Objective To explore the mechanism of HMGB1 and TLR4 in pancreatic tissue of rats with severe acute pancreatitis and the intervention effect of Ulinastatin .Methods The 54 SD rats were completely random divided into control group ,SAP group and Ulinastatin treatment group ,and each group was divided into three groups :6 ,12 h and 24 h groups (each group n=6) .In con‐trol group ,we turned the pancreatic tissue ,in SAP group ,the SAP model was made with 5% taurocholic acid ;and in the treatment group ,and intravenous injection of ulinastatin was conducted after the SAP model was successfully made .Then we observed the pancreatic tissue pathology in the three groups .The amylase in serum was detected by EPS‐G7 assay ,the HMGB1 in serum and pancreatic tissue was detected by ELISA assay ,the expression levels of HMGB1 and TLR4 in pancreatic tissue were detected by Envision two‐step immunoassay .Results Compared with control group ,the amylase of each time point in SAP group and treatment group were significantly higher ,and the pathology changed obviously (P<0 .05) ,and the SAP model was successfully made .The HMGB1 expression in pancreatic tissue and serum started increase at 6 h ,increased quickly at 12 h and maintained the increasing trend to 24 h in SAP group and it was significantly higher at the same time point compared with that of control group (P<0 .05);at the same time point ,the HMGB1 in treatment group was significantly lower than that of SAP group (P<0 .05);in SAP group , the expression of TLR4 in pancreatic tissue started increasing at 6 h ,reached its peak at 12 h and started decreasing at 24 h ,it was significantly higher than the control group at the same time point (P<0 .05) .At the same time point ,the TLR4 was significantly lower in the treatment group than SAP group (P<0 .05) .Conclusion The proinflammatory effect of HMGB1 in SAP rats pancre‐atic could be partly combine its receptor TLR4 and MyD88‐dependent pathway through implementation ,and the protecting mecha‐nism of Ulinastatin could be interrupt the HMGB1 and TLR4 signaling pathway in SAP rats pancreatic tissue .

Objective To summarize the application of endovascular treatment of the acute ruptured intracranial aneurysms with the new Trufill detachable coil system.Methods Thirty five patients with the acute ruptured intracranial aneurysms were treated with DCS or DCS Orbit within 72 hours. Results All 35 cases were successful with compact embolization in 29 aneurysms,95% in 3 aneurysms,90% in 2 aneurysms,80% in 1 anearysm.One case hemorrhaged during operation and 1 case had thrombosis after operation,but with good prognosis of both.One case died of pneurmonia.Thirty cases achieved clinic follow-up 1 to 15 months after operation with only one rebleeing.Sixteen cases achieved DSA follow-up 3 to 12 months after the operation.Partial recurrence of the occluded aneurysm was shown in 1 case.Conclusions Trufill DCS or DCS Orbit is a safe,reliable and effective therapy for the endovascular treatment of intracraranial aneurysms.

To identify the active constituents in vitro and blood-absorbed ingredients in vivo from Yin Chen Hao decoction provides scientific evidence for probing its prevention and treatment mechanism on acute liver injury. An ultrahigh performance liquid chromatography quadrupole-time of flight-mass spectrometry (UPLC-QTOF/MS) method was applied for analysis of Yin Chen Hao decoction and the serum samples of mice with con-A induced acute liver injury after preventive oral administration for 14 days (the use of all laboratory animals in this study was approved by the Ethics Committee of the Naval Medical University, 19YF1459400). A total of 90 chemical constituents were identified from Yin Chen Hao decoction, mainly were flavonoids, terpenoids, tannins, quinones. 5 prototype compounds were identified in the serum, including chrysophanol, deoxyrhapontin-8-O-gallate, mussaenosidic acid, herniarin, emodin. The established UPLC-QTOF/MS method could efficiently and sensitively identify the constituents in vitro and blood-absorbed ingredients of Yin Chen Hao decoction, primarily clarify the material basis of its hepatoprotective effect, and provided a scientific basis for the quality marker selection and the pharmacodynamic material basis research on the decoction.

OBJECTIVETo investigate the effect of total flavonoids of astragalus on the expression of endoplasmic reticulum chaperone, calumenin and connecxin 43 (CX43) in suckling mouse myocardium with myocarditis caused by coxsackievirus B3 (CVB3).

METHODSThe primary culture of suckling mouse myocardium cells were randomly divided into control group, CVB3 infected group and total flavonoids of astragalus group. Firstly, to confirm the identity of the suckling mouse myocardium, α-SMA was monitored by immunohistochemistry method. Then the protein expression changes of endoplasmic reticulum chaperone-glucose regulatory protein 78 ( GRP78), calumenin and CX43 were detected by Western blot.

