Objective To evaluate the effect of Jian Pi Bu Shen prescription on inflammatory factors and iron metabolism in the brain of T2DM model mice.Methods A total number of 30 healthy 12-week-old male mice were used in the present study.The groups were randomly assigned to one of the following experimental groups:(1) control group:n=5,the mice were maintained on a normal diet for 4 weeks;(2) model group:n=25,the mice were maintained a high fat diet for 4 weeks.Then,the mice were deprived of food for 12 hours before a single intraperitoneal injection of streptozotocin (STZ,30 mg/kg).Then,the blood glucose levels were measured randomly 3 times within 24 hours after injection.The mice whose blood glucose was less than 16.7 mmol/l would receive another single intraperitoneal injection of STZ.Finally,we got a total number of 19 mice meeting the criteria of animal model we described above.The final 19 mice were randomized to 2 groups:diabetes group (n=10)and Jian Pi Bu Shen (JPBS) group(n=9).JPBS group received gavage administration of JPBS Prescription 7.4 g/kg/d(8weeks).Diabetes group and control group were maintained treated with saline for 8 weeks.Mice were decapitated 24 hours after the last drug treatment.The mice brain tissue slices were prepared for pathological observation.To examine the effects of JPBS prescription on neuroinflammation and iron metabolism in cerebrum and hippocampi,the relative mRNA levels of IL-6,IL-1β,DMT1,FPN1 and CP were tested by RT-PCR.Results mRNA levels of IL-6,IL-1β and DMT1 in the brains of diabetes group were higher while the levels of FPN1 and CP were lower than that of the control group (P＜0.01).Compared with diabetes group,in JPBS group,mRNA levels of IL-6,IL-1β and DMTl in cerebrum and hippocampi were decreased while the levels of FPN1 and CP were increased (P＜0.01).The brain tissue slices of diabetes group showed neuron loss and signs of neurodegeneration.But JPBS group attenuated neurodegenerative change.Conclusion JPBS prescription can protect neuron from apoptosis,suppress neuroinflammation and attenuate iron metabolism,which may be one of the mechanisms of traditional Chinese medicine in treating cognitive dysfunction.

OBJECTIVE To establish an in vitro test method and to evaluate the genotoxicity of chemicals using primary cultured mouse hepatocytes and the changes in phosphorylated histone H2AX(γH2AX)expression levels to provide a more reliable marker of the identification of genotoxicity. METHODS Hepatocytes were isolated from BALB/c mice by an improved two-step collagenase diges?tion method and then cultured in sandwich configuration. The primary cultured hepatocytes were treat?ed with various concentrations of four known genotoxic agents bleomycin(BLM),benzo(a)pyrene〔B (a)p〕,styrene and styrene-7,8-oxide(SO)within the range of 40 μmol · L-1 and two non-genotoxic agents azathioprine(Aza)and ciclosporin A(CsA)at different time points within 24 h. The cytotoxicity induced by these toxicants was assessed by CCK-8 assay. Then,the changes in γH2AX expression levels in treated cells were determined by flow cytometry. RESULTS The four genotoxic agents could be detected and two non-genotoxic agents could not be detected by this method. The γH2AX expression level was the highest when hepatocytes were exposed to BLM and SO for 3 h,or B(a)p and styrene for 6 h(P<0.01). The production of γH2AX was 25.67,18.36,12.43 and 14.25 for the four types of genotoxic agents,respectively,and was approximately 19,13,9 and 11 times that of the vehicle control group(P<0.01)at the optimum time point and concentration. There was a significant positive corre?lation between the indicated concentrations of genotoxic chemicals and γH2AX expression levels(P<0.01). In addition,the production ofγH2AX indicated no marked increase in two non-genotoxic agents such as Aza and CsA in comparison with the control group. CONCLUSION This test method can effec?tively distinguish genotoxic agents from non-genotoxic agents,and direct genotoxic agents from indirect genotoxic agents in the absence of S9. γH2AX might be a reliable marker for the identification of the potential genotoxicity of chemicals.

