Objective:To determine whether heme oxygenase-2(HO-2) gene deletion can attenuate oxidative injury induced by free Fe2+. Methods:Stereotactic injection of 10 μl sterile FeCl2 (10 mmol/L) was made into the right striata of HO-2 knockout mice and wild-type mice. Brain edema severity was measured at 24 h. Cell viability, protein oxidation, and lipid oxidation of the basal ganglia were determined at 72 h. Western blot analysis was applied for heme oxygenase-1 (HO-1) measurement.Results: Brain water content significantly decreased in HO-2 knockout mice at 24 h compared with wild-type mice. Protein oxidation and lipid oxidation significantly decreased in HO-2 knockout mice at 72 h compared with wild-type mice, while the striatal cell viability increased significantly. HO-1 expression at baseline and 72 h was also similar to that in wild-type mice. Conclusion:These results show that HO-2 gene deletion can protect basal ganalia cells from free Fe2+ -mediated oxidative stress injury,suggesting that selective inhibition of HO-2 may have a protective effect on brain oxidative injury.

AIM To investigate the pharmacokinetic behaviors of total flavonoids from Epimedii Folium in osteoporotic rats in vivo.METHODS Twelve rats were divided into model group and sham group,after which the osteoporotic rat model was established by removing bilateral ovaries.After intragastric administration with total flavonoids (500 mg/kg),HPLC-DAD was applied to detecting the plasma concentrations of total flavonoids' prototype glycosides (epimedin A,epimedin B,epimedin C,icariin) and their metabolites (sagittatoside A,sagittatoside B,2-O-rhamnosylicariside Ⅱ,baohuoside Ⅰ,icaritin) at thirteen time points (0.083,0.25,0.5,0.75,1,2,3,4,6,8,12,24 and 48 h),then the plasma concentration-time curves were drawn,followed by the calculation of pharmacokinetic parameters.RESULTS Doubled peaks were observed in the plasma concentration-time curves of total flavonoids' prototype glycosides and their metabolites in both groups.Compared with the sham group,the integrated AUC and Cmax in the model group were significantly decreased (P ＜ 0.01),as well as the prolonged t1/2 (P ＜ 0.01).CONCLUSION The in vivo absorption and metabolism of total flavonoids from Epimedii Folium are much slower in the state of osteoporosis,thus affects the efficacy.

The article summarized relevant theories and successful practical experience about medical resource integration, analyzed the background of regional medical-trust in Shanghai, and discussed three different model of regional medical-trust building, and their own advantages and disadvantages. Furthermore it discussed the main framework of regional medical-trust pilot reform,including administrative and operational model, insurance-payment model and visiting-doctor model. Then, it introduced the reform strategies of regional medical-trust pilot and present progress.

Objective To establish a method to validate the result of transcriptome sequencing using duplex PCR tech -nology combined with capillary electrophoresis .Methods According to a previous study on transcriptome sequencing , eight differentially expressed genes were chosen as target genes for examination .The mRNA expression level of these genes was detected using duplex PCR combined with agarose gel electrophoresis , duplex PCR combined with capillary electropho-resis and Q-PCR, respectively.Then, the verification efficiency of each method was evaluated carefully .Results The ver-ification efficiency of duplex PCR combined with agarose gel electrophoresis was 50%, while that of duplex PCR combined with capillary electrophoresis and Q-PCR was both 100%.Conclusion Combination of duplex PCR technology with capil-lary electrophoresis can be used as an alternative method to validate the results of transcriptome sequencing .

Objective To study the clinical manifestations,endoscopic features,pathological features,treatment and prognosis of patients with duodenal neuroendocrine carcinoma (DNEC).Methods The clinical data of 9 patients with duodenal neuroendocrine carcinoma who were admitted to our hospital from December 2006 to December 2014 were retrospectively analyzed.Results There were 6 males and 3 females.The mean age was 61.5 years (range 48 ～75 years).The clinical manifestations were abdominal pain (n =7),jaundice (n =4),melena (n =1) and asymptomatic (n =1).The DNEC was usually solitary in the duodenum.The operations included duodenopancreatectomy (n =5),surgical resection (n =2),subtotal gastrectomy (n =1),and 1 patient was palliated by common bile duct stenting using an endoscopic retrograde cholangio-pancreatographic (ERCP) approach.The patients were followed up for 3 ～ 40 months after operation.For the 5 patients who underwent radical excision 4 were alive.One patient died from liver metastasis.For the 4 patients who underwent palliative therapy,one was alive,two died and one lost to follow-up.Conclusions The clinical manifestations of duodenal neuroendocrine carcinoma were non-specific.Endoscopic,pathologic and immumohisotochemical tests were important in the diagnosis.Surgical resection improved the prognosis of these patients.

