Hypoxic-ischemic (HI) brain damage poses a high risk of death or lifelong disability, yet effective treatments remain elusive. Here, we demonstrated that miR-100-5p levels in the lesioned cortex increased after HI insult in neonatal mice. Knockdown of miR-100-5p expression in the brain attenuated brain injury and promoted functional recovery, through inhibiting the cleaved-caspase-3 level, microglia activation, and the release of proinflammation cytokines following HI injury. Engineered extracellular vesicles (EVs) containing neuron-targeting rabies virus glycoprotein (RVG) and miR-100-5p antagonists (RVG-EVs-Antagomir) selectively targeted brain lesions and reduced miR-100-5p levels after intranasal delivery. Both pre- and post-HI administration showed therapeutic benefits. Mechanistically, we identified protein phosphatase 3 catalytic subunit alpha (Ppp3ca) as a novel candidate target gene of miR-100-5p, inhibiting c-Fos expression and neuronal apoptosis following HI insult. In conclusion, our non-invasive method using engineered EVs to deliver miR-100-5p antagomirs to the brain significantly improves functional recovery after HI injury by targeting Ppp3ca to suppress neuronal apoptosis.
Animals ; MicroRNAs/metabolism* ; Extracellular Vesicles/metabolism* ; Mice ; Recovery of Function/physiology* ; Hypoxia-Ischemia, Brain/therapy* ; Mice, Inbred C57BL ; Antagomirs/administration & dosage* ; Male ; Animals, Newborn ; Apoptosis/drug effects* ; Brain Injuries/metabolism* ; Glycoproteins ; Peptide Fragments ; Viral Proteins

Objective To investigate the safety and efficacy of endoscopic thyroid surgery through axillary approach in the treatment of unilateral papillary thyroid carcinoma.Methods A total of 135 patients admitted to Yunnan Cancer Hospital from April 2022 to November 2022 were selected.According to the surgical method,69 patients were in the endoscopic group and 66 patients were in the open surgery group.The clinical data,operation time,intraoperative blood loss,postoperative drainage volume,postoperative hospitalization stay,complications,cosmetic satisfaction,scar evaluation,postoperative swallowing pain and blood calcium,blood phosphorus,PTH levels of the two groups were observed.Results There were no significant differences in general data,pathological features,number of lymph node dissection,and perioperative complications between the two groups(P>0.05).The operation time and postoperative drainage volume in the endoscopic group were significantly higher than those in the open surgery group.The intraoperative blood loss,postoperative hospital stay,pain score,serum calcium,serum phosphorus,PTH levels and cosmetic satisfaction in the endoscopic group were significantly better than those in the open group(P<0.05).Conclusion Transaxillary approach endoscopic thyroid surgery for the treatment of single-sided papillary thyroid carcinoma is safe,feasible,and provides better protection of the parathyroid glands,postoperative swallowing pain,and cosmetic satisfaction.

