Genetic characteristic analysis of slight-to-moderate sensorineural hearing loss in children / 临床耳鼻咽喉头颈外科杂志

Objective:To analyze genetic factors and phenotype characteristics in pediatric population with slight-to-moderate sensorineural hearing loss. Methods:Children with slight-to-moderate sensorineural hearing loss of and their parents, enrolled from the Chinese Deafness Genome Project, were studied. Hearing levels were assessed using pure tone audiometry, behavioral audiometry, auditory steady state response（ASSR）, auditory brainstem response（ABR） thresholds, and deformed partial otoacoustic emission（DPOAE）. Classification of hearing loss is according to the 2022 American College of Medical Genetics and Genomics（ACMG） Clinical Practice Guidelines for Hearing Loss. Whole exome sequencing（WES） and deafness gene Panel testing were performed on peripheral venous blood from probands and validations were performed on their parents by Sanger sequencing. Results:All 134 patients had childhood onset, exhibiting bilateral symmetrical slight-to-moderate sensorineural hearing loss, as indicated by audiological examinations. Of the 134 patients, 29（21.6%） had a family history of hearing loss, and the rest were sporadic patients. Genetic causative genes were identified in 66（49.3%） patients. A total of 11 causative genes were detected, of which GJB2 was causative in 34 cases（51.5%）, STRC in 10 cases（15.1%）, MPZL2 gene in six cases（9.1%）, and USH2A in five cases（7.6%）.The most common gene detected in slight-to-moderate hearing loss was GJB2, with c. 109G>A homozygous mutation found in 16 cases（47.1%） and c. 109G>A compound heterozygous mutation in 9 cases（26.5%）. Conclusion:This study provides a crucial genetic theory reference for early screening and detection of mild to moderate hearing loss in children, highlighting the predominance of recessive inheritance and the significance of gene like GJB2, STRC, MPZL2, USH2A.

Association of 24hour movement behaviors with emotional and behavioral problems among left-behind children / 中国学校卫生

Objective@#To examine the association of 24 hour movement behaviors with emotional and behavioral problems among left behind children, so as to provide a theoretical reference for the practice of 24 hour activity interventions to promote emotional and behavioral problems in this population.@*Methods@#From February to May 2023, 1 117 left behind children in grades 4-6 from 10 primary schools in five cities in Zhejiang Province were selected using a convenient cluster sampling method to conduct a questionnaire survey examining 24 hour movement behaviors, as well as emotional and behavioral problems. The general linear model was adopted to analyze the association between satisfying the 24 hour movement behavior guidelines, and emotional and behavioral problems among left behind children.@*Results@#The sleep duration compliance rate was the highest (52.19%), while the moderate-to-vigorous PA (MVPA) compliance rate was the lowest (17.73%). The compliance rate of the three activities accounted for 7.43 %. There was a dose response between the number of guidelines satisfied, and the emotional and behavior of left behind children; that was, satisfaction of a higher number of guidelines was associated with a lower risk of emotional and behavioral problems among left behind children (difficulty factor: β=-0.56, 95%CI =-1.23--0.19; strength factor: β=0.50, 95%CI =-0.48-1.22, P < 0.01). Compared to satisfying none of the guidelines, satisfying the guidelines for screen time ( β=-0.23, 95%CI =-2.18- -0.14 ) and sleep duration ( β=-0.13, 95%CI =-1.66--0.11) was negatively correlated with the difficulty factor, while satisfying the guideline for MVPA ( β=0.13, 95%CI =0.09-1.08) and sleep duration ( β=0.18, 95%CI =0.09-1.40) was positively associated with the strength factor. In addition, satisfying two or all three of the guidelines was more strongly associated with these outcomes than satisfying one of the recommendations ( P <0.01).@*Conclusions@#Meeting the 24 hour movement behavior guidelines can improve emotional and behavioral problems among left behind children. It is necessary to raise their awareness of the effect of satisfying the 24 hour movement behavior guidelines and formulate comprehensive intervention measures.

