Construction of multi-enzyme cascade reactions and its application in the synthesis of bifunctional chemicals / 生物工程学报

The synthesis of fine chemicals using multi-enzyme cascade reactions is a recent hot research topic in the field of biocatalysis. The traditional chemical synthesis methods were replaced by constructing in vitro multi-enzyme cascades, then the green synthesis of a variety of bifunctional chemicals can be achieved. This article summarizes the construction strategies of different types of multi-enzyme cascade reactions and their characteristics. In addition, the general methods for recruiting enzymes used in cascade reactions, as well as the regeneration of coenzyme such as NAD(P)H or ATP and their application in multi-enzyme cascade reactions are summarized. Finally, we illustrate the application of multi-enzyme cascades in the synthesis of six bifunctional chemicals, including ω-amino fatty acids, alkyl lactams, α, ω-dicarboxylic acids, α, ω-diamines, α, ω-diols, and ω-amino alcohols.

Predictive value of Apelin-13 on coronary artery lesion in Kawasaki disease / 中华实用儿科临床杂志

Objective:To investigate the relationship between the level of Apelin-13 and coronary artery lesion (CAL) in patients with Kawasaki disease (KD), and assess the predictive value of Apelin-13 for CAL in acute phase of KD.Methods:A total of 240 children with KD treated in Chengdu Women and Children′s Central Hospital from September 2017 to October 2019 were recruited, and were divided into KD with CAL (KD-CAL) group and KD without CAL (KD-NCAL) group.Thirty children with acute upper respiratory infection and 30 healthy children were recruited into the febrile control group and the healthy control group, respectively.Blood routine and serum levels of albumin, C-reactive protein (CRP), N-terminal pro-brain natriuretic peptide (NT-proBNP) and Apelin-13 were mea-sured in KD children prior to intravenous gamma globulin injection and after the diagnosis of children in the febrile control group and physical examination of children in the healthy control group.The clinical data of children in each group were compared, and the risk factors of KD complicated with CAL and the predictive value of Apelin-13 were determined by using receiver operating characteristic (ROC) curve and multiple Logistic regression analysis. Results:Apelin-13 and hemoglobin in children with KD were significantly decreased compared with those in the healthy control group and fever control group (all P<0.001). However, white blood cell(WBC) count, platelet count, CRP and NT-proBNP in KD group were significantly increased compared with those in the healthy control group and fever control group (all P<0.001). Serum albumin in KD children was significantly lower than that in the healthy control group ( P=0.004), and there was no difference when compared with the fever control group ( P=0.485). Apelin-13 and hemoglobin were significantly decreased in KD-CAL group compared with KD-NCAL group ( t=10.102, P<0.001; t=2.034, P=0.043), while NT-proBNP and CRP were significantly increased ( t=5.982, 3.728, all P<0.001). Multiple logistic regression analysis showed that Apelin-13 and NT-proBNP were independent predictors of CAL in KD.The ROC curve analysis showed that the cut-off value of Apelin-13 for predicting CAL was 2.99 μg/L, with an area under the curve (AUC) of 0.869 (95% CI: 0.820-0.909), sensitivity of 77.78% and specificity of 88.67%.While NT-proBNP cutoff value of 822 ng/L yielded sensitivity of 57.78% and specificity of 84.62% for predicting CAL with an AUC of 0.718(95% CI: 0.656-0.774). Conclusions:Apelin-13 plays a protective role in KD complicated with CAL, and could be used to predict CAL in the acute phase of KD.

Mechanism of Cervi Cornu Pantotrichum in Treatment of Osteoarthritis Based on Network Pharmacology / 中国实验方剂学杂志

ObjectiveTo explore the mechanism of Cervi Cornu Pantotrichumin in the treatment of osteoarthritis by network pharmacology. MethodThe active ingredients and the corresponding targets of Cervi Cornu Pantotrichumin were screened out by a Bioinformatics Analysis Tool of Molecular mechANism of Traditional Chinese Medicine （BATMAN-TCM）. The targets related to osteoarthritis were obtained through GeneCards and Online Mendelian Inheritance in Man （OMIM）. The targets corresponding to the active ingredients and those related to osteoarthritis were intersected to reveal the common targets， and STRING was adopted to build a protein-protein interaction （PPI） network. DAVID was used for gene ontology （GO） annotation and Kyoto encyclopedia of genes and genomes （KEGG） pathway enrichment on the anti-osteoarthritis targets of Cervi Cornu Pantotrichumin， and R x64 3.6.3 was employed to produce the advanced bubble charts of GO terms and KEGG pathways. Cytoscape 3.7.2 was used to establish the “Chinese medicinal herb-active ingredient-target-signaling pathway” network. In vitro experiments were performed to detect the viability of RAW 264.7 cells exposed to oxidative stress and the tumor necrosis factor （TNF）-α level in RAW 264.7 cells with inflammation under the treatment by Cervi Cornu Pantotrichumin. ResultA total of 20 active ingredients of Cervi Cornu Pantotrichum were obtained， of which ceramide， 6'-O-β-D-glucosylgentiopicroside， cerebroside， oleuropein， sphingomyelin， and cholesterol ferulate did not meet the screening conditions. Therefore， a total of 14 active ingredients were finally screened out， and 303 and 3 093 targets of active ingredients and osteoarthritis were respectively obtained. The two target sets were taken to intersect， which revealed 92 common targets. GO annotation and KEGG pathway enrichment showed that the targets were mainly involved in redox process， positive regulation of RNA polymerase Ⅱ promoter transcription， inflammatory response， protein synthesis， osteoclast differentiation， TNF signaling pathway， signaling pathways in cancer， mammalian target of rapamycin （mTOR） signaling pathway， mitogen-activated protein kinase （MAPK） signaling pathway， and cyclic adenosine monophosphate （cAMP） signaling pathway. The results of in vitro experiments showed that a certain concentration of protein in Cervi Cornu Pantotrichum significantly increased the viability of RAW 264.7 cells exposed to H2O2-induced oxidative damage （P<0.05， P<0.01） and reduced the level of TNF-α in the RAW 264.7 cells experiencing lipopolysaccharide （LPS）-induced inflammation （P<0.05）. ConclusionBased on the network pharmacology method， the mechanism of the multi-component， multi-target and multi-pathway treatment of OA by antler antler was explained， and the anti-inflammatory and antioxidant activities of antler antler were confirmed， which provided theoretical guidance and scientific basis for further research on the treatment of OA by antler antler.

