Label-free target identification for natural products based on proteomics / 药学学报

Target identification and verification of natural products is an important and challenging work in the field of chemical biology. It is also an important job for researchers to apply chemical proteomics technology to biomedicine in order to identify target proteins of natural products. Target identification is critical to understanding its mechanisms and developing natural products as molecular probes and potential therapeutic drugs. Traditional approaches of small molecule target identification based on affinity have been shown to be successful, such as click-chemical probes, radioisotope labeling or photosensitized small-molecule probes. Nevertheless, these technologies require purified candidate target proteins, and modified small molecules with probes or linkers, such as adding agarose beads, biotin labels, fluorescent labeling or photo-affinity labeling. Many structure-activity relationship studies should be performed to ensure that the addition of small molecule labels undisturbed the original biological activity of the small molecules. Unfortunately, all these modifications are likely to alter their biological activity or binding specificity. To overcome the bottleneck of "target recognition", researchers have developed a series of new techniques for unmodified drug target identification. In this article, we reviewed the target identification techniques of natural product without structural modification in order to provide reference for the development of natural products.

The technologies of small molecule ligand-target protein interaction and high throughput ligand screening / 药学学报

The interaction of drug and target protein is a critical part of new drug discovery. It is the premise for drugs to exert therapeutic effects by targeting specific binding sites of target proteins and thereby affecting its pharmacological activity. Currently, a variety of techniques are exploited to detect the interaction between drug ligands and target proteins. For example, cellular thermal shift assay (CETSA) and differential scanning fluorimetry (DSF) based on thermodynamics, mass spectrometry and nuclear magnetic resonance technology, etc. In addition, high-throughput ligand screening technology provides technical convenience for the search of specific ligand, and is a powerful tool to efficiently identify the interaction between drug ligand and target protein. Here, we summarize the detection techniques of interaction between small molecules and target proteins, and discuss the application of high-throughput ligand screening technology in drug research.

Influence of autologous adipose stem cell matrix gel on wound healing and scar hyperplasia of full-thickness skin defects in rabbit ears / 中华烧伤杂志