Correlation between clinical distribution characteristics of streptococcal pharyngitis in children and seasonal variations in Ziyang Area> / 公共卫生与预防医学

Objective To explore the correlation between clinical distribution characteristics of streptococcal pharyngitis in children and seasonal variations in Ziyang area, so as to provide basis for disease prevention and control. Methods A multistage and stratified random sampling technique was used to investigate 583 children with streptococcal pharyngitis attending Ziyang first people's Hospital from January 2022 to January 2023. The clinical data were recorded. The pharyngeal specimens were cultured for streptococci test. The number of streptococcal pharyngitis cases per season was counted. The metereological conditions (average barometric pressure, temperature, rainfall, and wind speed) were recorded. Pearson method was used to discuss the correlation between metereological factors and streptococcal pharyngitis onset. Results A total of the 583 children, 329 were male and 254 were female. The main age of onset was 7-12 years old, with a total of 227 cases (38.94%), followed by 199 cases (34.13%) aged 3-6 years old, 126 cases (21.61%) aged 1-2 years old, and 31 cases (5.32%) under 1 year old. A total of 614 strains of pathogenic bacteria were detected, of which 479 strains of Streptococcus hemolyticus were dominant, accounting for 78.01%, followed by 175 strains of Streptococcus pyogenes, accounting for 28.50%. Seasonally, 192 cases of streptococcal pharyngitis occurred in spring, 51 in summer, 72 in autumn and 268 in winter. In Ziyang, spring and winter were characterized by high mean wind speeds and barometric pressure, while summer and autumn were characterized by high mean temperatures and heavy rainfall. Pearson correlation analysis revealed that the prevalence rate streptococcal pharyngitis was positively correlated with average wind speed and barometric pressure (P<0.05), and negatively correlated with mean temperature and rainfall (P<0.05). Conclusion In Ziyang, streptococcal pharyngitis occurs mostly in children over 5 years old, and the main pathogen is Streptococcus hemolyticus. The onset of the disease is mostly in spring and winter, which is closely related to the seasonal variations of the region.

Development of auxiliary early predicting model for human brucellosis using machine learning algorithm / 中华预防医学杂志

Using machine learning algorithms to construct an early prediction model of brucellosis to improve the diagnosis efficiency of Brucellosis. This study was a case-control study. 2 381 brucellosis patients from Beijing Ditan Hospital affiliated to Capital Medical University were retrospectively collected as case group, and healthy people from Beijing Chaoyang Hospital affiliated to Capital Medical University were collected as control group from May 9, 2011 to November 29, 2021. The relevant clinical information and full blood count results of 13 257 data were collected and five algorithms of machine learning were used to construct an early predication model of brucellosis by using machine learning: random forest, Naive Bayes, decision tree, logistic regression and support vector machine;14 074 data (2 143 cases incase group and 11 931 cases in control group) were used to establish the early predication model of brucellosis, and 1 564 (238 cases in case group and 1 326 cases in control group) data were used to test the predication efficiency of the brucellosis model. The results showed that the support vector machine algorithm has the best predication performance by comparing the five machine learning models. The area under receiver curve (AUC) of receiver operating characteristic (ROC) was 0.991, and the accuracy, precision, specificity and Recall were 95.6%, 95.5%, 95.4% and 95.9%, respectively. Based on the SHAP plot, platelet distribution width (PDW) and basophil relative value (BASO%) results were low, and men with high coefficient of variation (R-CV), erythrocyte hemoglobin concentration (MCHC), and platelet volume (MPV) were predicted to be at high risk of brucellosis. Platelet distribution width (PDW) contributed the most to the prediction model, followed by red blood cell distribution width coefficient of variation (R-CV). In conclusion, the establishment of a high-precision early predication method of brucellosis based on machine learning may be of great significance for the early detection and treatment of brucellosis patients.

A preliminary prediction model of depression based on whole blood cell count by machine learning method / 中华预防医学杂志

This study used machine learning techniques combined with routine blood cell analysis parameters to build preliminary prediction models, helping differentiate patients with depression from healthy controls, or patients with anxiety. A multicenter study was performed by collecting blood cell analysis data of Beijing Chaoyang Hospital and the First Hospital of Hebei Medical University from 2020 to 2021. Machine learning techniques, including support vector machine, decision tree, naïve Bayes, random forest and multi-layer perceptron were explored to establish a prediction model of depression. The results showed that based on the blood cell analysis results of healthy controls and depression group, the accuracy of prediction model reached as high as 0.99, F1 was 0.975. Receiver operating characteristic curve area and average accuracy were 0.985 and 0.967, respectively. Platelet parameters contributed mostly to depression prediction model. While, to random forest differential diagnosis model based on the data from depression and anxiety groups, prediction accuracy reached 0.68 and AUC 0.622. Age, platelet parameters, and average volume of red blood cells contributed the most to the model. In conclusion, the study researched on the prediction model of depression by exploring blood cell analysis parameters, revealing that machine learning models were more objective in the evaluation of mental illness.