Preparation of nanocapsules of active ingredients of Garcinia hanburyi and evaluation of their antidiabetic activity / 中国药房

OBJECTIVE To prepare Gambogic acid （GA） nanocapsules （GA-LNCs） and Neogambogic acid （NGA） nanocapsules（NGA-LNCs），and to evaluate their antidiabetic activities. METHODS Using water as the aqueous phase ，medium- chain triglyceride as the oil phase and polyethylene glycol monostearate as the surfactant ，GA-LNCs and NGA-LNCs were prepared by phase inversion method. Using entrapment efficiency and drug-loading amount as index ，the formulation technologies of above 2 nanocapsules were optimized by simplex lattice design. Its physical and chemical properties were investigated. The diabetic mice model was established. GA-LNCs and NGA-LNCs （1.92 and 2.42 mg/kg respectively ）were given intragastrically ，once a day ，for consecutive 6 weeks. The fasting blood glucose of mice ，the activities of superoxide dismutase （SOD）and glutathione peroxidase （GSH-Px），the contents of malondialdehyde （MDA），total cholesterol （TC），triglyceride （TG），high-density lipoprotein cholesterol（HDL-C）and low-density lipoprotein cholesterol （LDL-C）were all detected. RESULTS The optimal formulation of 2 kinds of nanocapsules included 60％ water，10％ medium-chain triglyceride ，30％ polyethylene glycol monostearate （total amount of the three was 2 g）and 35 mg GA or NGA . The encapsulation efficiencies of GA-LNCs and NGA-LNC obtained by the optimal formulation were （92.01±0.68）％ and（93.12±2.11）％；the drug-loading amount were （0.99±0.21）％ and（1.21±0.22）％， respectively. GA-LNCs and NGA-LNCs were yellow ，homogeneous and transparent liquid without precipitation. They were spherical in microscopic shape ， and had obvious shell- Δ 基金项目：吉林省科技发展计划项目（No.20200404090YY）；吉 membrane structure. The particle sizes were （28.11 ± 9.76） 林省教育厅科学技术研究项目（No.JJKH20210372KJ） ＊硕士研究生 。研究方向 ：植物药 。E-mail：zhanhe0108@163. and（22.06±6.84）nm；Zeta potential were （－4.09±1.00） com and（－17.40±1.32）mV，and polydispersity were 0.93±0.06 # 通信作者：讲师，博士。研究方向：中药有效成分治疗疾病的作 and 0.74±0.12. The results of animal experiments showed that 用机制。E-mail：chenweijia_jlau@163.com both GA-LNCs and NGA-LNCs could sig nificantly increase 中国药房 2022年第33卷第9期 China Pharmacy 2022Vol. 33 No. 9 ·1075· the activities of SOD and GSH-Px and the seru m content of HDL-C （P＜0.05 or P＜0.01）in model mice ，and significantly decreased the fasting blood glucose and the serum contents of MDA ， TC， TG and LDL-C （P＜0.05 or P＜0.01）. CONCLUSIONS GA-LNCs，NGA-LNCs prepared in this study are good in physical and chemical properties and have good anti-diabetes activity.

Quality of life of patients with locally advanced rectal cancer after neoadjuvant therapy and sphincter-preserving surgery / 中华胃肠外科杂志