RESULTS(1) Compared with that of the control group, the GRP78 expression level in CVB3 infected group was improved, the expression levels of calumenin and CX43 were all reduced. (2) Compared with that of CVB3 infected group, GRP78 expression level was decreased, and the expression levels of calumenin and CX43 were increased in total flavonoids of astragalus group.

CONCLUSIONCVB3 infection may cause endoplasmic reticulum stress of rat myocardium cells by increasing the expression of GRP78 and decreasing the expression of calumenin and CX43. On the other hand, total flavonoids of astragalus can reduce the expression of GRP78 and increase the expression of calumenin and CX43.The results of this experiment may be closely related to the effects of anti-arrhythmia with viral myocarditis caused by CVB3.

Animals ; Astragalus Plant ; chemistry ; Blotting, Western ; Calcium-Binding Proteins ; metabolism ; Cells, Cultured ; Connexin 43 ; metabolism ; Coxsackievirus Infections ; drug therapy ; Endoplasmic Reticulum ; metabolism ; Endoplasmic Reticulum Stress ; drug effects ; Flavonoids ; pharmacology ; Heat-Shock Proteins ; metabolism ; Mice ; Myocarditis ; drug therapy ; virology ; Myocardium ; cytology ; Myocytes, Cardiac ; drug effects ; virology ; Rats

Objective To study adrenomedullin (AM) mRNA and protein expression level in myocardium of autoimmune myocarditis animal models induced by immunization of mice with lactobacillus casei cell wall element(LCWE). Methods Forty-five Balb/c male mice were randomly divided into experimental group (n = 30) and control group (n = 15), which were intraperitoneally injected with LCWE and phosphate buffered solution(PBS) at day 0,3,5 and 10,respectively. Sera and myocardium samples were gained 14,21 and 28 days after the first immunization. AM expression levels were determined by semiquantitative reverse transcriptase-polymerase chain reaction(RT- PCR) and immunchistochemistry,and mycardial histopathological lesions were observed. The anti- myosin antibodies in different stages were examined by an ELISA. Results There were myocardial necrosis or inflammatory infiltration in the experimental group, but myocardial lesions were not found in the control group. Anti - myosin antibodies were detected in sera of experimental mice,but not in control group. Immunchistochemistry findings demonstrated that AM expression level was higher in the experimental group than in the control group( P

Objective To explore the relationship among the prevertebral soft tissue swelling and dysphagia rate after anterior cervical diskectomy and fusion(ACDF),and to investigate the prevertebral soft tissue swelling and dysphagia rate after Zero-p or traditionaI cage and titanium plate for one-level lesion of cervical myelopathy.Methods The clinical data of 54 patients with one-level lesion (C5/6) of cervical myelopathy who undelwent anterior cenrical discectomy and fusion by Zero-p (n =25) or traditional cage and titanium plate (n =29) were analyzed.The postoperative prevertebral soft tissue swelling was measured by lateral radiographs.Patients were divided into the swelling group (n =24) and the non-swelling group(n =30) based on the degree of prevertebral soft tissue swelling and the incidences of dysphagia were analyzed.Patients were divided into the Zero-p group (n =25)and the Cage group (n =29) based on surgical treatment,the postoperative prevertebral soft tissue swelling and dysphagia rate were compared.Results The rate of dysphagia in swelling group was 45.8％,which was higher than 13.3％ in non-swelling group,the difference was significant(P ＜0.05).The postoperative prevertebral soft tissue swelling was 6.22 mm averagely after Zreo-p,which was less than that after traditional cage and titanium plate for anterior cervical discectomy with fusion(9.25 mm),the difference was significant (P ＜ 0.05).The incidence of dysphagia in Zero-p group was 12％,which was lower than 41.4％ in Cage group,and the difference was statistically significant (P ＜ 0.05).Conclusion It is a clinical significance to evaluate the degree of prevertebral soft tissue swelling by cervical lateral X-ray after ACDF,when the degree of prevertebral soft tissue swelling is greater,the incidence of complications such as dysphagia is higher.In addition,The Zero-p for the treatment of single one-level lesion of cervical myelopathy(C5/6) has a lower degree of prevertebral soft tissue swelling and dysphagia rate than the traditional Cage and titanium plate fusion.

