Blaps rynchopetera affects proliferation, migration, and invasion of non-small cell lung cancer: a study based on network pharmacology and in vivo and in vitro experiments / 中国中药杂志

Network pharmacology, molecular docking, and in vivo and in vitro experiments were employed to study the molecular mechanism of Blaps rynchopetera Fairmaire in the treatment of non-small cell lung cancer(NSCLC). The components of B. rynchopetera were collected by literature review, and the active components were screened out through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). PharmMapper was used to obtain the targets of the active components. The targets of NSCLC were obtained from DrugBank, GeneCards, OMIM, TTD, and PharmGKB. The Venn diagram was drawn to identify the common targets shared by the active components of B. rynchopetera and NSCLC. The "drug component-target" network and protein-protein interaction(PPI) network were constructed by Cytoscape, and the key targets were screened by Centiscape. Gene Ontology(GO) annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment of the above key targets were performed by DAVID. AutoDock and PyMOL were used for the molecular docking between the key targets and corresponding active components. A total of 31 active components, 72 potential targets, and 11 key targets of B. rynchopetera against NSCLC were obtained. The active components of B. rynchopetera had good binding activity with key targets. Further, the serum containing B. rynchopetera was prepared and used to culture human lung adenocarcinoma A549 cells. The CCK-8 assay was employed to determine the inhibition rates on the growth of A549 cells in blank control group and those exposed to different concentrations of B. rynchopetera-containing serum, cisplatin, and drug combination(B. rynchopetera-containing serum+cisplatin) for different time periods. The cell migration and invasion of A549 cells were detected by cell scratch assay and Transwell assay, respectively. Western blot was employed to determine the expression levels of B-cell lymphoma-2(Bcl-2), Bcl-2-associated X(Bax), caspase-3, cell division cycle 42(CDC42), proto-oncogene tyrosine-protein kinase SRC, and vascular endothelial growth factor(VEGF) in A549 cells. C57BL/6 mice were inoculated with Lewis cells and randomly assigned into a model control group, a B. rynchopetera group, a cisplatin group, and a drug combination(B. rynchopetera+cisplatin) group, with 12 mice per group. The body weight and the long diameter(a) and short diameter(b) of the tumor were monitored every other day during treatment, and the tumor volume(mm~3) was calculated as 0.52ab~2. After 14 days of continuous medication, the mice were sacrificed for the collection of tumor, spleen, and thymus, and the tumor inhibition rate and immune organ indexes were calculated. The tissue morphology of tumors was observed by hematoxylin-eosin(HE) staining, and the positive expression of Bax, Bcl-2, caspase-3, CDC42, SRC, and VEGF in the tumor tissue was detected by immunohistochemistry. The results indicated that B. rynchopetera and the drug combination regulated the expression levels of Bax, Bcl-2, caspase-3, CDC42, SRC, and VEGF to inhibit the proliferation, migration, and invasion of A549 cells and Lewis cells, thus playing a role in the treatment of NSCLC via multiple ways.

The value of cardiac MRI in the risk stratification in patients with hypertrophic cardiomyopathy / 中华心血管病杂志