Objective: To investigate quality of life (QoL) of patients with locally advanced rectal cancer (LARC) who underwent low anterior resection with protective stoma under neoadjuvant therapy mode, and to explore the changes of QoL of patients from before neoadjuvant therapy to 12 months after stoma reversal. Methods: A descriptive case series study was carried out. A retrospective study was performed on patients with mid and low LARC who received complete neoadjuvant long course radiotherapy and chemotherapy, followed by radical low anterior resection (LAR) combined with protective stoma at Peking Union Medical College Hospital from December 2017 to January 2020. Inclusion criteria: (1) patients with rectal MRI assessment of mT3-4b or mN1-2 without distant metastasis (M0) before neoadjuvant therapy; (2) distance from tumor lower margin to the anal verge <12 cm; (3) rectal adenocarcinoma confirmed by biopsy before neoadjuvant therapy; (4) complete cycle of neoadjuvant therapy; (5) patients undergoing radical LAR with sphincter preservation and protective ostomy; (6) patients receiving follow-up for more than 12 months after stoma reversal. Exclusion criteria: (1) patients as grade Ⅳ to Ⅴclassified by the American Society of Anesthesiologists (ASA); (2) patients with multiple primary colorectal cancer; (3) patients with history of other malignant tumors in the past 5 years; (4) patients of emergency surgery; (5) pregnant or lactating women; (6) patients with history of severe mental illness; (7) patients with contraindication of MRI, radiotherapy, chemotherapy, or surgical treatment. A total of 83 patients were enrolled, including 51 males and 28 females with median age of 59 years and mean BMI of (24.4±3.1) kg/m(2). EORTC QLQ-CR29, international erectile function index (IIEF), Wexner constipation score and low anterior resection syndrome (LARS) score were applied to investigate the QoL of the patients before neoadjuvant therapy, 3 and 12 months after ostomy reversal, including rectal anal function and sexual function. M (P25, P75) was used for the scores of the scale. Results: (1) EORTC QLQ-CR29 score showed that before neoadjuvant therapy, before surgery, 3 months and 12 months after ostomy reversal, anxiety [64.4 (52, 0, 82.5), 75.3 (66.0, 89.5), 82.6 (78.5, 90.0), 83.6 (78.0, 91.0)] and concern about body image [76.8 (66.0, 92.0), 81.1 (76.5, 91.5), 85.5 (82.5, 94.0), 86.1 (82.0, 92.0)] were improved (all P<0.01); pelvic pain [5.4 (2.0, 8.0), 5, 0 (2.0, 7.8), 3.9 (1.0, 5.0), 3.0 (1.0, 5.0)], urinary incontinence [15.7 (7.0, 22.0), 11.1 (0, 17.5), 10.0 (0, 17.0), 9.9 (0, 16.0)], impotence [14.3 (4.2, 19.0), 12.2 (0, 16.8), 5.6 (0, 10.0), 5.2 (0.2, 8.0)], urinate [26.4 (13.0, 38.5), 13.9 (0, 20.0), 13.4 (2.5, 21.5), 13.2 (2.0, 20.0)] and mucous bloody stool [4.7 (3.0, 6.0), 2.6 (0, 5.0), 2.2 (0, 5.0), 1.9 (0, 4.0)] were improved as well (all P<0.01). The scores fluctuated in the improvement of male sexual function, abdominal pain, dry mouth, worry about body mass change, skin pain and dyspareunia, but the symptoms were significantly improved after ostomy reversal compared with before neoadjuvant therapy (all P<0.05). There were no significant changes in female sexual function, dysuria, dysgeusia and fecal incontinence after ostomy reversal compared with before neoadjuvant therapy (all P>0.05). (2) IIEF scale showed that all scores were similar before and after neoadjuvant therapy (all P>0.05). (3) Rectal and anal function scale revealed that before neoadjuvant therapy, before operation, 3 months and 12 months after stoma reversal, gas incontinence [3.1 (0, 4.0), 2.3 (0, 4.0), 1.8 (0, 4.0), 1.2 (0, 3.0)] and urgent defecation [7.2 (0, 11.0), 5.2 (0, 11.0), 2.9 (0, 9.0), 1.7 (0, 0)] were improved (all P<0.001). In terms of improving incomplete emptying sensation, the symptoms fluctuated, but the symptoms improved significantly after ostomy reversal compared with before neoadjuvant therapy (all P<0.05). While the symptoms of assistance with defecation [0 (0, 0), 0.7 (0, 1.0), 0.6 (0, 1.0), 0.7 (0, 1.0)] and defecation failure [0.2 (0, 0), 1.0 (0, 2.0), 0.8 (0, 1.5), 0.8 (0, 1.0)] showed a worsening trend (all P<0.001). Stratified analysis was performed on patients with different efficacy of neoadjuvant therapy to compare the changes in QoL before and after neoadjuvant therapy. Patients with less sensitive and more sensitive neoadjuvant therapy showed similar changes in function and symptoms. Patients with less sensitive therapy showed significant improvement in dysuria, urinary incontinence, skin pain and dyspareunia (all P<0.05), and the symptom of defecation frequency in more sensitive patients was significantly improved (P<0.05). Conclusions: For patients with LARC, neoadjuvant radiochemotherapy combined with radical LAR and protective stoma can improve QoL in many aspects. It is noted that patients show a worsening trend in the need for assistance with defecation and in defecation failure.