Objective: To investigate the influence of autologous adipose stem cell matrix gel on wound healing and scar hyperplasia of full-thickness skin defects in rabbit ears, and to analyze the related mechanism. Methods: Experimental research methods were adopted. The complete fat pads on the back of 42 male New Zealand white rabbits aged 2 to 3 months were cut to prepare adipose stem cell matrix gel, and a full-thickness skin defect wound was established on the ventral side of each ear of each rabbit. The left ear wounds were included in adipose stem cell matrix gel group (hereinafter referred to as matrix gel group), and the right ear wounds were included in phosphate buffer solution (PBS) group, which were injected with autologous adipose stem cell matrix gel and PBS, respectively. The wound healing rate was calculated on post injury day (PID) 7, 14, and 21, and the Vancouver scar scale (VSS) scoring of scar tissue formed on the wound (hereinafter referred to as scar tissue) was performed in post wound healing month (PWHM) 1, 2, 3, and 4. Hematoxylin-eosin staining was performed to observe and measure the histopathological changes of wound on PID 7, 14, and 21 and the dermal thickness of scar tissue in PWHM 1, 2, 3, and 4. Masson staining was performed to observe the collagen distribution in wound tissue on PID 7, 14, and 21 and scar tissue in PWHM 1, 2, 3, and 4, and the collagen volume fraction (CVF) was calculated. The microvessel count (MVC) in wound tissue on PID 7, 14, and 21 and the expressions of transforming growth factor β1 (TGF-β1) and α smooth muscle actin (α-SMA) in scar tissue in PWHM 1, 2, 3, and 4 were detected by immunohistochemical method, and the correlation between the expression of α-SMA and that of TGF-β1 in scar tissue in matrix gel group was analyzed. The expressions of vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF) in wound tissue were detected by enzyme-linked immunosorbent assay on PID 7, 14, and 21. The number of samples at each time point in each group was 6. Data were statistically analyzed with analysis of variance for repeated measurement, analysis of variance for factorial design, paired sample t test, least significant difference test, and Pearson correlation analysis. Results: On PID 7, the wound healing rate in matrix gel group was (10.3±1.7)%, which was close to (8.5±2.1)% in PBS group (P>0.05). On PID 14 and 21, the wound healing rates in matrix gel group were (75.5±7.0)% and (98.7±0.8)%, respectively, which were significantly higher than (52.7±6.7)% and (90.5±1.7)% in PBS group (with t values of 5.79 and 10.37, respectively, P<0.05). In PWHM 1, 2, 3, and 4, the VSS score of scar tissue in matrix gel group was significantly lower than that in PBS group (with t values of -5.00, -2.86, -3.31, and -4.45, respectively, P<0.05). Compared with the previous time point within the group, the VSS score of scar tissue at each time point after wound healing in the two groups was significantly increased (P<0.05), except for PWHM 4 in matrix gel group (P>0.05). On PID 7, the granulation tissue regeneration and epithelialization degree of the wounds between the two groups were similar. On PID 14 and 21, the numbers of fibroblasts, capillaries, and epithelial cell layers in wound tissue of matrix gel group were significantly more than those in PBS group. In PWHM 1, 2, 3, and 4, the dermal thickness of scar tissue in matrix gel group was significantly thinner than that in PBS group (with t values of -4.08, -5.52, -6.18, and -6.30, respectively, P<0.05). Compared with the previous time point within the group, the dermal thickness of scar tissue in the two groups thickened significantly at each time point after wound healing (P<0.05). Compared with those in PBS group, the collagen distribution in wound tissue in matrix gel group was more regular and the CVF was significantly increased on PID 14 and 21 (with t values of 3.98 and 3.19, respectively, P<0.05), and the collagen distribution in scar tissue was also more regular in PWHM 1, 2, 3, and 4, but the CVF was significantly decreased (with t values of -7.38, -4.20, -4.10, and -4.65, respectively, P<0.05). Compared with the previous time point within the group, the CVFs in wound tissue at each time point after injury and scar tissue at each time point after wound healing in the two groups were significantly increased (P<0.05), except for PWHM 1 in matrix gel group (P>0.05). On PID 14 and 21, the MVC in wound tissue in matrix gel group was significantly higher than that in PBS group (with t values of 4.33 and 10.10, respectively, P<0.05). Compared with the previous time point within the group, the MVC of wound at each time point after injury in the two groups was increased significantly (P<0.05), except for PID 21 in PBS group (P>0.05). In PWHM 1, 2, 3, and 4, the expressions of TGF-β1 and α-SMA in scar tissue in matrix gel group were significantly lower than those in PBS group (with t values of -2.83, -5.46, -5.61, -8.63, -10.11, -5.79, -8.08, and -11.96, respectively, P<0.05). Compared with the previous time point within the group, the expressions of TGF-β1 and α-SMA in scar tissue in the two groups were increased significantly at each time point after wound healing (P<0.05), except for the α-SMA expression in matrix gel group in PWHM 4 (P>0.05). There was a significantly positive correlation between the expression of α-SMA and that of TGF-β1 in scar tissue in matrix gel group (r=0.92, P<0.05). On PID 14 and 21, the expressions of VEGF (with t values of 6.14 and 6.75, respectively, P<0.05) and EGF (with t values of 8.17 and 5.85, respectively, P<0.05) in wound tissue in matrix gel group were significantly higher than those in PBS group. Compared with the previous time point within the group, the expression of VEGF of wound at each time point after injury in the two groups was increased significantly (P<0.05), and the expression of EGF was decreased significantly (P<0.05). Conclusions: Adipose stem cell matrix gel may significantly promote the wound healing of full-thickness skin defects in rabbit ears by promoting collagen deposition and expressions of VEGF and EGF in wound tissue, and may further inhibit the scar hyperplasia after wound healing by inhibiting collagen deposition and expressions of TGF-β1 and α-SMA in scar tissue.

Developmental effects of TCIPP and TnBP on zebrafish (Danio rerio) embryos / 中华预防医学杂志

Objective: To investigate the toxicity of tris (2-chloropropyl) phosphate (TCIPP) and tributyl phosphate (TnBP) on the growth and development of zebrafish embryos, as well as to explore the underlying mechanisms at the transcriptional level. Methods: With zebrafish as a model, two hpf zebrafish embryos were exposed to TCIPP and TnBP (0.1, 1, 10, 100, 500, and 1 000 μmol/L) using the semi-static method, and their rates of lethality and hatchability were determined. The transcriptome changes of 120 hpf juvenile zebrafish exposed to environmentally relevant concentrations of 0.1 and 1 μmol/L were measured. Results: The 50% lethal concentrations (LC50) of TCIPP and TnBP for zebrafish embryos were 155.30 and 27.62 μmol/L (96 hpf), 156.5 and 26.05 μmol/L (120 hpf), respectively. The 72 hpf hatching rates of TCIPP (100 μmol/L) and TnBP (10 μmol/L) were (23.33±7.72)% and (91.67±2.97)%, which were significantly decreased compared with the control group (P<0.05). Transcriptome analysis showed that TnBP had more differential genes (DEGs) than TCIPP, with a dose-response relationship. These DEGs were enriched in 32 pathways in total, including those involved in oxidative stress, energy metabolism, lipid metabolism, and nuclear receptor-related pathways, using the IPA pathway analysis. Among them, three enriched pathways overlapped between TCIPP and TnBP, including TR/RXR activation and CAR/RXR activation. Additionally, DEGs were also mapped onto pathways of LXR/RXR activation and oxidative stress for TnBP exposure only. Conclusion: Both TCIPP and TnBP have growth and developmental toxicities in zebrafish embryos, with distinct biomolecular mechanisms, and TnBP has a stronger effect than TCIPP.