Objective: To explore the value of cardiac magnetic resonance imaging (CMR) in the risk stratification of hypertrophic cardiomyopathy (HCM). Methods: HCM patients who underwent CMR examination in Fuwai Hospital between March 2012 and May 2013 were retrospectively enrolled. Baseline clinical and CMR data were collected and patient follow-up was performed using telephone contact and medical record. The primary composite endpoint was sudden cardiac death (SCD) or and equivalent event. The secondary composite endpoint was all-cause death and heart transplant. Patients were divided into SCD and non-SCD groups. Cox regression was used to explore risk factors of adverse events. Receiver operating characteristic (ROC) curve analysis was used to assess the performance and the optimal cut-off of late gadolinium enhancement percentage (LGE%) for the prediction of endpoints. Kaplan-Meier and log-rank tests were used to compare survival differences between groups. Results: A total of 442 patients were enrolled. Mean age was (48.5±12.4) years and 143(32.4%) were female. At (7.6±2.5) years of follow-up, 30 (6.8%) patients met the primary endpoint including 23 SCD and 7 SCD equivalent events, and 36 (8.1%) patients met the secondary endpoint including 33 all-cause death and 3 heart transplant. In multivariate Cox regression, syncope(HR=4.531, 95%CI 2.033-10.099, P<0.001), LGE% (HR=1.075, 95%CI 1.032-1.120, P=0.001) and left ventricular ejection fraction (LVEF) (HR=0.956, 95%CI 0.923-0.991, P=0.013) were independent risk factors for primary endpoint; Age (HR=1.032, 95%CI 1.001-1.064, P=0.046), atrial fibrillation (HR=2.977, 95%CI 1.446-6.131, P=0.003),LGE% (HR=1.075, 95%CI 1.035-1.116, P<0.001) and LVEF (HR=0.968, 95%CI 0.937-1.000, P=0.047) were independent risk factors for secondary endpoint. ROC curve showed the optimal LGE% cut-offs were 5.1% and 5.8% for the prediction of primary and secondary endpoint, respectively. Patients were further divided into LGE%=0, 0<LGE%<5%, 5%≤LGE%<15% and LGE%≥15% groups. There were significant survival differences between these 4 groups whether for primary endpoint or secondary endpoint (all P<0.001) and the accumulated incidence of primary endpoint was 1.2% (2/161), 2.2% (2/89), 10.5% (16/152) and 25.0% (10/40), respectively. Conclusion: LGE is an independent risk factor for SCD events as well as all-cause death and heart transplant. LGE is of important value in the risk stratification in patients with HCM.

Blaps rynchopetera combined with cyclophosphamide affects proliferation and apoptosis of lung cancer cells via Wnt/β-catenin signaling pathway / 中国中药杂志

This study aims to investigate the effects of Blaps rynchopetera Fairmaire and/or cyclophosphamide on the proliferation and apoptosis of lung cancer cells and decipher the underlying mechanism. B. rynchopetera and cyclophosphamide-containing serum and blank serum were prepared from SD rats. Cell counting kit-8(CCK-8) assay was employed to examine the proliferation of lung cancer cell lines A549 and Lewis treated with corresponding agents. The Jin's formula method was used to evaluate the combined effect of the two drugs. According to the evaluation results, appropriate drug concentrations and lung cancer cell line were selected for subsequent experiments, which included control, B. rynchopetera, cyclophosphamide, B. rynchopetera + cyclophosphamide, and B. rynchopetera + Wnt/β-catenin pathway agonist lithium chloride(LiCl) groups. Immunocytochemistry was employed to measure the expression of proliferation-related proteins in Lewis cells after drug interventions. Flow cytometry was employed to determine the cell cycle and apoptosis. The expression levels of proliferating cell nuclear antigen(PCNA), cyclinD1, B-cell lymphoma 2(Bcl-2), Bcl-2-assiocated X protein(Bax), Wnt1, and β-catenin were determined by Western blot. The results showed that B. rynchopetera and/or cyclophosphamide significantly inhibited the proliferation of A549 and Lewis cells. Compared with B. rynchopetera alone, the combination increased the inhibition rate on cell proliferation. The combination of B. rynchopetera and cyclophosphamide demonstrated a synergistic effect according to Jin's formula-based evaluation. Compared with the control group, the B. rynchopetera, cyclophosphamide, and B. rynchopetera + cyclophosphamide groups showed increased proportion of Lewis cells in G_0/G_1 phase, increased apoptosis rate, up-regulated expression of Bax, and down-regulated expression of PCNA, cyclinD1, Bcl-2, Wnt1, and β-catenin. Compared with the cyclophosphamide group, the combination group showed increased proportion of cells in G_0/G_1 phase, increased apoptosis rate, up-regulated expression of Bax, and down-regulated expression of PCNA, cyclinD1, Bcl-2, Wnt1, and β-catenin. Compared with the B. rynchopetera group, the B. rynchopetera + LiCl group had deceased proportion of cells in G_0/G_1 phase, decreased apoptosis rate, down-regulated expression of Bax, and up-regulated expression of PCNA, cyclinD1, Bcl-2, Wnt1, and β-catenin. The results indicated that B. rynchopetera could inhibit the proliferation, arrest the cell cycle, and induce the apoptosis of lung cancer cells by inhibiting the Wnt/β-catenin signaling pathway. Moreover, B. rynchopetera had a synergistic effect with cyclophosphamide.

