Recent advances in deorphanization of GPR35 and its functions in related diseases / 药学学报

G protein-coupled receptors (GPCRs) represent the largest family of membrane proteins and are the target of approximately half of all therapeutic drugs. There are ～300 orphan GPCRs, which have great potential in drug development. G protein-coupled receptor 35 (GPR35), a rhodopsin-like orphan GPCR, is widely involved in immune regulation, gastrointestinal disorders, cardiovascular diseases, cancer, as well as other diseases, suggesting its great potential as a therapeutic target in a variety of diseases. However, the current research on GPR35 is insufficient, including the true endogenous ligand has not been confirmed, the molecular mechanism of its role in disease is not fully understood, and there is a lack of effective intervention strategies targeting GPR35. This article summarizes the deorphatization of GPR35, GPR35-related signaling pathways and their association with various diseases, in order to provide a reference for in-depth study of GPR35 in diseases and development of drugs targeting GPR35.

Exploring the material basis of genipin-induced hepatotoxicity in vitro / 药学学报

The current study explored the hepatotoxicity among closed-ring genipin, open-ring tautomer of genipin and gardenia blue that generated from genipin and amino acid reaction using HepaRG cells to identify the material basis of genipin-induced hepatotoxicity in vitro. The effects of temperature, pH value and different kinds of amino acids on the chemical structure tautomerism between closed-ring and open-ring tautomer of genipin and the production of gardenia blue were investigated firstly, which aimed to explicit the conditions that could distinguish the closed-ring genipin and its open-ring tautomer, and the conditions generating gardenia blue, which were applied to prepare different kinds of gardenia blue; the CCK-8 kit was employed to analyze the hepatotoxicity of closed-ring genipin, open-ring tautomer of genipin and gardenia blue. From the results, it was found that, the structure transformation from close-ring to open-ring of genipin could be inhibited under the condition with acid environment; being essential groups to generate gardenia blue, the primary amino group and the open-ring tautomer of genipin reacting to generate the dihydropyridine ring was probably the key structure of gardenia blue; the structure characteristics existed apparent distinction at the reactive temperature of 37 ℃ and 80 ℃; compared to the culture condition with pH = 7.4, the concentration of genipin with close-ring in culture medium was significantly increased at pH = 5, but the cell viability did not decreased; the cell toxicity of gardenia blue was apparently lower than open-ring tautomer of genipin, and even some kinds of gardenia blue showed growth promoting effect on HepaRG cells. Here, it was suggested potentially that open-ring tautomer of genipin be the important material basis to induce hepatotoxicity, which could provide a cue and lay a foundation for the elucidation of the underlying mechanism of genipin-induced hepatotoxicity.

Soybean isoflavones alleviate cerebral ischemia/reperfusion injury in rats by inhibiting ferroptosis and inflammatory cascade reaction / 南方医科大学学报

OBJECTIVE@#To explore the mechanism that mediates the effect of soybean isoflavones (SI) against cerebral ischemia/reperfusion (I/R) injury in light of the regulation of regional cerebral blood flow (rCBF), ferroptosis, inflammatory response and blood-brain barrier (BBB) permeability.@*METHODS@#A total of 120 male SD rats were equally randomized into sham-operated group (Sham group), cerebral I/R injury group and SI pretreatment group (SI group). Focal cerebral I/R injury was induced in the latter two groups using a modified monofilament occlusion technique, and the intraoperative changes of real-time cerebral cortex blood flow were monitored using a laser Doppler flowmeter (LDF). The postoperative changes of cerebral pathological morphology and the ultrastructure of the neurons and the BBB were observed with optical and transmission electron microscopy. The neurological deficits of the rats was assessed, and the severities of cerebral infarction, brain edema and BBB disruption were quantified. The contents of Fe2+, GSH, MDA and MPO in the ischemic penumbra were determined with spectrophotometric tests. Serum levels of TNF-α and IL-1βwere analyzed using ELISA, and the expressions of GPX4, MMP-9 and occludin around the lesion were detected with Western blotting and immunohistochemistry.@*RESULTS@#The rCBF was sharply reduced in the rats in I/R group and SI group after successful insertion of the monofilament. Compared with those in Sham group, the rats in I/R group showed significantly increased neurological deficit scores, cerebral infarction volume, brain water content and Evans blue permeability (P < 0.01), decreased Fe2+ level, increased MDA level, decreased GSH content and GPX4 expression (P < 0.01), increased MPO content and serum levels of TNF-α and IL-1β (P < 0.01), increased MMP-9 expression and lowered occludin expression (P < 0.01). All these changes were significantly ameliorated in rats pretreated with IS prior to I/R injury (P < 0.05 or 0.01).@*CONCLUSION@#SI preconditioning reduces cerebral I/R injury in rats possibly by improving rCBF, inhibiting ferroptosis and inflammatory response and protecting the BBB.

