Abstract: Objective To analyze the antimicrobial resistance rate and risk factors of multi drug resistant organisms (MDRO) in bloodstream infection for rational treatment. Methods　A total of 696 cases of bloodstream infections of Staphylococcus aureus, Enterococcus, Enterobacteriaceae (excluding Salmonella and Shigella), Pseudomonas aeruginosa and Acinetobacter in our hospital from 2017 to 2021 were selected, and 711 pathogenic strains were isolated from their whole blood samples. The antimicrobial resistance rates of various multi drug resistant strains were analyzed and the risk factors of MDRO infection were analyzed. Results　696 non repeated cases were screened out from 13 187 whole blood culture specimens, with a positive rate of 5.3%, and a total of 711 blood influenza pathogens were detected, among them, 350 strains of MDRO were detected with a detection rate of 49.23% (350/711). Among the pathogenic bacteria of bloodstream infection, Escherichia coli was the most, with 277 strains accounting for 38.96% (277/711), of which 201 strains were MDRO, accounting for 57.43% (201/350); followed by Klebsiella pneumoniae and Staphylococcus aureus, with 155 strains accounting for 21.80% (155/711) and 89 strains accounting for 12.52% (89/711), among which 43 strains of Klebsiella pneumoniae MDRO accounted for 12.29% (43/350) and 38 strains of Staphylococcus aureus MDRO accounted for 10.86% (38/350). The change trend of the three pathogens during 2017-2021 was not obvious. The drug sensitivity test showed that Escherichia coli and Klebsiella pneumoniae were highly resistant to cephalosporins and fluoroquinolones, and the drug resistance rate of aminoglycosides was relatively low. They had almost no resistance to cephalosporins and carbapenems. Staphylococcus aureus has a high resistance rate to lincomycin and macrolides, but no resistance to oxazolidinone, glycopeptides and glycylcyclins. There were 350 cases of MDRO infection and 361 cases of non MDRO infection. Univariate analysis showed that the age, sex, cardiovascular and cerebrovascular history, renal insufficiency, lung disease, hypoalbuminemia, hepatobiliary disease, electrolyte disorder and anemia of the patients had no statistical significance in MDRO infection (P>0.05); diabetes, urinary tract infection, surgical operation and burn were the influencing factors of MDRO (P<0.05). According to logistic analysis, diabetes, urinary tract infection, surgical operation and burn were the risk factors of MDRO infection (P<0.05). Conclusion　The infection of MDRO in patients with bloodstream infection is serious, and early prevention and control should be paid attention to, and the principle of graded use of antibiotics should be strictly observed, and the rational application should be carried out to actively and effectively control the production of MDRO.

Objective To investigate the incidence of Keshan disease(KSD) in Shandong province and to supply evidence for scientific control of the disease.Methods According to the scheme of KSD monitoring in Shandong province,the KSD cases were searched in 7 counties,and representative 3 counties and 6 villages were selected as key monitoring sites.In each site,about 420 residents were checked by asking detailed disease history,physical examination,and electrocardiography (ECG) tracings.Suspected cardiac abnormalities were taken chest posteroanterior X-ray film.At the same time,residents hair and food samples were collected to detect selenium levels in internal and external environments,and residents' income and per capita share of grain and other basic information were collected.Results ①Two hundred and fifty-nine medical units were searched,1132 cases of myocardial disease were found out and 638 suspected cases were identified and 142 chronic KSD cases were diagnosed.②In the 6 monitoring sites,2538 residents were surveyed and 91 cases of KSD were detected(of which 77 cases of potential,14 cases of chronic),the detection rate was 3.58％.A total of 2127 residents were traced ECG and the incidence of abnormal ECG was 24.5％ (521/2127),of which ST-T changes,T-wave changes,sinus bradycardia,sinus arrhymia,sinus tachycardia,and atrial premature beats et al were more common.Of the 75 X-ray films,39 cases had enlarged heart(in which 21 of mild,13 of moderate,5 of severe).③A total of 406 hair and grain samples were collected,respectively,and the selenium content of hair was approaching the level of appropriate,and the selenium content of food was still low.The annual per capita incomes of each site were between 3000 - 5900 Yuan,and residents main staple food was flour.Conclusions KSD in Shandong province is in a relatively stable situation.But latent and chronic KSD cases can still be detected.The internal environment selenium levels are elevated since the local living standards and dietary nutrition are improved.

Objective This study is to explore the expression of CIP2A mRNA in hepatocellular carcinoma (HCC), and its correlations with clinicopathologic features and prognosis of HCC patients.Methods CIP2A mRNA expression was analyzed in four liver cancer cell lines (Hep-G2, MHCC97,SMMC-7721 and BEI-7402), one immortalized liver cell line L-O2, neoplastic tissues and adjacent matched non-neoplastic liver tissues in 120 HCC patients and normal liver tissues of 20 cases using semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). The correlations between CIP2A mRNA and clinicopathologic features and prognosis of HCC were analyzed. Results CIP2A mRNA was detected in Hep-G2, MHCC-97H, SMMC-7721 and BEL-7402, but not in L-O2.The positive rate of CIP2A mRNA expression was significantly increased in HCC tissues (78.3%)than in adjacent matched non-neoplastic liver tissues (28.3%) and normal liver tissues (5.0%,P＜0. 01). CIP2A mRNA expression was correlated with tumor size, differentiation and TNM stage (P＜0.05). Patients with positive expression of CIP2A mRNA had lower overall survival and diseasefree survival rates. Conclusions CIP2A mRNA, which is highly expressed in liver cancer cell lines and HCC tissues, may be involved in hepatocarcinogenesis. CIP2A mRNA may be a valuable biomarker for assessing the prognosis of HCC.