Objective:To assess the efficacy of trastuzumab combined with neoadjuvant chemotherapy in the treatment of human epidermal growth factor receptor-2 (Her-2)positive breast cancer patients,and to explore its influencing factors of prognosis of breast cancer.Methods:The clinical materials of 112 Her-2 positive breast cancer patients were collected and they were divided into combined treatment group (trastuzumab + neoadj uvant chemotherapy)and single chemotherapy group (without trastuzumab ). SPSS 1 9.0 software was employed to calculate and analyze their clinical characteristics.The survival rate and prognosis were analyzed by Kaplan-Meier method,Log-rank test, and Cox regression. Results:Among the 112 Her-2 positive breast cancer patients, 23 cases were treated with trastuzumab,89 cases were treated without trastuzumab.The disease-free survival (DFS)in combined treatment group and single chemotherapy group had significant difference (P=0.012).And there was no significant difference of overall survival (OS)between two groups (P=0.064).The HR negative group had 18 (32.7%)patients with 5-level of Miller and Payne (MP)classification which was higher than HR positive group (5/46,10.9%)(P=0.009).In univariate analysis,the tumor size,node status at diagnosis and node status after operation were the influencing factors of DFS in the Her-2 positive breast cancer patients;the tumor size,node status at diagnosis,MP classification and node status after operation were the influencing factors of OS in the Her-2 positive breast cancer patients.The result of multivariate analysis indicated that the tumor size, node status at diagnosis,and with or without radiotherapy were the independent influencing factors of DFS and OS in the Her-2 positive breast cancer patients. Conclusion:The breast lesions in the Her-2 positive breast cancer patients with negative HR are relieved after treated with trastuzumab combined with neoadjuvant chemotherapy. The combination of trastuzumab and neoadj uvant chemotherapy can significantly improve the DFS and has a positive influence in the prognosis of Her-2 positive breast cancer patients.

Objective To optimize the quality management of project completion,improve the quality of scientific research outcomes,as well as promote the sustainable development of medical science and technology.Methods Based on the statistical analysis of the completion and postponement of the 2016-2018 provincial basic research projects in a medical school,explored the potential factors of project postponement.Identified possible problems in project execution and management,and furtherly,proposed effective countermeasures and suggestions for improvement.Results The main factors identified causing the postponement of project completion include the technique bottleneck of the experiment,unsatisfied research outcomes,long term of manuscript review,not well organized process management and so on.To deal with those problems,proposals including enhancing the publicity and education,optimizing the incentive system,reinforcing the whole process management,improving the multi-level management and strengthening the construction of scientific research integrity were put forward.Conclusions The quality management of project completion requires an improvement in the delicacy management of scientific research projects and a more comprehensive enhancement in cognition,rules and regulations,management means and scientific research integrity construction.

Objective To examine the efficacy, safety, economic benefits and social function of conventional antipsychotics combined with agomelatine in the treatment of schizophrenia patients with obsessive-compulsive symptoms. Methods Eighty schizophrenic patients with obsessive-compulsive symptoms were randomly divided into two groups. The study group was treated with conventional antipsychotic drugs combined with agomelatin, and the control group combined with clomipramine for 8 weeks. Positive and negative symptom scale (PANSS) and Yale-Brown obsessive-compulsion scale (Y-BCOS) were used to evaluate the symptoms at before treatment, at discharge and one month after discharge. Social disability screening scale (SDSS), treatment emergent symptom scale (TESS) and the economic benefits was used to evaluate the social function, treatment efficacy and economic status. Results Before treatment, there was no significant difference in the scores of each scale between the two groups (P＞0.05). There was no significant difference in PANSS scores between the two groups at all time points (P＞0.05). The difference between Y-BCOS score and pre-treatment value was higher in the study group than in the control group (P<0.05). The difference between SDSS score and pre-treatment value was higher in the study group than in the control group (P<0.05). The TMRs were lower in the study group than in the control group at one month after discharge (P<0.05). The TESS score was lower in the study group than in the control group at discharge and one month after discharge. The cost and income were higher and the cost-effect ratio was lower in the study group than in the control group at one month after discharge (P<0.05). PANSS and Y-BCOS were positively correlated with TMR, SDSS and CER (P<0.05), but not with TESS at one month after discharge (P＞0.05). TESS was positively correlated with TMR, SDSS and CER (P<0.05). Conclusion The treatment of conventional antipsychotics combined with agomelatine in schizophrenia patients with obsessive-compulsive symptoms are safe and effective. Patients can achieve better social function, good economic and social benefits.