Objective To study the features and patterns of adverse drug reactions (ADR) induced by lentinan injection; To provide references for rational medication. Methods By using the method of retrospective analysis from 1994 to 2015, publicly reported 22 of lentinan injection ADR case report were analyzed. Results Clinical manifestations of lentinan injection ADR could be involved in a variety of organs, also could cause systemic damage. ADR associated with patient age at the same time, inappropriate drug dosage, solvent selection are factors that lead to adverse reactions. Conclusion When using lentinan injection, attention should be paid to the supervision of special population, medication should be strict according to the instructions and medication education should be strengthened, so as to reduce the occurrence of ADR and improve the satisfaction of patients.

Objective: To investigate the clinical features of adult B-cell acute lymphoblastic leukemia (B-ALL) with E2A-PBX1 fusion gene positive. Methods: The clinical data of 91 Philadelphia chromosome negative B-ALL patients who received chemotherapy regularly in Nanfang Hospital of Southern Medical University from March 2015 to December 2017 were collected. According to the fusion gene detection results, the patients were divided into E2A-PBX1 fusion gene positive group and E2A-PBX1 fusion gene negative group. The clinical features and prognosis of both groups were retrospectively analyzed. And then E2A-PBX1 fusion gene negative group was further divided into MLL-AF4 fusion gene positive group and the other ALL groups,which were compared with E2A-PBX1 fusion gene positive group in the prognosis. Results: There were 11 ALL patients with E2A-PBX1 fusion gene positive, and 80 ALL patients with E2A-PBX1 fusion gene negative. The level of lactic dehydrogenase (LDH) in E2A-PBX1 fusion gene positive group was higher than that in E2A-PBX1 fusion gene negative group [4 063 U/L (1 070- 9 554 U/L) vs. 454 U/L (103- 18 651 U/L), U=-4.700, P < 0.01], and there were no statistically significant differences in age, gender, white blood cell count and extramedullary invasion (all P > 0.05). The immunophenotypes of ALL patients with E2A-PBX1 fusion gene positive were all common B-cell phenotype. Out 4 of 7 ALL patients showed the different expression of Philadelphia-like ALL phenotype CRLF2 or phosphorylated CRKL or phosphorylated STAT5 by using flow cytometry. The complete remission (CR), minimal residual disease (MRD)-negative and the recurrence for 11 cases of E2A-PBX1 fusion gene positive group included 9, 7, 8 cases, respectively after first course of induction chemotherapy. The CR, MRD-negative and the recurrence for 80 cases of E2A-PBX1 fusion gene negative group included 71, 53, 26 cases, respectively after the first course of induction chemotherapy. There were no statistically significant differences in the CR and MRD-negative between the two groups after the first course of induction chemotherapy (P= 0.721, P= 0.487), but there was a statistical difference in the recurrence (χ²= 7.751, P= 0.012). The median follow-up time was 17 months (1-44 months), and the 1-year overall survival (OS) rate and 1-year event-free survival (EFS) rate of E2A-PBX1 fusion gene positive ALL group were lower than those of the negative group (OS: 43.6% vs. 70.0%, P= 0.020; EFS: 13.6% vs. 60.0%, P= 0.002). Subgroup analysis showed that there were no statistical differences between E2A-PBX1 fusion gene positive group and MLL-AF4 fusion gene positive group in 1-year OS rate and 1-year EFS rate (P= 0.617, P= 0.984). Conclusions E2A-PBX1 fusion gene positive rate is low in adult B-ALL patients with a good response to traditional chemotherapy in the early stage, but its cumulative recurrence rate is high. It is a high-risk cytogenetic abnormality which is similar to MLL gene rearrangement and needs to explore novel therapy strategies.

OBJECTIVETo construct a mouse that specifically expresses Cre recombinase in hepatocyte.

METHODSA hepatocyte specific transgenic construct containing mouse albumin promoter, the Cre recombinase gene and the poly (A) of human growth factor gene was generated. The linearized constructs were introduced into the fertilized eggs by microinjection to obtain the transgenic mice. The transcriptional specificity of Cre recombinase was detected by reverse transcription polymerase chain reaction (RT-PCR). The expression and function of Cre recombinase were detected by PCR and Southern Blot after crossing the Alb-Cre transgenic mice with the Smad4 conditional knockout mice.

RESULTSThe linearized constructs were microinjected into 837 fertilized eggs, and then the 797 effective eggs of microinjected eggs were implanted into the oviducts of 27 pseudo pregnant mice. In the 53 offspring, there were 6 mice carrying the transgene identified by polymerase chain reaction (PCR) and Southern Blot. Cre recombinase transcripts were detected in the livers and testis of the Alb-Cre transgenic mice using RT-PCR. The Cre recombinase was expressed in the livers of the double heterozygous for Alb-Cre and Smad4 floxed allele, and the exon 8 floxed by loxP site was deleted.