Comparison of machine learning and Logistic regression model in predicting acute kidney injury after cardiac surgery: data analysis based on MIMIC-Ⅲ database / 中华危重病急救医学

Objective:To establish an acute kidney injury (AKI) prediction model in patients after cardiac surgery by extreme gradient boosting (XGBoost) machine learning model, and to explore the risk and protective factors for AKI in patients after cardiac surgery.Methods:All patients who underwent cardiac surgery in Medical Information Mart for Intensive Care-Ⅲ (MIMIC-Ⅲ) database were enrolled, and they were divided into AKI group and non-AKI group according to whether AKI developed within 14 days after cardiac surgery. Their clinical characteristics were compared. Based on five-fold cross-validation, XGBoost and Logistic regression were used to establish the prediction model of AKI after cardiac surgery. And the area under the receiver operator characteristic curve (AUC) of the models was compared. The output model of XGBoost was interpreted by Shapley additive explanations (SHAP).Results:A total of 6 912 patients were included, of which 5 681 (82.2%) developed AKI within 14 days after the operation, and 1 231 (17.8%) did not. Compared with the non-AKI group, the main characteristics of AKI group included older age [years: 68.0 (59.0, 76.0) vs. 62.0 (52.0, 71.0)], higher incidence of emergency admission and complicated with obesity and diabetes (52.4% vs. 47.8%, 9.0% vs. 4.0%, 32.0% vs. 22.2%), lower respiratory rate [RR; bpm: times/min: 17.0 (14.0, 20.0) vs. 19.0 (15.0, 22.0)], lower heart rate [HR; bpm: 80.0 (67.0, 89.0) vs. 82.0 (71.5, 93.0)], higher blood pressure [mmHg (1 mmHg ≈ 0.133 kPa): 80.0 (70.7, 90.0) vs. 78.0 (70.0, 88.0)], higher hemoglobin (Hb), blood glucose, blood K + level and serum creatinine [SCr; Hb (g/L): 122.0 (109.0, 136.0) vs. 120.0 (106.0, 135.0), blood glucose (mmol/L): 7.3 (6.1, 8.9) vs. 6.8 (5.7, 8.5), blood K + level (mmol/L): 4.2 (3.9, 4.7) vs. 4.2 (3.8, 4.6), SCr (μmol/L): 88.4 (70.7, 106.1) vs. 79.6 (70.7, 97.2)], lower albumin (ALB) and triacylglycerol [TG; ALB (g/L): 38.0 (35.0, 41.0) vs. 39.0 (37.0, 42.0), TG (mmol/L): 1.4 (1.0, 2.0) vs. 1.5 (1.0, 2.2)] as well as higher incidence of multiple organ dysfunction syndrome (MODS) and sepsis (30.6% vs. 16.2%, 3.3% vs. 1.9%), with significant differences (all P < 0.05). In the output model of Logistic regression, important predictors were lactic acid [Lac; odds ratio ( OR) = 1.062, 95% confidence interval (95% CI) was 1.030-1.100, P = 0.005], obesity ( OR = 2.234, 95% CI was 1.900-2.640, P < 0.001), male ( OR = 0.858, 95% CI was 0.794-0.928, P = 0.049), diabetes ( OR = 1.820, 95% CI was 1.680-1.980, P < 0.001) and emergency admission ( OR = 1.278, 95% CI was 1.190-1.380, P < 0.001). Receiver operator characteristic curve (ROC curve) analysis showed that the AUC of the Logistic regression model for predicting AKI after cardiac surgery was 0.62 (95% CI was 0.61-0.67). After optimizing the XGBoost model parameters by grid search combined with five-fold cross-validation, the model was trained well with no overfitting or overfitting. ROC analysis showed that the AUC of XGBoost model for predicting AKI after cardiac surgery was 0.77 (95% CI was 0.75-0.80), which was significantly higher than that of Logistic regression model ( P < 0.01). After SHAP treatment, in the output model of XGBoost, age and ALB were the most important predictors of the final outcome, where age was the risk factor (average |SHAP value| was 0.434), and ALB was the protective factor (average |SHAP value| was 0.221). Conclusions:Age is an important risk factor for AKI after cardiac surgery, and ALB is a protective factor. The performance of machine learning in predicting cardiac and vascular surgery-associated AKI is better than the traditional Logistic regression. XGBoost can analyze the more complex relationship between variables and outcomes, and can predict the risk of postoperative AKI more accurately and individually.