Research progress of interleukin-1 and its receptor antagonist Anakinra in Kawasaki disease / 中华实用儿科临床杂志

Kawasaki disease (KD) is an acute vasculitis that often occurs in children under 5 years of age, leading to coronary artery aneurysms.It is the leading cause of acquired heart disease in children in many countries.Coronary artery stenosis, thrombosis, and even myocardial infarction may occur in the long-term course of KD, which seriously threaten the health of children.The etiology and pathogenesis of KD are complex, and it is recognized that KD is caused by the interaction of multiple factors like the heredity, immunity, inflammation, and environmental factors.Interleukin-1 plays an important role in the occurrence and progression of KD.This study mainly reviews the research progress of interleukin-1 and its receptor antagonist Anakinra in KD.

Effect of Tiaoshen acupuncture on anxiety after methamphetamine withdrawal / 中国针灸

OBJECTIVE@#To compare the therapeutic effect between Tiaoshen acupuncture combined with psychotherapy and simple psychotherapy on anxiety after methamphetamine withdrawal.@*METHODS@#A total of 78 patients were randomized into an observation group (39 cases, 2 cases dropped off) and a control group (39 cases, 1 case dropped off). Psychotherapy was given in the control group. On the basis of the treatment in the control group, Tiaoshen acupuncture was applied at Baihui (GV 20), Shenting (GV 24), Benshen (GB 13), Neiguan (PC 6) and Shenmen (HT 7) in the observation group. The treatment was given once a day, 6 days were as one course and totally 4 courses were required in both groups. The scores of Hamilton anxiety scale (HAMA), quality of life for drug addicts (QOL-DA) and Pittsburgh sleep quality index (PSQI) before and after treatment were observed in both groups.@*RESULTS@#After treatment, the various scores and the total scores of HAMA, QOL-DA and PSQI were decreased compared before treatment in both groups (P<0.05), and the scores of somatic anxiety factor, the psychic anxiety factor and the total score of HAMA, each various score and the total score of QOL-DA as well as the scores of sleep quality, time to fall asleep, sleep time, daytime dysfunction and the total score of PSQI in the observation group were lower than those in the control group (P<0.05).@*CONCLUSION@#Tiaoshen acupuncture combined with psychotherapy can relieve the anxiety in patients with anxiety after methamphetamine withdrawal, improve the quality of life and sleep, the therapeutic effect is superior to the simple psychotherapy.

Clinical observation of Tiaoshen acpuncture for dry eye syndrome with yin deficiency of liver and kidney / 中国针灸

OBJECTIVE@#To compare the curative effect of Tiaoshen acupuncture combined with artificial tears and artificial tears alone for dry eye syndrome with yin deficiency of liver and kidney.@*METHODS@#A total of 70 patients of dry eye syndrome with yin deficiency of liver and kidney were randomized into an acupuncture combined with medication group (35 cases, 2 cases dropped off) and a medication group (35 cases, 3 cases dropped off). In the medication group, 0.1% sodium hyaluronate eye drop was applied, 3 times a day, 1 drop each time. On the basis of the treatment as the medication group, Tiaoshen acupuncture was applied at Shenting (GV 24), Shenmen (HT 7), Benshen (GB 13), Taixi (KI 3), Taichong (LR 3), Guangming (GB 37), Fengchi (GB 20), Tongziliao (GB 1), Yuyao (EX-HN 4) in the acupuncture combined with medication group, Tongziliao (GB 1) and Yuyao (EX-HN 4) were connect with electroacupuncture, the needles were retained for 30 min, once a day, 6 times a week. Both groups were treated for 2 weeks. Before and after treatment, the clinical symptom score, SchirmerⅠtest (SⅠT), break-up time (BUT), corneal fluorescein staining (FL) score and Hamilton anxiety scale (HAMA) score were observed in the two groups, and the clinical efficacy was compared in the two groups.@*RESULTS@#Compared before treatment, the clinical symptom scores, corneal FL and HAMA scores were decreased (P<0.05), the levels of SⅠT and BUT were increased after treatment in the two groups (P<0.05). After the treatment, the clinical symptom score, FL and HAMA scores in the acupuncture combined with medication group were lower than the medication group (P<0.05), the levels of SⅠT and BUT in the acupuncture combined with medication group were higher than the medication group (P<0.05). The total effective rate in the acupuncture combined with medication group was 90.9% (30/33), which was higher than 71.9% (23/32) in the medication group (P<0.05).@*CONCLUSION@#Tiaoshen acupuncture combined with artificial tears could promote the secretion of tears for patients of dry eye syndrome with yin deficiency of liver and kidney, repair corneal defect and prolong tear film break-up time, and alleviate anxiety state, its curative effect is better than simple artificial tears.