Ruscogenin alleviates LPS-triggered pulmonary endothelial barrier dysfunction through targeting NMMHC IIA to modulate TLR4 signaling

Pulmonary endothelial barrier dysfunction is a hallmark of clinical pulmonary edema and contributes to the development of acute lung injury (ALI). Here we reported that ruscogenin (RUS), an effective steroidal sapogenin of Radix Ophiopogon japonicus, attenuated lipopolysaccharides (LPS)-induced pulmonary endothelial barrier disruption through mediating non-muscle myosin heavy chain IIA (NMMHC IIA)‒Toll-like receptor 4 (TLR4) interactions. By in vivo and in vitro experiments, we observed that RUS administration significantly ameliorated LPS-triggered pulmonary endothelial barrier dysfunction and ALI. Moreover, we identified that RUS directly targeted NMMHC IIA on its N-terminal and head domain by serial affinity chromatography, molecular docking, biolayer interferometry, and microscale thermophoresis analyses. Downregulation of endothelial NMMHC IIA expression in vivo and in vitro abolished the protective effect of RUS. It was also observed that NMMHC IIA was dissociated from TLR4 and then activating TLR4 downstream Src/vascular endothelial cadherin (VE-cadherin) signaling in pulmonary vascular endothelial cells after LPS treatment, which could be restored by RUS. Collectively, these findings provide pharmacological evidence showing that RUS attenuates LPS-induced pulmonary endothelial barrier dysfunction by inhibiting TLR4/Src/VE-cadherin pathway through targeting NMMHC IIA and mediating NMMHC IIA‒TLR4 interactions.

Erratum: Author correction to 'Ruscogenin alleviates LPS-triggered pulmonary endothelial barrier dysfunction through targeting NMMHC IIA to modulate TLR4 signaling' Acta Pharmaceutica Sinica B 12 (2022) 1198-1212

[This corrects the article DOI: 10.1016/j.apsb.2021.09.017.].

Effect of acupuncture for dysphagia after stroke based on fiberoptic endoscopic swallowing function evaluation / 中国针灸

OBJECTIVE@#To observe the effect of acupuncture combined with regular treatment and swallowing function training on pharyngeal motor, sensory function and penetration-aspiration function in patients with dysphagia after stroke.@*METHODS@#A total of 60 patients with dysphagia after stroke were randomly divided into a control group and an observation group, 30 patients in each group. Both groups were treated with conventional treatment and swallowing function training; in addition, the observation group was treated with acupuncture at Lianquan (CV 23), Fengfu (GV 16), Yifeng (TE 17). All the treatments were given once a day, 5 days a week, for totally 4 weeks. In the two groups, the pharyngeal motor and sensory function, penetration-aspiration scores were evaluated by fiberoptic endoscopic evaluation of swallowing (FEES), and the Kubota water swallowing test scores were assessed before and after treatment, and the clinical effects were compared.@*RESULTS@#After treatment, the pharyngeal motor and sensory function in the two groups were all higher than those before treatment (P<0.05), and those in the observation group were better than the control group (P<0.05). After treatment, the penetration-aspiration scores and Kubota water swallowing test scores in the two groups were all lower than those before treatment (P<0.05), and those in the observation group were lower than the control group (P<0.05). The total effective rate was 93.3% (28/30) in the observation group, which was better than 73.3% (22/30) in the control group (P<0.05).@*CONCLUSION@#Acupuncture combined with regular treatment and swallowing training could improve the pharyngeal motor and sensory function, and penetration-aspiration scores in patients with dysphagia after stroke.