Study on antidepressant effect of total alkaloids of Fibraurea recisa / 中国中药杂志

This study aimed to investigate the antidepressant effects of total alkaloids of Fibraurea recisa in HT22 cells damaged by corticosterone (CORT) in vitro and in a mouse model of chronic unpredictable mild stress (CUMS) as well as the underlying mechanisms.In cellular experiments,the viability of CORT-damaged HT22 cells was detected using cell counting kit-8 (CCK-8),and the cell apoptosis was detected by Hoechst 33258 staining.In animal experiments,C57BL/6N mice were randomly divided into the control group,model group,low (100 mg·kg~(-1)),medium (200 mg·kg~(-1)) and high (400 mg·kg~(-1))-dose of total alkaloids of F.recisa groups,and positive control group.After 21 days of CUMS exposure,their depressive behaviors were observed in behavioral and Morris water maze tests.The serum levels of 5-hydroxytryptamine (5-HT),dopamine (DA),and norepinephrine (NE) were assessed by ELISA.The expression levels of apoptosis-related proteins Bcl-2,Bax and cleaved caspase-3 in HT22 cells and mouse hippocampus were detected by Western blot.The results suggested that total alkaloids of F.recisa alleviated the damage of HT22 cells induced by CORT in a dose-dependent manner.The Hoechst 33258 staining uncovered that total alkaloids of F.recisa better reduced the blue spots and inhibited cell apoptosis.The results of animal experiments showed that total alkaloids of F.recisa significantly improved the depression-like behaviors of mice and increased the serum levels of 5-HT,DA and NE as compared with those in the model group.The Western blot assays revealed a significant up-regulation of Bcl-2 protein expression,but an obvious reduction in Bax and cleaved caspase-3protein expression in the total alkaloids of F.recisa group.In conclusion,total alkaloids of F.recisa inhibited depression possibly by regulating the apoptosis-related protein expression or elevating the monoamine neurotransmitter levels in the brain.

Transcatheter closure of atrial septal defect with deficient rim in children / 中华实用儿科临床杂志

Objective:To evaluate the feasibility of transcatheter atrial septal defect(ASD) closure with deficient rim.Methods:From January 2017 to November 2019, patients at the Department of Pediatric Cardiology, Chengdu Women′s and Children′s Central Hospital were diagnosed as the secondary ASD and divided into 2 groups based on whether it has deficient rim[the deficient rim group (experimental group) and non deficient rims group (control group)]. The complications should be followed for 1-2 years.Results:A total of 66 patients, including 17 males (25.8%) and 49 females (74.2%), had the median age of 4 years and 2 months (2 years and 1 month-16 years), and the median body mass was 15.0 kg, ranging from 9.0 kg to 60.0 kg, with 23 cases (34.8%) in the experimental group and 43 cases (65.1%) in the control group.There were no statistically significant differences in gender, age, body weight, size of ASD, fluoroscopic dose, electrocardiogram, and pulmonary artery pressure between the two groups (all P>0.05). The immediate success rate was 95.4%(63/66 cases). There were no statistically significant differences between the surgical success rate [91.3%(21/23 cases) vs.97.6%(42/43 cases)] and the incidence of residual shunt [30.4%(7/23 cases) vs.16.2%(7/43 cases)](all P>0.05). And there were no statistically significant differences of the incidence of residual shunt between groups at each follow-up point ( P>0.05). No arrhythmia occurred in the experimental group during follow-up, and 1 case of atrioventricular block in the control group persisted until the time of publication.A total of 4 cases of frequent atrial premature beats or non-paroxysmal atrial tachycardia returned to normal at the follow-up node 6 months after intervention. Conclusions:Under the selection of appropriate cases and skilled catheter technology, the transcatheter treatment of ASD in children with deficient rims is feasible.

Application progress of imaging examination and cardiac catheterization in diagnosis, treatment and long-term management of cardiovascular sequelae of Kawasaki disease: interpretation of the Japanese Circulation Society/Japanese Society for Cardiovascular Surgery 2020 Guideline on Diagnosis and Management of Car-diovascular Sequelae in Kawasaki Disease / 中华实用儿科临床杂志

The application indications of imaging examination and cardiac catheterization in the diagnosis, treatment and follow-up of Kawasaki disease, especially cardiovascular sequelae, are further improved by the Japanese Circulation Society/Japanese Society for Cardiovascular Surgery 2020 Guideline on Diagnosis and Management of Cardiovascular Sequelae in Kawasaki Disease that also standardizes the long-term management program of Kawasaki disease in three different stages, namely, school, the adolescent/young adult and adulthood stage.In order to enhance the understanding of domestic medical staff with the latest knowledge, this paper focuses on the application progress of diagnostic imaging and cardiac catheterization in the diagnosis, treatment and long-term management of cardiovascular sequelae of Kawasaki disease in the guide.

Correlation of heart rate variability and heart rate deceleration capacity with intravenous immunoglobulin-resistant Kawasaki disease / 中华实用儿科临床杂志

Objective:To investigate the relationship of heart rate variability (HRV), heart rate deceleration capacity (DC) and intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD) in children with the acute stage of KD.Methods:A total of 679 patients with KD in Chengdu Women and Children′s Central Hospital from August 2015 to May 2019 were selected.In healthy control group, 150 children obtained physical examination at the same time.Prospective cohort study was applied to analyze the data.According to the effect of initial IVIG treatment within 14 days, patients were divided into IVIG-sensitive group and IVIG-resistant group.General clinic information, HRV, DC, blood routine, liver function, cardiac troponin I (cTnI), N-terminal pro-B-type natriuretic peptide (NT-proBNP), high sensitivity C-reactive protein(hs-CRP) and erythrocytesedimentation rate (ESR) before initial IVIG treatment of the 2 groups were compared.Multivariate Logistic regression was applied to analyze the risk factors of IVIG-resistant KD. Results:Among 679 KD patients, 3 cases were lost, among the rest 676 cases, 586 cases were in IVIG-sensitive group, and 90 cases were in IVIG-resistant group.The HRV and DC indexes of IVIG-sensitive group and IVIG-resistant group were lower than those of the healthy control group, and the differences among the 3 groups were statistically significant (all P<0.05). Meanwhile, standard deviation of N-N intervals (SDNN) [(65.84±38.22) ms vs.(82.56±21.41) ms, P=0.004], and low frequency (LF)[ (192.59±114.10) ms 2vs. (258.18±162.75) ms 2, P=0.048] of IVIG-resistant group were lower than those of IVIG-sensitive group.White blood cell (WBC), platelets(PLT), hs-CRP, ESR, alanine aminotransferase(ALT), cTnI and NT proBNP in IVIG sensitive group and IVIG-resistant group were all higher than those in the healthy control group (all P<0.05). Further more, ESR[(90.32±37.91) mm/1 h vs. (65.81±25.34) mm/1 h, P=0.019], cTnI [(0.83±0.35) μg/L vs. (0.52±0.18) μg/L, P=0.037] and NT-proBNP [(854.64±293.02) ng/L vs. (584.95±177.11) ng/L, P=0.011] in IVIG-resistant group were higher than those of IVIG-sensitive group.Multivariate Logistic regression analysis demonstrated that SDNN ( OR=0.783, 95% CI: 0.0341-0.979, P=0.021), and NT-proBNP ( OR=1.195, 95% CI: 1.061-1.428, P=0.34) were independent risk factors for predicting IVIG-resistant KD. Conclusions:SDNN and NT-proBNP may be independent predictors of IVIG-resistant KD.