Roles and perspectives of inflammatory factors in diabetic macular edema / 国际眼科杂志(Guoji Yanke Zazhi)

Diabetic retinopathy is the leading cause of blindness in the working-age population, in which diabetic macular edema(DME)is the most common reason resulting in the vision impairment. Studies showed that inflammation factors play an important role in the pathogenesis and development of DME. Chronic hyperglycemia activates several biochemical pathways, leading to retinal hypoxia, oxidative stress and chronic inflammation. Intraretinal inflammation-related cells, such as microglia, monocytes/macrophages, Müller cells and retinal pigment epithelial cells, become activated and release a large number of inflammation-related factors and mediators, including the complement system, vascular endothelial growth factor(VEGF), placental growth factor(PlGF), tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), IL-6 and IL-8, etc., resulting in the breakdown of the blood-retinal barrier and neuronal degeneration. In addition, up-regulatethe expression of intercellular adhesion molecule-1(ICAM-1)and vascular cell adhesion molecule-1(VCAM-1)by retinal vascular endothelial cells increased the adhesion of leukocyte and leukostasis, further aggravating retinal hypoxia and breakdown of the blood-retinal barrier, leading to the increased retinal vascular leakage and macular edema. Therefore, early treatment with anti-VEGF and anti-inflammatory are pivotal for the treatment of DME. In this review, we will discuss the role of inflammation factors in the pathogenesis of DME and the research status of the targeted drugs targeting inflammation, so as to provide reference for the treatment of DME.

Research progress on the role and intervention strategies of NRP1 in colorectal cancer / 药学学报

Colorectal cancer (CRC) is one of the most common malignant tumors in the world, and its incidence and mortality are among the top three of all malignant tumors. In recent years, CRC is becoming more common in younger patients. Currently, surgery is the main or first treatment of early stage CRC, however, up to 50% patients have recurrence and metastasis post-surgery. While chemotherapy and radiotherapy are often used as adjuvant treatment after surgery or as main treatment options for late stage CRC, they usually induce severe adverse effects. Safe and effective treatments for CRC are still lacking. Therefore, it is essential to discover new therapies for CRC. Neuropilin 1 (NRP1), as a transmembrane glycoprotein, is reported to highly express in CRC, and its overexpression is demonstrated to be closely related to the occurrence and development of CRC. NRP1 is involved in angiogenesis, tumor growth, autophagy, and lipid metabolism, which is expected to be a potential new target for the treatment of CRC. This paper reviews the role of NRP1 in CRC, including its molecular structure, expression in CRC, as well as its connection with autophagy and metabolism. The regulatory factors of NRP1 in CRC were introduced, including vascular endothelial growth factor (VEGF), semaphorin 3A (SEMA3A), transforming growth factor-β (TGF-β), etc. The potential intervention strategies of CRC targeting NRP1 were summarized in order to provide reference for the diagnosis and prevention of CRC.

Characteristic chromatogram and index components content of substance benchmark of Xuanfu Daizhe Decoction / 中国中药杂志

The methods for determining the characteristic chromatogram and index components content of Xuanfu Daizhe Decoction were established to provide a scientific basis for the quality evaluation of substance benchmarks and preparations. Eighteen batches of Xuanfu Daizhe Decoction were prepared with the decoction pieces of different batches and of the same batch were prepared respectively, and the HPLC characteristic chromatograms of these samples were established. The similarities of the chromatographic fingerprints were analyzed. With liquiritin, glycyrrhizic acid, 6-gingerol, ginsenoside Rg_1, and ginsenoside Re as index components, the high performance liquid chromatography was established for content determination with no more than 70%-130% of the mass average as the limit. The results showed that there were 19 characteristic peaks corresponding to the characteristic chromatograms of 18 batches of Xuanfu Daizhe Decoction, including 8 peaks representing liquiritin, 1,5-O-dicaffeoylqunic acid, ginsenoside Rg_1, ginsenoside Re, 1-O-acetyl britannilactone, ginsenoside Rb_1, glycyrrhizic acid, and 6-gingerol, and the fingerprint similarity was greater than 0.97. The contents of liquiritin, glycyrrhizic acid, 6-gingerol, and ginsenosides Rg_1 + Re in the prepared Xuanfu Daizhe Decoction samples were 0.53%-0.86%, 0.61%-1.2%, 0.023%-0.068%, and 0.33%-0.66%, respectively. Except for several batches, most batches of Xuanfu Daizhe Decoction showed stable contents of index components, with no discrete values. The characteristic chromatograms and index components content characterized the information of Inulae Flos, Ginseng Radix et Rhizoma, Glycyrrhizae Radix et Rhizoma, and Zingiberis Rhizoma Recens in Xuanfu Daizhe Decoction. This study provides a scientific basis for the further research on the key chemical properties of substance benchmark and preparations of Xuanfu Daizhe Decoction.

