OBJECTIVE To investigate the ameliorative effect and potential mechanism of imperatorin （IMP） on doxorubicin （DOX） resistance in breast cancer. METHODS The effects of maximum non-toxic concentration （100 μg/mL） of IMP combined with different concentrations of DOX （12.5， 25， 50， 75， 100 μg/mL） on the proliferation of MCF-7/DOX cells were determined by MTT method. MCF-7/DOX cells were divided into blank control group （1‰ dimethyl sulfoxide）， DOX group （50 μg/mL）， IMP+DOX group （100 μg/mL IMP+50 μg/mL DOX） and IMP group （100 μg/mL）. mRNA and protein expressions of multidrug resistance protein 1 （MDR1） and multidrug resistance-associated protein 1 in each group were measured. The relevant pathways and targets involved in the improvement of DOX resistance in breast cancer cells by IMP were screened and validated by using transcriptome sequencing technology， along with gene ontology （GO） enrichment analyses and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses. RESULTS Compared with DOX alone， the combination of IMP and DOX reduced the half inhibitory concentration of DOX on MCF-7/DOX cells from 81.965 μg/mL to 43.170 μg/mL， the reverse fold was 1.90， and the mRNA expression of MDR1 was significantly down-regulated （P＜0.05）. The results of GO enrichment analyses and KEGG pathway enrichment analyses indicated that the reversal of DOX resistance in breast cancer by IMP was mainly associated with the regulation of biological processes such as detoxification， multiple biological processes， and cell killing. The main pathway involved was the p53 signaling pathway， and the key targets mainly included constitutively photomorphogenic protein 1 （COP1）， cyclin E1 （CCNE1）， growth arrest and DNA damage-inducible protein 45A E-mail：tangxilan1983@163.com （GADD45A） and GADD45B. The results of the verification experiments showed that compared with DOX group， there was a trend of up-regulation of COP1 mRNA， and significant down- regulation of CCNE1， GADD45A， and GADD45B mRNA expression in IMP+DOX group （P＜0.05）. CONCLUSIONS The effect of IMP in ameliorating DOX resistance in breast cancer is related to its regulation of COP1， CCNE1， GADD45A and GADD45B targets in the p53 signaling pathway.

Objective To establish an audit team at the Clinical Trial Institution and explore the feasibility of a new model involving clinical pharmacists in auditing clinical trial projects in hospitals.Methods The audit team consists of 6 clinical pharmacists trained as clinical trial auditors by the National Medical Products Administration Institute of Executive Development and specialized coaching by experts from other hospitals.Results The audit team completed a total of 16 audit reports and identified 189 problems,including 128 general problems,58 important problems and 3 serious problems.The institution,sponsors,investigators and subjects were all involved.Conclusion Based on the actual situation of our hospital,the mode of clinical pharmacists establishing audit teams in medical institutions can effectively improve the quality management level of drug clinical trial projects.

Objective To systematically evaluate the intervention effect of social psychological intervention on the health status of patients with bariatric surgery(BS).Methods 8 databases,including PubMed,PsycInfo,and Embase and Clinic Trials,were retrieved to recruit randomized controlled trials with computer from database establishing time to Sep.2022.Independent quality evaluation was conducted by 2 researchers,and Meta-analysis was performed by the RevMan5.3 software.Results Totally 23 RCTs were included.The meta-analysis showed that psychosocial interventions in BS patients improve emotional eating and binge eating behavior[SMD=-0.44,95％CI(-0.78,-0.09),P=0.010;MD=-5.88,95％CI(-8.65,-3.11),P＜0.001],promote better quality of life[SMD=0.30,95％CI(0.02,0.59),P=0.040]and physical mobility,alleviates anxiety and depression[SMD=-0.37,95％CI(-0.67,-0.08),P=0.010;SMD=-0.59,95％CI(-0.84,-0.33),P＜0.001].However,the effect on improving eating disorders[MD=-0.01,95％CI(-0.19,0.18),P=0.950]is not significant,and subgroup analysis results of different intervention measures and follow-up times showed that there was no statistically significant difference in weight changes between the social psychological intervention group and the control group.Conclusion Psychosocial intervention can effectively improve the mental state and eating behavior of the bariatric surgery patients,improve the quality of life and increase physical activity of patients.However,the effect of intervention on eating disorder and weight change is still unclear.More high-quality clinical studies need to be carried out for further verification.