Objective To evaluate the efficacy and accuracy of hammering reverse guide wire technique for safe placement of anterior column retrograde intramedullary screw in pelvic and acetabular surgery.Methods From September 2015 to March 2018,46 patients with pelvic or/and acetabular fracture involving the anterior column were treated with hammering reverse guide wire technique for safe placement of anterior column retrograde intramedullary screw at Department of Orthopaedics,Lishui Municipal Central Hospital.They were 28 men and 18 women,aged from 21 to 85 years (mean,55.6 years).There were 34 pelvic ring fractures,9 acetabular fractures and 3 combined pelvic ring and acetabular fractures.After the anterior lateral spine of pubic tuberosity was drilled by a guide pin and drill bit as the entry point,a reverse guide wire was knocked into the bone lightly by a hammer.For each retrograde intramedullary screwing into the acetabular anterior column,we recorded operation time,fluoroscopic frequency,and attempts to establish an acceptable screw pathway by the guide pin.The accuracy of screwing and the quality of fracture reduction were evaluated by imaging examination.For each patient,we recorded fracture union time and complications.Functional recovery of the pelvis and acetabulum was assessed by postoperative physical examination at the last follow-ups.Results The operation time of retrograde intramedullary screwing for the 46 patients averaged 28.9 minutes (from 16 to 55 minutes);the fluoroscopy frequency averaged 16.3 times (from 9 to 35 times);an acceptable screw pathway was established by the first attempt in 43 of the 46 patients (93.5％) and re-established after adjustment of the guide pin in the other 3.Forty patients were followed up for an average of 15.2 months(from 6 to 36 months).Postoperative CT scan and three-dimensional reconstruction showed that all the screws had been placed safely and accurately in the acetabular anterior column.Implant loosening and fracture displacement occurred in one case and lower limb thrombosis in another.No nail breakage,fracture nonunion,incision necrosis or infection,neurovascular injury or femoral head necrosis was observed.All fractures united after an average of 14.7 weeks (from 12 to 18 weeks).According to the Majeed scoring at the last follow-ups,the pelvic and acetabular function was evaluated as excellent in 29 cases,as good in 9,and as fair in 2,giving an excellent and good rate of 95.0％.Conclusion Hammering reverse guide wire technique is an effective method for safe placement of anterior column retrograde intramedullary screw in pelvic and acetabular surgery,because it can increase accuracy of screwing and reduce intraoperative radiation,operation time and incidence of complications though it is simple.