Effect of Suanzaoren Tang on Energy Metabolism of Myocardial Mitochondria in Aged Rats with Chronic Rapid Eye Movement Sleep Deprivation / 中国实验方剂学杂志

Objective:To study the mechanism of Suanzaoren Tang in regulating the energy metabolism of myocardial mitochondria in aged rats with chronic rapid eye movement （REM） sleep deprivation through the sirtuin 3 （SIRT3）/superoxide dismutase2 （SOD2） signaling pathway. Method:Fifty male Wistar rats were randomly divided into the control group， model group， estazolam group （0.18 mg·kg^-1·d^-1）， and low- （6.48 g·kg^-1·d^-1） and high-dose （12.96 g·kg^-1·d^-1） Suanzaoren Tang groups. Rats in all groups except for the control group received subcutaneous injection of <italic>D</italic>-galactose and then were deprived of sleep using the multiple platform method after the last administration. Following successful modeling， the rats in each group were treated with intragastric administration of the corresponding drugs for seven consecutive days. The morphology of myocardial mitochondria was observed under a transmission electron microscope. The content of adenosine triphosphate （ATP） in rat hypothalamus was detected by colorimetry， while the malondialdehyde （MDA） content and the SOD activity in myocardium were measured by spectrophotometry. Real-time polymerase chain reaction （Real-time PCR） and Western blot were conducted to determine the mRNA and protein expression levels of SIRT3 and SOD2 in rat myocardium. The localization of SIRT3 was detected by immunofluorescence staining. Result:Compared with the control group， the model group exhibited a disordered arrangement of myocardial filaments， accompanied by filament rupture and dissolution， obviously swollen mitochondria arranged in disorder， and blurring and even rupture of most mitochondrial cristae. Besides， the content of ATP and SOD activity in the myocardium decreased significantly （<italic>P<</italic>0.01）， whereas that of MDA increased significantly （<italic>P<</italic>0.01）. The mRNA and protein expression levels of SIRT3 and SOD2 were down-regulated significantly （<italic>P<</italic>0.01）， and the average fluorescence intensity of SIRT3 protein declined significantly （<italic>P<</italic>0.01）. The comparison with the model group revealed that high-dose Suanzaoren Tang enabled the myocardial filaments to be neatly arranged， relieved the mitochondrial damage and swelling， only manifested as partial mitochondrial cristae rupture， significantly increased ATP content， SOD activity， as well as SIRT3 and SOD2 mRNA and protein expression levels （<italic>P<</italic>0.01）， reduced the content of MDA （<italic>P<</italic>0.01）， and enhanced the average fluorescence intensity of SIRT3 protein （<italic>P<</italic>0.05）. The myocardial mitochondrial injury in the estazolam group was also alleviated. The activity of SOD and the SIRT3 and SOD2 mRNA and protein expression levels in the myocardium were significantly elevated （<italic>P<</italic>0.01）， while the activity of MDA was significantly lowered （<italic>P<</italic>0.01）. In the low-dose Suanzaoren Tang group， the improvement in myocardial mitochondrial injury was not obvious. However， both the SOD activity and SOD2 protein expression were significantly increased （<italic>P<</italic>0.05）. Conclusion:Suanzaoren Tang ameliorates the myocardial mitochondria injury and abnormal energy metabolism induced by chronic REM sleep deprivation in aged rats possibly by up-regulating the SIRT3 and SOD2 expression.