To explore the potential mechanism of frankincense volatile oil in the prevention and treatment of cardiac hypertrophy based on in vitro cell experiment and network pharmacology. METHODS: The anti-hypertrophic effect of frankincense volatile oil was investigated by isoproterenol induced H9c2 cardiomyocytes hypertrophy model. The active chemical components and targets of frankincense volatile oil and targets associated with cardiac hypertrophy were obtained by CNKI, Pubmed, Pubchem databases, etc. String database and Cytoscape 3.8.0 software were used to construct protein-protein interaction network (PPI) and a network of "drug-active component-key target-disease" of frankincense volatile oil in order to screen the key targets of frankincense volatile oil against cardiac hypertrophy. The fluorescent quantitative PCR experiments were performed to verify those key targets. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation analysis of key target genes were performed using David online analysis tool. RESULTS: In vitro cell experiments showed that frankincense volatile oil significantly inhibited the isoproterenol induced increases in cardiomyocytes surface area and protein synthesis, and upregulations of ANP and β-MHC mRNA. A total of 87 active components and 36 ingredient-disease targets of frankincense volatile oil were screened. Network analysis showed that ESR1, NOS3, PTGS2, TNF, MAPK14, and PPARG were key targets. Fluorescence quantitative PCR experiments results indicated that frankincense volatile oil inhibited isoproterenol induced upregulations of ESR1, PTGS2, TNF, and MAPK14 mRNA levels, and downregulations of NOS3, PPARG mRNA levels, respectively. In addition, the GO functional enrichment analysis showed that its biological pathways mainly included lipopolysaccharide-mediated signaling pathway, positive regulation of nitric oxide biosynthetic process, caveola, enzyme binding, etc. The KEGG pathway enrichment analysis included 22 KEGG pathways, which were closely related to VEGF signaling pathway, TNF signaling pathway, sphingolipid signaling pathway and others. CONCLUSION: The active components of frankincense volatile oil may regulate VEGF signaling pathway, TNF signaling pathway, Sphingolipid signaling pathway by acting on ESR1, NOS3, PTGS2, TNF, MAPK14 and PPARG targets, thereby affecting the regulation of lipopolysaccharide-mediated signaling pathway, positive regulation of nitric oxide biosynthetic process, caveola, and enzyme binding, and improving cardiac hypertrophy.

Objective:To establish a protein-protein interaction (PPI) network of 5 microRNA (miRNA) target genes differentially expressed in the plasma of coal-burning fluoride exposed population, and to screen genes and gene modules with important roles.Methods:Five miRNA (hsa-miRNA-3131, hsa-miRNA-4516, hsa-miRNA-6501-5p, hsa-miRNA-10b-5p, hsa-miRNA-4683) target genes differentially expressed in the plasma of coal-burning fluoride exposed population screened by our previous study were mapped to the STRING online database (https://string-db.org), and the PPI network was screened. The Cytoscape v3.6.0 software was used to visualize the PPI network, the topological attribute values degree and betweenness centrality were obtained by the NetworkAnalyzer plug-in, and the central node was filtered in the network (the node with the highest degree and the highest betweenness centrality). At the same time, the maximal clique centrality (MCC) analysis method in the CytoHubba plug-in was used to determine the important nodes in the PPI network. The cluster analysis was conducted by the MCODE plug-in, and the gene modules were screened in the PPI network. The protein names contained in the gene modules were submitted online to the KOBAS v3.0 database (http://kobas.cbi.pku.edu.cn/), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was performed on the gene modules selected by the MCODE plug-in.Results:The PPI network of target genes was consisted of 1 035 nodes and 4 346 edges. The degree (101) and betweenness centrality (0.010 723 89) of ubiquitin A-52 residue ribosomal protein fusion product 1 (UBA52) were the highest, which was the central node of the PPI network. According to MCC analysis, UBA52 was an important node in the PPI network. The top 5 gene modules were selected from the PPI network, and the highly enriched gene pathways in the KEGG pathway enrichment analysis of the 5 gene modules included ubiquitin mediated proteolysis, spliceosome, endocytosis, neuroactive ligand-receptor interaction and vesicular transport.Conclusion:The PPI network of 5 miRNA target genes differentially expressed in the plasma of people exposed to coal-burning pollution of fluoride is successfully established, and the UBA52 gene and the 5 main pathways of gene modules are selected.