Objective To analyse the risk factors associated with spontaneous intestinal perforation (SIP) in extremely premature infants/extremely low birth weight infants. Method From January 2015 to December 2018, infants with gestational age (GA)<28 weeks or birth weight (BW)<1000 g admitted to our neonatal intensive care unit were enrolled to the retrospective nested case-control study.The clinical data of SIP infants (SIP group) and infants with the same GA but without SIP (control group) were randomly selected and compared. Multivariable Logistic regression was used to analyse the risk factors of SIP. Result A total of 409 extremely premature infants/extremely low birth weight infants were born during the study period. Among them, 25 SIP infants and 55 controls were enrolled. The incidence of SIP in infants with GA 22～25 weeks was 11.8％(16/136), which is higher than infants with GA 26～27 weeks (2.0％, 5/247) (χ2=16.057, P<0.001). The incidence of SIP in infants with BW 400～749 g was 13.0％(14/108), which is higher than infants with BW 750～999 g (3.4％, 8/236) (χ2=11.343, P=0.001). Multivariate Logistic regression analysis showed that twins (OR=4.153, 95％CI 1.392～12.384, P=0.011), umbilical veins catheterization (OR=15.942, 95％CI 1.026～247.789, P=0.048) and ibuprofen use within 3 days after birth (OR=15.387, 95％CI 1.519～155.883, P=0.021) were independent risk factors of SIP. Conclusion The smaller the GA and BW, the higher the incidence of SIP. Twins,umbilical veins catheterization and ibuprofen use early after birth may be independent risk factors of SIP.

Objective:To study the role of SUMOylation in the process of therapeutic hypothermia on neural stem cells (NSCs) in neonatal hypoxic-ischemic encephalopathy.Methods:SUMOylation is an essential post-translational modification involving small ubiquitin-like modifiers (SUMOs). Primary-cultured NSCs from mice were assigned into four groups: control group, hypoxia group, hypothermia group and hypoxia+hypothermia group. Western Blot was used to detect the protein levels of SUMO2/3, hypoxia-inducible factor-1α (HIF-1α), peroxisome proliferator-activated receptor γ coactivator factor 1α (PGC-1α) and octamer binding transcription factor 4 (Oct4). The diameters of NSCs were compared. ELISA was used to detect lactate dehydrogenase (LDH) level. Apoptosis was examined using flow cytometry. Immunofluorescence method was used to measure the differentiation of NSCs into neuronal cells.Results:Compared with the control group, the levels of SUMO2/3, HIF-1αand PGC-1α in NSCs of the hypoxia group increased 33%, 126% and 140%, respectively ( P<0.05). Compared with the control group, the levels of SUMO2/3 and PGC-1α in NSCs of the hypothermia group increased 52% and 536%, respectively ( P<0.05). Compared with the hypoxia group, the levels of SUMO2/3, HIF-1α, PGC-1α and Oct4 in the hypoxia+hypothermia group increased 44%, 40%, 230% and 59%, respectively ( P<0.05). The diameters of NSCs in hypoxia group, hypothermia group and hypoxia+hypothermia group were smaller than control group, and hypoxia+hypothermia group smaller than hypoxia group ( P<0.05). No significant differences existed in LDH levels between hypothermia group and control group ( P>0.05). LDH level in hypoxia+hypothermia group were significantly lower than hypoxia group ( P<0.05). No significant differences existed in the cell death rates between hypothermia group and control group ( P>0.05). The cell death rate in hypoxia+hypothermia group was significantly lower than hypoxia group ( P<0.05). Compared with the control group, the expressions of Nestin in both hypoxia group and hypothermia group were increased, but neuron specific enolase (NSE) were decreased ( P<0.05). Compared with hypoxia group and hypothermia group, the level of Nestin in hypoxia+hypothermia group was further increased, while NSE was further decreased ( P<0.05). Conclusions:Therapeutic hypothermia may increase the tolerance of NSCs to hypoxia by enhancing SUMO modification of proteins, providing theoretical basis for the treatment of hypoxic-ischemic encephalopathy with therapeutic hypothermia.

OBJECTIVETo investigate the effect of occupational exposure to toluene diisocyanate (TDI) on the workers' health.