Effects of acupoint thread-embedding therapy on serum apelin and GLP-1 in type 2 diabetes mellitus patients with obesity due to dampness-heat encumbering spleen / 针灸推拿医学（英文版）

Objective: To observe the effects of acupoint thread-embedding therapy on serum apelin and glucagon-like peptide-1 (GLP-1) in type 2 diabetes mellitus patients with obesity due to dampness-heat encumbering spleen.Methods: Sixty-six patients were randomly divided into a control group and an observation group according to the random number table method, with 33 cases in each group. Patients in the control group were treated with exenatide and metformin, while patients in the observation group were treated with additional acupoint thread-embedding. After 12-week treatment, the obesity-related indicators, including body mass index (BMI), waist circumference and body fat rate, the glycometabolism indicators, including fasting blood glucose, 2 h postprandial blood glucose and glycosylated hemoglobin, and the lipid metabolism indicators, including total cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C), as well as serum apelin and GLP-1 levels were observed in patients of the two groups. Results: After treatment, the BMI, waist circumference and body fat rate of patients in the two groups were all reduced (all P<0.05), and were lower in the observation group than in the control group (all P<0.05); the fasting blood glucose, 2 h postprandial blood glucose and glycosylated hemoglobin levels of patients in both groups were all decreased (all P<0.05), and were significantly lower in the observation group than in the control group (all P<0.05); the TC level was decreased (P<0.05), while the TG and LDL-C levels did not change significantly in the control group (both P>0.05); the TC, TG and LDL-C levels were all significantly reduced in the observation group (all P<0.05), lower than those in the control group (all P<0.05); the serum apelin level was decreased (P<0.05) and the serum GLP-1 level was increased (P<0.05) in the observation group, statistically different from those in the control group (both P<0.05). Conclusion: Combined with the conventional medication, acupoint thread-embedding therapy can significantly improve the obesity-related indicators, glycometabolism and lipid metabolism in type 2 diabetes mellitus patients with obesity due to dampness-heat encumbering spleen. This may be achieved by regulating the serum apelin and GLP-1 levels.

A four-component combination derived from Huang-Qin Decoction significantly enhances anticancer activity of irinotecan / 中国天然药物

Huang-Qin Decoction (HQD) is a classic prescription for diarrhea in Chinese medicine treatment. Recent studies have demonstrated that HQD and its modified formulation PHY906 could ameliorate irinotecan (CPT-11) induced gastrointestinal (GI) toxicity and enhance its anticancer therapeutic efficacy. Nevertheless, which constituents in HQD are effective is still unclear so far. The study aims to screen out the key bioactive components combination from HQD that could enhance the anticancer effect of CPT-11. First, the potential bioactive constituents were obtained through system pharmacology strategy. Then the bioactivity of each constituent was investigated synthetically from the aspects of NCM460 cell migration, TNF-α release of THP-1-derived macrophage and MTT assay in HCT116 cell. The contribution of each constituent in HQD was evaluated using the bioactive index E

Overview of systematic reviews on Shenmai Injection in prevention and treatment of diseases / 中国中药杂志

To summarize and evaluate the efficacy and safety of Shenmai Injection in the treatment of viral myocarditis, shock, pulmonary heart disease, coronary heart disease, neutropenia and tumor chemotherapy, so as to provide supportive evidences for clinical rational use of Shenmai Injection. By searching literatures about studies on the systematic reviews on Shenmai Injection in treatment of viral myocarditis, shock, pulmonary heart disease, coronary heart disease, neutropenia and tumor chemotherapy from the main Chinese and English databases. Primary efficacy and safety outcome measures were selected for comparative analysis and summary, and the appraisal tool of AMSTAR 2 was used to evaluate the included studies.A total of 36 systematic reviews(published from 2005 to 2020) were included, involving viral myocarditis, shock, pulmonary heart disease, malignant tumor and coronary heart disease. The number of cases included in each type of the above diseases was 3 840, 2 484, 12 702, 28 036 and 27 082, respectively. The comparison results showed that, Shenmai Injection combined with conventional/western medicine treatment groups had better efficacy than conventional/western medicine groups alone in the prevention and treatment of the above five diseases. The main adverse reactions of Shenmai Injection reported in the included studies were facial flushing, rash, palpitation, etc., but the incidence was low and the general symptoms were mild, so no special treatment was needed. Therefore, the application of Shenmai Injection on the basis of conventional treatment or western medicine treatment had better prevention and treatment efficacy of the diseases. It was suggested that more multi-center and larger sample-size randomized controlled trials should be carried out in the future, and the relevant reporting standards should be strictly followed in systematic reviews, so as to improve the scientificity and transparency of the study.