ObjectiveTo explore the mechanism of Jianpi Yishen Huazhuo prescription in the improvement of ovarian function in polycystic ovary syndrome （PCOS）. MethodSeventy female SD rats in SPF grade were randomly divided into 6 groups， 15 in the blank group and 15 in the model group， 10 in the metformin group （0.1 g·kg^-1·d^-1）， and 10 in the low （1.275 g·kg^-1·d^-1）， medium （2.55 g·kg^-1·d^-1）， and high-dose （5.10 g·kg^-1·d^-1） Jianpi Yishen Huazhuo prescription groups. The blank group was given normal saline （10 mL·kg^-1·d^-1） by gavage and ordinary feed， and the other groups were given letrozole （1 mg·kg^-1·d^-1） by gavage combined with high-fat feed for 21 days to induce the model of PCOS. After modeling， the blank group and model group were given equal volume normal saline by gavage， and each drug group was given the corresponding dose of the drug by gavage for 30 days. The changes in body mass and fasting blood glucose （FPG） of rats before and after modeling were compared. Hematoxylin eosin （HE） staining was used to observe the morphological change in the ovaries of rats in each group. The serum levels of follicle stimulating hormone （FSH）， luteinizing hormone （LH）， testosterone （T）， anti-Mullerian hormone （AMH）， and estradiol （E₂） were measured by enzyme-linked immunosorbent assay （ELISA）， and the LH/FSH ratio was calculated. Immunohistochemical staining （IHC） and Western blot were used to detect the protein expression levels of nucleoside binding oligomerization domain protein like receptor 3 （NALP3）， apoptosis-associated speck-like protein （ASC）， cysteine protease-1 （Caspase-1）， nuclear transcription factor-κB （NF-κB）， interleukin-1β （IL-1β）， interleukin-18 （IL-18）， and interleukin-6 （IL-6） in the rat ovaries. ResultAs compared with the blank group， large follicles with polycystic expansion were found in the ovaries of the model group， no dominant follicles were found， the granular layer of follicles decreased and arranged loosely， and the number of corpus luteum decreased significantly. Serum T， LH， AMH and LH/FSH increased in the model group （P<0.05， P<0.01）， while FSH and E₂ decreased （P<0.05， P<0.01）. The relative protein expression levels of NALP3， ASC， Caspase-1， NF-κB， IL-1β， IL-18， and IL-6 increased （P<0.05， P<0.01） in the ovaries of the model group. Compared with the model group， the low， medium， and high-dose Jianpi Yishen Huazhuo prescription groups and the metformin group showed growing follicles and corpus luteum at all levels， the number of cystic expanding follicles decreased， the thickness of follicular granular layer increased， the number of follicular fluid increased， mature follicles were visible， and the local morphology of oocytes was complete. Serum T， LH， AMH， and LH/FSH in these groups decreased （P<0.05， P<0.01）， while E₂ and FSH increased （P<0.05）. The relative protein expressions of NALP3， ASC， Caspase-1， NF-κB， IL-1β， IL-18， and IL-6 in the ovaries of these groups decreased （P<0.05， P<0.01）. There was no significant difference among the treatment groups. ConclusionBy inhibiting the activation of NLRP3 inflammasome， Jianpi Yishen Huazhuo prescription reduces the release of NALP3， ASC， Caspase-1， NF-κB， IL-18， IL-1β， and IL-6 inflammatory factors in ovarian tissues， regulates endocrine level， and effectively reduces PCOS inflammatory statu， so as to play a role in improving ovarian function.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder.Its typical symptoms include social disorder, stereotyped behavior and restrictive interest.In addition, sensory abnormality is also a common symptom of ASD individuals.Pre-attentive processing is an automatic cognitive process that takes place before attention and is independent of consciousness, which reflects the ability to automatically detect changes in the environment of brain.Many researches show that the sensory abnormality and social ability disorder in ASD patients may be related to the defects in the pre-attentive processing stage.Mismatch negativity (MMN) is the most commonly used indicator of pre-attentive processing.ASD individuals show abnormal MMN in response to both social and non-social stimulus.Among them, the pre-attentive processing defect of non-social stimuli in ASD individuals is manifested as the amplitude or latency of MMN induced by single tones, voice or visual stimuli, which is different from that of normal people.The pre-attentive processing defect of social stimuli in ASD individuals is manifested as the amplitude or latency of MMN induced by emotional voice and emotional face, which is different from that of normal people.This result not only helps to find the physiological mechanism of sensory and social disorders in ASD individuals, but also provides theoretical support for MMN as an auxiliary diagnostic index of ASD.Future research on the pre-attentive processing of ASD individuals should pay more attention to enriching the research paradigms of MMN and adopting more kinds of social stimuli.At the same time, the influence of ASD genetic factors on MMN can also be one of the concerns of future research.

Objective:To investigate the predictive value of MRI radiomics model in assessing the early response to concurrent chemoradiotherapy for locally advanced cervical squamous cell carcinoma.Methods:A total of 367 patients with pathologically proven locally advanced cervical squamous cell carcinoma (International Federation of Gynecology and Obstetrics stage ⅡB-ⅣA) in Liaoning Cancer Hospital & Institute from January 2013 to June 2019 were retrospectively collected. The patients were unable to undergo surgery and received complete concurrent chemoradiotherapy. Pelvic plain MRI, DWI and dynamic contrast-enhanced MRI were performed within 2 weeks before treatment and at the end of the 4th week of treatment. Patients were divided into complete response (CR) group ( n=247) and non-CR group ( n=120) according to response evaluation criteria in solid tumors 1.1. The patients were divided into a training set ( n=256) and a validation set (n=111) via a randomized split method at a ratio of 7∶3. Two radiologists drew the region of interest on the DWI, T 2WI and contrast-enhanced T 1WI (delayed phase) images before treatment to form the volume of interest finally. Totally 1 906 radiomics features were extracted from 3 single sequence images, respectively. Feature correlation analysis and tree model were used for feature selection. Three classifier learning algorithms, namely logistic regression (LR), support vector machine and random forest, were used for machine learning and the best classifier was selected. Based on the best classifier, 3 single sequence radiomics models were built, and a multi-sequence combined model was obtained by multivariate LR analysis. The differences in the area under the receiver operating characteristic curve (AUC) of the 3 single sequence models and the multi-sequence combined model were compared by DeLong test. The clinical application value of the multi-sequence combined model was evaluated by decision analysis curve. Results:In the training set and validation set, the LR classifier model had the best performance. Based on the LR classifier, AUCs of DWI, T 2WI, contrast-enhanced T 1WI and combined sequences in the training set were 0.77, 0.74, 0.79 and 0.86, respectively, and AUCs in the validation set were 0.71, 0.66, 0.75 and 0.77, respectively. In the training set, the AUC of multi-sequence combined model was higher than those of DWI, T 2WI and contrast-enhanced T 1WI sequence models, and the differences were statistically significant ( Z=3.01, 3.56, 2.83; P=0.003, 0.001, 0.005). In the validation set, the AUC of multi-sequence combined model and T 2WI model had significant difference ( Z=2.46, P=0.015). The decision analysis curve showed that when the threshold probability was in the range of 0.44 to 0.88, the multi-sequence combined model yielded a net benefit. Conclusion:Based on the LR classifier, the combined model built by radiomics features of multi-sequence MRI images has predictive value for assessing the early response of concurrent chemoradiotherapy for locally advanced cervical squamous cell carcinoma.