Objective To evaluate the effect of BML-111 on NF-κB pathway during acute lung injury induced by hemorrhagic shock and resuscitation in rats.Methods Thirty-two adult male Sprague-Dawley rats,weighing 200-250 g,were randomly divided into 4 groups (n =8 each) using a random number table:sham operation group (group S),hemorrhagic shock and resuscitation group (group HSR),BML-111 group,and BML-111 + BOC-2 (lipoxin A4 receptor antagonist) group (group BOC-2).The animals were anesthetized with intraperitoneal pentobarbital sodium.Hemorrhagic shock was induced by blood letting and maintained for 30 min.The animals were then resuscitated for 30 min by infusion of the shed blood and lactated Ringer's solution.In group BOC-2,BOC-2 (50 μg/kg) was injected intraperitoneally before blood letting.In BML-111 and BOC-2 groups,BML-111 (1 mg/kg) was injected intraperitoneally at the beginning of resuscitation.The rats were sacrificed at 2 h after the end of resuscitation and lungs were removed for determination of pathological changes,myeloperoxidase (MPO) activity,intercellular adhesion molecule-1 (ICAM-1) expression (by immunohistochemistry),tumor necrosis factor-alpha (TNF-α) content (by ELISA),and NF-κB p65 and IκB-α expression (by Western blot).Results Compared with group S,the MPO activity,ICAM-1 expression,and TNF-α content were significantly increased,NF-κB p65 expression was up-regulated,and IκB-α expression was down-regulated in group HSR.Compared with group.HSR,the MPO activity,ICAM-1 expression,and TNF-α content were significantly decreased,NF-κB p65 expression was down-regulated,IκB-α expression was up-regulated,and pathological changes of lung were attenuated in group BML-111.Compared with group BML-111,the MPO activity,ICAM-1 expression,and TNF-α content were significantly increased,NF-κB p65 expression was up-regulated,and lκ:B-α expression was down-regulated,and pathological changes of lung were aggravated in group BOC-2.Conclusion BML-1 11 inhibits activation of NF-κB pathway and inflammatory responses,thus mitigating acute lung injury induced by hemorrhagic shock and resuscitation in rats.

Objective To investigate the radiosensitization effects of the combination treatment of clioquinol (CQ) and zinc on human cervical cell line HeLa in vitro.Methods Cells were divided into the 4 groups:controls,drug,radiation,and combined drug and radiation group.Cytotoxic effect of CQ and zinc on cell viability was determined by CCK-8 assay.Radiosensitization effect of CQ and zinc on HeLa cells was detected by colongenic assay,and the single-hit multi-target model was used to stimulate the doseresponse curve of survival and to calculate radiosensitization parameters.The cell cycle and apoptosis of HeLa cells were analyzed with flow cytometry.Luciferase reporter assay was used to study NF-κB activity of HeLa cells.Results The combination of CQ and zinc inhibited cell growth in a dose-dependent manner (F =188.00,P ＜ 0.01).The mean lethal dose was 3.16 and 2.04 Gy for radiation group and combined drug and radiation group,respectively,and hence the SER was 1.55.Compared with the radiation group,the ratio of G2-phase cells in the combined drug and radiation group decreased(t =10.39,P ＜ 0.05),the apoptosis rate increased at 24 h post-irradiation (t =5.64,P ＜ 0.01),and the NF-κB activity decreased (t =21.42,P ＜ 0.05).Compared to the control group,the NF-κB activity increased in the radiation group(t=6.23,P＜0.05),but decreased in the drug group(t =12.48,P＜0.05).Conclusions The combination of CQ and zinc could increase the radiosensitivity of HeLa cells by decreasing the ratio of G2-phase cells,increasing apoptosis and the inhibiting of NF-κB activity.

Objective To explore therapeutic effects and mechanisms of radical scavenger edaravone on experimental cerebral hemorrhage.Methods Two hundred-forty male SD rats were divided randomly into four groups:control group,cerebral hemorrhage group,edaravone treatment group before operation (A) and edaravone treatment group after operation (B).Experimental cerebral hemorrhage model was made according to the method reported by Rosenberg.Water quantity contained in brain and nervous missing sign were observed,meanwhile the levels of superoxide dismutase (SOD) and malondialdehyde (MDA) in brain tissue were measured.Results Compared with cerebral hemorrhage group,nervous missing sign and water quantity contained in brain obviously changed in edaravone treatment group (P