Otological and hearing characteristics in children with Turner syndrome / 中华耳鼻咽喉头颈外科杂志

Objective: To explore the otological and hearing characteristics in children with Turner syndrome (TS), to determine risk factors of hearing loss, and to discuss algorithms for future surveillance. Methods: The clinical data of otolaryngology in children with TS from January 2018 to April 2020 were reviewed retrospectively. A total of 46 female children with TS, aged from 5 to 18 years were enrolled. Karyotypes included 17 cases (37.0%) of monosomy, 16 cases (34.7%) of mosaicism, and 13 cases (28.3%) of abnormal X chromosome structures. The otoscopic characteristics, audiological performance, and otologic diagnoses were evaluated. Multivariate logistic regression and Mann-Whitney U test were used for statistical analysis. Results: The most common otologic comorbidity was otitis media with effusion (OME), including 20 cases (43.5%) with 33 ears (35.9%). 14 cases (30.4%) were diagnosed with hearing loss. The regression analysis revealed that the age (OR=1.345, 95%CI: 1.072-1.760) and comorbidity of OME (OR=9.460, 95%CI: 2.065-60.350) were risk factors associated with hearing loss. In TS with OME, when compared with the mean air conduction threshold, the hearing loss of the group with pars flaccida retractions was significantly higher ((24.3±13.8) dB HL vs. (14.4±4.2) dB HL, U=59.500, P=0.008) than that of the group with none retractions. Conclusion: OME and hearing loss are common in children with TS. As age increases or suffers from OME, the risk of hearing loss increases.

Studies on fingerprints and efficacy-related substance of classical prescription Zhuru Decoction / 中国中药杂志

Based on fingerprint and network pharmacology,the whole process quality control of Zhuru Decoction was conducted and efficacy-related substances were predicted.The fingerprints of raw materials,decoction pieces and Zhuru Decoction were established,and 25 common peaks were identified,including 9 common chromatographic peaks of 3'-hydroxy puerarin,puerarin,3'-methoxy puerarin,puerarin,aperioside,daidzin,daidzein,liquiritin,glycyrrhizic acid and 6-gingerol, with similarity all greater than 0.95.The main groups of pharmacodynamic substances can be transferred from raw materials,decoction pieces to Zhuru Decoction step by step,with a clear affiliation relationship.Based on the testability and traceability,the active ingredients were screened,and the network relationship of "component-target-pathway" was constructed and analyzed for the nine chemical components screened by network pharmacology.The enriched pathways included energy metabolism,alcoholism,and smooth muscle contraction and relaxation-related pathways.The nine active components of Zhuru Decoction may achieve the effects of clearing heat, alleviating a hangover, harmonizing stomach and stopping vomiting through these signaling pathways.Based on transitive and traceable properties of the above 9 components as well as their close relationship to the efficacy of Zhuru Decoction,these 9 components can be identified as potential efficacy-related substances and provide basis for the overall quality control of Zhuru Decoction.

Impact of “Elaphurus davidianus return home project” on the transmission of schistosomiasis in Poyang Lake areas / 中国血吸虫病防治杂志

Objective To investigate the prevalence of Schistosoma japonicum infections in Elaphurus davidianus released to Poyang Lake areas and evaluate the impact of the project of “E. davidianus released to wild environments for natural reproduction and growth” “(E. davidianus return home project”) on the transmission of schistosomiasis in Poyang Lake areas. Methods During the period from April 2018 to December 2019, the population distribution, inhabiting activity and natural reproduction of E. davidianus released to Poyang Lake areas were investigated by means of GPS and artificial observations. The S. japonicum infection was identified in animal feces in E. davidianus inhabitats using a hatching test, and snail distribution was surveyed in E. davidianus inhabiting grass islands using a systematic sampling method. Results A total of 51 E. davidianus were released to the Poyang Lake areas in 2018, which subsequently produced 5 E. davidianus habitats in Yinlong Lake, Longkou, Nanchi Lake, Lianzi Lake and Zhu Lake. E. davidianus was found to predominantly inhibit in grass islands, farmlands and forest lands in hilly regions around the Poyang Lake areas. The natural reproduction rate of E. davidianus was 25% in the habitats in 2019, and the mean density of snails was 0.009 to 0.039 snails/0.1 m2 in E. davidianus inhabitats; however, no S. japonicum infection was identified in snails. In addition, the mean densities of wild E. davidianus and bovine feces were 4.6 samples/hm2 and 2.1 samples/hm2, Conclusions The E. davidianus released to Poyang Lake areas may get infections with S. japonicum, and cause schistosomiasis transmission through fecal contamination in grass islands. The impact on and the prevalence of S. japonicum infection was 4.35% and 13.16% (P = 0.236), respectively; however, the intensities of S. japonicum infections were “+++” and “+”, respectively. Conclusions The E. davidianus released to Poyang Lake areas may get infections with S. japonicum, and cause schistosomiasis transmission through fecal contamination in grass islands. The impact on local schistosomiasis transmission and the response strategy requires to be investigated following the release of E. davidianus to lake regions, to ensure the achievement of the goal of schistosomiasis elimination and the successful implementation of the “E. davidianus return home project” in Poyang Lake areas.