Objective:To investigate the value of tumor hemodynamics and morphological features from conventional dynamic contrast-enhanced MRI (DCE-MRI) scan before surgery in predicting postoperative recurrence time in breast cancer patients.Methods:A retrospective analysis of 58 patients with breast cancer who had recurred after operation from November 2012 to December 2014 in Liaoning Cancer Hospital was performed. According to the recurrence time, the patients were divided into early recurrence group (≤2 years after surgery, 33 cases) and late recurrence group (>2 years after surgery, 25 cases). All patients underwent routine DCE-MRI scans before surgery, and hemodynamic features of the three-dimensional volume of the tumor and the morphological and textural features of the tumor in each phase were extracted by computer. The counts and measurement data of patients in early recurrence group and late recurrence group were compared by Fisher′s exact probability method and Mann-Whitney U test, and receiver operating characteristic (ROC) curves were drawn. The multivariate logistic regression was used to calculate the combined efficacy in predicting early recurrence and late recurrence. Kaplan-Meier method was used to analyze the survival prognosis, and Log-Rank test was used to compare the differences in survival curves between groups. Results:There was no significant difference in background parenchymal enhancement, lesion margin, lesion internal enhancement characteristics, lesion morphology, time-signal intensity curve type and the degree of whole-breast vascularity increase between early recurrence and late recurrence groups ( P>0.05).There were significant differences in the maximum concentration of contrast (Max Conc), the area under the time signal curve (AUC) and the maximum slope value of the time signal curve (Max Slope) ( P<0.05). Comparative analysis of the radiomics parameters of 8 phases DCE-MRI found that the sphericity of morphological characteristic parameters in the phase 3 was statistically different between the early recurrence and late recurrence groups ( P=0.03). Area under the ROC curve of AUC, Max Conc, Max Slope and parameter sphericity of phase 3 morphological characteristics for predicting early and late recurrence were 0.664, 0.659, 0.684 and 0.670, respectively. The area under the ROC combined with the above four parameters for prediction was 0.765, with a specificity of 63.6% and a sensitivity of 84.0%; the predictive efficacy was higher than that of univariate. Fifty-eight patients were followed up for 17 to 64 months with a median follow-up of 47 months. The disease-free survival and overall survival in the early recurrence group were significantly lower than those in the late recurrence group, and the difference was statistically significant ( P<0.05). Conclusion:It is of certain value to predict the postoperative recurrence time of breast cancer based on the tumor hemodynamic characteristics combined with morphological characteristics from preoperative non-invasive conventional DCE-MRI.

OBJECTIVE:To establish a method for simultaneous determination of 5 constituents in Phyllanthus emblica,and to conduct principal component analysis and cluster analysis of contents of 5 polyphenolic constituents in P. emblica from different producing areas of Guangxi. METHODS:HPLC method was adopted to determine the contents of gallic acid,epigallocatechin, corilagin,terminalia biphenyl acid and ellagic acid in P. emblica. The determination was performed on Agilent Eclipse XDB column with mobile phase consisted of acetonitrile-0.1％ phosphoric acid aqueous solution (gradient elution) at the flow rate of 1.0 mL/min. The detection wavelength was set at 220 nm,and column temperature was 25 ℃. The sample size was 20 μL. The results of content determination was processed by principal component analysis and cluster analysis. RESULTS:The linear range of gallic acid, gallocatechin, corilagin, chebulagic acid and ellagic acid were 1.994-31.90, 0.1598-2.556, 4.533-45.33, 14.75-88.49, 2.956-47.30 μg/mL(r≥0.9998),respectively. The limits of detection were 0.0256,0.0271,0.0529,0.1867,0.1331 μg/mL;the limits of quantitation were 0.0851,0.0893,0.1706,0.6152,0.4419 μg/mL,respectively. RSDs of precision,stability(24 h) and reproducibility tests were all<2.0％(n=6 or n=7). The average recoveries were 96.19％-101.49％(RSD=0.98％-1.41％, n=6). 12 batches of samples had 3 main components. They could be divided into 2 categories. P. emblica from Rong county of Yulin city in Guangxi Zhuang Autonomous Region had highest comprehensive principal component score and best quality. CONCLUSIONS:Established method is simple,accurate and reliable,and can be used for the simultaneous determination of gallic acid,gallocatechin,corilagin,chebulagic acid and ellagic acid in P. emblica. The quality of P. emblica from different producing areas in Guangxi is different.

