Objective To explore whether combined olmesartan angiotensin Ⅱ receptor type 1 blocker(ARB) and angiotensin-converting enzyme inhibitor(ACEI) temocapril have synergistic effect on reversal of left ventricular hypertrophy (LVH) in stroke-prone spontaneously hypertensive rats (SHRsp). Methods Fourty-four SHRsps and 11 Wistar-Kyoto rats(WKY) were divided randomly into 5 groups:WKY-control group, SHRsp-control group, SHRsp-olmesartan 10 mg/(kg?d)group, SHRsp-temocapril 10 mg/(kg?d)group, and SHRsp-Olmesartan 3 mg/(kg?d)+temocapril 3 mg/(kg?d) group for 6 weeks. Hearts weight were measured and histologically studied. The mRNA expression of angiotensin Ⅱ receptor type 1(AT1R) and integrin ?1 in myocardium was detected by RT-PCR. Results Olmesartan, temocapril and the their combination significantly reduced systolic blood pressure in a similar magnitude. Combination therapy was shown not greater effect in reversal of LVH than by olmesartan alone, although the effect by both of them was greater than temocapril monotherapy. The mRNA levels of AT1R and integrin ?1 in SHRsp were significantly decreased by treatment with olmesartan, temocapril, or combination therapy. Olmesartan and combination therapy result in greater decreases in expression of AT1R and integrin ?1 mRNA in myocardium than that by temocapril. Conclusion Compared with olmesartan alone, the combination of ARS and ACEI didn't show synergistic effect on reversal of left ventricular hypertrophy as were down-regulation of AT1R and suppression of integrin ?1 mRNA in myocardium.

Objective To understand pathological TDP-43 features in the central nervous systems of patients with clinically and autopsy confirmed motor neuron disease (MND).Methods The clinical and histopathological features of 4 cases with MND confirmed by autopsy were summarized; anti-ubiquitin (Ub) and anti-TDP-43 immunohistochemical staining were carried out on tissue of brains and spinal cords from 4 cases with MND and 3 control cases without history of neurological disorders.Results These 4 cases presented with typical clinical and histologic features of MND.Ub-positive inclusions were observed in brain and spinal cord from 3 cases with the Ub-positive inclusions of skein-round-and lewy body-like structures.Strong TDP-43 pathological staining in brain and spinal cord was identified in 2 cases with MND presented as neuronal and glial cytoplasmic inclusions with various shapes.The TDP-43 positive inclusions were widely distributed in the motor cortex of brain and the anterior horn of spinal cord.TDP-43 weak staining in the spinal cord tissue was observed in 1 case with MND.No Ub-and TDP-43 positive inclusions were found in 3 control cases.Conclusion There is widespread pathological TDP-43 expression in the central nervous system of MND.TDP-43 positive inclusions in MND have relatively high specificity.It is worth further study on their formation mechanism.

BACKGROUND: It has been found that vascular endothelial growth factor can induce the differentiation of bone marrow mesenchymal stem cells into endothelial cells, but can the vascular endothelial growth factor gene promote the differentiation of bone marrow mesenchymal stem cells into vascular endothelial cells in the damaged organ under the hypoxic environment? OBJECTIVE: To observe whether human bone marrow mesenchymal stem cells induced by vascular endothelial growth factor could differentiate into vascular endothelial cells under hypoxia. METHODS: The third passage of human bone marrow mesenchymal stem cells were cultured in vitro. Cells in the control group were cultured with conventional culture medium, while those in experimental group were cultured with adenovirus vector containing vascular endothelial growth factor in 5% O2. After 2 weeks of culture, morphological observation and surface-related molecular detection were performed. The levels of vascular endothelial growth factor and endothelial nitric oxide synthase were detected by ELISA. The expression of endothelin and prostacyclin was detected by RT-PCR and western blot assay. RESULTS AND CONCLUSION: (1) The number of cells in the control group was more than that in the experimental group. The cells in the control group were crowded and arranged irregularly, showing a fiber-like growth, while those in the experimental group were mostly triangular or polygonal, exhibiting a colony-like growth. (2) CD31 was negative in the control group, while CD105 was positive and the positive rate was 99.7%, indicating that the cells still showed the phenotype of bone marrow mesenchymal stem cells. The positive rate ofCD31 was significantly increased to 30.33% in the experimental group and the positive rate of CD105 expression was decreased to 58.11%, indicating a typical phenotype of endothelial cells. (3) Compared with the control group, the expression of endothelin, vascular endothelial growth factor and endothelial nitric oxide synthase increased significantly in the experimental group (P < 0.05), and the expression of prostacyclin decreased significantly (P < 0.05). All these findings indicate that vascular endothelial growth factor can promote the differentiation of human bone marrow mesenchymal stem cells into vascular endothelial cells under hypoxia.