Intracellular aggregation of peptide-reprogrammed small molecule nanoassemblies enhances cancer chemotherapy and combinatorial immunotherapy

The intracellular retention of nanotherapeutics is essential for their therapeutic activity. The immobilization of nanotherapeutics inside target cell types can regulate various cell behaviors. However, strategies for the intracellular immobilization of nanoparticles are limited. Herein, a cisplatin prodrug was synthesized and utilized as a glutathione (GSH)-activated linker to induce aggregation of the cisplatin prodrug/IR820/docetaxel nanoassembly. The nanoassembly has been reprogrammed with peptide-containing moieties for tumor-targeting and PD-1/PD-L1 blockade. The aggregation of the nanoassemblies is dependent on GSH concentration. Evaluations

Relationship of children′s unexplained chest pain and/or chest distress with catecholamine and heart rate variability / 中华实用儿科临床杂志

Objective:To explore the changes of sympathetic and parasympathetic activity in children with chest pain and/or chest distress of unknown cause based on their plasma catecholamine and heart rate variability indexes, and to analyze the predictive value of each index in diagnosing pediatric sympathetic excitation-related chest pain and/or chest distress by used receiver operating characteristics (ROC) curve analysis.Methods:Fifty-seven children who complained of unexplained chest pain and/or chest distress and had no organic diseases according to routine examinations in the Chengdu Women′s and Children′s Hospital from June 2017 to June 2019 were enrolled in the study group.There were 22 males and 35 females, aged 5-15 years old[(8.40±0.35) years old]. Meanwhile, 54 healthy children in the same period were enrolled in the healthy control group, including 21 males and 33 females, aged 5-15 years old (8.87±0.36) years old]. The disease history enquiring, physical examination, chest X-ray, 12-lead electrocardiogram, echocardiogram, blood routine test and biochemical test excluded the organic heart, lung, digestive tract and chest wall diseases in both groups.Their blood samples were collected to detect catecholamine and they were monitored by dynamic electrocardiogram.SPSS 25.0 software was used for statistical analysis and ROC curve analysis.Results:The study group exhibited higher dopamine, adrenaline and norepinephrine levels than those in the healthy control group[(0.83±0.04) nmol/L vs.(0.54±0.03) nmol/L, (0.76±0.04) nmol/L vs.(0.56±0.03) nmol/L and(3.59±0.18) nmol/L vs.(2.51±0.15) nmol/L], and the differences were statistically significant( t=4.906, 3.611, 4.596, all P<0.01). The levels of standard deviation of NN intervals, standard deviation of all mean 5-minutes NN intervals, standard deviation of all NN intervals for all 5-minute segments of 24 hours, root mean squared successive difference and proportion of NN 50 in the total number of NN intervals in the study group were lower than those in the healthy control group [(110.49±2.81) ms vs.(132.13±2.55) ms, (86.37±3.26) ms vs.(118.96±2.00) ms, (33.46±2.21) ms vs.(68.91±1.29) ms, (37.63±1.22) ms vs.(48.93±1.75) ms and(17.37±1.45)% vs.(22.22±1.61)%], and the differences were statistically significant( t=-5.710, -8.419, -13.862, -5.354, -2.245, all P<0.05). The area under the curve of plasma dopamine, adrenaline and norepinephrine in the diagnosis of pediatric sympathetic excitation-related chest pain and/or chest distress were 0.753, 0.689 and 0.746, respectively, higher than that of all heart rate variability indexes. Conclusions:Children′s unexplained chest pain and/or chest distress is highly related with autonomic nervous dysfunction (increased sympathetic activity and decreased parasympathetic activity). The level of plasma catecholamine can be used to reflect the changes of sympathetic activity in these children and diagnose sympathetic excitation-related chest pain and/or chest distress.Psychological counseling and relaxation therapy are supposed to be effective in redu-cing sympathetic activity, improving subjective symptoms and elevating their quality of life.

Research progress of hydrogel used for regeneration of nucleus pulposus in intervertebral disc degeneration / 中国修复重建外科杂志

Objective: To summarize the research progress of hydrogels for the regeneration and repair of degenerative intervertebral disc and to investigate the potential of hydrogels in clinical application. Methods: The related literature about the role of hydrogels in intervertebral disc degeneration especially for nucleus pulposus was reviewed and analyzed. Results: Hydrogels share similar properties with nucleus pulposus, and it plays an important role in the regeneration and repair of degenerative intervertebral disc, which can be mainly applied in nucleus pulposus prosthesis, hydrogel-based cell therapy, non-cellular therapy, and tissue engineering repair. Conclusion: Hydrogels are widely used in the regeneration and repair of intervertebral disc, which provides a potential treatment for intervertebral disc degeneration.

Wedge osteotomy combined with internal fixation for ulnar olecranon fracture of Mayo type ⅡB / 中华创伤骨科杂志

Objective To investigate the clinical efficacy and safety of wedge osteotomy combined with internal fixation for ulnar olecranon fracture of Mayo type ⅡB.Methods From July 2014 to December 2017,8 patients with ulnar olecranon fracture of Mayo type ⅡB were treated with wedge osteotomy of the ulnar olecranon combined with internal fixation.They were 6 men and 2 women,from 28 to 45 years of age (mean,31.4 years).The wedge osteotomy was planned preoperatively according to the literature data and the osteotomy lengths were measured postoperatively to confirm the safe range for the surgery.Fracture healing was evaluated by regular X-ray follow-up and therapeutic effects were assessed by the range of elbow motion and the Broberg-Morry scoring system.Results On average in this group,the olecranon osteotomy was 6.2 mm in length on the articular sudace and 14.5 mm at the basal part.The olecranon was shortened by 4.6 cm on average after operation.All the 8 patients were followed up for 14 to 20 months (average,16.4 months).The clinical fracture healing time ranged from 12 to 16 weeks,with an average of 14.3 weeks.Follow-ups revealed no fracture displacement,pain or internal fixation failure.No significant differences were found between the affected and the contralateral sides in the flexion,extension or range of motion of the elbow joint at 3 months or at one year after surgery (P ＞ 0.05).According to the Broberg-Morry scoring system,5 cases were rated as excellent,2 as good and one as fair at 3 months after surgery.The final follow-ups found no traumatic arthritis or joint instability.Conclusions As a new treatment alternative,wedge osteotomy combined with internal fixation can obtain satisfactory curative outcomes for ulnar olecranon fractures of Mayo type ⅡB.The wedge osteotomy was performed in a safe range for this group.