Development of auxiliary early predicting model for human brucellosis using machine learning algorithm / 中华预防医学杂志

Using machine learning algorithms to construct an early prediction model of brucellosis to improve the diagnosis efficiency of Brucellosis. This study was a case-control study. 2 381 brucellosis patients from Beijing Ditan Hospital affiliated to Capital Medical University were retrospectively collected as case group, and healthy people from Beijing Chaoyang Hospital affiliated to Capital Medical University were collected as control group from May 9, 2011 to November 29, 2021. The relevant clinical information and full blood count results of 13 257 data were collected and five algorithms of machine learning were used to construct an early predication model of brucellosis by using machine learning: random forest, Naive Bayes, decision tree, logistic regression and support vector machine;14 074 data (2 143 cases incase group and 11 931 cases in control group) were used to establish the early predication model of brucellosis, and 1 564 (238 cases in case group and 1 326 cases in control group) data were used to test the predication efficiency of the brucellosis model. The results showed that the support vector machine algorithm has the best predication performance by comparing the five machine learning models. The area under receiver curve (AUC) of receiver operating characteristic (ROC) was 0.991, and the accuracy, precision, specificity and Recall were 95.6%, 95.5%, 95.4% and 95.9%, respectively. Based on the SHAP plot, platelet distribution width (PDW) and basophil relative value (BASO%) results were low, and men with high coefficient of variation (R-CV), erythrocyte hemoglobin concentration (MCHC), and platelet volume (MPV) were predicted to be at high risk of brucellosis. Platelet distribution width (PDW) contributed the most to the prediction model, followed by red blood cell distribution width coefficient of variation (R-CV). In conclusion, the establishment of a high-precision early predication method of brucellosis based on machine learning may be of great significance for the early detection and treatment of brucellosis patients.

A preliminary prediction model of depression based on whole blood cell count by machine learning method / 中华预防医学杂志

This study used machine learning techniques combined with routine blood cell analysis parameters to build preliminary prediction models, helping differentiate patients with depression from healthy controls, or patients with anxiety. A multicenter study was performed by collecting blood cell analysis data of Beijing Chaoyang Hospital and the First Hospital of Hebei Medical University from 2020 to 2021. Machine learning techniques, including support vector machine, decision tree, naïve Bayes, random forest and multi-layer perceptron were explored to establish a prediction model of depression. The results showed that based on the blood cell analysis results of healthy controls and depression group, the accuracy of prediction model reached as high as 0.99, F1 was 0.975. Receiver operating characteristic curve area and average accuracy were 0.985 and 0.967, respectively. Platelet parameters contributed mostly to depression prediction model. While, to random forest differential diagnosis model based on the data from depression and anxiety groups, prediction accuracy reached 0.68 and AUC 0.622. Age, platelet parameters, and average volume of red blood cells contributed the most to the model. In conclusion, the study researched on the prediction model of depression by exploring blood cell analysis parameters, revealing that machine learning models were more objective in the evaluation of mental illness.

Research progress of amniotic membrane transplantation in the treatment of ophthalmic diseases / 国际眼科杂志(Guoji Yanke Zazhi)

Amniotic membrane is the innermost membrane in human placenta. It supports epithelialization and has the characteristics of anti-fibrosis, anti-inflammation and anti-angiogenesis. It is gradually widely used in ophthalmic surgery and other surgical operations. In recently years, the amniotic membrane has been used more frequently in ophthalmic clinic and has achieved better curative effect. This article reviews the application of amniotic membrane transplantation in ocular diseases such as ocular burn, conjunctival disease, corneal disease, pterygium, glaucoma and macular hole. It is expected that amniotic membrane transplantation will bring new ideas for the treatment of ocular diseases.

