse inner ears in the mNGF group. CONCLUSION: The mNGF improves hearing in A/J mice by preserving SGN and OHC in the cochleae.

Expression of calcitonin gene-related peptide, adenosine A2a receptor and adenosine A1 receptor in experiment rat migraine models.

A migraine is a disabling neurovascular disorder characterized by a unilateral throbbing headache that lasts from 4 to 72 h. The headache is often accompanied by nausea, vomiting, phonophobia and photophobia, and may be worsened by physical exercise. The trigeminovascular system (TVS) is speculated to have an important role in migraines, although the pathophysiology of this disorder remains to be elucidated. Trigeminal ganglion (TG) and spinal trigeminal nucleus caudalis (TNC) are important components of the TVS. Several clinical cases have provided evidence for the involvement of the brainstem in migraine initiation. Electrical stimulation of the trigeminal ganglion (ESTG) in rats can activate TVS during a migraine attack. Calcitonin gene-related peptide (CGRP) is an important vasoactive compound produced following TVS activation. Numerous studies have revealed that adenosine and its receptors have an important role in pain transmission and regulation process. However, only a few studies have examined whether adenosine A2a receptor (A2aR) and adenosine A1 receptor (A1R) are involved in migraine and nociceptive pathways. In the present study, CGRP, A2aR and A1R expression levels were detected in the TG and TNC of ESTG models through reverse transcription-quantitative polymerase chain reaction and western blot analysis. Tianshu capsule (TSC), a type of Chinese medicine, was also used in the ESTG rat models to examine its influence on the three proteins. Results demonstrated that CGRP, A2aR and A1R mediated pain transmission and the regulation process during migraine and the expression of the three proteins was regulated by TSC.

Attenuation of hearing loss in DBA/2J mice by anti-apoptotic treatment.

DBA/2J mice are characterized by early onset hearing loss at about 3-4 weeks of age. Mutations in cadherin 23 (Cdh23) and fascin-2 (Fscn2) are responsible for the phenotypes, but the underlying mechanism is unknown. In the present study, DBA/2J mice displayed progressive hair cell loss and degeneration of spiral ganglion neurons (SGNs) after 2 weeks of age; however, the mRNA level of Caspase-3 in the inner ears was much higher at 2 weeks of age than that at 4 or 8 weeks of age. Moreover, transcriptional levels of Caspase-3 and Caspase-9 in the inner ears of DBA/2J mice were significantly higher than those of C57BL/6J mice at 2 or 8 weeks of age. Immunohistochemistry localized Caspase-3 and Caspase-9 mainly to the hair cells, SGNs and stria vascularis of the cochleae. To determine the significance of caspase-dependent apoptosis in the hearing loss, the pan-caspase inhibitor Z-VAD-FMK was given intraperitoneally to DBA/J2 mice over an 8-week period starting at one week of age. Blockage of caspases preserved hearing in the mice by more than 10 dB (dB) sound pressure level (SPL) of the ABR thresholds and significantly reduced outer hair cell loss at the basal turns of the cochleae. These results demonstrate that apoptosis in the cochleae of DBA/J2 mice contributes to the early onset of hearing loss, which can be attenuated by anti-apoptotic treatment.

Caspase-mediated apoptosis in the cochleae contributes to the early onset of hearing loss in A/J mice.

A/J and C57BL/6 J (B6) mice share a mutation in Cdh23 (ahl allele) and are characterized by age-related hearing loss. However, hearing loss occurs much earlier in A/J mice at about four weeks of age. Recent study has revealed that a mutation in citrate synthase (Cs) is one of the main contributors, but the mechanism is largely unknown. In the present study, we showed that A/J mice displayed more severe degeneration of hair cells, spiral ganglion neurons, and stria vascularis in the cochleae compared with B6 mice. Moreover, messenger RNA accumulation levels of caspase-3 and caspase-9 in the inner ears of A/J mice were significantly higher than those in B6 mice at 2 and 8 weeks of age. Immunohistochemistry localized caspase-3 expression mainly to the hair cells, spiral ganglion neurons, and stria vascularis in cochleae. In vitro transfection with Cs short hairpin RNA (shRNA) alone or cotransfection with Cs shRNA and Cdh23 shRNA significantly increased the levels of caspase-3 in an inner ear cell line (HEI-OC1). Finally, a pan-caspase inhibitor Z-VAD-FMK could preserve the hearing of A/J mice by lowering about 15 decibels of the sound pressure level for the auditory-evoked brainstem response thresholds. In conclusion, our results suggest that caspase-mediated apoptosis in the cochleae, which may be related to a Cs mutation, contributes to the early onset of hearing loss in A/J mice.