SUN's abdominal acupuncture for depression after methamphetamine withdrawal: a randomized controlled trial / 中国针灸

OBJECTIVE@#To compare the clinical effect of SUN 's abdominal acupuncture and conventional acupuncture in the treatment of depression after methamphetamine withdrawal.@*METHODS@#A total of 80 female patients with depression after methamphetamine withdrawal were randomly divided into an observation group (40 cases, 1 case dropped off) and a control group (40 cases, 2 cases dropped off). The control group was treated with conventional acupuncture at Baihui (GV 20), Yintang (GV 29), Taichong (LR 3), Shenmen (HT 7), Neiguan (PC 6), Danzhong (GV 17), and the observation group was treated with SUN 's abdominal acupuncture at area 1 of the abdomen and area 8 of the abdomen. Both groups were treated once a day, 30 min each time, 6 days as a course of treatment, 1 day rest between treatment courses, a total of 4 courses of treatment. The scores of withdrawal symptoms, Hamilton depression scale (HAMD), Pittsburgh sleep quality index (PSQI) scale and serum serotonin (5-HT) level were compared between the two groups before and after treatment.@*RESULTS@#After treatment, the scores of withdrawal symptoms, HAMD and the various scores and total score of PSQI scale in the two groups were all lower than before treatment (P<0.01), and the scores of withdrawal symptoms, HAMD and the sleep quality, time to fall asleep, sleep time scores and total score of PSQI in the observation group were lower than the control group (P<0.05, P<0.01). After treatment, the serum 5-HT level of the two groups was increased (P<0.01), and that in the observation group was higher than the control group (P<0.05).@*CONCLUSION@#SUN 's abdominal acupuncture can improve withdrawal symptom, depression and sleep quality, increase serum 5-HT content in treatment of depression after methamphetamine withdrawal, and has better effect than conventional acupuncture.

Polyphyllin I promotes cell death via suppressing UPR-mediated CHOP ubiquitination and degradation in non-small cell lung cancer / 中国天然药物

Polyphyllin I (PPI) purified from Polyphyllarhizomes displays puissant cytotoxicity in many kinds of cancers. Several researches investigated its anti-cancer activity. But novel mechanisms are still worth investigation. This study aimed to explore PPI-induced endoplasmic reticulum (ER) stress as well as the underlying mechanism in non-small cell lung cancer (NSCLC). Cell viability or colony-forming was detected by MTT or crystal violet respectively. Cell cycle, apoptosis, reactive oxygen species (ROS) and mitochondrial membrane potential were assessed by flow cytometry. Gene and protein levels were evaluated by qRT-PCR and immunoblotting respectively. Protein interaction was determined by immunoprecipitation or immunofluorescence assay. Gene overexpression or silencing was carried out by transient transfection with plasmids or small interfering RNAs. The Cancer Genome Atlas (TCGA) database was used for Gene Set Enrichment Analysis (GSEA), survival analysis, gene expression statistics or pathway enrichment assay. PPI inhibited the propagation of NSCLC cells, increased non-viable apoptotic cells, arrested cell cycle at G2/M phase, induced ROS levels but failed to decrease mitochondrial membrane potential. High levels of GRP78 indicates poor prognosis in NSCLC patients. PPI selectively suppressed unfolded protein response (UPR)-induced GRP78 expression, subsequently protected CHOP from GRP78-mediated ubiquitination and degradation. We demonstrated that the natural product PPI, obtained from traditional herbal medicine, deserves for further study as a valuable candidate for lead compound in the chemotherapy of NSCLC.