Objective To explore the value of MRI in differential diagnosis of breast medullary carcinoma and fibroadenoma.Methods Data of 11 patients with medullary carcinoma (medullary carcinoma group) and 36 patients with fibroadenoma (fibroadenoma group) confirmed with pathology were analyzed retrospectively.MRI characteristics were analyzed and compared between the two groups.Results The age of patients in medullary carcinoma group was greater than those in fibroadenoma group (t=2.791,P=0.008).There were statistical differences of the maximum diameter of lesions,internal enhancement characteristics,necrotic and cystic degeneration of lesions,un-enhanced T2WI signal intensity of lesions,DWI signal intensity of lesions and time-signal intensity curve (TIC) type (all P＜0.05),while no statistical difference of lesion numbers,morphology and edge of lesions was found between the two groups (all P＞0.05).Conclusion The features of MRI are helpful to differential diagnosis of medullary carcinoma and fibroadenoma of the breast.

Objective To investigate the value of differential diagnosis of benign and malignant of breast cystic lesion with thin-wall in MRI. Methods Retrospective analysis from January 2012 to December 2016 Liaoning Cancer Hospital diagnosis confirmed by surgery and pathology, and a total of 81 lesions (76 patients) of breast cystic lesions with thin-wall on MRI enhanced images (thickness no more than 5 mm, mural node less than 10 mm and solid position less than 50％)were enrolled. All patients underwent bilateral breast plain scan and dynamic contrast-enhanced scan. Using MRI breast imaging reporting and data system (BI-RADS) standard to analyze the MRI plain scan and dynamic contrast-enhanced scan images. Analysis of the margin of the lesion, internal enhancing features and time signal intensity curve (TIC) type and other characteristics. The feature of wall margin, thickness and enhancement form, mural nodules and internal septation morphological were analysed by Chi-square test. TIC type and wall nodule position were analysed by Fisher method. Wall nodule sizes were analysed by using independent sample t test. Results Of the 81 lesions, 67 were benign lesions and 14 were malignant. Among benign lesions, 56 were with well-defined margin, 58 were with uniform wall thickness and 7 were with mural nodule. Among malignant lesions, 5 were with well-defined margin, 8 were with uniform wall thickness and 9 were with mural nodule, which showed statistically significant difference between benign and malignant lesions (P<0.05). Of the 9 malignant lesions with wall nodules, 7 were located outside the wall, 1 between the wall, and 1 within the wall. Of the 7 benign lesions with wall nodules, 4 were located between the wall, 1 within the wall and 2 outside the wall, which were significant difference in the location of nodules between benign and malignant lesion (χ2=6.228,P=0.043). There was no significant difference between benign and malignant lesions in the homogeneous enhancing, internal separations and wall nodule size (P>0.05). Nine lesions can not obtain TIC to analyse enhancement degree due to thin linear enhancement of cyst wall. Through the analysis of TIC type of 58 benign lesions and 14 malignant lesions, Type Ⅰ and type Ⅱ TIC were more commonly presented in benign lesions. Type Ⅱ and type Ⅲ were more commonly found in malignant lesions, and TIC types were statistically different (P<0.05). There was no significant difference in the degree of cystic wall enhancement (P>0.05). Conclusion Most of breast cystic lesion with thin-wall are benign lesion, cystic wall enhancement characteristics combined with time-signal intensity curve helps to find malignant lesion.

Polylactic acid is synthesized indirectly by the polymerization method, according to the standard GB/T 16886.18-2011, the evaluation parameters and methods about chemical characterization of polylactic acid have been established. By using rigorous and comprehensive comparative analysis, the chemical equivalency of domestic and imported polylactic acid materials has been proved, along with the "Medical Device Biology Evaluation and Review Guide", paving the way of using domestic polylactic acid in implantable medical devices.
Equipment and Supplies ; Lactic Acid ; Polyesters ; chemistry ; Polymers