Neonatal testicular torsion: a study of 17 cases / 中国新生儿科杂志

Objective:To study the clinical manifestations and treatment of neonatal testicular torsion (NTT) and to summarize the experience of diagnosis and treatment.Methods:The clinical data of the patients with NTT admitted to the Department of Pediatric Urology in Guangzhou Women and Children's Medical Center from January 2015 to January 2021 were analyzed retrospectively. The data included demographic information, testicular torsion duration, clinical presentation, ultrasonography findings, surgical procedures, pathological results, follow-ups, and prognosis.Results:A total of 17 cases were enrolled in this study, and the median age was 5.2 d, ranging from 1 d to 17 d; the weight ranging from 2 800 g to 4 000 g. 11 cases of left testicular torsion and 6 cases of right testicular torsion. The median time from onset to medical attention was 3.8 d, ranging from 10 h to 15 d. The first manifestations being reported were scrotal swelling, color change, or painless mass. Emergency ultrasound revealed that the blood flow signal in the testis was significantly reduced or disappeared, and heterogeneous mass echoes were detected in the scrotum. Surgical exploration was performed in all 17 cases and confirmed to be testicular torsion. There were 15 cases of extravaginal torsion and 2 cases of intravaginal torsion. There were 6 cases of clockwise torsion and 11 cases of anticlockwise torsion. The average degree of twisted testis was 450.8°, ranging from 270° to 720°. The rate of orchiectomy was 88.2% (15/17). All patients were followed up for a minimum of 1 year postoperatively. None of the patients experienced postoperative bleeding or infection at the scrotal incision site. There were no instances of recurrent testicular torsion, and the contralateral testicles showed no abnormalities. In 2 cases where the affected testicle was preserved, ultrasound reevaluation at 6 months postoperatively revealed atrophy of the affected testicle.Conclusions:NTT is rare in clinics and lacks specificity, with a high rate of testis loss. When the newborns exhibit scrotal swelling, color change, or other abnormalities, testicular torsion cannot be ruled out, and early surgical exploration is required.

Practice in the Construction of Specialized Subject in National Regional Medical Centers / 中国医院管理

The construction of national regional medical centers is an important initiative for the reform of the na-tional medical service system,and 125 national regional medical centers have been approved nationwide.As one of the first batch of 10 national regional medical center projects approved,the Chongli Branch of Peking University Third Hospital,in accordance with the positioning of"Ice and Snow Sports Medical Center",features the treatment of sports trauma diseases,adopts the model of"large specialty,small comprehensive",and takes the principle of homogeneous development,utilizing the brand,technology and talent advantages of the Peking University Third Hospital,has rapidly improved the medical service capacity of the Chongli Branch,and successfully completed the medical security tasks of the Beijing 2022 Winter Olympic Games and Winter Paralympic Games.Peking University Third Hospital Headquarters and Chongli Branch were awarded the title of"Outstanding Contribution to the Beijing Winter Olympics and Winter Paralympics"by the State Council of the CPC Central Committee respectively.

Current situation of trademark registration and brand protection of grade-A tertiary hospitals in China / 中华医院管理杂志

Objective:To investigate the trademark registration situation of grade-A tertiary hospitals in China, so as to analyze the current situation of hospital brand protection and explore suggestions for hospital brand protection.Methods:The top 50 hospitals ranked in the 2021 National Hospital Comprehensive Ranking by the Hospital Management Research Institute of Fudan University, excluding military hospitals, were selected as the sample hospitals. The trademark registration information of the 50 sample hospitals was queried through the China Trademark Website of the Trademark Office of China National Intellectual Property Administration on March 15, 2023, and the registration of the full name, abbreviation, hospital emblem and other trademarks of the hospitals was counted. Results:Among the 50 sample hospitals, 26 hospitals already held hospital brand trademarks, which meant that at least one of the hospital′s full name, abbreviation, and emblem was registered as a trademark, accounting for 52%; 7 hospitals did not hold any trademarks, accounting for 14%; 17 hospitals held other trademarks but did not hold hospital brand trademarks, accounting for 34%. Among the 26 hospitals that already held brand trademarks, 11 hospitals only registered in one category. There were 3 hospitals with expired registered trademarks.Conclusions:Nearly half of the sample hospitals did not hold hospital brand trademarks, indicating that the trademark registration and brand protection of tertiary hospitals in China need to be strengthened. It is suggested to establish a hospital brand protection system, clarify the trademark management department, standardize the responsibilities of trademark management, and improve the use of trademarks, so as to do a good job in hospital trademark registration and brand protection.