Study on Mechanism of Quercetin in Heart Failure Based on Network Pharmacology and Experimental Validation / 中国实验方剂学杂志

Objective:To predict the therapeutic targets and related signaling pathways of quercetin in the treatment of heart failure （HF） by network pharmacology and molecular docking methods，and further clarify its mechanisms through <italic>in vitro</italic> cell model. Method:The pharmacological targets of quercetin were obtained by SwissTargetPrediction and Targetnet databases； the heart failure related targets were obtained by Online Mendelian Inheritance in Man（OMIM），GeneCards and Therapeutic Target Database（TTD） databases； the protein-protein interaction（PPI） network was analyzed by STRING database（Search Tool for Recurring Instances of Neighbouring Genes），and the PPI network diagram of quercetin for heart failure target was established. Cytoscape 3.7.2 software was used for analyzing and screening the anti-heart failure network nodes of quercetin，and the obtained targets were enriched with gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） analysis by DAVID database. In order to explore the mechanism of quercetin in the treatment of heart failure，we used cell model to verify the function in heart failure treatment. Results:The predicted results showed that there were 23 targets for the treatment of heart failure，such as Matrix Metallopeptidase-9（MMP-9），androgen receptor（AR），coagulation factor 2（F2），insulin like growth factor 1 receptor（IGF1R），epidermal growth factor receptor（EGFR），janus kinase-2（JAK2），cytochrome P450 family 19 subfamily A member 1（CYP19A1），estrogen receptor-1（ESR1），tumor necrosis factor（TNF），protein tyrosine phosphatase receptor type C（PTPRC） and cytochrome P450 family 17 subfamily A member 1（CYP17A1） etc. The results suggest that quercetin may play a role in the treatment of heart failure by intervening in the physiological processes of cardiovascular cell proliferation and metabolism，regulating hypoxia-inducible factor 1 （HIF-1）signaling pathway and steroid hormone biosynthesis. Conclusion:Quercetin has the characteristics of multi-target，multi-channel and multi-channel in the treatment of heart failure. It may play a role in the treatment of heart failure by regulating MMP-9，EGFR and other key genes，participating in the biological process of cardiac and vascular cell proliferation and metabolism.

Clinical observation of acupuncture on restless leg syndrome / 中国针灸

OBJECTIVE@#To observe the clinical therapeutic effect of acupuncture (acupuncture for regulating the spirit) on restless leg syndrome and its concomitance symptoms of sleep disorder and anxiety, and to provide theoretical basis for the clinical application of acupuncture.@*METHODS@#A total of 60 patients were randomized into an observation group and a control group, 30 cases in each one. Conventional acupuncture at lower limbs' acupoints such as Zusanli (ST 36), Yanglingquan (GB 34) and Xuanzhong (GB 39) was applied in the control group. On the basis of the control group, acupuncture at Baihui (GV 20), Shenting (GV 24) and Benshen (GB 13) was added in the observation group. In both groups, the treatment was given once a day, 6 times a week, one week as a course and totally 3 courses were required. Scores of international restless leg syndrome rating scale (IRLS), Pittsburgh sleep quality index (PSQI) and Hamilton anxiety scale (HAMA) were observed before and after treatment in the two groups.@*RESULTS@#Compared before treatment, scores of IRLS, PSQI and HAMA after treatment were decreased in both groups (<0.05), and the improvement in the observation group was superior to the control group (<0.05).@*CONCLUSION@#On the basis of conventional acupuncture, acupuncture can effectively relieve the discomforts of the lower limbs in patients with restless leg syndrome, improve the sleep disorder and anxiety, which is better than conventional acupuncture.

2018 China guideline for diagnosis and treatment of senile osteoporosis / 中国实用内科杂志

According to the procedures for the development of evidence-based medicine guidelines, a multi-disciplinary guideline development working group was established, after three rounds of discussions by the consensus expert group, a new evidencebased guideline for diagnosis and treatment of senile osteoporosis in China(2018) was developed. The grading of recommendations assessment, development and evaluation(GRADE) system was used to rate the quality of evidence and the strength of recommendations. Recommendations were derived from evidence body, and at the same time considered the balance of benefits and harms as well as values and preferences of Chinese patients. The guideline development working group developed 15 recommendations for the diagnosis and treatment of senile osteoporosis. The guideline covered the screening for senile osteoporosis, risk assessment, diagnosis, basic treatment, multiple anti-osteoporosis drugs, therapeutic effect monitoring and evaluation of senile osteoporosis. This guideline aims to serve as a tool for clinicians and patients for best decisions-making in China.