Objective To explore the expressions and distributions of glial cell line -derived neurotrophic factor (GDNF)and itstyrosine kinase receptor RET in the terminal rectums of fetal rats with congenital anorectal malfor-mations (ARM)at different gestationalage,and to explore their effects on the enteric nervous system in the terminal rectum of ARMfetal rats.Methods Thirty -five SD pregnancy rats were divided into a saline group (n =1 0)and an ethylenethiourea experiment group (n =25)by simple randomized study.The fetal rats were removed from the pregnant rats at the gestational 1 6 d,1 8 d and 20 d.The fetal rats were divided into the saline control group,the ethylenethiourea control group (fetal rats without ARM)and the ethylenethiourea malformation group (ARM fetal rats)by the naked eye and dissecting microscope.HE staining was used to observe the morphology and the intestinal ganglion cells in the terminal rectum were counted.The immunohistochemical staining and Western blot methods were used to observe the distributions of GDNF and RET in the rectum at the gestational 1 6 d,1 8 d and 20 d.The quantitative real -time poly-merase chain reaction (qRT -PCR)was used to detect the expression of GDNF mRNA in the fetal rats in the terminal rectum at the gestational 1 6 d,1 8 d and 20 d.Results HE staining:the development of anorectal terminal in 3 groups of fetal rats was unclear at the gestational 1 6 d.A small amount of scattered nerve plexuses were observed in the muscu-lar layer.The nuclei were small and sparse.The axons and cytoplasms were less.The serosal layer,muscular layer,sub-mucosa,mucosal layer and glands in the terminal rectum were gradually clear in the saline control group and the ethyle-nethiourea control group at the gestational 1 8 d and 20 d.The intermuscular submucosal nerve plexuses increased gra-dually (1 1 .400 ±3.1 34 and 1 1 .200 ±3.425 at the gestational 1 8 d;66.1 00 ±4.954 and 67.600 ±5.481 at the gesta-tional 20 d).While,the layer was unclear in the ethylenethiourea malformation group and the nerve plexus was less (7.800 ±1 .989 at the gestational 1 8 d,and 25.200 ±3.048 at the gestational 20 d),and the difference was statistical-ly significant compared with 2 control groups (F =7.591 ,271 .833,all P <0.05).Immunohistochemistry satning:the expressions of GDNF and RET in all layers of the intestinal wall in the 3 groups of fetal rats were unclear at the gesta-tional 1 6 d and only a few positive cells were observed.The GDNF and RET were expressed in the mucosal layer and submucosa of the terminal rectum as well as intermuscular nerve plexus in the saline control group and the ethylene-thioured control group at the gestational 1 8 d and 20 d.With the continuous development of the embryo,their expression intensities were gradually increased.The expressions of GDNF and RET positive cells were decreased gradually in the ethylenethiourea malformation group.The difference was significant statistically compared with 2 control groups (all P <0.05).qRT -PCR:the expressions of GDNF mRNA showed no statistical difference among 3 groups at the gestational 1 6 d (P >0.05);the expressions of GDNF and RET protein were 1 03.624 ±27.533 and 1 05.1 84 ±1 9.634 at the ges-tational 1 8 d;1 51 .496 ±33.622 and 1 50.738 ±21 .423 at the gestational 20 d in 2 control groups.Compared with the ethylenethiourea malformation group (79.1 69 ±1 1 .697 at the gestational 1 8 d;94.873 ±1 1 .309 at the gestational 20 d),and the difference were statistically significant (all P <0.05).Conclusions The expressions of GDNF and its tyrosine kinase receptor RET had a certain temporal correlation in the terminal rectum of normal fetal rats at different gestational ages and ARM.Moreover,the abnormal expressions of GDNF and its tyrosine kinase receptor RET in the dis-tal rectum of ARMfetal rats can affect the development of enteric nervous system.

Objective To evaluate whether flexible ambrosia,by which people can take special prebiotics instead of dining to alleviate their sense of hunger is a healthy, safe and effective weight loss method by analyzing the effects of flexible ambrosia on body weight, body composition, physiological and chemical indexes of young volunteers.Methods Young volunteers were tested on flexible ambrosia for seven days using special prebiotics instead of normal food.Body weight, waist circumference, body composition and blood biochemical indexes ( blood pressure, blood glucose, liver function, renal function, blood electrolyte, and blood lipid ) were measured and recorded before and after the test respectively.The volunteers′subjective feelings ( hunger, energy, fatigue, etc) were recorded during the test every day by way of e-form records.Results All volunteers of the flexible ambrosia test reduced their body weight, body mass index (BMI), waist circumference, visceral fat index (VAI) and body fat rate (Fat,%)significantly (P<0.01)in seven days, while the body water rate, muscle mass, body protein and bone did not significantly change or rise.There was no significant functional abnormity of the liver kidney, or blood electrolytes and blood lipid.All volunteers were in good physical condition, high-spirited and slept well, high quality sleep, without any obvious hunger and fatigue response in seven days.Conclusion Flexible ambrosia seems to be a healthy, safe and effective method, and provides an important scientific basis and reference for weight loss in the military.

