Objective To explore the possible mechanism for the neuroprotective effect of ifenprodil by investigating its effects on inducible nitric oxide synthase (iNOS) expression and activity and apoptosis in the ischemic penumbra following focal cerebral ischemia-reperfusion (I/R) in rats.Methods Fifty-four adult male SD rats weighing 280-320 g were randomly divided into 3 groups ( n = 18 each) : I sham operation group (group S) ; II focal cerebral I/R group (group I/R) and Ⅲ ifenpradil preconditioning group (group IF) received intraperitoneal ifenprodil 10 mg/kg before focal cerebral I/R. Focal cerebral I/R was induced by middle cerebral artery occlusion (MCAO) . A 3-0 nylon thread with rounded tip was inserted into right internal jugular vein and threaded cranially until resistance was met. MCAO was maintained for 2 h. At 48 h after reperfusion, the animals were assessed for neurological function which was scored (0 = no functional deficit, 4 = unable to crawl, unconscious) and then decapitated. The brains were immediately removed for microscopic examination and determination of iNOS protein expression and activity, NO content and apoptosis in the ischemic core (IC) and penumbra (IP). Results Ifenprodil pretreatment significantly decreased the cerebral infarct size and neurological scores in group IF as compared with group I/R. In group I/R the iNOS activity was increased compared with group S.The iNOS activity and NO content were significantly lower in IP than in IC in group IR and IF. The TUNEL-positive cells were also mainly confined to IP. Compared with group I/R, in group IF the iNOS protein expression was significantly down-regulated in IC and IP and the iNOS activity and NO content in IC and IP were suppressed and TUNEL-positive cells were significantly reduced in IP. Conclusion Ifenprodil pretreatment has protective effect against cerebral I/R injury by inhibiting iNOS protein expression in IP, suppressing iNOS activity and NO content and reducing apoptosis.

Objective To investigate the clinical features ,diagnosis and treatment of cesarean scar pregnancy (CSP) .Methods We retrospectively analyzed the medical history ,clinical manifestation ,diagnoses ,treatments and outcomes of 42 patients with ec‐topic pregnancy in the cesarean scar .Results All cases got diagnosed by transvaginal ultrasound .The error rate of first diagnosis was 40 .4% (17/42) .There were 25 cases of conservative therapy ,in which 12 cases were resolved with laparoscopic surgery and 1 case resolved with open surgery ;in the first process 15 cases were carried out laparoscopic surger in which 1 case were converted to laparotomy ;abdominal surgery were underwented in 1 case and were cured .Only one case underwent abdominal total hysterectomy as of failure after uterine artery embolization .After initial conservative treatment 3 cases were hospitalized again and 2 cases under‐went reoperation .41 patients were successfully retained the uterus and normal menstrual cycle returned at two months after opera‐tion .Conclusion The early diagnosis for CSP mainly depended on ultrasound and the thickness of incision muscle layer is an impor‐tant basis for choice of treatment .Checking the thickness of incision muscle layer for CSP mainly depended on ultrasound ,and lapa‐roscopic surgery is an ideal method for diagnosis and treatment of CSP .

Objective To evaluate the effect of hydrogen sulfide combined with mild hypothermia on cerebral ischemia-reperfusion (I/R) injury in rats. Methods Eighty male SD rats, aged 3 months, weighing 250-300 g, were randomly divided into 5 groups ( n = 16 each): sham operation group (group S), cerebral I/R group,mild hypothermia group (group M), sodium hydrosulfide group (group NaHS) and NaHS + mild hypothermia group (group NM). In group I/R, M, NaHS and NM, cerebral I/R was induced by occlusion of 4 vessels (cauterization of bilateral vertebral arteries and 15 min occlusion of bilateral common carotid arteries) followed by reperfusion. In group NaHS and NM, intraperitoneal NaHS 14 μmol/kg was injected immediately after reperfusion, while the equal volume of normal saline was injected in the other three groups. At the same time, the rectal temperature was reduced to 32-33 ℃ within 15 min, lasting for 6 h, in group M and NM, while it was maintained at 36-37 ℃by physical method in other groups. Twelve rats of each group were sacrificed after 6 h of reperfusion, and then the hippocampus was removed for determination of the content of H2 S by using spectrophotometer and the expression of p-CREB and BDNF mRNA by using Western blot and RT-PCR respectively. Four rats in each group were sacririced after 72 h of reperfusion and then the hippocampus was removed for microscopic examination. Results The cerebral I/R injury was attenuated in group M, NaHS and NM compared with group I/R, with the slightest injury in group NM. The H2S content was significantly higher in group I/R, M, NaHS and NM than in group S, and in group NaHS and NM than in group I/R and M. The expression of p-CREB and BNDF mRNA was significantly higher in group I/R, M, NaHS and NM than in group S, and in group M, NaHS and NM than in group I/R. The BDNF mRNA expression was significantly higher in group NM than in group M and NaHS. There was no significant difference in the H2S content and the expression of p-CREB and BNDF mRNA between group NaHS and M.Conclusion Hydrogen sulfide combined with mild hypothermia can attenuate cerebral I/R injury by up-regulating the expression of p-CREB and BDNF mRNA in hippocampus in rats.