Causes and clinical features of children with traumatic brain injury: a retrospective analysis of 126 cases / 中国当代儿科杂志

OBJECTIVE@#To investigate the causes and clinical features of children with traumatic brain injury (TBI) who need hospitalization or emergency observation.@*METHODS@#A retrospective analysis was performed for the clinical data of 126 children with TBI who were admitted to the emergency department from January 1, 2014 to August 31, 2016, including causes of injury and clinical features.@*RESULTS@#Of the 126 children, there were 95 boys and 31 girls, with a mean age of 2.8 years (range 0.8-5.5 years). The children aged <1 year accounted for 38.1% (48/126), and 26 children died. The two most common types of TBI were epidural hematoma (54.0%) and subarachnoid hemorrhage (50.8%). Of the 126 children, 83 (65.9%) had a Glasgow Coma Scale score of ≤8 within 24 hours after admission. There were different causes of TBI and places where TBI occurred in different age groups. The two leading causes of TBI were falls (51.6%) and road traffic injuries (42.9%). Compared with those in the other age groups, the children in the age <1 year group were most likely to experience injury due to falls (46%; P=0.023). Thirty-five percent of all TBI due to road traffic injuries occurred in the children aged 3-6 years (P<0.001). Most TBI cases occurred at home (47.6%) or on roads/streets (45.2%). Among those who experienced TBI at home, the children aged <1 year accounted for the highest proportion of 48% (P=0.002), and 53% of the patients aged 3-6 years experienced TBI on roads/streets. The most common cause of death in children with TBI was road traffic injury, which accounted for 69%. Among those who died, the children aged <1 year accounted for the highest proportion (62%).@*CONCLUSIONS@#There are different causes of TBI and places where TBI occurs in different age groups. Among children with TBI, the children aged <1 year account for the highest proportion and have the highest number of deaths, with falls at home as the most common cause of TBI. Children aged 3-6 years tend to suffer TBI due to road traffic injury. Road traffic injury is the leading cause of death.

Reversal of multidrug resistance by icaritin in doxorubicin-resistant human osteosarcoma cells / 中国天然药物

Multidrug resistance (MDR) is one of the major obstacles in cancer chemotherapy. Our previous study has shown that icariin could reverse MDR in MG-63 doxorubicin-resistant (MG-63/DOX) cells. It is reported that icariin is usually metabolized to icariside II and icaritin. Herein, we investigated the effects of icariin, icariside II, and icaritin (ICT) on reversing MDR in MG-63/DOX cells. Among these compounds, ICT exhibited strongest effect and showed no obvious cytotoxicity effect on both MG-63 and MG-63/DOX cells ranging from 1 to 10 μmol·L. Furthermore, ICT increased accumulation of rhodamine 123 and 6-carboxyfluorescein diacetate and enhanced DOX-induced apoptosis in MG-63/DOX cells in a dose-dependent manner. Further studies demonstrated that ICT decreased the mRNA and protein levels of multidrug resistance protein 1 (MDR1) and multidrug resistance-associated protein 1 (MRP1). We also verified that blockade of STAT3 phosphorylation was involved in the reversal effect of multidrug resistance in MG-63/DOX cells. Taken together, these results indicated that ICT may be a potential candidate in chemotherapy for osteosarcoma.

Reversal of multidrug resistance by icaritin in doxorubicin-resistant human osteosarcoma cells / 中国天然药物

Multidrug resistance (MDR) is one of the major obstacles in cancer chemotherapy. Our previous study has shown that icariin could reverse MDR in MG-63 doxorubicin-resistant (MG-63/DOX) cells. It is reported that icariin is usually metabolized to icariside II and icaritin. Herein, we investigated the effects of icariin, icariside II, and icaritin (ICT) on reversing MDR in MG-63/DOX cells. Among these compounds, ICT exhibited strongest effect and showed no obvious cytotoxicity effect on both MG-63 and MG-63/DOX cells ranging from 1 to 10 μmol·L. Furthermore, ICT increased accumulation of rhodamine 123 and 6-carboxyfluorescein diacetate and enhanced DOX-induced apoptosis in MG-63/DOX cells in a dose-dependent manner. Further studies demonstrated that ICT decreased the mRNA and protein levels of multidrug resistance protein 1 (MDR1) and multidrug resistance-associated protein 1 (MRP1). We also verified that blockade of STAT3 phosphorylation was involved in the reversal effect of multidrug resistance in MG-63/DOX cells. Taken together, these results indicated that ICT may be a potential candidate in chemotherapy for osteosarcoma.