Kidney injury and decreased chemosensitivity of tumor cells are obstacles with cisplatin (CDDP) chemotherapy. Down-regulation of the organic cation transporter 2 (OCT2) and multidrug resistance-associated protein 2 (MRP2) is a key means to alleviate CDDP-induced kidney injury and increase chemosensitivity. Astragaloside IV (AS IV) is obtained from the well-known traditional Chinese herb Astragalus membranaceus. This study explored the role of AS IV in preventing kidney injury and enhancing the antitumor effect of CDDP by suppressing OCT2 expression in kidney and MRP2 in tumors. This project was reviewed and approved by the Animal Ethics Committee of the First Hospital of Jilin University. The effects of AS IV on CDDP inhibition of tumor growth and promotion of apoptosis were assessed in Lewis lung tumor (LLC)-bearing mice by H&E and TUNEL staining. Kidney injury was assessed by serum biochemical parameters and H&E staining. We used Western blotting and immunohistochemistry assays to detect OCT2 and MRP2 expression in kidney and tumor. The concentration of CDDP in kidney and tumor was measured by HPLC-MS/MS. AS IV enhanced CDDP chemosensitivity by increasing tumor cell apoptosis and slowing tumor growth, and decreased kidney injury as evidenced by lower blood creatinine (Cr) and blood urea nitrogen (BUN). Co-administration of AS IV suppressed MRP2 overexpression induced by CDDP in tumor tissues and may be an important mechanism for enhancing CDDP chemosensitivity. Moreover, AS IV reduced CDDP-induced kidney injury in mice along with suppression of OCT2 expression in kidney. The concentration of CDDP was increased in tumor but decreased in kidney. In total, AS IV not only enhanced the antitumor effect of CDDP by suppressing MRP2 expression in tumor cells, but also decreased kidney injury induced by CDDP. The results provide new insight into the combined use of a chemotherapy drug and natural ingredients to treat cancer.

Objective To evaluate the therapeutic effects of poly(N-isopropylacrylamide)adriamycin magnetic nanoparticles(ADM-PNIPAM-Fe_3O_4)on liver VX2 tumor in rabbits via transcatheter arterial chemoembolization.Methods VX2 tumor pieces were successfully implanted into liver lobes of rabbits with liver tumors formation.All the animals were randomly divided into 4 groups of 8 each.Group A(control group)injected with 10 ml physiologic saline,Group B(ADM group)treated with free adriamycin (1 mg/kg)via arterial infusion,Group C(ADM-PNIPAM group)ADM-PNIPAM(1.5 mg/kg)was infused through arterial route,Group D(ADM-PNIPAM-Fe_3O_4+M group)ADM-PNIPAM-Fe_3O_4(2 mg/kg)was infused through arterial route;all were in individual doses,respectively;meanwhile an persistant magnet with intensity of 0.4 T was stabilized at the tumor region.Spiral CT scans were performed to measure size of liver tumors and evaluate lung metastasis at 1 day before operation and 14 days after operation.All experimental animals were sacrficed on the 15th days after operation and followed by pathologic and histologic examination of the tumor and lung specimens including changes befor and after the operation with correlative comparisons.Results There were no significant difference in volumes of tumors among 4 groups at 1 day before operation.The average tumor volume in the group A was(23.87?7.02)cm~3 at 14 days after operation;(7.70?1.53)cm3 in group B;(4.29?0.25)cm~3 in group C;(2.05?0.18)cm~3 in group D. The average tumor volumes in the group B,group C and group D were significantly smaller than that in the control group A at same time after operation and there was significant difference among the three experimental groups.According to the order of tumor sizes from small to large was as follows:group D＜group C＜group B＜group A.It showed that the average size of group D(ADM-PNIPAM-Fe_3O_4+M group) was the smallest among the 4 groups.Lung metastatic rates were 100%,66.7%,37.5% and 12.5% in group A,group B,group C and group D at 14 days after operation,respectively.Lung metastatic rates of group D was lower than that of group A,but there were no significant differences among group A,B and C.But pathological examination showed that there were lesser number of lung metastatic tumors in group B and C than that of group A .The intratumoral necrotic degrees showed as group D＞group C＞group B＞group A. Conclusions ADM-PNIPAM-Fe_3O_4 treatment for liver tumor via vascular interventional method combined with magnetic field localized in the lesion possesses significant inhibitory effect on tumor growth of liver VX2 tumor in rabbits.ADM-PNIPAM-Fe_3O_4 is thus initially confirmed as a kind of effective praeputium in interventional chemoembolization.