Clinical effect and safety of clopidogrel combined with aspirin in antithrombotic therapy for children with Kawasaki disease complicated by small/medium-sized coronary artery aneurysms / 中国当代儿科杂志

OBJECTIVE@#To study the clinical effect and safety of clopidogrel combined with aspirin in antithrombotic therapy for children with Kawasaki disease (KD) complicated by coronary artery aneurysm (CAA).@*METHODS@#A total of 77 KD children who were diagnosed with multiple small/medium-sized CAAs by echocardiography between January 2013 and June 2018 were enrolled. They were randomly divided into observation group with 38 children (treated with clopidogrel and aspirin) and control group with 39 children (treated with low-molecular-weight heparin and aspirin). All children were followed up regularly, and the first 3 months of the course of the disease was the observation period. The children were observed in terms of the change of the coronary artery and the incidence of complications.@*RESULTS@#At month 3 of follow-up, among the children in the observation group, 6 had normal coronary artery, 11 had coronary artery retraction, 19 had stable coronary artery, and 2 progressed to giant coronary aneurysm; among the children in the control group, 7 had normal coronary artery, 12 had coronary artery retraction, 19 had stable coronary artery, and 1 progressed to giant coronary aneurysm; there was no significant difference in the change of the coronary artery between the two groups (P>0.05). There were 2 cases of epistaxis and 6 cases of skin ecchymosis in the observation group, and 1 case of epistaxis and 7 cases of petechiae and ecchymosis at the injection site in the control group, and no other serious bleeding events were observed in either group.@*CONCLUSIONS@#Clopidogrel combined with low-dose aspirin is safe and effective in antithrombotic therapy for children with KD complicated by CAA.

Advance in studies on pharmacokinetics of baicalin / 中国中药杂志

Scutellariae baicalensis is one of the most important traditional Chinese medicinal herbs, mainly distributed in Shandong and Hebei provinces. It has significant pharmacological effects such as antimicrobial activity, anti-inflammatory and antioxidation. Baicalin is one of its main effective components. However, baicalin's low bioavailability has restricted its clinical application. In recent decades, extensive studies have been carried out on the metabolism of baicalin at home and abroad. In order to provide scientific references for baicalin's further studies, this paper would not only review the advances in pharmacokinetics research of baicalin and Chinese herbal preparations containing baicalin, but also make a summary on research status of baicalin.

Gold nanorods together with HSP inhibitor-VER-155008 micelles for colon cancer mild-temperature photothermal therapy

Enhancing the heat-sensitivity of tumor cells provides an alternative solution to maintaining the therapeutic outcome of photothermal therapy (PTT). In this study, we constructed a therapeutic system, which was composed of methoxy-polyethylene-glycol-coated-gold-nanorods (MPEG-AuNR) and VER-155008-micelles, to evaluate the effect of VER-155008 on the sensitivity of tumor cells to heat, and further investigate the therapeutic outcome of MPEG-AuNR mediated PTT combined with VER-155008- micelles. VER-155008- micelles down-regulate the expression of heat shock proteins and attenuate the heat-resistance of tumor cell. The survival of HCT116 cells treated with VER-155008- micelles under 45 °C is equal to that treated with high temperature hyperthermia (55 °C) . Furthermore, we proved either the MPEG-AuNR or VER-155008- micelles can be accumulate in the tumor site by photoacoustic imaging and fluorescent imaging. anti-cancer evaluation showed that tumor size remarkably decreased (smaller than 100 mm or vanished) when treated with combing 45 °C mild PTT system, which contrasted to the tumor size when treated with individual 45 °C mild PTT (around 500 nm) or normal saline as control (larger than 2000 nm). These results proved that the VER-155008- micelles can attenuate the heat-resistance of tumor cells and enhance the therapeutic outcome of mild-temperature photothermal therapy.

Correlation of heart rate variability and procalcitonin, high sensitivity C-reactive protein in children with Kawasaki disease in the acute stage / 中华实用儿科临床杂志