Initial experience with ablation of the innervation surrounding sinus and atrioventricular nodes to treat paroxysmal bradyarrhythmia / 中华医学杂志(英文版)

BACKGROUND@#The symptomatic bradyarrhythmia is Class I indication for pacing therapy which is not a radical cure. The present study aimed to assess the feasibility and to present the initial results of the restricted ablation of the parasympathetic innervation surrounding sinus and atrioventricular (AV) nodes for treating patients with bradyarrhythmia.@*METHODS@#A total of 13 patients with cardiogenic syncope were included from May 2008 to June 2015. Under the guidance of fluoroscopy and /or three-dimensional geometry by 64-slice spiral computed tomography, atrial activation sequence in sinus rhythm was mapped. Chamber geometry was reconstructed manually or automatically using the Niobe II magnetic navigation system integrated with the CARTO-remote magnetic technology (RMT) system. Cardioneuroablation was targeted at the high-amplitude fractionated electrograms surrounding the regions of His bundle and the site with the earliest activation in sinus rhythm. Areas surrounding the sinus node, AV node, and the phrenic nerve were avoided.@*RESULTS@#Thirteen patients completed the studies. Ablation was successfully performed in 12 patients and failed in one. The high-frequency potential was recorded in atrial electrograms surrounding the sinus or AV nodes in all the patients and disappeared in 15 s after radiofrequency applications. The vagal reaction was observed before the improvement of the sinus and AV node function. No complications occurred during the procedures. Patients were followed up for a mean of 13.0 ± 5.9 months. During the follow up ten patients remained free of symptoms, and two patients had a permanent cardiac pacemaker implanted due to spontaneous recurrence of syncope. The heart rate of post-ablation was higher than pre-ablation (69.0 ± 11.0 vs. 49.0 ± 10.0 beats/min, t = 4.56, P = 0.008). The sinus node recovery time, Wenckebach block point, and atrium-His bundle interval were significantly shorter after ablation (1386.0 ± 165.0 vs. 921.0 ± 64.0 ms, t = 7.45, P = 0.002; 590.0 ± 96.0 vs. 464.0 ± 39.0 ms, t = 2.38, P = 0.023; 106.0 ± 5.0 vs. 90.0 ± 12.0 ms, t = 9.80, P = 0.013 before and after ablation procedure, respectively).@*CONCLUSIONS@#Ablation of sinoatrial and AV nodal peripheral fibrillar myocardium electrical activity might provide a new treatment to ameliorate paroxysmal sinus node dysfunction, high degree AV block, and vagal-mediated syncope.

Quantitative proteomics and bioinformatics analyses of human coronary artery endothelial cell injury induced by Kawasaki disease / 中国当代儿科杂志

OBJECTIVE@#To study the biomarkers for human coronary artery endothelial cell (HCAEC) injury induced by Kawasaki disease (KD) using isobaric tags for relative and absolute quantitation (iTRAQ) proteomics.@*METHODS@#HCAECs cultured with the serum of children with KD were used as the KD group, and those cultured with the serum of healthy children was used as the healthy control group. The iTRAQ technique was used to measure the expression of proteins in two groups. The data on proteins were analyzed by bioinformatics. Western blot was used for the validation of protein markers.@*RESULTS@#A total of 518 significantly differentially expressed proteins were identified (with an absolute value of difference fold of >1.2, P<0.05). The gene ontology analysis showed that the differentially expressed proteins were significantly enriched in biological processes (including cellular processes, metabolic processes, and biological regulation), cellular components (including cell parts, cells, and organelles), and molecular functions (including binding, catalytic activity, and molecular function regulators). The KEGG analysis showed that the proteins were significantly enriched in the signaling pathways of ribosomes, PI3K-Akt signaling pathway, and transcriptional dysregulation in cancer. The PPI network showed that the top 9 protein markers in relation density were PWP2, MCM4, MCM7, MCM5, MCM3, MCM2, SLD5, HDAC2, and MCM6, which were selected as the protein markers for coronary endothelial injury in KD. Western blot showed that the KD group had significantly lower expression levels of the protein markers HDAC2, PWP2, and MCM2 than the healthy control group (P<0.05).@*CONCLUSIONS@#The serum of children with KD significantly changes the protein expression pattern of HCAECs and affects the signaling pathways associated with the cardiovascular system, which provides a new basis for the pathophysiological mechanism and therapeutic targets of KD.