BACKGROUND:Talus cartilage injury is a common motor system disease.This type of injury will affect the patient's daily life and work ability,and may worsen the condition if left untreated.Surgical treatment is commonly used,but the selection of surgical methods and the evaluation of medium-and long-term follow-up results have always been difficult clinical problems. OBJECTIVE:To explore the influence of T1ρ technique on the range of quantitative evaluation of talus osteochondral injury on the choice of surgical method and the results of medium-and long-term follow-up. METHODS:A total of 154 patients with osteochondral injury of talus admitted to The Second Hospital of Tangshan from January 2019 to August 2022 were retrospectively selected as the study subjects.The lesion site of talus was examined by MRI before operation,and the T1ρ and T2 values of different types were compared.Different surgical methods were selected according to the different T1ρ values.Group A(n=73)was treated with microfracture surgery with T1ρ<45 ms;group B(n=81)was treated with autogenous bone and cartilage transplantation with T1ρ≥45 ms.The general clinical characteristics and curative effects of patients under different surgical methods were compared;the important factors of postoperative recurrence were analyzed by multivariate Logistic regression,and the relationship between T1ρ value and postoperative recurrence was analyzed by restricted cubic spline graph,y=1-1/(1+e-z)regression equation to build a prediction model.The stability of the model was verified by cross-checking method. RESULTS AND CONCLUSION:(1)Classification of talus osteochondral injury in 154 patients(type Ⅰ:36 cases;type Ⅱ:37 cases;type Ⅲ:40 cases;type Ⅳ:41 cases),T1ρ and T2 values of the four groups were statistically significant(P<0.05);pairwise comparison was also statistically significant(all P<0.05).(2)After treatment of 154 patients,7 cases(4.6％)had local swelling,3 cases(2.0％)had pain aggravation,and 5 cases(3.3％)had wound infection.There were 2 cases(1.3％)with poor cartilage healing.(3)After treatment,there were statistically significant differences between groups A and B in terms of American Orthopaedic Foot&Ankle Society score,visual analog scale score,plantar flexor motion range,dorsoextension motion range,subchondral bone marrow edema volume,interleukin-6,interleukin-8,C-reactive protein,procalcitonin,platelet-derived growth factor,transforming growth factor-β1,and efficacy(P<0.05).The total effective rate of group B(90％)was higher than that of group A(85％)(P<0.05).(4)Age(OR=1.589,95％CI:0.305-1.252,P=0.036),interleukin-6(OR=1.737,95％CI:0.974-5.254,P=0.049),interleukin-8(OR=1.385,95％CI:1.066-4.355,P=0.034),C-reactive protein(OR=1.957,95％CI:1.323-2.178,P=0.035),transforming growth factor-β1(OR=1.459,95％CI:0.897-2.455,P=0.038),T1-ρ(OR=1.687,95％CI:0.854-3.321,P=0.026),T2(OR=1.843,95％CI:0.657-2.454,P=0.036),complications(OR=1.719,95％CI:0.654-3.464,P=0.019),and classification of osteochondral injury of talus(OR=3.789,95％CI:1.023-5.897,P=0.028)were independent risk factors for postoperative recurrence.Microfracture surgery(OR=0.751,95％CI:0.321-1.264,P=0.012)and autogenous bone and cartilage grafting(OR=0.649,95％CI:0.246-1.356,P=0.023)were independent protective factors for recurrence after medium-and long-term follow-up.(5)When T1ρ value≤35 ms,the risk of postoperative recurrence decreased rapidly,and when T1ρ value>35 ms,the risk of postoperative recurrence increased rapidly.(6)Further stepwise regression analysis showed that these nine risk factors were most closely associated with postoperative recurrence,and the formula for postoperative recurrence was obtained.The probability of postoperative recurrence was calculated using the regression equation.When P=0.75,the maximum value of Jorden index was 77.728,indicating that the model has a better prediction effect.(7)It is indicated that the quantitative evaluation of T1ρ before operation can effectively guide the selection of surgical methods,improve the success rate of surgery and the quality of life of patients.