CONCLUSIONA hepatocyte-specific Cre transgenic mouse was generated successfully. The Cre recombinase expressed specifically in liver and could mediate the recombination between loxP sites in vivo.

Animals ; Female ; Hepatocytes ; metabolism ; Humans ; Integrases ; genetics ; Mice ; Mice, Transgenic ; Viral Proteins ; genetics

OBJECTIVESome neonates especially premature infants, low birth weight infants and extremely low birth weight infants have limited endogenous energy stores. It is necessary to establish continuous administration of postnatal nutrition. The use of parenteral nutrition (PN) in neonates with immaturity of digestive system and intentionally delayed feedings has gained widespread acceptance. PN has been shown to provide sufficient nutrients to maintain growth in newborn infants. The major complication of PN in neonates is PN-associated cholestasis (PNAC). It remains a significant and frequent clinical problem for neonatal practitioners. In some cases, progressive liver damage, liver failure and death may become inevitable. In order to analyze the risk factors of the PNAC in neonates and to provide the evidence of safety and efficiency in clinical nutrition support, the clinical data of 612 neonates who had received PN for more than 5 days during the past 20 years were reviewed.

METHODSRetrospective analysis on data collected from April 1985 to March 2005 was performed. The records of 612 neonates were divided into two groups according to the established Nutrition Support Team (NST) in our hospital. Each group included two sub-groups. Seventy neonates of the first group were divided into PNAC group (n = 6) and non-PNAC group (n = 64); these patients were seen between 1st April 1985 and 31st March 1995. The remaining 542 neonates of the second group who were also divided into 2 groups, i.e. PNAC group (n = 12) and non-PNAC group (n = 530) who were seen from 1st April 1995 through 31st March 2005. The incidence of PNAC between the first group and the second group was compared and the associated factors were analyzed. The PNAC was defined when serum level of direct-bilirubin exceeded 1.5 mg/dl or direct-bilirubin greater than 50% of the bilirubin and excluding cholestasis resulted from other diseases.

RESULTSThe total incidence of PNAC in neonates who had received TPN for more than 5 days was 2.94%. The incidence of PNAC of the first and the second decade was 8.57% and 2.21%, respectively (OR = 0.242, 95% CI = 0.088 approximately 0.666). The average gestational age (GA) and birth weight (BW) of PNAC group were less than those of the non-PNAC group (GA: (33 +/- 5) w vs. (36 +/- 4) w, P = 0.009; OR = 0.827, 95% CI = 0.698 approximately 0.980. BW: (2003 +/- 743) g vs. (2393 +/- 764) g, P = 0.045; OR = 1.001, 95% CI = 0.999 approximately 1.002). The PN duration and calorie intake of PNAC group was longer than that of the non-PNAC group (PN duration: 32 +/- 30 d vs. (13 +/- 10) d, P = 0.000; OR = 1.072, 95% CI = 1.032 approximately 1.112. Calorie intake: [(272 +/- 46) kJ/(kg.d)] [(65.0 +/- 10.9) kcal/(kg.d)] (1 kcal = 4.184 kJ) vs. [(232 +/- 55) kJ/(kg.d) (55.5 +/- 13.1) kcal/(kg.d)], (P = 0.002; OR = 1.066, 95% CI = 1.012 approximately 1.122), but the weight gain in the non-PNAC group had a tendency to increase as compared to that of the PNAC group [(20 +/- 27) g/d vs. (9 +/- 19) g/d, P = 0.175].

CONCLUSIONSThe incidence of PNAC was associated with the longer duration of PN, the smaller age at initiation of PN, the higher calorie intake, prematurity and lower birth weight. Establishment of the nutrition support team can normalize the practice of the PN administration and decrease the incidence of the complication with nutrition support. It is a favorable mode and it can provide a safer, more effective and reasonable means in clinical nutrition support. To avoid PNAC, it is suggested that the administration of enteric feeding should start as soon as possible, which may enhance effective contraction of gallbladder and secretion of gastrointestinal hormones, and it is best to avoid high calorie of PN and control the calorie intake under 251.04 approximately 334.72 kJ/(kg.d) [60 approximately 80 kcal/(kg.d)].

Cholestasis ; complications ; epidemiology ; etiology ; Female ; Gestational Age ; Humans ; Incidence ; Infant ; Infant, Low Birth Weight ; physiology ; Infant, Newborn ; Infant, Premature ; growth & development ; Male ; Parenteral Nutrition ; adverse effects