METHODSA total of 76 workers exposed to TDI (exposure group) and 64 management staff members (control group) were selected from a factory as the study subjects. Area sampling was performed for the place with exposure to TDI according to the method in GBZ 159-2004 Specifications of air sampling for hazardous substances monitoring in the workplace, and gas chromatography was applied to measure the concentration of TDI in workplace air. The workers' personal information was collected with questionnaire, pulmonary ventilation function was determined with a portable spirometer, hematological parameters were analyzed by automatic blood analyzer and blood chemistry analyzer, and the indicators of oxidative damage and energy metabolism were measured by the reagent kit provided by Nanjing Jiancheng Bioengineering Institute. SPSS 17 software was applied for statistical analysis.

RESULTSThe exposure group had significantly lower forced vital capacity (FVC), forced expiratory volume in 1 second(FEV1.0), and FEV1.0/FVC ratio than the control group (P <0.05). Compared with the control group, the exposure group had significantly higher red blood cell count, platelet distribution width, mean platelet volume, lymphocyte count, and neutrophil count(P<0.01), and significantly lower activities of lactate dehydrogenase(LDH), superoxide dismutase, and succinodehydrogenase (SDH)(P <0.01). In the exposure group, the length of exposure was negatively correlated with the activities of SDH and LDH in the serum (r=-0.319, P <0.05; r=-0.239, P <0.05), and the length of exposure was not found to be correlated with the activity of SOD and pulmonary function indices.

CONCLUSIONTDI can induce inflammatory response and lung ventilation function impairment in workers exposed to TDI, as well as oxidative stress and imbalance of energy metabolism. Therefore, it can cause damage to workers' health, and protective measures should be enhanced.

Case-Control Studies ; Erythrocyte Count ; Forced Expiratory Volume ; Humans ; Inflammation ; physiopathology ; L-Lactate Dehydrogenase ; blood ; metabolism ; Leukocyte Count ; Lung ; physiopathology ; Occupational Exposure ; adverse effects ; Pulmonary Ventilation ; Succinate Dehydrogenase ; blood ; metabolism ; Superoxide Dismutase ; metabolism ; Toluene 2,4-Diisocyanate ; adverse effects ; Vital Capacity

OBJECTIVE： To establish a method for simultaneous determination of spinosin and jujuboside A in the seads of Ziziphus jujuba， and to investigate its quality grading standard. METHODS： HPLC-ELSD method was adopted. The separation was carried out on Inertsil ODS-SP column with mobile phase consisted of acetonitrile-water （gradient elution） at the flow rate of 1.0 mL/min. The column temperature was 30 ℃， the temperature of drift tube was 90 ℃， the flow of carrier gas was 2.9 L/min and injection volume was 20 μL. The thickness， width， length and 100-grain quality of the medicinal materials were used as indicators to investigate the appearance traits. SPSS 22.0 software was used to analyze the correlation of the contents of spinosin and jujuboside A， its appearance traits with the quality constant of TCM， and establish a quality classification standard for the seads of Z. jujuba. RESULTS： The linear range of spinosin and jujuboside A were 1.03-6.18 μg/mL （r＝0.999 7）， 1.05-6.30 μg/mL （r＝0.999 8）； the limits of quantitation were 0.171， 0.174 μg/mL， respectively； the limits of detection were 0.052， 0.053 μg/mL， respectively. RSDs of precision， stability and reproducibility tests were all lower 2％. The recoveries were 99.01％-102.97％ （RSD＝1.39％， n＝6）， 97.94％-101.03％ （RSD＝1.13％， n＝6）， respectively. Correlation analysis results showed that the length， width， 100-grain quality spinosin content and jujuboside A content of the medicinal materials were positively correlated with the quality constant of TCM. The results of quality classification for 30 batches of medicinal materials showed that S1-S4 and S7-S12 were first-class products； S5， S6， S13-S17 and S20-S30 were second-class products； S18 and S19 were third-class products. CONCLUSIONS： Established content determination method is simple， precision， accurate and stable， and can be used for simultaneous determination of spinosin and jujuboside A in the seads of Z. jujuba. Established quality grading standard of the seads of Z. jujuba can be used to evaluate the quality.