Mechanism of Wuling Capsules against hepatic fibrosis based on network pharmacology and animal experiments / 中国中药杂志

The present study aimed to explore the underlying mechanism of Wuling Capsules in the treatment of hepatic fibrosis(HF) through network pharmacology, molecular docking, and animal experiments. Firstly, the chemical components and targets of Wuling Capsules against HF were searched from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), Traditional Chinese Medicines Integrated Database(TCMID), GeneCards, and literature retrieval. The protein-protein interaction(PPI) network analysis was carried out on the common targets by STRING database and Cytoscape 3.9.1 software, and the core targets were screened, followed by Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses. Enrichment analysis was conducted on the core targets and the "drug-core component-target-pathway-disease" network was further constructed. Subsequently, molecular docking between core components and core targets was conducted using AutoDock Vina software to predict the underlying mechanism of action against HF. Finally, an HF model induced by CCl_4 was constructed in rats, and the general signs and liver tissue morphology were observed. HE and Masson staining were used to analyze the liver tissue sections. The effects of Wuling Capsules on the levels of inflammatory factors, hydroxyproline(HYP) levels, and core targets were analyzed by ELISA, RT-PCR, etc. A total of 445 chemical components of Wuling Capsules were screened, corresponding to 3 882 potential targets, intersecting with 1 240 targets of HF, and 47 core targets such as TNF, IL6, INS, and PIK3CA were screened. GO and KEGG enrichment analysis showed that the core targets mainly affected the process of cell stimulation response and metabolic regulation, involving cancer, PI3K-Akt, MAPK, and other signaling pathways. Molecular docking showed that the core components of Wuling Capsules, such as lucidenic acid K, ganoderic acid B, lucidenic acid N, saikosaponin Q2, and neocryptotanshinone, had high affinities with the core targets, such as TNF, IL6 and PIK3CA. Animal experiments showed that Wuling Capsules could reduce fat vacuole, inflammatory infiltration, and collagen deposition in rat liver, decrease the levels of inflammatory cytokines TNF-α, IL-6, and HYP, and downregulated the expressions of PI3K and Akt mRNA. This study suggests that the anti-HF effect of Wuling Capsules may be achieved by regulating the PI3K-Akt signaling pathway, reducing the levels of TNF-α and IL-6 inflammatory factors, and inhibiting the excessive deposition of collagen.

Research progress on electrical impedance tomography in pulmonary perfusion / 生物医学工程学杂志

Electrical impedance tomography (EIT) is an emerging technology for real-time monitoring based on the impedance differences of different tissues and organs in the human body. It has been initially applied in clinical research as well as disease diagnosis and treatment. Lung perfusion refers to the blood flow perfusion function of lung tissue, and the occurrence and development of many diseases are closely related to lung perfusion. Therefore, real-time monitoring of lung perfusion is particularly important. The application and development of EIT further promote the monitoring of lung perfusion, and related research has made great progress. This article reviews the principles of EIT imaging, lung perfusion imaging methods, and their clinical applications in recent years, with the aim of providing assistance to clinical and scientific researchers.

Relationship between early postoperative recovery and frailty after digestive endoscopy-assisted minimally invasive surgery under intravenous anesthesia in the elderly / 中华麻醉学杂志