Lung metastases at the initial diagnosis of high-grade osteosarcoma: prevalence, risk factors and prognostic factors. A large population-based cohort study

ABSTRACT BACKGROUND: Osteosarcoma is the most prevalent malignant bone tumor in children and adolescents. Lung metastases are associated with poor prognosis. OBJECTIVE: The aim here was to explore the prevalence of and risk and prognostic factors for lung metastases in high-grade osteosarcoma patients. DESIGN AND SETTING: Retrospective cohort study based on the Surveillance, Epidemiology and End Results (SEER) database in the United States. METHODS: Data on 1,408 high-grade osteosarcoma patients registered in the SEER database between 2010 and 2015 were extracted. From these, all patients with high-grade osteosarcoma and initial lung metastasis were selected for analysis on risk and prognostic factors for lung metastases. Overall survival was estimated. RESULTS: There were 238 patients (16.90%) with lung metastases at diagnosis. Axial location, tumor size > 10 cm (odds ratio, OR 3.19; 95% confidence interval, CI: 1.58-6.45), higher N stage (OR 4.84; 95% CI: 1.94-12.13) and presence of bone metastases (OR 8.73; 95% CI: 4.37-17.48) or brain metastases (OR 25.63; 95% CI: 1.55-422.86) were significantly associated with lung metastases. Younger age and surgical treatment (hazard ratio, HR 0.46; 95% CI: 0.30-0.71) favored survival. Median survival was prolonged through primary tumor surgery. CONCLUSIONS: The factors revealed here may guide lung metastasis screening and prophylactic treatment for osteosarcoma patients. A primary tumor in an axial location, greater primary tumor size, higher lymph node stage and presence of bone or brain metastases were significantly correlated with lung metastases. The elderly group (≥ 60 years) showed significant correlation with poor overall survival. For improved survival among high-grade osteosarcoma patients with lung metastases, aggressive surgery on the primary tumor site should be encouraged.

Effects of general anesthesia combined with epidural block or transverse abdominis plane block on intraoperative anesthetic dosages, stress response and inflammatory response in patients undergoing radical resection of colorectal cancer / 医学研究生学报

Objective The choice of perioperative analgesia regimens for radical resection of colorectal cancer is still controversial. The purpose of this study was to compare the effects of general anesthesia combined with epidural block or transverse abdominis plane block on surgical recovery of patients, and provide a basis for the choice of analgesic methods for radical resection of colorectal cancer. Methods The clinical data of 118 patients who underwent laparoscopic radical resection of colorectal cancer under general anesthesia in Affiliated Hospital of Nantong University between February 2016 and May 2018 were retrospectively analyzed, and the patients were divided into group A (epidural block, n=61) and group B (transverse abdominis plane block, n=57) according to anesthesia regimens. The two groups were given the same general anesthesia induction and maintenance medication. The dosages of general anesthetics in two groups were recorded, and the postoperative recovery situations (including first anal exhaust time, eating time, ambulation time, hospital stay and visual analogue scale score) were compared, and the stress indexes of heart rate (HR), mean arterial pressure (MAP), blood oxygen saturation (SpO2), cortisol (Cor) and norepinephrine (NE)], immune indexes of CD4+, CD8+, CD4+/CD8+, total T lymphocyte count and natural killer cell (NK) count and inflammation indicators of human chemokine CXC ligand 8 (CXCL8), interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) were detected in two groups at different time points. Results The dosage of sufentanil in group A was lower than that in group B [(25.36±4.74) μg vs (28.43±3.69) μg] (P<0.001). The first anal exhaust time, eating time and first ambulation time in group A were shorter than those in group B (P<0.05). The VAS scores in group A were lower than those in group B at different time points (P<0.001). The levels of HR, MAP, Cor and NE in group A were lower than those in group B at T2~T3, and the SpO2 at T2 was lower than that in group B [(5.11±0.31)% vs (5.96±0.34)%] (P<0.05). At 24h after operation, the CD8+ and total T cell in group A were lower than those in group B [(20.79±13.02)% vs (26.91±10.22)%, (60.23±8.97)% vs (64.33±12.76)%] while the CD4+/CD8+ and NK cell count were higher than those in group B [(1.66±0.63) vs (1.25±0.95), (27.71±10.98)% vs (20.02±1.74) %] (P<0.05). The levels of CXCL8, IL-6 and TNF-α were lower than those in group B (P<0.05). There was no significant difference in the incidence rate of adverse reactions between group A and group B (3.28% vs 5.26%) (P>0.05). Conclusion General anesthesia combined with epidural block can reduce the dosages of anesthetic drugs in radical resection of colorectal cancer, reduce the body stress response and inflammatory response, and weaken the early immunosuppressive effects, and its overall analgesic effects are better than those of combined transverse abdominis plane block.