Altered Splicing in Stable Cell Strains Expressing Mini-hF9 Gene with Nonsense Mutation / 中国实验血液学杂志

OBJECTIVE@#To investigate the molecular mechanism in stable cell strains expressing Mini-hF9 gene with nonsense mutation.@*METHODS@#Mini-hF9 gene and its nonsense mutants were transfected into HeLa cells independently, and stable cell strains were obtained after G418 resistance screening and monoclonal transformation. The altered splicing and protein expression of mRNA in Mini-hF9 gene in stable cell strains were detected by using RT-PCR and Western blot.@*RESULTS@#The wild type and nonsense mutated human coagulation factor IX stable cell strains were constructed successfully, which were named HeLa-F9-WT, HeLa-F9-M1 and HeLa-F9-M2. Only normal splicing Norm was detected in the wild-type cell strain HeLa-F9-WT; Norm and Alt-S1 splicing were detected in HeLa-F9-M1; while Norm, Alt-S1 and Alt-S2 splicing were detected in HeLa-F9-M2.@*CONCLUSION@#The nonsense associated altered splicing (NAS) pathway, which generated alternately spliced transcripts, might be triggered in coagulation factor IX gene with nonsense mutation.

Role of cardiac magnetic resonance imaging in myocarditis patients with biopsy negative: a retrospective case series study / 中华心血管病杂志

Objective: To analyze the cardiac magnetic resonance (CMR) imaging feature of clinically diagnosed myocarditis patients with negative endocardial biopsy (EMB) results, and to further demonstrate the diagnostic value of CMR in these patients. Methods: This was a retrospective case series study. Fourteen patients, who were clinically diagnosed as myocarditis according to 2013 European Society of Cardiology (ESC) clinical diagnostic criteria for myocarditis, but with negative EMB results, were enrolled. All patients underwent CMR examinations. The morphological, functional and histological changes of the heart were assessed based on black blood sequence, cine sequence, T2W-STIR sequence and contrast agent late gadolinium enhancement,(LGE). Results: There were 10 males and 4 females in this cohort, the age was (25.6±13.2) years. The interval between symptom onset and CMR was 21 (13, 60) days, and the interval between symptom onset and EMB was 19 (9, 40) days. There were 13 patients with abnormal CMR results including myocardial oedema, fibrosis, decreased ejection fraction, pericardial effusion or increased cardiac chamber dimension. Nine out of 14 patients had CMR morphological and/or functional abnormalities, including 1 case of left atrium enlargement, 1 case of left ventricle enlargement, 3 cases of right ventricle enlargement, 4 cases of increased left ventricular end diastolic volume index. Left ventricular ejection fraction was<50% in three cases, right ventricular ejection fraction was<40% in 5 cases, and pericardial effusion depth>3 mm was detected in 3 cases. Of the 14 patients, 11 had histological changes, of which 6 had T2 ratio≥2. Among the 10 patients (10/14) with positive LGE, the most common patterns were subepicardial LGE of the lateral wall and/or midwall LGE of the septum (n=9); 2 cases showed extensively subendocardial LGE of the left ventricular wall. No LGE involved in the right ventricular wall in the whole cohort. Conclusion: CMR plays a complementary role in the diagnosis of myocarditis in clinically diagnosed myocarditis patients with negative EMB findings.

Research progress on whitening of brown adipose tissues / 中国药理学通报

Brown adipose tissues can consume energy by generating heat. The whitening of BAT will damage its thermogenic function and cause diseases related to obesity and metabolic disorders. It is of great significance to slow down or inhibit the process of BAT whitening. This article reviews the inducing factorsand the key regulators of brown adipose tissue whitening, hoping to provide some ideas for the prevention and treatment of obesity and metabolic disorders.