Objective:To clarify the risk factors for post-operative central nervous system infection (PCNSI) to provide references for prevention and treatment of PCNSI.Methods:A total of 397 patients with neurosurgery diseases, admitted to and accepted 403 surgeries in our hospital from February 1 st, 2015 to December 30 th, 2015, were chosen in our study; their clinical data were collected. The incidence of PCNSI was analyzed. Risk factors for PCNSI were analyzed by univariate analysis and multivariate Logistic regression analysis. The ajusted specific infection rate of PCNSI was calculated in 12 chief surgeons who performed≥8 operations during the study period to assess the influence of surgeons in PCNSI incidence. Results:The PCNSI incidence in these 397 patients was 9.2% (37/403). The cerebrospinal fluid (CSF) culture positive rate was 29.7% (11/37), including 6 (54.6%) with positive gram staining. Univariate analysis showed that as compared with the non-infected group (366 surgeries), patients in the PCSNI group (37 surgeries) had significantly higher National Nosocomial Infections Surveillance (NNIS) scale, significantly higher proportion of patients with preoperative stay>6 d, significantly longer operative duration, and statistically higher proportion of involvement of scrub nurses with experience in fewer than 8 procedures ( P<0.05). Multivariate Logistic regression analysis showed operative duration ( OR=1.389, 95%CI: 1.202-1.606, P=0.000) and involvement of scrub nurses with experience in fewer than 8 procedures ( OR=2.860, 95%CI: 1.276-6.412, P=0.011) were independent risk factors for PCNSI. After adjustment by NNIS scale, the ajusted specific infection rate of PCNSI in 12 chief surgeons was 20.0%, 23.0%, 17.3%, 18.2%, 13.4%, 12.5%, 6.3%, 8.0%, 5.2%, 4.0%, 0.0%, and 0.0%, respectively, enjoying obvious differences. Conclusion:Specialized infection control training should give to surgeons with high adjusted specific infection rate of PCNSI; this training, shortening operative duration, and training of neurosurgery specialist nurses will be important measures to reduce PCNSI incidence.

The 16th Chinese Symposium on Burn Medicine and the 2021 Congress of Burn Medicine Branch of China International Exchange and Promotion Association for Medical and Healthcare (CPAM) and the 2021 International Summit Forum of Burns in Chongqing was successfully held in Chongqing, from May 19th to 21st in 2021. A total of more than 500 specialists and scholars across the country attended the meeting. The theme of this congress was "Burn Medicine: standardization and internationalization" . With the meetings being held in the one main venue and three branch venues and elite forum, the related hot topics and difficult problems were discussed warmly in multiple dimensions. During the conference, Founding Congress of 6th Editorial Committee of Chinese Journal of Burns, the Standing Committee and whole Committee of Chinese Burn Association, and the Congress of Burn Medicine Branch of CPAM were held in pragmatic and efficient manners.

Objective To establish an model of fluorosis with human primary osteoblasts in vitro and to detect the influences of different doses of sodium fluoride (NaF) on histone acetylation of CyclinD1,cyclindependent kinases 4 (CDK4) gene in human osteoblasts,then to explore the molecular mechanism of skeletal fluorosis from epigenetic perspective of the cell cycle regulation related genes.Methods Human primary osteoblasts from bone tissues of trauma surgery healthy people (car accident) were isolated by enzyme digestion and identified.The osteoblasts were treated with 0,125,250,500 and 1 000 μmol/L NaF for 72 h.The level of histone acetylation (H3K9,H3K14,H4K12,H4K16) in the transcription regulatory region (ChIP1 region) and in the coding region (ChIP2 region) of CyclinD1 and CDK4 genes were detected by quantitative chmmatin immuno-precipitation (Q-ChIP).Results ①After human osteoblasts were treated with 0,125,250,500 and 1 000 μmol/L NaF,respectively,the levels of histone acetylation of H3K9 in ChIP1 transcription regulatory region of CyclinD1 gene were 1.152 ± 0.104,1.174 ± 0.187,1.090 ± 0.176,1.170 ± 0.197 and 1.147 ± 0.097,respectively,the differences were not statistically significant (F =0.524,P ＞ 0.05);the average levels of histone acetylation of H3K14 were 1.495 ± 0.117,1.465 ± 0.069,1.470 ± 0.187,1.760 ± 1.089 and 1.341 ± 0.443,the differences were not statistically significant (F =0.841,P ＞ 0.05);the levels of histone acetylation of H4K12 were 1.239 ± 0.286,0.702 ± 0.063,0.765 ± 0.370,1.011 ± 0.321 and 1.319 ± 0.026,the differences were not statistically significant (F =2.329,P ＞ 0.05);the levels of histone acetylation of H4K16 were 1.452 ± 0.217,1.621 ± 0.165,1.462 ±0.090,1.510 ± 0.146 and 1.564 ± 0.154,the differences were not statistically significant (F =0.123,P ＞ 0.05).②The levels of histone acetylation of H3K9 in ChIP1 transcription regulatory region of CDK4 were 1.472 ± 0.163,1.580 ± 0.161,1.585 ± 0.132,1.451 ± 0.136 and 1.560 ± 0.039,the differences were not statistically significant (F =0.461,P ＞ 0.05);the levels of histone acetylation of H3K14 were 0.919 ± 0.149,0.900 ± 0.059,0.911 ±0.162,0.663 ± 0.049 and 0.841 ± 0.122,the differences were not statistically significant (F =0.974,P ＞ 0.05);the levels of histone acetylation of H4K12 were 0.456 ± 0.142,0.911 ± 0.126,0.969 ± 0.185,1.110 ± 0.146 and 0.931 ± 0.141,the differences were not statistically significant (F=5.459,P ＞ 0.05);the levels of histone acetylation of H4K16 were 1.315 ± 0.083,1.374 ± 0.153,1.423 ± 0.055,1.300 ± 0.132 and 1.385 ± 0.696,the differences were not statistically significant (F =1.663,P ＞ 0.05).③The differences of histone acetylation levels of H3K9,H3K14,H4K12 and H4K16 in ChIP2 coding region of CyclinD1 and CDK4 genes were not statistically significant between NaF treatment groups (F =0.392,0.823,0.999,0.397,0.705,0.049,1.065,0.196,P ＞ 0.05).Conclusion The histone acetylation of CyclinD1 and CDK4 may not be involved in the transcriptional regulation in human primary osteoblasts treated with fluoride.