Objective To investigate the role of acid-sensing ion channel 1a(ASIC1a) in global cerebral ischemia-reperfusion injury in rats.Methods Forty male SD rats weighing 250-300 g were randomly divided into 4 groups (n =10 each): sham operation group (group S),cerebral ischemia-reperfusion group (group I/R),solvent control group (group SC) and group PcTX1 (a ASIC1 a blocker,group P).Global cerebral ischemia-reperfusion was induced by four-vessel occlusion.PcTX1(500 ng/ml)6 μl or solvent 6 μl was injected into the crerbral ventricular at the begining of reperfusion in groups P and SC respectively.The rats were sacrificed at 24 h of reperfusion,and then the hippocampi were removed for determination of Caspase-3,Bcl-2 and Bax protein expression and microscopic examination.Results Compared with group S,the expression of Caspase-3,Bcl-2 and Bax protein was up-regulated in groups I/R,SC and P (P ＜ 0.05).Compared with group I/R,the expression of Caspase-3 and Bax was down-regulated,and the expression of Bcl-2 was up-regulated in group P ( P ＜ 0.05).There was no significant difference in Caspase-3,Bcl-2 and Bax protein expression between groups I/R and SC (P ＞ 0.05).The histopathologic damage was ameliorated in group P as compared with group I/R.Conclusion ASIC1a can induce global cerebral ischemia-reperfusion injury in rats by up-regulating Caspase-3 and Bax expression,and down-regulating Bcl-2 expression and inducing apoptosis.

ObjectiveTo evaluate the efficacy,safety and clinical value of anterior urethral fusion to treat diphallia.MethodsA 17-year-old male patient with complete penile diphallia was treated in March 2011.The physical examination showed two completely separated mature penis; urethrography,and urethroscope showed the two urethras were completely separated and entered the bladder respectively.Two anterior urethras were incised respectively at ventral sides ( from the meatus to bulbar urethra) and then two incised anterior urethras were splintered by a continuous suture with 4-0 polyglactin sutures in side and side.Two penises were splintered into one.The nocturnal penile tumescence test and the penis vibration thresholds were assessed before,and after surgery..ResultsThe patient was followed up for 12 months.There was no hematoma,urinary fistula,urinary incontinence and other complications postoperatively.The penis was recovered with normal appearance; urination and morning erection of penile were normal.6 months after surgery,there was no significant difference in the nocturnal penile tumescence and penis vibration thresholds detection ( P ＞ 0.05).ConclusionThe operation of anterior urethral fusion is a safe and efficient surgical treatment to treat partial complete penile diphallia with less complication and no worse effect on urination and erection of penile.

