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 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.

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 compare effectiveness,performance,and complications between ultrasound-guided selective cervical nerve root block and interscalene brachial plexus block for patients undergoing arthroscopic surgery in perioperative period.Methods Seventy patients scheduled for arthroscopic surgery,25 males and 45 females,aged 18-75 years,were randomly divided into two groups.They were given either selective cervical nerve root block (group S,n =35) or interscalene brachial plexus block (group ISB,n=35).In group S,C5 and C6 nerve roots were given 0.5％ ropivacaine 5 ml respectively;In group ISB,patients were given 0.5％ ropivacaine 10 ml under ultrasound guidance.The primary outcome:VAS score and forearm modified Bromage scale (MBS) score were recorded at 4,12 and 24 hours after surgery;Secondary outcomes:cumulative tramadol consumption,the patients' satisfaction rate and adverse effects were recorded.Results The VAS scores in group S was significantly lower than that in group ISB at 12 hours after surgery (1.7±0.8 vs 3.6±0.7,P＜0.05).The forearm MBS scores in group S was significantly higher than that in group ISB 4 hours after surgery (P＜0.01).Compared with group ISB,the amount of tramadol consumption was lower at 24 hours after surgery [(37.5±35.9) mg vs (112.5±43.5) mg,P＜0.05)].The satisfaction rate of group S was higher than group ISB (88％ vs 56％,P＜0.05).There was no significant difference in side effects between the two groups.Conclusion In arthroscopic surgery,the selective cervical nerve root block is superior to the brachial plexus block.

Objective:To compare the adjuvant chemotherapy project and survival prognosis of patients with stage Ⅱ/Ⅲ colon cancer in different age groups.Methods:In this retrospective study, the clinical data of 770 colon cancer patients undergoing radical resection were collected in the First Affiliated Hospital of Soochow University from Jan 2013 to Dec 2017. Patients were categorized into 3 groups based on age at onset of colon cancer: young group (18-49 years old, 112 cases), middle-aged group (50-64 years old, 351 cases) and older group (65-75 years old, 307 cases).Results:The young group had fewer complications, and the probability of cancer deposit, vascular tumor thrombus and nerve invasion was lower than the middle-aged and older group (12.5% vs. 15.4% vs. 14.3%; 7.1% vs. 9.4% vs. 8.5%; 2.7% vs .8.8% vs. 5.5%), but the probability of signet-ring cell carcinoma and mucinous adenocarcinoma was higher (5.4% vs. 1.4% vs. 1.6%; 14.3% vs. 11.4% vs. 13.4%), the proportion of patients with stage Ⅲ was greater (49.1% vs. 45.0% vs. 47.2%), and they were more willing to receive postoperative chemotherapy (83.9% vs. 81.8% vs. 60.3%). Among patients with stage Ⅱ and Ⅲ colon cancer, the young group and the middle-aged group were 3-4 times more likely to receive adjuvant chemotherapy than the elderly group [ OR=4.153 (95% CI:1.964-8.785), 2.906 (95% CI:1.845-4.579), 3.120 (95% CI:1.310-7.429), 3.588 (95% CI: 1.964-6.556)]. Of those patients who received chemotherapy, young and middle-aged patients had a higher percentage of multiagent regimen use than older patients [ OR=2.050 (95% CI:0.937-4.488), 2.750 (95% CI:1.536-4.923)]. Among patients treated with surgery alone, no significant differences were observed in survival among age groups. Among patients who received surgery and adjuvant chemotherapy, a significantly better survival was observed for young and middle-aged patients with stage Ⅲ [ HR=0.284 (95% CI:0.127-0.632), 0.521 (95% CI:0.333-0.816)] than their older counterparts. Conclusions:Among patients with stage Ⅱ/Ⅲ colon cancer, young and middle-aged patients are more likely to undergo adjuvant chemotherapy and use more radical chemotherapy regimen. Young and middle-aged patients with stage Ⅱ colon cancer had overuse of chemotherapy, but did not result in expected survival improvement.

Ubiquitinating enzyme damaged-DNA binding protein 2 (DDB2) is a rind of DDB1 and CUL4-associated factors (DCAF), and identifies belonging to the family of ubiquitinating E3 enzymes. DDB2 combines with CUL4-DDB1 to form the ubiquitin ligase complex, and identifies targets protein substrate specificity to make the substrate ubiquitin and degradation. It affects the development of tumors through various pathways, such as DNA damage repair, cell cycle regulation and apoptosis, cell invasion and metastasis, cell premature senescence, cell proliferation and cancer stem cell population. This paper reviews the progress of the relationship between DDB2 and the development, treatment and prognosis judgment of tumors.