Objective To explore the association of H3K14 acetylation (ac) with arsenicosis induced by coal-burning and arsenic-induced genetic damage,which might help us to find an biomarker to monitor the arsenicosis and arsenic-induced toxicity.Methods Totally 151 arsenicosis subjects were recruited from Jiaole Village of Xingren County,Guizhou.According to "National Principle for Diagnosis of Arsenicosis" (WS/T 211-2001),the arsenicosis group was divided into 3 subgroups:mild poisoning (n =62),intermediate poisoning (n =50) and severe poisoning (n =39).The control group was comprised of 78 healthy villagers from Jiaole Village who were exhibited no signs of arseniasis.The hair,the urine and the peripheral blood samples were collected from the subjects.The contents of arsenic in the hair samples were analyzed with inductively coupled plasma mass spectrometry.Histones were extracted from human peripheral blood lymphocytes (PBLCs) using the method of acid extraction.The levels of H3K14ac was measured with a sandwich enzyme-linked immunosorbent assay (ELISA).The rate of micronucleus (MN) and chromosome aberration (CA) of peripheral blood lymphocytes were examined by genetic methods.The levels of urinary 8-hydroxy-2 deoxyguanosine (8-OHdG) in all the subjects were measured with the high performance liquid lhromatography-mass spectrometry (HPLC-MS).Results ①The association of arsenic-exposure with arsenicosis induced by coal-burning and H3K14ac:The levels of hair arsenic in arsenicosis group [0.27(0.15-0.39) μg/g] was significant higher than that in control group [0.15 (0.08-0.20) μg/g,F=10.736,P ＜ 0.01].The degree of arsenicosis was positive correlation with the hair-arsenic level (r =0.363,P ＜ 0.05).The levels of H3K14ac was also positive correlation with the hair-arsenic level (r =0.385,P ＜ 0.05).②The association of H3K14ac and arsenicosis induced by coal-burning:The levels of H3K14ac in arsenicosis group (4.07 ± 4.03) was 2.5-fold higher than that in control group (1.62-± 1.19,F =19.753,P ＜ 0.01).H3K14ac was a risk factor of arsenicosis,the risk of arsenicosis increased correspondingly with the levels of H3K14ac [OR (95％CI) =1.779 (1.323-2.392),P ＜ 0.01].③The correlation of H3K14ac and the degree of arsenicosis:Based on the degree of arsenicosis,we found a significant difference in the levels of H3K14ac among the four groups (F =7524,P ＜ 0.01).Compared with the non-poisoning group (1.62 ± 1.19),the levels of H3K14ac in mild poisoning,intermediate poisoning and severe poisoning subgroups (3.70 ± 3.20,4.95 ± 5.47,3.49 ± 2.62) were increased (all P ＜ 0.01),but there were no significant differences in the levels of H3K14ac between the mild poisoning,intermediate poisoning and severe poisoning subgroups (P ＞ 0.05).(④)The genetic damage of all subjects:The rate of MN (2.03 ± 1.55) and CA (12.44 ± 5.01) in arsenicosis group were significantly higher than those in control group (MN:1.17 ± 0.97,Wald =14.121;CA:6.29 ± 2.41,Wald =83.164,P ＜ 0.05).Urinary 8-OHdG was increased in arsenicosis group than that in control group [(3.80 ± 3.88),(2.33 ±1.34) μg/g Cr,F =6.116,P ＜ 0.05].⑤The association of H3K14ac with genetic damage:The results revealed that H3K14ac modification was positively correlated with the rate of CA (β =0.84,P ＜ 0.01).The level of H3K14ac was not significantly associated with the rate of MN and urinary 8-OHdG (MN:β =0.10,P ＞ 0.05;8-OHdG:β=0.05,P ＞ 0.05).Conclusions The increase of H3K14ac modification in human peripheral blood lymphocytes is a risk factor of arsenic poisoning.Additionally,the dysregulation of H3K14ac was significant association with arsenic-induced chromosomal aberrations.