Objective:To evaluate the relationship between early postoperative recovery and frailty after digestive endoscopy-assisted minimally invasive surgery under intravenous anesthesia in the elderly.Methods:This study retrospectively selected hospitalized patients, aged ≥65 yr, scheduled for elective gastrointestinal endoscopic treatment.Early postoperative recovery time was defined as the period from the end of propofol administration to the achievement of a modified Aldrete score of 9.All the patients were divided into 2 groups according to whether the early recovery time after operation was less than 75%: normal early postoperative recovery time group and delayed early postoperative recovery time group.Frailty was assessed using the frailty phenotype (FP score 0-5), and the patient was diagnosed as frail (FP ≥3) or non-frail (FP 0-2). The age, sex, height, weight, smoking history, American Society of Anesthesiologists (ASA) Physical Status classification, type of operation, and baseline mean arterial pressure and heart rate were recorded.Logistic regression analysis was used to identify the risk factors for delayed early postoperative recovery time after minimally invasive digestive endoscopy under intravenous anesthesia in elderly patients.Results:A total of 214 patients were enrolled and divided into normal early postoperative recovery time group ( n=169) and delayed early postoperative recovery time group ( n=45). There were significant differences in frailty, age, drinking history of more than 10 yr, preoperative ASA Physical Status classification and propofol administration time between delayed early postoperative recovery time group and normal early postoperative recovery time group ( P<0.05). The results of logistic regression analysis indicated that frailty, age, ASA Physical Status classification Ⅲ, and propofol administration time were independent risk factors for the occurrence of delayed early postoperative recovery ( P<0.05). Conclusions:Frailty, age, ASA Physical Status classification Ⅲ and propofol administration time are independent risk factors for delayed early postoperative recovery time following digestive endoscopy-assisted minimally invasive surgery under intravenous anesthesia in elderly patients.

Application of routine laboratory data in combination with machine learning in the differential diagnosis of lung tuberculosis / 中华检验医学杂志

Objective:To investigate the application value of establishing the differential diagnosis model of pulmonary tuberculosis using routine laboratory data.Methods:The retrospective study was conducted. The routine laboratory data of newly diagnosed patients with pulmonary tuberculosis and other pulmonary diseases in Beijng Jishuitan Hospital and Beijing Hepingli Hospital from May 2015 to November 2021were collected. According to the random numbers showed in the computer, all the 11516 patients were divided into training dataset and test dataset with a ratio of 9∶1. Four machine learning algorithms, Support Vector Machine, Random Forest, K-Nearest Neighbor and Logistic Regression, were used to build models and select features. The diagnostic accuracy of each model was verified by using the 10-fold cross-validation method and the performance of each model was evaluated by using the receptor operator of characteristic (ROC) curve.Results:Random Forest was selected as the optimal machine learning algorithm to build the best feature model in the study. According to importance scale of factors, the differential diagnosis model of pulmonary tuberculosis consisting of 37 non-specific test indexes. In the validation set and test set the accuracy and area under curve (AUC) of the models were 0.747 and 0.736, the sensitivity, specificity and accuracy were 68.03% and 68.75%, 70.91% and 67.90%, 70.30% and 68.12%, respectively.Conclusion:A key tool in the differential diagnosis model of pulmonary tuberculosis was established by routine laboratory data in combination with machine learning. The results of this study need to be further verified by more data from medical institutions.

Quantitative proteomics revealed extensive microenvironmental changes after stem cell transplantation in ischemic stroke / 医学前沿

The local microenvironment is essential to stem cell-based therapy for ischemic stroke, and spatiotemporal changes of the microenvironment in the pathological process provide vital clues for understanding the therapeutic mechanisms. However, relevant studies on microenvironmental changes were mainly confined in the acute phase of stroke, and long-term changes remain unclear. This study aimed to investigate the microenvironmental changes in the subacute and chronic phases of ischemic stroke after stem cell transplantation. Herein, induced pluripotent stem cells (iPSCs) and neural stem cells (NSCs) were transplanted into the ischemic brain established by middle cerebral artery occlusion surgery. Positron emission tomography imaging and neurological tests were applied to evaluate the metabolic and neurofunctional alterations of rats transplanted with stem cells. Quantitative proteomics was employed to investigate the protein expression profiles in iPSCs-transplanted brain in the subacute and chronic phases of stroke. Compared with NSCs-transplanted rats, significantly increased glucose metabolism and neurofunctional scores were observed in iPSCs-transplanted rats. Subsequent proteomic data of iPSCs-transplanted rats identified a total of 39 differentially expressed proteins in the subacute and chronic phases, which are involved in various ischemic stroke-related biological processes, including neuronal survival, axonal remodeling, antioxidative stress, and mitochondrial function restoration. Taken together, our study indicated that iPSCs have a positive therapeutic effect in ischemic stroke and emphasized the wide-ranging microenvironmental changes in the subacute and chronic phases.