Effects of Exchange Transfusion on Renal Function, Inflammatory Factors and Blood Internal Environment in Children with Hyperbilirubinemia / 昆明医科大学学报

Objective To study the effects of exchange transfusion on renal function, inflammatory factors and blood internal environment in children with hyperbilirubinemia. Methods Neonates with hyperbilirubinemia treated in neonatal intensive care unit of the hospital between February 2015 and March 2017 were selected as the research subjects and divided into two groups by random number table method. Combined group received exchange transfusion combined with blue ray irradiation, and control group received blue ray irradiation. The serum levels of bilirubin, renal function indexes, inflammatory response indexes and oxidative stress response indexes were measured 24 hours after the treatment. Results 24 hours after the treatment,serum TBIL,BUN,Cr,β2-MG, CysC, TRF, CRP, IL-6, TNF-α, MDA and AOPP levels of combined group were greatly lower than those of control group whereas SOD, CAT and GSH-Px contents were greatly higher than those of control group. Conclusion Exchange transfusion can improve the renal function and inhibit the inflammatory and oxidative stress response in children with hyperbilirubinemia.

Effects of Different Types of Electroacupuncture on Expression of High Mobility Group Box Protein-1 and Interleukin-10 in Hippocampus of APP/PS1 Mice / 中国康复理论与实践

@#Objective To compare the effect of impulse electroacupuncture (impulse-EA) and music electroacupuncture (music-EA) for Tongdu Qishen on spatial learning and memory, and expression of cytokine in the hippocampus of APP/PS1 mice. Methods A total of 32 APP/PS1 double transgenic male mice were randomly divided into model group (n=8), drug group (n=8), impulse-EA group (n=8) and music-EA group (n=8), the same background and age male C57BL/6 mice were observed as normal group (n=8). The impulse-EA group and music-EA group accepted EA at Baihui (GV20) and Yintang (GV29), connected with their own electroacupuncture stimulators, for 20 minuts, then, they were pricked Renzhong (GV26) for a while. The drug group accepted donepezil hydrochloride 0.92 mg/kg intra-gastrically. The normal group, model group and drug group were grabbed and bounded in the same way. After 15 days of treatment, they were assessed with Morris water maze. The expression of high mobility group box pro-tein-1 (HMGB1) and interleukin-10 (IL-10) in hippocampus were measured with immunohistochemistry and Western blotting. Results The escape latency shortened inEA groups compared with that of the model group since the fourth day of Morris water maze training (P<0.05), and it was the least in the music-EA group; and the ratio of swimming across the target quadrant increased (P<0.05), but there was no significant difference between EA groups (P>0.05). The ex-pression of HMGB1 decreased (P<0.05) and the expression of IL-10 increased (P<0.05) in EA groups com-pared with that of the model group, and HMGB1 decreased more and IL-10 increased more in the music-EA group than in the impulse-EA group (P<0.05), according to the measurement in immunohistochemistry, not in Western blotting. Conclusion Both impulse-EA and music-EA based on Tongdu Qishen can promote the recovery of the learning and memory in APP/PS1 mice, and music-EA may do more effectively in inhibition of pro-inflammatory factors and promotion of the anti-inflammatory factors.

Neural stem cell-derived exosomes inhibit apoptosis of neurons induced by hypoxia neural cells / 中国病理生理杂志

AIM: To investigate whether neural stem cell-derived exosomes promote the viability and inhibit the apoptosis of neurons under cobalt chloride(CoCl2)-induced hypoxia in vitro.METHODS:The exosomes were isolated based on ultracentrifugation.The exosomal markers,ALG-2-interacting protein X(Alix)and tumor susceptibility gene 101 (TSG101)were identified by Western blot.The shape of exosomes was observed under transmission electron microscope (TEM).The size distributions of exosomes were analyzed by nanoparticle analysis(qNano).The neurons were exposed in CoCl2at different doses(200~600 μmol/L)for 24 h.The exosomes were co-cultured with the neurons pre-treated with CoCl2.The viability and apoptosis of the neurons were measured by CCK-8 assay and TUNEL method.RESULTS: The exosomes released from the neural stem cells expressed exosomal markers Alix and TSG 101.They also displayed a cup-shaped appearance observed under TEM and their sizes were(95.0 ±23.5)nm(n=370).The neuronal viability was sig-nificantly inhibited by CoCl 2in a dose-dependent manner(P<0.05).After treatment with exosomes,the viability of the neuron pre-treated with CoCl2was increased and the apoptotic rate was decreased(P<0.05).CONCLUSION: Neural stem cell-derived exosomes promote the viability and inhibit the apoptosis of rat neurons uneder hypoxia.