Objective To analyze the clinical effect of uterine artery ligation combined with modified uterine compression suture in the prevention and treatment of postpartum hemorrhage.Methods A total of 107 patients with refractory cesarean section who were treated with uterine artery ligation combined with modified uterine compression suture were selected as treatment group.Of the patients treated with conventional treatment,83 patients were included in the control group.The effective hemostasis rate,clinical curative effect,incision infection,postpartum hemorrhage,blood transfusion rate,mattress rate and postoperative morbidity were compared between the two groups.Results The amount of intraoperative blood loss (1 106 ± 458.78) mL in the treatment group was significantly higher than (753.6 ±302.30)mL in the control group,the difference was statistically significant (t =1.892,P ＜ 0.05).The 24h total blood loss of the the treatment group [(1 028.89 ± 375.87) mL] was significantly higher than (813.87 ± 312.15) mL of the control group (t =3.872,P ＜ 0.05).The postoperative 24h blood loss in the treatment group [(70.86 ±19.30)mL] was lower than (73.50 ± 21.20)mL in the control group,and the difference was not statistically significant (t =0.045,P ＞ 0.05).The transfusion rate in the treatment group was 27.10％,which in the control group was higher than 10.84％,the difference was statistically significant between the two groups (x2 =7.722,P ＜ 0.05).The effective hemostasis rate in the treatment group was 99.66％ (106/107),which was significantly higher than 96.39％ in the control group (x2 =6.263,P ＜ 0.05).The rate of puerperal infection was 7.48％ in the treatment group,which in the control group was 6.02％,there was no significant difference between the two groups (P ＞ 0.05).The incision infection rate and postoperative morbidity rate were 0.00％ in the treatment group and the control group,and the two groups were treated with Ⅱ / A healing.Conclusion Uterine artery ligation combined with improved uterine compression suture in the prevention and treatment of postpartum hemorrhage has good hemostasis effect,hysterectomy rate is low,it is worthy of promoting and application.

Objective:To investigate the protective effects of Elabela(ELA) on the renal injury of db/db mice and its possible mechanism.Methods:Sixteen eight-week-old male db/db mice were intraperitoneally injected with ELA(5 mg·kg -1·day -1) or equivalent normal saline( n=8) for 8 weeks. Eight age-matched male db/m mice received equivalent normal saline injection as normal control. At the end of the experiment, blood and urine samples were obtained for HbA 1C and urinary albumin/creatinine(ACR) measurements. Immunohistochemistry was used to observe the expression of ELA. Histopathological changes in kidney tissue were observed by HE staining and Masson staining. The levels of collagen type Ⅳ(Col-Ⅳ) and transforming growth factor-β1(TGF-β1) as well as Yes-associated protein(YAP) phosphorylation in kidney tissue were examined by western blot. Results:Immunohistochemistry results showed that ELA expression was decreased in the renal tissue of db/db mice as compared with that of db/m mice( P<0.05). After ELA treatment, ACR and blood pressure were markedly decreased in db/db mice( P<0.05), but without significant changes in the body weight and HbA 1C. Renal tubular epithelial cells edema, basement membrane thickening, and increased collagen fiber in db/db were improved by ELA administration. Compared with db/m mice, the levels of TGF-β1 and Col-Ⅳ expression, as well as YAP phosphorylation were significantly increased in renal tissue of db/db mice(0.98±0.08 vs 0.68±0.10, 1.10±0.14 vs 0.51±0.08, 3.38±0.72 vs 0.81±0.13, all P<0.05), which were down-regulated after ELA administration(0.80±0.06, 0.51±0.05, 2.21±0.22, all P<0.05). Conclusion:ELA may improve the renal injury of db/db mice by regulating the signaling pathway of YAP, thereby delaying the development of diabetic nephropathy.

Objective:To assess the renal-protective effect of Elabela (Ela) on diabetic kidney disease (DKD), and explore its potential mechanism.Methods:db/db mice were randomly divided into diabetic group and Ela intervention group, while db/m mice were taken as normal control group. The mice in the Ela intervention group were intraperitoneally injected with Ela-21 5 mg·kg -1·d -1 for 8 weeks. At the end of the experiment, urinary albumin/creatinine ratio (UACR) was measured. The renal pathological changes were observed by HE and PAS staining. The expression of aquaporin 2(AQP2) examined by immunohistochemistry. The level of collage Ⅳ(Col-Ⅳ) and AQP2 in renal tissue was analyzed by Western blot. The human renal tubular epithelial cells (HK-2) were incubated with high glucose medium and further interfered with apelin receptors (APJ)-siRNA. Western blot analysis was used to detect the effect of Ela intervention on Col-Ⅳ and AQP2 expression. Finally, to clarify the possible mechanism of Ela regulating AQP2, the interaction between Ela-induced APJ activation and arginine vasopressin (AVP)-evoked arginine vasopressin receptor 2 (AVPR2) activation was investigated by NanoBit ? technology. Results:(1) Without affecting blood glucose and body weight, Ela intervention significantly reduced the UACR in db/db mice, and attenuate pathological changes of the kidney, as well as expression of Col-Ⅳ and AQP2. (2) Ela treatment could remarkably inhibit the high glucose-induced the expression of Col-Ⅳ and AQP2, which was reversed by interfering with APJ. (3) AVP-induced downstream β-Arrestin-2 signaling transduction via AVPR2 was obviously antagonized by interaction of Ela and APJ, further suggesting that the inhibitory effect of Ela on AQP2 may be related to antagonizing AVP/AVPR2 signaling.Conclusion:Ela exerts renal protection by inhibiting the expression of AQP2 through APJ.