Biopathway construction of plant natural products / 药学学报

Plant natural products (PNPs) are important sources of innovative drugs. They are mainly obtained by isolation or extraction from plants. Low content and with structural analogues in plants result in high production cost, which restricts the research and application of PNPs. While biopathway construction by synthetic biology provides an alternative for production of PNPs. By biosynthetic pathway analysis of PNPs and reconstructing the biopathway in microorganisms, we can produce PNPs in cell factories efficiently. Recently, several predominantly international reports about biosynthesis of PNPs and its synthetic biology production, triggered the researches of PNPs. Abundant traditional Chinese medicine resources and profound cultural heritage of Chinese medicine make biosynthesis pathway analysis of PNPs to be a research hotspot. And some of the studies have achieved significant progress. Here, recent progress in the biosynthesis of plant natural products and its synthetic biology was reviewed. In particular, the application of new methods and technologies in recent years were summarized and discussed. This will provide reference for the biopathway construction of plant natural products.

Analysis and health risk assessment, including recommendation of limits for heavy metals and harmful elements in Chinese patent medicines / 药学学报

Heavy metals and other harmful elements in traditional Chinese medicines inflict serious damage on public health. Therefore, risk assessment of Chinese raw materials has gained increasing attention. To date, few reports have been published on the health risk assessment of heavy metals and harmful elements in Chinese patent medicines. To gain a comprehensive understanding of heavy metals and other harmful elements in Chinese patent medicines and to establish proper limits, residual Pb, Cd, As, Hg, Cu and Cr in 15 054 samples of 295 drugs was analyzed with regard to distribution and variation between elements and dosage forms. In addition, in accord with procedures including hazard identification, hazard characterization, exposure assessment and risk characterization, basic procedures and specific parameters for risk assessment of heavy metals and harmful elements in Chinese patent medicines were clarified based on the health risk assessment of 14 787 samples and 276 drugs. A method and equation for establishing residual limits is proposed. The results show that content and target hazard quotients (THQs) of the investigated elements in all samples showed a skewed distribution approaching 0. Content of Pb, As, Cu, Hg, Cd or Cr in the samples exceeded 100 mg·kg-1 and the content of Pb, As, or Cu in individual samples exceeded 1 000 mg·kg-1. THQs of 586 samples and four drugs were above 1. We believe that the health risk of Hg, Pb and As in Chinese patent medicines with dosage forms of pill, capsule, tablet and powder, especially those in raw powder preparations, warrant concern.

Late gadolinium enhancement distribution pattern of left ventricular wall in patients with dilated cardiomyopathy: a preliminary study / 中华心血管病杂志

Objective: To investigate the distribution pattern of late gadolinium enhancement (LGE) in left ventricular free wall of patients with dilated cardiomyopathy (DCM). Methods: A total of 130 consecutive DCM patients who were hospitalized in our hospital, underwent both CMR and CTA examinations and met the inclusion and exclusion criteria including negative results of coronary angiography or coronary CTA, were retrospective included in this study. The LGE pattern, extent and distribution in left ventricular free wall were analyzed. Results: Left ventricular free wall LGE was detected in 56 out of 130 DCM patients. LGE was observed in both septal and free wall in 53 out of 56 patients with LGE (94.6%). Prevalence of NYHA classification Ⅲ/Ⅳ, intraventricular block, paroxysmal ventricular tachycardia, and secondary mitral insufficiency was significantly higher, while left ventricular ejection fraction was significantly lower, left ventricular end-diastolic/systolic volume, left ventricular end-diastolic/systolic volume index and left ventricular end-diastolic diameters values were larger in patients with LGE than without LGE (all P<0.05). In terms LGE pattern among these 56 patients, percent of involved myocardial segments in patients with subepicardial LGE (n=19) was significantly higher than patients with intermural LGE (n=30), patients with transmural LGE (n=21), and patients with subendocardial LGE (n=9)(60.8%(127/209) vs. 32.4%(107/330), 32.5%(75/231), 26.3%(26/99), respectively, all P < 0.01). Transmural LGE was most likely to involve the left ventricular inferior lateral basal (18/21) and mid (13/21) segment, followed by anterior lateral basal (15/21) and mid (11/21) segments and inferior mid segment (9/21). Subepicardial LGE was more likely to occur in the inferior lateral basal (13/19) and mid (16/19) segment, anterior lateral basal (13/19) and mid (15/19) segment, anterior lateral basal (13/19) and mid (15/19) segment, lateral apical (13/19), anterior and inferior mid segment (12/19 and 10/19), and apical segment (15/19 and 10/19). Intermural LGE mostly involved the anterior and inferior basal (19/30, 16/30) and mid (18/30 and 14/30) segment. There were 33 cases of single LGE pattern and 23 cases of multiple LGE pattern. Percent of involved myocardial segments was significantly higher in multiple LGE group than single LGE group (60.9% (154/253) vs. 49.9%(181/363), P = 0.007). Of 130 patients, 23 received heart transplantation, of which 6 patients had septal LGE alone and 17 patients had septal and free wall LGE. The rate of heart transplantation in the latter group was higher (32.1% (17/53)vs. 13.6%(6/44), P=0.034). Conclusions: There are several LGE distribution patterns in left ventricular wall among DCM patients.