BACKGROUND:Kalikrein 1 is an important component of the kalikrein-kinin system. Studies have shown that kalikrein can protect the cardiovascular system by promoting angiogenesis and inhibiting myocardial inflammation, but there is no report on its effect on inducing differentiation of stem cels. OBJECTIVE: To determine the transfection efficiency of kalikrein 1 adenoviral vector in rat bone mesenchymal stem cels. METHODS:Using adenovirus as a vector, the target gene kalikrein 1 was transfected into rat bone marrow mesenchymal stem cels. Fluorescence microscopy, MTT method and flow cytometry were used to investigate the effect of transfection and determine the optimal multiplicity of infection. RESULTS AND CONCLUSION:Adenovirus carrying kalikrein 1 was successfuly transfected into rat bone marrow mesenchymal stem cels. Results from flow cytometry showed that the transfection efficiency was associated with the multiplicity of infection. When the multiplicity of infection was 150, the transfection efficiency was 80.8%. MTT results showed that when the multiplicity of infection was 200, the cel growth was inhibited remarkably. These findings indicate that adenovirus-mediated kalikrein 1 can be successfuly transfected into rat bone marrow mesenchymal stem cels with the optimal multiplicity of infection=150.

Objective To explore the clinical effects of laparoscopic combined with gastroscopic surgery for the gastric stromal tumors (GSTs) from the muscularis propria.Methods The clinical data of 25 patients with GSTs from the muscularis propria who were admitted to the Qianfoshan Hospital Affiliated to Shandong University between January 2011 and January 2014 were retrospectively analyzed.Patients received the general anaesthesia by endotracheal intubation.The pneumoperitoneum was done by an arc incision of 0.5 cm above margin of the umbilical cord and then laparoscopy was placed for exposing and gastroscopy was placed for confirming the location of the tumor.A laparoscope was placed in the cavity via the trocar at the navel,and the other two trocars penetrated both the abdominal and stomach walls.With gastroscopic monitoring,the operation was carried out in the gastric lumen using laparoscopic instruments and the tumor was resected.The tumor tissue was removed orally using a gastroscopic basket,and puncture holes and perforations were sutured using titanium clips.The proton pump inhibitor and antibiotics were used as the conventional therapy for 3 days,while adjuvant therapy with a usage of imatinib was applied to patients who were confirmed with the high-risk GSTs by pathological examination after tumors resection,and the other patients did not receive adjuvant therapy.Gastroscopic reexamination was done every 3 months within postoperative 1 year and then every 6 months after 1 year.Abdominal CT reexamination was done every 6 months within postoperative 1 year and then every 1 year after 1 year.The followup was done till December 2014.Results All the 25 patients received successfully modified laparoscopic combined with gastroscopic surgery without conversion to open surgery and postoperative complication.The operation time,volume of intraoperative blood loss,diameter of tumor,duration of postoperative abdominal pain and duration of hospital stay were (79 ± 4) minutes,(28 ± 3) mL,(2.6 ± 0.3) cm,(2.8 ± 0.3) days and (6.3 ± 0.3) days,respectively.GSTs were confirmed by postoperative pathological examination.The mitotic count was (3.3 ± 0.3) /50 HPF and reached R0 resection.Extremely low risk was detected in 3 patients,low risk in 19 patients,intermediate risk in 3 patients and no high risk was detected.Two of 3 patients with intermediate risk took the medicines following instructions without the adverse drug reaction,and 1 of 3 patients refused to take the medicines due to low income.All the patients were followed up for 12-36 months without the recurrence or metastasis of tumors.Conclusion Modified laparoscopic combined with gastroscopic surgery is feasible and effective for the treatment of gastric stromal tumors (GSTs) from the muscularis propria.