Analysis of Crucial Transcription Factors of Berberine Against Cerebral Ischemia Based on Transcriptomics and Proteomics / 中国实验方剂学杂志

ObjectiveOn the basis of determining the protective effect of berberine （BBR） on cerebral ischemia， crucial transcription factors （TFs） of BBR against cerebral ischemia was identified by using transcriptome and proteome sequencing. MethodThe model of middle cerebral artery occlusion （MCAO） was established by thread embolization. The sham operation group， model group， low-dose group of BBR （dose of 37.5 mg·kg-1·d-1） and high-dose group of BBR （75 mg·kg-1·d-1） were set up. The rats were killed after continuous intragastric administration for 7 days. The pharmacodynamics was evaluated by Longa score and cerebral infarction rate， and the expressions of inflammatory cytokines， such as interleukin （IL）-1β， tumor necrosis factor （TNF）-α and monocyte chemotactic protein-1 （MCP-1） were measured by enzyme-linked immunosorbent assay （ELISA）. Then， RNA-Seq technique was used to detect the differentially expressed genes （DEGs） before and after BBR intervention， and DAVID 6.8 was used for enrichment analysis of DEGs. CatTFREs technique was used to detect differential TFs before and after BBR intervention， and DAVID 6.8 and STRING 11.0 were used for enrichment analysis and TFs association analysis. Finally， by integrating the activity of TFs and the changes of downstream target genes， crucial TFs were identified and the related regulatory network was constructed by Cytoscape 3.7.1. ResultCompared with the sham operation group， the neurological impairment was significant in the model group （P<0.01）， and compared with the model group， the low and high dose BBR groups could significantly reduce the neurological function damage （P<0.01） and decrease the rate of cerebral infarction （P<0.01）. Transcriptome data analysis showed that BBR was involved in the recovery process after cerebral ischemia mainly by affecting cell adhesion， brain development， neuron migration， calcium signaling pathway， cyclic adenosine monophosphate （cAMP） signaling pathway， inflammatory response and other related functions and signaling pathways. Proteomic data analysis showed that the differentially expressed TFs after BBR intervention interfered with cerebral ischemia mainly by regulating cell differentiation， immune system process， cell proliferation and other biological processes. In addition， integration analysis of TFs and DEGs revealed that transcription factor CP2-like 1 （TFCP2L1）， nuclear factor erythroid-2 like 1 （NFE2L1）， neurogenic differentiation protein 6 （NeuroD6） and POU domain， class 2， transcription factor 1 （POU2F1） were crucial TFs against cerebral ischemia-reperfusion injury mediated by BBR. ConclusionBBR has obvious protective effect on cerebral ischemia-reperfusion injury and its crucial TFs include TFCP2L1， NFE2L1， NeuroD6 and POU2F1.

Molecular Mechanism Analysis of Dengzhan Shengmai Capsules Against Chronic Cerebral Hypoperfusion / 中国实验方剂学杂志

ObjectiveBased on the protective effect of Dengzhan Shengmai capsules （DZSM） on chronic cerebral hypoperfusion （CCH）， network pharmacology was employed to investigate the molecular mechanism. MethodCCH model was established by right common carotid artery ligation. The mice were divided into sham operation group， model group， ginaton group （48 mg·kg-1）， DZSM low- and high-dose groups （0.040 5， 0.162 g·kg-1）. The efficacy was evaluated by the Morris water maze test and open-field test. The underlying mechanism of DZSM for CCH was analyzed by network pharmacology and verified by molecular biology experiments. PubChem， GeneCards， Metascape and other databases were used for targets collection and enrichment analysis. Besides， the association of ingredients targets of DZSM with disease targets of CCH， core target network and chemical components-core targets-pathways network were constructed by STRING 11.0 and Cytoscape 3.7.1. ResultThe escape latency of CCH mice significantly shortened on the 3rd to 5th day after DZSM low-dose treatment， the crossing times， time spent in the target quadrant， movement distance and distance in the central region of CCH mice significantly increased after DZSM low-dose and high-dose treatment. The results of network pharmacology indicated that DZSM might play a key role by regulating inflammatory response， phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway， cytokine-cytokine receptor interaction， tumor necrosis factor （TNF） signaling pathway， blood circulation， angiogenesis， extracellular matrix and other related biological processes and pathways， and acting as targets such as interleukin-6 （IL-6）， TNF， insulin-like growth factor 1 （IGF1）， vascular endothelial growth factor A （VEGFA）， epidermal growth factor （EGF）. The results of biological experiments showed that DZSM could reduce the expression of IL-6 in brain tissue of CCH mice. ConclusionDZSM provides a protective effect during CCH， and its multi-component， multi-pathway， multi-target mechanism is also revealed， which provides a basis for further study of the mechanism.