The Characteristics and Survival Outcomes in Patients Aged 70 Years and Older with Nasopharyngeal Carcinoma in the Intensity-Modulated Radiotherapy Era / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: We aim to examine nasopharyngeal carcinoma (NPC) characteristics and survival outcomes in patients aged 70 years and older in the intensity-modulated radiotherapy (IMRT) era. MATERIALS AND METHODS: From 2006 to 2013, 126 non-metastatic NPC patients aged ≥ 70 years who were treated with IMRT +/‒ chemotherapy were included. Adult Comorbidity Evaluation 27 (ACE-27) was used to measure patient comorbidities. The overall survival (OS) and cancer-specific survival (CSS)were calculatedwith the Kaplan-Meier method, and differenceswere compared using the log-rank test. The Cox proportional hazards model was used to carry out multivariate analyses. RESULTS: For the entire group, only two patients (1.6%) presented stage I disease, and up to 84.1% patients had stage III-IVB disease. All patients had a comorbidity score of 0 in 24 (19.0%), 1 in 45 (35.7%), 2 in 42 (33.3%), and 3 in 15 (11.9%) patients. The main acute grade during radiotherapy was 3-4 adverse events consisting of mucositis (25.4%), bone marrow suppression (16.7%), and dermatitis (8.7%). After treatment, four patients (3.2%) developed temporal lobe injury. Five-year CSS and OS rates were 67.3% (95% confidence interval [CI], 58.6% to 77.4%) and 54.0% (95% CI, 45.6% to 63.9%), respectively. Five-year OS was significantly higher for ACE-27 score 0-1 than ACE-27 score 2-3 (72.9% and 39.9%, respectively; p 0.05). CONCLUSION: Our findings suggest IMRT +/– chemotherapy has a manageable toxicity and provides an acceptable survival in patients aged ≥ 70 years with NPC. ACE-27 score was significantly associated with survival outcomes in this group population.

Factors in first-time adrenocorticotropic hormone therapy and their influence on spasm control time in infantile spasms: a Cox proportional-hazards regression model analysis / 中国当代儿科杂志

OBJECTIVE@#To investigate the factors in first-time adrenocorticotropic hormone (ACTH) therapy and their influence on spasm control time in infants with infantile spasms.@*METHODS@#A total of 72 infants with infantile spasms who were admitted from January 2008 to October 2013 were enrolled. Their clinical data were collected, and the exposure factors for infantile spasms were selected. A Cox proportional-hazards regression model analysis was performed for these factors to analyze their influence on spasm control time.@*RESULTS@#Clarification of the etiology (known or unexplained etiology), frequency of spasms before treatment, and presence or absence of combination therapy (ACTH used alone or in combination with magnesium sulfate) had a significant influence on spasm control time in infants with infantile spasms. The infants with a known etiology had a significantly shorter spasm control time than those with unexplained etiology, and the infants with a low frequency of spasms before treatment and receiving ACTH combined with magnesium sulfate early had a significantly longer spasm control time than their counterparts (P<0.05).@*CONCLUSIONS@#For infants with infantile spasms at initial diagnosis, etiology should be clarified, which may helpful for evaluating prognosis. A combination of ACTH and magnesium sulfate should be given as soon as possible, which may improve their prognosis.