Objective To investigate the incidence and high risk factors of brain injury in very low birth weight infants(VLBWI),to reduce the morbidity of brain injury,and improve the developmental outcome of VLBWI. Methods Data of 181 VLBWI admitted in the neonatal intensive care unit(NICU)between October 2008 and September 2009 were retrospectively analyzed. The difference in basic information,maternity diseases,treatment and complication were analyzed between two groups(brain injury group and normal newborn group),and Logistic regression analysis was adopted to analyze the risk factors for brain injury. Results Seventy-eight of the 181 neonates(43.09%)were found to have brain injury,including 67 neonates(37.01% )with periventricular/intraventricular hemorrhage(43 with intraventricular hemorrhage(IVH)gradeⅠ,12 with IVH grade Ⅱ,10 with IVH grade Ⅲ,and 2 with IVH grade Ⅳ)and 12 neonates(6.63%,one complicated with IVH grade Ⅲ)with periventricular leukomalacia. The younger the gestational age,the higher the brain injury rate was observed. Concerning the brain injury rate,there were no differences in gender,single birth/plural births,birth weight,the mode of delivery,fetal distress,premature rupture of membrane,hypertension during pregnancy,placenta abruption,and intrauterine growth restriction(IUGR)between these two groups(P ＞ 0.05). The difference in therapeutic measures such as pulmonary surfactant therapy,nasal continuous positive airway pressure(nCPAP),conventional mechanical ventilation,and high-frequency oscillatory ventilation was significant(P ＜ 0.05),except aminophylline therapy(P ＞ 0.05). As to the complication,there were significant differences in the incidences of asphyxia,neonatal respiratory distress syndrome(NRDS),hypercapnia,metabolic acidosis,hyperglycemia,anemia,and personal digital assistant(PDA)(P < 0.05). However,there was no difference in the incidences of hypoglycemia,sepsis,thrombocytopenia,apnea,pulmonary hemorrhage,and hyperbilirubinemia between these two groups(P ＞ 0.05). Further Logistic regression analysis showed that NRDS,high-frequency oscillatory ventilation,and PDA were the main risk factors for brain injury in VLBWI. Conclusions VLBWI is the high-risk population of brain injury. Pulmonary surfactant therapy,nCPAP,conventional mechanical ventilation,high-frequency oscillatory ventilation,asphyxia,NRDS,hypercapnia,metabolic acidosis,hyperglycemia,anemia,and PDA were confirmed to be the high-risk factors for brain injury in VLBWI. And,NRDS,high-frequency oscillatory ventilation and PDA were main risk factors.

Objective To evaluate whether small endoscopic sphincterotomy (EST) plus balloon dilation (EPBD) can replace endoscopic sphincterotomy (EST) alone for patients with common bile duct (CBD) stones.Methods From May 2008 to April 2011,462 patients with CBD stones were randomly divided into two groups.The success rate of complete stone removal after the first session,the rate of using mechanical lithotripsy (ML),the short-term complications,the procedure time and fluo roscopy time were compared between the two groups.Results Overall ductal clearance did not differ between the two groups (96.5％ vs 93.5％,P＞0.05).The complication rates at 24 hours were 6.9％ for the small EST plus EPBD group and 11.7％ for the EST group (P＞0.05).However,the rate of complete stone removal after the first session using small EST plus EPBD was significantly higher than EST alone (86.2％ vs 70.4％,P＜0.05).ML was required significantly more often in the EST group when compared with the small EST plus EPBD group (34.8％ vs 12.1％,P＜0.05).The total procedure time and total fluoroscopy time in the small EST plus EPBD group were significantly shorter than the EST group [(38.6±15.5) min vs (47.1±20.2) min,P＜0.05 and (17.3± 7.0) min vs (26.5±10.8) min,P＜0.05].Conclusions Compared with EST,small EST plus EPBD was safe and more efficacious for bile duct stones.In the future,small EST plus EPBD probably can replace EST to be the first treatment of choice for bile duct stones.

Objective To summarize the characteristics of treatment and outcomes of extremely low birth weight infants (ELBWI).Methods The clinical data of 81 cases of ELBWI admitted to Bayi Children's Hospital Affiliated to General Hospital of Beijing Military Command from October 1st.2008 to August 31st.2011 were retrospectively analyzed.The survival rate and mortality of ELBWI with different gestational age and birth weight were compared with Chi-square test.Results Of 81 ELBWI,43 were male and 38 were female; the mean gestational age at birth was (28.4 ±2.1) weeks; the average birth weight was (903.5 ± 95.4) g.Complications of them included respiratory distress syndrome (68/81,84.0％),patent ductus arteriosus (47/81,58.0％),retinopathy of prematurity (41/81,50.6％),intraventricular hemorrhage (23/81,28.4％),bronchopulmonary dysplasia (17/81,21.0％),sepsis (15/81,18.5％),periventricular leukomalacia (2/81,2.5％) and necrotizing enterocolitis (1/81,1.2％).Among 81 infants,96.3％ (n =78)received oxygen inhalation with the average time was 19.1 d (median 11 d,0-121 d) ; 70.4％ (n=57)received pulmonary surfactant; 27.2％ (n =22) received nasal continuous positive airway pressure;34.6％ (n =28) received normal frequency mechanicalfrequency ventilation.All 47 ELBWI with patent ductus arteriosus received ibuprofen treatment,among which 6 cases received arterial canal ligation after failure of ibuprofen treatment.20 out of 41 cases of retinopathy of prematurity received laser surgery.Total parenteral nutrition was required in 74 infants(91.4％),the average age of beginning enteral feeding was 5.2 d (median 6 d,0-17 d)and achieved full gastrointestinal feeding time was 31 d (median 28 d,7-65 d).The survival rate of ELBWI with gestational age of ≤26,-28 and ＞28 weeks was 25.0％ (4/16),72.0％ (18/25) and 77.5％ (31/40),respectively; the corresponding mortality was 12.5％ (2/16),8.0％ (2/25) and 2.5％ (1/40),respectively.The survival rate of ELBWI with birth weight ≤800,-900 and ＞900 g was 33.3％ (4/12),58.3％ (14/24) and 77.8％ (35/45),respectively; and corresponding mortality of them was 16.7％ (2/12),8.3％ (2/24) and 2.2％ (1/45),respectively.Conclusions The outcome of ELBWI is closely related to gestational age and birth weight.Professional and sophisticated treatment might improve the survival rate and general outcome of ELBWI.