OBJECTIVETo investigate the changes of genetic damage in patients with arsenism caused by coal-burning in 9 years. To analyze the relationship between the changes of genetic damage and disease progression and provide a basis for condition monitoring.

METHODSOf 206 arsenism patients from the area with endemic arsenism in Guizhou province were tracking surveyed in February 1998 and divided into 4 groups, including suspicious, mild, moderate and severe poisoning group. Another 67 healthy residents from a neighbour township 12 km away where arsenic was not prevalent were surveyed. Over a 9-year follow-up, 131 arsenism patients and 45 controls with the complete biochemical indexes among them were selected as subjects in December 2006. Arsenic (As) concentration of urine and hair were detected by silver diethyldithiocarbamate spectrophotometry (Ag-DDC). Micronucleis (MN) and chromosome aberrations (CA) were analyzed by conventional methods. DNA single-strand breaks of peripheral blood were measured by single cell gel electrophoresis (SCGE), and the tail lengths of comet were used to measure DNA damage.

RESULTSAmong the control, suspicious, mild, moderate and severe arsenic poisoning group, the As contents of urine and hair were respectively (34.16 ± 10.25), (52.35 ± 22.41), (62.26 ± 31.13), (71.43 ± 49.92), (78.45 ± 50.64) µg/L and (1.37 ± 0.56), (3.69 ± 1.78), (4.88 ± 3.49), (5.21 ± 3.10), (6.25 ± 4.04) µg/g in 2006, which were lower than that 9 years before (urine as contents were (36.07 ± 20.70), (73.65 ± 41.33) , (90.92 ± 82.14) , (126.55 ± 107.31) and (139.44 ± 90.90) µg/L, and hair As contents were (1.41 ± 1.18), (4.85 ± 4.20), (5.72 ± 4.07) , (6.43 ± 4.32) and (7.19 ± 4.68) µg/g, respectively, F value was 10.63, 7.72, 14.66, 11.00 respectively, all P values were < 0.05). Except for suspicious poisoning group, the differences of urine As contents in the other groups all showed significance (P < 0.05). The incidences of MN were (0.238 ± 0.130) %, (0.268 ± 0.192) %, (0.283 ± 0.157) % and (0.391 ± 0.233)%; the incidences of CA were (14.36 ± 5.44) %, (18.09 ± 6.49) %, (19.38 ± 5.63)% and (19.83 ± 5.84) %; the tail lengths of comet were (29.88 ± 13.81) , (29.84 ± 12.80) , (34.50 ± 9.88) and (41.58 ± 12.98) µm respectively in 2006 for all poisoning groups; which were higher than that 9 years before(the incidences of MN were (0.163 ± 0.051) %, (0.186 ± 0.117) %, (0.196 ± 0.104) % and (0.273 ± 0.142) %; the incidences of CA were (13.18 ± 5.17)%, (14.48 ± 6.61)%, (15.67 ± 8.49) % and (16.90 ± 8.38) %; the tail lengths of comet were (15.07 ± 12.93) , (19.57 ± 8.80) , (27.03 ± 10.77) and (34.71 ± 14.95) µm) , except for the incidences of MN and CA in suspicious poisoning group and of MN in mild poisoning group , the differences of the three indexes in the other groups were significant (P < 0.05) . The state of illness of arsenic poisoning patients aggravated 9 years later. With the increase of urine and hair As contents and the development of arsenism, the incidences of MN, CA and the tail lengths of comet of all poisoning groups increased. There were positive correlations among them (r values were respectively 0.212, 0.316, 0.232, 0.263, 0.321, 0.654 and 0.760) (P < 0.05).

CONCLUSIONThe exacerbation of genetic damage was related to constantly high arsenic loads. The accumulation of genetic damage and its irreversibility might be one of the important reasons of the development of arsenism and cancer.