Mechanism study of orientin protecting rat heart from myocardial ischemia/reperfusion injury based on mitochondrial quality control / 中草药

Objective To investigate the regulation effects of orientin on mitochondrial quality control in cardiomyocytes of rats with myocardial ischemia/reperfusion injury (MIRI). Methods A total of 75 Sprague-Dawley male rats were randomly divided into five groups: sham group, model group, and orientin preconditioning groups (1.0, 2.0, and 4.0 mg/kg). Except for sham group, all rats were exposed to modeling of MIRI with ligation of left anterior descending coronary artery (LADCA) for 30 min, and then releasing for 120 min. Mitochondrial membrane potential (MMP) and opening of mitochondrial permeability transition pore (mPTP) were detected by Microplate Reader; Activity of mitochondrial respiratory chain complexes I-IV was detected by Spectrophotometer; Cardiomyocyte apoptosis was detected by TUNEL method; Apoptosis and mitophagy related proteins were detected by Western Blot and the interaction between Parkin and p62 on mitochondria were detected by Co-IP. Results Orientin significantly restored MMP, mPTP opening threshold and activity of mitochondrial respiratory chain complexes I-IV, and reduced cardiomyocyte apoptosis. Additionally, orientin can dramatically inhibit the protein expression level apoptosis and mitophagy related proteins and weaken the interaction between Parkin and p62. Conclusion Orientin has a significant protective effect on cardiomyocyte mitochondria in MIRI rats. Its underlying mechanism is related to inhibition of hyperactivity of mitophagy in cardiomyocytes via Parkin-dependent and Parkin-independent signaling pathways.

Prognostic factors of surgery for idiopathic macular hole / 上海交通大学学报（医学版）

Idiopathic macular hole (IMH) refers to full thickness defects of retinal neuroepithelial layer in macular area without clear reasons, and par plana vitrectomy with internal limiting membrane peeling (ILMP) has been routine operation to treat IMH. There are many possible factors influencing the prognosis of surgery, including age, sex, duration of disease, visual acuity before operation, stage and diameter of IMH, various MH index, surgical techniques, dyeing agent, vitreous tamponade, head position after operation, recoverment of ellipsoid zone, and so on. A comprehensive analysis of these prognostic factors could contribute to predict the patients' recoverment and communicate better with patients. It could also help to exclude confounding factors when the new clinical trials were conducted. Furthermore, more prospective clinical trials are needed to obtain high quality evidence.

Value of Pediatric Early Warning Score in identifying the condition of critically ill children / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the value of Pediatric Early Warning Score (PEWS) in identifying the condition of critically ill children.</p><p><b>METHODS</b>A total of 120 children who were transferred to the pediatric intensive care unit (PICU) from the general ward during hospitalization or admitted to the PICU after emergency treatment in the Xiangya Hospital of Central South University from January to December, 2016 were enrolled as the PICU group. The other 120 children who were admitted to the general ward in the hospital were used as the control group. According to the disease type, the PICU group was further divided into two subgroups: respiratory/circulatory system diseases (n=55) and nervous/other system diseases (n=65). The PEWS score on admission was recorded, and the receiver operating characteristic (ROC) curve was used to analyze the value of PEWS in evaluating patients' condition.</p><p><b>RESULTS</b>The PICU group had a significantly higher PEWS score than the control group (P<0.05). The respiratory/circulatory system disease subgroup had a significantly higher PEWS score than the nervous/other system disease subgroup (P<0.05). In predicting whether the child was admitted to the PICU, PEWS had a sensitivity of 85%, a specificity of 95%, and an area under the ROC curve (AUC) of 0.951 (95% confidence interval: 0.923-0.980) at the optimal cut-off value of 3.5 (PEWS score). The AUC of PEWS was 0.768 in the nervous/other system disease subgroup and 0.968 in the respiratory/circulatory system disease subgroup. The mortality rate of children with a PEWS score of >6, 4-6 and ≤3 was 40%, 21% and 0 respectively (P<0.001).</p><p><b>CONCLUSIONS</b>PEWS can well identify disease severity in critically ill children, and it has different sensitivities in children with different varieties of diseases. PEWS has a good value in predicting children's prognosis.</p>