Objective To investigate the relationship of heart rate variability (HRV) and procalcitonin (PCT),high sensitivity C-reactive protein (hs-CRP) and erythrocyte sedimentation rate (ESR) in children with Kawasaki disease (KD) in the acute stage,and to investigate their value in diagnosis and prognosis of KD especially incomplete KD (iKD).Methods Two hundred and twenty patients with KD in Chengdu Women and Children's Central Hospital from August 2012 to October 2015 were selected.According to the diagnostic criteria,patients with KD were divided into a typical KD group and an iKD group.According to the status of coronary artery damage,the patients with KD were divided into coronary artery lesion (CAL) group and no coronary artery lesion(NCAL) group.Another 100 healthy children were selected as healthy control group.All the children received 24 h dynamic electrocardiogram and were given tests of blood PCT,hs-CRP and ESR.The differences of HRV,PCT,hs-CRP and ESR between the CAL group and the NCAL group,between the typical KD group and iKD group were compared.The correlations of HRV and PCT,hs-CRP and ESR were analyzed.Results Of 220 KD patients,182 cases were in the typical KD group and 38 cases in the iKD group;64 cases in the CAL group and 156 cases in the NCAL group.The mean levels of HRV were lower in KD group than those in healthy control group (all P ＜ 0.05),especially those in the CAL group fell more obviously.The differences in the standard deviation of N-N intervals(SDNN),percent ages of N-N 50 in the total number N-N intervals (PNN50) and low frequency (LF) between the CAL group,the NCAL group and the healthy control group were all statistically significant(all P ＜0.05).The mean levels of HRV,PCT and hs-CRP had no statistically significant difference between typical KD and iKD groups (all P ＞ 0.05).The mean level of ESR had a statistically significant difference between 2 groups (P ＜ 0.05).SDNN was negatively correlated with PCT,hs-CRP and ESR (r =-0.443,-0.364,-0.427,all P ＜ 0.05).Conclusion In patients with KD in the acute stage,the decrease of HRV can be correlated with inflammatory reaction.HRV can be used as valuable predictors for coronary artery lesion in patients with KD,but its help in the early diagnosis of iKD has not found.

Value of red blood cell distribution width on evaluation of severity of acute heart failure in children / 中华实用儿科临床杂志

Objective To investigate the correlation between red blood cell distribution width (RDW) and the cardiac function in children with acute heart failure,and to explore the clinical value in evaluating the degree of heart failure.Methods From July 2013 to October 2015,75 cases of children with acute heart failure who were hospitalized in Chengdu Women and Children's Central Hospital were collected and assigned as 3 groups.Heart function classification was done by using a modified Ross scoring system,and each group included 25 cases of class Ⅱ,Ⅲ,Ⅳ.Indices of red blood cell,haemoglobin,RDW,concentration of plasma N-terminal pro brain natriuretic peptide (NT-proBNP),and left ventricular ejection fraction (LVEF) were recorded.SPSS 17.0 software was statistically used for comparing cach index among groups and correlation analysis.Results Red blood cells and haemoglobin were not statistically different among groups (F =0.802,1.372,all P ＞ 0.05).RDW,NT-proBNP concentration and LVEF were significantly different among groups (F =31.388,29.300,x2 =56.952,all P ＜ 0.01),and significantly increased with the progression in the order of class Ⅳ group ＞ class Ⅲ group ＞ class Ⅱ group [RDW:(16.6 ± 1.3) ％ ＞ (15.4 ± 1.1) ％ ＞ (13.9-± 1.3) ％,NT-proBNP:(506.6 ± 190.2) ng/L ＞ (1 028.1 ± 356.8) ng/L ＞ (1 884.1 ± 358.6) ng/L,all P ＜ 0.01].According to LVEF =50％ as the cut-off point,children with acute heart failure were divided into LVEF decreased group and LVEF retention group,former group's RDW and NT-proBNP were significantly higher than the latter group[RDW:(16.7 ± 1.3)％ vs.(13.9 ±1.1)％,NT-proBNP:(1 787.4-±368.6) ng/Lvs.(657.4-± 291.1) ng/L,all P ＜0.01].According to NT-proBNP levels,the children with acute heart failure were divided into low,medium,and high NT-proBNP group,and RDW in the high NT-proBNP group[(17.3 ±0.9)％] was significantly higher than that of medium [(15.4 ± 0.7) ％],and that of low level group [(13.7 ± 1.2) ％] (all P ＜ 0.01).The correlation analysis between RDW,NT-proBNP as well as LVEF showed that RDW was significantly positive correlated with NT-proBNP (r =O.869,P ＜ 0.01),and negatively related with LVEF (r =-0.962,P ＜ 0.01).Conclusions RDW is closely related to the cardiac function in children with acute heart failure.RDW is increased with the aggravating of acute heart failure,which can indirectly reflect the NT-proBNP concentration and LVEF change and suggests that RDW can be used as a convenient and useful index monitoring the level of cardiac function in children with acute heart failure,and the assessment of the severity of acute heart failure.

Analysis of the results of 838 cases of myocardial injury markers in neonates / 中国基层医药

Objective To investigate the diagnostic value and significance of myocardial injury markers in neonates.Methods A retrospective analysis of 838 cases of myocardial injury markers in neonates,the total positive rate of hs -cTnI and the positive rates of hs -cTnI(hypersensitivity cardiac troponin I)in different kinds of neonatal disease were calculated,the levels of abnormalities consistent rate in hs -cTnI and CK -MBmass(creatine kinase MB mass)were compared with hs -cTnI and MYO(Myoglobin).Results The total positive rate of hs -cTnI was 40.33% in the 838 neonates.The highest incidence of myocardial injury was neonatal sepsis (57.14%),followed by neonatal pulmonary hemorrhage (55.56%)and neonatal convulsions (54.55%).The abnormalities consistent rate of hs -cTnI and CK -MBmass was better than hs -cTnI and MYO (85.50% vs 28.11%,χ2 =226.9,P <0.05). Conclusion Neonatal hospitalized children often complicated by myocardial injury;As a biochemical myocardial injury marker,the hs -cTnI detection is important for early detection of myocardial injury,it should be recommend as routine test items;CK -MBmass has better correlation with hs -cTnI than MYO,which can provide guide for doctors to interpret the data of myocardial injury markers.