Expression and Significance of Circulating microRNA-29b in Adult Fulminant Myocarditis / 中国医学科学院学报

Objective To explore the expression profiles of circulating microRNA(miRNA)and potential markers for the diagnosis of adult fulminant myocarditis(FM). Methods The expression profiles of circulating miRNA were determined by microarray analysis and verified by real-time quantitative PCR.The key role of circulating miRNA in FM was determined via KEGG pathway enrichment.The correlations between miRNA and cardiac function parameters in patients with FM were analyzed.The receiver operating characteristic(ROC)curve was established to evaluate the sensitivity and specificity of circulating miRNA in the diagnosis of FM. Results Compared with healthy controls,the FM patients had up-regulated expression levels of miR-29b(t=18.925,P<0.001)and miR-125b(t=5.981,P=0.029)in the plasma.After treatment,the expression levels of miR-29b(t=12.943,P<0.001)and miR-125b(t=14.016,P<0.001)were significantly down-regulated.KEGG pathway enrichment showed that the targets of miR-29b were involved in inflammatory response and apoptosis pathways.The results of cell proliferation and apoptosis assay demonstrated the transfection of miR-29b mimic had a more significant inducing effect on cardiomyocyte apoptosis than that of miR-125b mimic(χ 2=6.168,P=0.047),whereas there was no significant difference in the inhibition of cell proliferation between the two groups(χ2=1.452,P=0.417).The expression levels of miR-29b and miR-125b were negatively correlated with left ventricular ejection fraction(r=-0.67,P=0.071;r=-0.49,P=0.003).They were positively correlated with cardiac troponin I level(r=0.61,P=0.019;r=0.52,P=0.016),interferon β level(r=0.42,P=0.014;r=0.36,P=0.021),and myocardial edema area(r=0.86,P=0.005;r=0.73,P=0.013).The ROC curve analysis demonstrated that miR-29b had higher sensitivity for the diagnosis of FM(93.6% vs.89.2%;t=0.896,P=0.795)and specificity(72.4% vs.59.6%;t=9.478,P=0.002)than miR-125b. Conclusion The circulating miR-29b may be a potential biomarker for the diagnosis of FM.

The Biphasic Effect of Retinoic Acid Signaling Pathway on the Biased Differentiation of Atrial-like and Sinoatrial Node-like Cells from hiPSC

Background and Objectives@#Although human-induced pluripotent stem cells (hiPSC) can be efficiently differentiated into cardiomyocytes (CMs), the heterogeneity of the hiPSC-CMs hampers their applications in research and regenerative medicine. Retinoic acid (RA)-mediated signaling pathway has been proved indispensable in cardiac development and differentiation of hiPSC toward atrial CMs. This study was aimed to test whether RA signaling pathway can be manipulated to direct the differentiation into sinoatrial node (SAN) CMs. @*Methods@#and Results: Using the well-characterized GiWi protocol that cardiomyocytes are generated from hiPSC via temporal modulation of Wnt signaling pathway by small molecules, RA signaling pathway was manipulated during the differentiation of hiPSC-CMs on day 5 post-differentiation, a crucial time point equivalent to the transition from cardiac mesoderm to cardiac progenitor cells in cardiac development. The resultant CMs were characterized at mRNA, protein and electrophysiology levels by a combination of qPCR, immunofluorescence, flow cytometry, and whole-cell patch clamp. The results showed that activation of the RA signaling pathway biased the differentiation of atrial CMs, whereas inhibition of the signaling pathway biased the differentiation of sinoatrial node-like cells (SANLCs). @*Conclusions@#Our study not only provides a novel and simple strategy to enrich SANLCs but also improves our under-standing of the importance of RA signaling in the differentiation of hiPSC-CMs.