Objective To evaluate the efficacy and safety of small endoscopic sphincterotomy (EST) plus large balloon dilataion (EPLBD) for removal of common bile duct (CBD) stones larger than 12mm.Methods From June 2009 to December 2011,a total of 198 patients with CBD stones were randomly divided into two groups to receive EPLBD (n =100) or EST only (n =98).The rate of complete stone removal after the first session,the overall success rate of stone removal,the rate of using mechanical lithotripsy (ML),the rate of post procedure complication,procedure time and fluoroscopy time were compared between the two groups.Results The rate of complete stone removal after the first session in EPLBD group (89.0％) was significantly higher than that in EST group (71.4％,P ＜ 0.05).ML was required significantly more often in EST group (35.7％) compared to EPLBD group (12.0％,P ＜0.05).Total procedure time and total fluoroscopy time in EPLBD group (39.3 ± 15.8 min and 14.2 ±5.2 min) were significantly shorter than those of EST group (48.4 ± 19.3 min and 24.2 ±9.4 min,P ＜0.05).There was no significant difference between two groups in overall success rate of stone removal (97.0％ in EPLBD vs.93.9％in EST group,P ＞ 0.05) and the complications rate (8.0％ in EPLBD vs.13.3％ in ESTgroup,P ＞0.05).Conclusion EPLBD is as safe and effective as EST for common bile duct stones,larger than 12mm,and is more efficient in terms of procedure time,use of ML and success rate of stone removal.

Objective:To evaluate the clinical efficacy and safety of SpyGlass-guided laser lithotripsy for large common bile duct (CBD) stones with diameter>2 cm.Methods:From August 2015 to August 2018, a total of 157 patients with large CBD stones at the First Affiliated Hospital of Shandong First Medical University who met the inclusion criteria were randomly divided into SpyGlass group ( n=78, underwent SpyGlass-guided laser lithotripsy) and laparoscopic common bile duct exploration (LCBDE) group ( n=79, underwent LCBDE) by using random numbers. Non-inferiority test was used for rates of one-time stone removal and total stone removal, and the non-inferiority margin was set to 10%. The transform rate, incidence of short-term complications, hospital stay, and quality of life (assessed by the gastrointestinal quality of life index) were compared between the two groups. Results:The total success rates of stone clearance were 92.3% (72/78) and 96.2% (76/79) in the SpyGlass group and LCBDE group, respectively ( P=0.023), with valid non-inferiority hypothesis. The one-time stone removal rates were 83.3% (65/78) and 96.2% (76/79), respectively ( P=0.124), with invalid non-inferiority hypothesis. There were no significant differences in the incidence of transform [7.7% (6/78) VS 3.8% (3/79), P=0.294] or short-term complications [5.1% (4/78) VS 10.1% (8/79), P=0.246] between the two groups. Compared with the LCBDE group, the SpyGlass group had a shorter hospital stay (5.65±0.94 d VS 8.84±1.54 d, P=0.001) and higher scores of gastrointestinal quality of life index (1 month after operation: 99.85±4.36 VS 91.51±5.47, P=0.001; 3 months after operation: 131.24±3.32 VS 112.32±7.77, P=0.001). Conclusion:For large CBD stones, the efficacy of SpyGlass-guided laser lithotripsy is not inferior to LCBDE, and it is less invasive. In the future, SpyGlass-guided laser lithotripsy could be an important option for the treatment of large CBD stones.