UFLC-Q-TOF-MS fingerprints of rhizome of Curcuma phaeocaulis and its vinegar processed products and inhibitory effect on thrombosis / 中国中药杂志

Both raw and vinegar products of the rhizome of Curcuma phaeocaulis are common drugs for promoting blood circulation and removing blood stasis in traditional Chinese medicine,which could be reflected in the inhibition of tail thrombosis in mice. As the traditional processing theory instructs,vinegar tastes sour and bitter,but can activate blood circulation and remove stasis after being infiltrated into the rhizome of C. phaeocaulis as an excipient. In this study,under the help of the ultrafast liquid chromatography-quadrupole time-offlight mass spectrometry( UFLC-Q-TOF-MS),the spectrum-effect relationship between the inhibition of tail thrombosis in mice and the rhizome of C. phaeocaulis both before and after the vinegar processing,were established to explore the functional changes of blood circulation and stasis after vinegar process. Based on the peak area from the fingerprint of UFLC-Q-TOF-MS of the alcohol extracts from the raw and vinegar-processed rhizome of C. phaeocaulis and their efficacy for inhibiting tail thrombosis,the correlation between the chromatography of UFLC-Q-TOF-MS and the inhibition of tail thrombosis in mice were analyzed by orthogonal partial least squares discriminant analysis( OPLS-DA) method. The results,produced by Simca-P software,showed that effective components consisted of eight peaks 16,24( aromadendrene oxide),3,11,22( dehydro-α-curcumene),19[( R)-(-)-α-curcumene],23 and 10 from the fingerprint,making great contribution to distinguish C. phaeocaulis raw products and the corresponding vinegar processed products. Therefore,from the perspective of inhibiting the formation of tail thrombosis in mice,the marker components could be found through the spectrum-effect relationship to distinguish C.phaeocaulis raw and vinegar products. This study provided new basis to explain the difference between the raw and the processed products of traditional Chinese medicine in the functional change of promoting blood circulation and removing blood stasis.

Chemical constituents from green walnut husks and their antitumor activity in vitro / 中国中药杂志

Fourteen chemical constituents, including 5-hydroxy-4-methoxy-1-tetralone(1), 4,8-dihydroxy-1-tetralone(2), 4,5-dihydroxy-α-tetralone(3), blumenol B(4), dehydrovomifoliol(5), megastigm-5-ene-3,9-diol(6), juglanin B(7), blumenol C(8), loliolide(9), oleracone B(10), syringarsinol(11), pinoresinol(12), methyl 4-hydroxy-3-methoxybenzoate(13), and isovanillic acid(14), were isolated from the dichloromethane fraction of 95% methanol extract of green walnut husks by silica gel and MCI column chromatography, and Pre-HPLC. Their structures were determined by spectroscopic methods, such as NMR, MS and so on. Among them, compounds 1, 4-6, 8-13 were isolated from the green walnut husks for the first time, and compounds 4-6, 8, 10, 12, 13 were isolated from the Juglans genus for the first time. All of isolates were detected their inhibitory activities against HeLa, HGC-27 and Ht-29 cell lines by the MTT assay. The result showed that compounds 2, 3, 7, 9 and 11 exhibited inhibitory activity against the tested cell line. The IC_(50) of 7 were 26.5, 9.0, 25.4 μmol·L~(-1), respectively.

Reformation and practice on teaching of molecular biology laboratory course in higher vocational education / 中国免疫学杂志

Molecular biology laboratory inspect curriculum is one of the core courses in medical laboratory major,and it is also practical Since the contents of the curriculum are dull and dry,and students admitted in the medical laboratory major in higher vocational colleges are composed of both arts students and science students,with relatively weak foundation on biology,so they generally feel difficult in learning of molecular biology courses,and thus with learning weariness.Therefore,in the molecular biology teaching in our college,we should take the task of molecular biology examination as the guide,leading to strengthen the training skills,with three modules of basic curriculum design for the integration of molecular biology theoretical knowledge into the training of skill knowledge,basic skills,and technology application,to construct the curriculum system of " serial architecture".Some of the experiments are designed by students themselves while several teaching and evaluation methods are innovated The results show that through the curriculum reform and practice,it can effectively stimulate students' learning interest and cultivate the students' innovation ability and practical ability,with obvious teaching effect.