Preliminary application of Early Start Denver Model in children with autism spectrum disorder / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the clinical effect of the Early Start Denver Model (ESDM) in children with autism spectrum disorder (ASD).</p><p><b>METHODS</b>Forty children aged 2-5 years who were diagnosed with ASD from September 2017 to January 2018 were enrolled in the study and were randomly divided into conventional intervention group and ESDM intervention group (n=20 each). Both groups were assessed by the Aberrant Behavior Checklist (ABC), Childhood Autism Rating Scale (CARS), and Clinical Global Impression-Severity (CGI-S) scale before intervention and by the ABC, CARS, CGI-S scale, and Clinical Global Impression-Improvement (CGI-I) scale after 3 months of intervention.</p><p><b>RESULTS</b>After 3 months of intervention, the total scores of ABC and CARS were both significantly decreased in the two groups (P<0.01); the scores on the social withdrawal and hyperactivity subscales of ABC were significantly decreased in the conventional intervention group (P<0.01), and the scores on the mood swings, social withdrawal, hyperactivity, and stereotyped behavior subscales of ABC were significantly decreased in the ESDM intervention group (P<0.01). Compared with the conventional intervention group, the ESDM intervention group had significantly greater changes in total score of ABC, scores on three subscales of ABC (mood swings, social withdrawal, and hyperactivity), and total score of CARS after intervention (P<0.05). After 3 months of intervention, the CGI-I scoring system showed that the disease improvement was significantly better in the ESDM intervention group than in the conventional intervention group (P<0.05).</p><p><b>CONCLUSIONS</b>Both conventional intervention and ESDM intervention can improve the social withdrawal and hyperactivity in children with ASD aged 2 to 5 years, but ESDM is more effective in improving the aberrant behavior of children with ASD.</p>

Prognostic factors of surgery for idiopathic macular hole / 上海交通大学学报（医学版）

Idiopathic macular hole (IMH) refers to full thickness defects of retinal neuroepithelial layer in macular area without clear reasons,and par plana vitrectomy with internal limiting membrane peeling (ILMP) has been routine operation to treat IMH.There are many possible factors influencing the prognosis of surgery,including age,sex,duration of disease,visual acuity before operation,stage and diameter of IMH,various MH index,surgical techniques,dyeing agent,vitreous tamponade,head position after operation,recoverment of ellipsoid zone,and so on.A comprehensive analysis of these prognostic factors could contribute to predict the patients' recoverment and communicate better with patients.It could also help to exclude confounding factors when the new clinical trials were conducted.Furthermore,more prospective clinical trials are needed to obtain high quality evidence.

Psychomotor retardation with neutropenia for more than one year in a toddler / 中国当代儿科杂志

A boy was admitted at the age of 17 months. He had psychomotor retardation in early infancy. Physical examination revealed microcephalus, unusual facies, and a single palmar crease on his right hand, as well as muscle hypotonia in the extremities and hyperextension of the bilateral shoulder and hip joints. Genetic detection identified two pathogenic compound heterozygous mutations, c.8868-1G>A (splicing) and c.11624_11625del (p.V3875Afs*10), in the VPS13B gene, and thus the boy was diagnosed with Cohen syndrome. Cohen syndrome is a rare autosomal recessive disorder caused by the VPS13B gene mutations and has complex clinical manifestations. Its clinical features include microcephalus, unusual facies, neutropenia, and joint hyperextension. VPS13B gene detection helps to make a confirmed diagnosis.