Objective To observe the effects of fosinopril(FOS),a new generation angiotensin-converting enzyme inhibitor(ACEI),on protein and mRNA expression of transforming growth factor-?_1(TGF-?_1) of rat glomerular mesangial cell(GMC) induced by lipopolysaccharide(LPS);to demonstrate the preventive mechanism against glomerular sclerosis by applying FOS.Methods The cultured GMC in classic way were divided into 3 groups:control group;LPS group;LPS+FOS group.TGF-?_1 concentration in GMC supernatant fluid was detected by ELISA;TGF-?_1 mRNA expression was determined by semiquantitative real-time RT-PCR.Results LPS group was obviously higher than control groups in TGF-?_1 secretion and mRNA expression,while LPS+FOS group decreased distinctively in TGF-?_1 secretion and mRNA expression compared with LPS group.Conclusions FOS has obviously inhibited on TGF-?_1 expression of rat GMC both at protein level and mRNA level,which reveals that it may be an important mechanism by FOS on restraining the development of glomerulosclerosis.

Objective To evaluate the clinical feasibility of localization CT enhanced image replacing plain CT scan image for target delineation and dose calculation.Methods Forty cases of NPC were collected and divided into two groups with different concentrations of contrast agents.The contours of planning target volume (PTV) and organs at risk (OARs) of each case were delineated in the plain scan image,and the contours of PTV and OARs were copied to the enhanced image.Two plans based on the plain scan image and the enhanced image were designed in the planning system of Eclipse.The dose distribution and OARs and MU were compared between the groups.Results No statistical differences were found in the dosimetry of PTV,OARs and MU (P＞0.05).Conclusion The image intensifier has little effect on the dose calculation of Eclipse for NPC.In the radiotherapy for NPC,the localization CT enhanced image can be used to replace the plain CT scan image for target delineation and dose calculation.

OBJECTIVETo investigate the renoprotective effect of adiponectin in streptozotocin (STz)-induced diabetic rats and explore its association with oxidation stress.

METHODSType 2 diabetes mellitus was induced in rats by high-lipids and high-sucrose feeding and intraperitoneal STZ injection. The recombinant plasmid pIRES2-EGFP-gAd expressing globular adiponectin was intraperitoneally injected in the rats mediated by liposome. Thirty-two Wistar rats were randomized into 4 groups, namely the normal control group (NC), diabetic group without any therapy (DM), diabetic group treated with pIRES2-EGFP-gAd (DA) and diabetic group treated with pIRES2-EGFP (DP). After the corresponding treatments for 8 weeks, the blood glucose, HbA1c and urine albumin excretion rate (UAER) were measured, and the kidneys were collected to determine the production of reactive oxygen species (ROS) and assess renal pathologies. Immunohistochemistry and Western blot were employed to determine the protein levels of endothelial nitric oxide synthesis (eNOS) and phosphorylated AMP-activated protein kinase (pAMPK).

RESULTSUAER and ROS production increased significantly in DM group as compared with that in the control group (P<0.05), while no significant differences were found in UARE among the DM, DA, and DP groups (P>0.05). Blood glucose level, HbA1c and ROS were significantly decreased in DA group in comparison with those in DM group (P<0.05). Glomerular hypetrophy, mesangial expansion, basal membrane thickening, tubular epithelial cells cavitation and exfoliation, and mononuclear lymphocyte infiltration occurred in DM group, while these changes were ameliorated in gAd transfection group. The renal expression levels of eNOS and p-AMPK proteins in DM group were significantly lower than those in the control group (P<0.05) and gAd transfection group (P<0.05).

CONCLUSIONSThe renoprotective effect of adiponectin may be at least partially mediated by the activation of the AMPK signaling passway, ROS production inhibition, relief of the oxidative stress, and up-regulation of eNOS expression in the renal tissue of diabetic rats.

Adiponectin ; biosynthesis ; genetics ; pharmacology ; Animals ; Antioxidants ; pharmacology ; Diabetes Mellitus, Experimental ; metabolism ; pathology ; Diabetic Nephropathies ; metabolism ; prevention & control ; Male ; Nitric Oxide Synthase Type III ; metabolism ; Oxidative Stress ; drug effects ; Protective Agents ; metabolism ; Random Allocation ; Rats ; Rats, Wistar ; Reactive Oxygen Species ; metabolism ; Transfection

Objective To evaluate the efficacy and adverse effects of gefitinib in the treatment of fe- male patients with advanced adenocarcinoma of lung who had failed to previous chemotherapy.Methods These patients received 250mg of gefitinib orally,once daily until disease progression or development of intol- erable toxic reaction.They were evaluated one month after treatment and every other month thereafter.Results Among the 27 evaluable patients,there were 1 CR(3.7%),11 PR(40.8%),10 SD(37.0%)and 5 PD(18.5%). The overall response rate was 44.5%(95% CI 29%～68%);and 22 patients(81.5%)gained profit(CR+PR+ SD)from the clinical therapy(95% CI 62%～94%);the mean TTP was 7.2 months.Symptomatic improvement rate was 80.0%.The main adverse effects were mild rash and diarrhea.Conclusion gefitinib has significant efficacy in the treatment of female patients with advanced tung cancer who had failed to previous chemother- apy.Adverse effects are mild.gefitinib is a suitable therapy for these patients.