Objective: To explore the clinical implications and prognostic value of TP53 gene mutation and deletion in patients with myelodysplastic syndromes (MDS) . Methods: 112-gene targeted sequencing and interphase fluorescence in situ hybridization (FISH) were used to detect TP53 mutation and deletion in 584 patients with newly diagnosed primary MDS who were admitted from October 2009 to December 2017. The association of TP53 mutation and deletion with several clinical features and their prognostic significance were analyzed. Results: Alterations in TP53 were found in 42 (7.2%) cases. Of these, 31 (5.3%) cases showed TP53 mutation only, 8 (1.4%) cases in TP53 deletion only, 3 (0.5%) cases harboring both mutation and deletion. A total of 37 mutations were detected in 34 patients, most of them (94.6%) were located in the DNA binding domain (exon5-8) , the remaining 2 were located in exon 10 and splice site respectively. Patients with TP53 alterations harbored significantly more mutations than whom without alterations (z=-2.418, P=0.016) . The median age of patients with TP53 alterations was higher than their counterparts[60 (21-78) years old vs 52 (14-83) years old, z=-2.188, P=0.029]. TP53 alterations correlated with complex karyotype and International prognostic scoring system intermediate-2/high significantly (P<0.001) . Median overall survival of patients with TP53 alterations was shorter than the others[13 (95%CI 7.57-18.43) months vs not reached, χ²=12.342, P<0.001], while the significance was lost during complex karyotype adjusted analysis in multivariable model. Conclusion TP53 mutation was more common than deletion in MDS patients. The majority of mutations were located in the DNA binding domain. TP53 alterations were strongly associated with complex karyotype and always coexisted with other gene mutations. TP53 alteration was no longer an independent prognostic factor when complex karyotype were occurred in MDS.

Objective: To evaluate clinical characteristics and prognosis of primary myelofibrosis (PMF) patients with thrombocytopenia in varied degrees. Methods: Clinical features and survival data of 1 305 Chinese patients with PMF were retrospectively analyzed. The prognostic value of thrombocytopenia in patients with PMF was evaluated. Results: 320 subjects (47%) presented severe thrombocytopenia (PLT<50×10⁹/L), 198 ones (15.2%) mild thrombocytopenia [PLT (50-99)×10⁹/L] and 787 ones (60.3%) without thrombocytopenia (PLT ≥ 100×10⁹/L). The more severe the thrombocytopenia, the higher the proportions of HGB<100 g/L, WBC<4×10⁹/L, circulating blasts ≥ 3%, abnormal karyotype and unfavourable cytogenetics (P<0.001, P<0.001, P=0.004, P<0.001 and P<0.001, respectively) were observed in this cohort of patients. The more severe the thrombocytopenia, the lower the proportion of JAK2V617F positive (P<0.001) was also noticed. Platelet count was positively correlated with splenomegaly, HGB and WBC (P<0.001, correlation coefficients were 0.131, 0.445 and 0.156, respectively). Platelet count was negative correlated with constitutional symptoms and circulating blasts (P=0.009, P=0.045, respectively; correlation coefficients were -0.096 and -0.056, respectively). The median survival of patients with severe thrombocytopenia, mild thrombocytopenia and without thrombocytopenia were 32, 67 and 89 months, respectively (P<0.001). Multivariate analysis identified thrombocytopenia in varied degrees (HR=1.693, 95%CI 1.320-2.173, P<0.001) and Dynamic Internation Prognostic Scoring System(DIPSS) prognostic model (HR=2.051, 95%CI 1.511-2.784, P<0.001) as independent risk factors for survival. Conclusion PMF patients with severe thrombocytopenia frequently displayed anemia, leucopenia, circulating blasts and short survival, so active treatment measures should be taken especially in these patients.