The cost effectiveness analysis of minimally invasive surgery and conservative treatment in elderly osteoporotic spinal fracture / 中国骨伤

<p><b>OBJECTIVE</b>To evaluate the cost effectiveness of conservative treatment, percutaneous vertebroplasty(PVP)and percutaneous kyphoplasty(PKP)for elderly osteoporotic vertebral compression fracture(OVCF).</p><p><b>METHODS</b>The clinical data of 152 patients with osteoporotic vertebral compression fractures, collected in the orthopedic department of 309th Hospital of PLA from October 2013 to July 2014, was retrospectively analyzed. According to the therapeutic methods, the patients who met the inclusion criteria were divided into conservative treatment group (51 cases), percutaneous vertebroplasty group (50 cases) and percutaneous kyphoplasty group(51 cases). The average medical cost (C) in hospital period and 1 year after discharging, and the treatment effect (E) according to standard of "cure" (VAS score less than or equal to 2) or "improvement" (VAS score was 3 to 8) was recorded. Then the C/E value indicated the cost effectiveness in different standards.</p><p><b>RESULTS</b>The average hospitalization days of the PVP and PKP group was 3 to 5 days with an average of(3.4±0.6) days. The conservative group was 12 to 15 days with an average of (14.0±0.6) days. During the hospitalization period, the cost effectiveness of the conservative group, PVP group and PKP group were RMB 1 253.88, 935.75, 983.99 yuan, respectively, according to the standard of "cure". The PVP group was superior to the PKP group and the latter was superior to the conservative group. If "improvement" was used as the standard of evaluation, the results were RMB 97.80, 449.16, 501.84 yuan, respectively, suggesting that the conservative group was better than the PVP group and the latter was better than the PKP group. After hospital discharge, the cost effectiveness of the conservative group, PVP group and PKP group were RMB 3 834.05, 1 878.41 and 1 916.11 yuan, respectively, according to the standard of "cure". The PVP group was superior to the PKP group and the latter exceeded the conservative group.</p><p><b>CONCLUSIONS</b>The study showed that the PVP was the best choice at the evaluation criterion of "cure", while taking "improvement" as the evaluation criterion, the conservative treatment was the best one. Either way, the PVP was the best choice after hospital discharge.</p>

Case-control studies of two kinds of method for the treatment of lumbar tuberculosis with psoas abscess / 中国骨伤

<p><b>OBJECTIVE</b>To compare two kinds of method for treating lumbar tuberculosis with psoas abscess, to provide reference for clinical reasonable select of therapy treatment.</p><p><b>METHODS</b>From January 2010 to January 2013,42 patients with lumbar tuberculosis combined with psoas abscess with obvious surgical indications were enrolled, including 24 males and 18 females with an average age of (38.5 ± 10.2) years old ranging from 21 to 63 years old. All patients were followed up for 18 to 24 months with an average of 20.9 months. Twenty-two patients underwent posterior vertebral body lesions cleared, bone graft fusion and internal fixation and percutaneous puncture catheter drainage for treatment of psoas major abscess as group A, and twenty patients underwent one-stage extraperitoneal approach to remove abscess, posterior vertebral body lesions cleared, bone graft fusion and internal fixation as group B. The operative time, loss of blood, length of hospital stay, clinical cure rate and other clinical results for the two groups were analyzed and compared.</p><p><b>RESULTS</b>The loss of blood was (452.3 ± 137.6) ml in group A and (603.5 ± 99.6) ml in group B, there was significant statistical difference (P < 0.05). The time of operation was (193.6 ± 91.2) min in group A and (230.5 ± 56.6) min in group B, there was significant statistical difference (P < 0.05). The time of operation and the loss of blood in group A were obviously less than which in group B. In group A 20 cases were cured and 2 cases relapsed, 19 cases were cured and 1 case relapsed in group B, there was no significant statistical differences between two groups regarding cure rate with chi-square test (χ² = 0.000, P = 1.000). All patients in two groups obtained good clinical curative effect. There were no significant statistical difference between two groups regarding for length of hospital stay with t-test (P > 0.05).</p><p><b>CONCLUSION</b>Lumbar spinal tuberculosis with psoas abscess is not absolute indications for anterior open operation. Compared with the combined anterior and posterior surgical procedure, the percutaneous puncture catheter drainage combined with posterior debridement, interbody fusion and internal fixation can achieve the same clinical effect but less trauma for the patients.</p>