Objective: To research the change of PR interval shortening in ECG examination in different periods of pregnancy. Methods: From March 2016 to August 2016, 616 pregnant women who underwent maternity examinations in the Women and Children's Hospital of Ningbo were selected in this study.According to the different gestational periods, they were divided into the early pregnancy group (198 cases), the mid-pregnancy group (232 cases) and the late pregnancy group (186 cases). And another 241 non-pregnant women who underwent health examination in our hospital during the same period were selected as controls.All pregnant and non-pregnant women were examined by electrocardiogram, and the results of electrocardiogram were analyzed.The average heart rate, the average PR interval and the shortened ratio of PR interval were compared between the two groups of women and women with different pregnancy periods, and the short PR interval distribution of women in different pregnancy periods was observed. Results: The average heart rate level, PR interval and PR interval shortening ratio of pregnant women and non-pregnant women were (76.55±7.81)times/min, (0.096±0.008)s, 12.66% and (72.56±6.49)times/min, (0.138±0.014)s, 4.98%, respectively.The average heart rate and the shortening ratio of PR interval in pregnant women were significantly higher than those in non-pregnant women, while the average PR interval in pregnant women was significantly lower than that in non-pregnant women, the differences were statistically significant (t=7.565, χ²=10.879, t=52.672, all P<0.05). With the increase of pregnancy cycle, the shorter the average heart rate and PR interval of pregnant women, the shorter the average PR interval.The average heart rate, PR interval and PR interval shortening ratio in the early pregnancy group, the mid-pregnancy group and the late pregnancy group were (75.41±6.65)times/min, (0.103±0.010)s, 8.59% and (77.03±7.12)times/min, (0.095±0.009)s, 11.21% and (79.74±8.43)times/min, (0.088±0.008)s, 18.82%, respectively.There were statistically significant differences among the three groups(t=16.720, 116.440, χ²=9.791, all P<0.05). Conclusion Pregnancy women are prone to have shorten PR interval, and its incidence increases with the increase of pregnancy cycle, but in most cases belongs to benign electrophysiological changes, and the prognosis is good without special treatment.It is of great significance for clinical diagnosis and treatment to reduce the outcome of bad pregnancy by observing the shortening of the PR interval of electrocardiogram during the pregnancy.

Objective:To investigate the factors affecting the prognosis of stage Ⅰa2-Ⅱa2 cervical cancer after laparoscopic radical hysterectomy (LRH), and to compare the prognosis and recurrence sites of patients with different colpotomy paths.Methods:The clinical data of 965 patients with stage Ⅰa2-Ⅱa2 cervical cancer who underwent LRH in the First Affiliated Hospital of Army Medical University from January 2015 to December 2018 were collected. The median age was 47.0 years of all patients with a median follow-up of 62 months (48-74 months). Cox regression was used to perform the univariate and multivariate analysis of the clinicopathological factors associated with the prognosis that included disease-free survival (DFS) and overall survival (OS). Patients were categorized into LRH through vaginal colpotomy (VC group, n=475) and LRH through intracorporeal colpotomy (IC group, n=490) according to the colpotomic approaches. The prognosis and recurrence sites of patients in each group were compared. Results:(1) During the follow-up period, 137 cases recurred (14.2%, 137/965) and 98 cases died (10.2%, 98/965). The 5-year DFS and OS were 85.8% and 89.9%, respectively. In univariate analysis, positive vaginal margin (PVM) was significantly affected the 5-year OS of patients with cervical cancer ( P=0.023), while clinical stage, maximum diameter of tumor, degree of pathological differentiation, lymph node metastasis (LNM), depth of cervical stromal invasion, parametrium involvement, and uterine corpus invasion (UCI) were significantly associated with 5-year DFS and OS in patients with cervical cancer (all P<0.05). In multivariate analysis, clinical stage ( HR=1.882, 95% CI: 1.305-2.716), LNM ( HR=2.178, 95% CI: 1.483-3.200) and UCI ( HR=3.650, 95% CI: 1.906-6.988) were independent risk factors of 5-year DFS (all P<0.001). Clinical stage ( HR=2.500, 95% CI: 1.580-3.956), LNM ( HR=2.053, 95% CI: 1.309-3.218), UCI ( HR=3.984, 95%C I: 1.917-8.280), PVM ( HR=3.235, 95% CI: 1.021-10.244) were independent risk factors of 5-year OS (all P<0.05). (2) Different colpotomy paths did not significantly affect the 5-year DFS and OS of patients with stage Ⅰa2-Ⅱa2 cervical cancer. The 5-year DFS in VC group and IC group were 85.9% and 85.6% ( P=0.794), and the 5-year OS were 90.8% and 89.3% ( P=0.966), respectively. Recurrence patterns consisted of intraperitoneal recurrence, pelvic recurrence, vaginal stump recurrence, and lymph node and distant metastasis. The intraperitoneal recurrence rate of VC group was significantly lower than that of IC group [0.6%(3/468) vs 2.3% (11/485), P=0.037], while the rates of pelvic recurrence, vaginal stump recurrence, lymph node and distant metastasis and overall recurrence were not significantly different between two groups (all P>0.05). Subgroup analysis of patients with different clinical stages, LNM and UCI showed that statistical differences of the intraperitoneal recurrence rates between two groups were only in patients without LNM (0.5% vs 2.3%, P=0.030) or without UCI (0.7% vs 2.3%, P=0.037). Conclusions:Clinical stage, LNM, PVM and UCI are independent risk factors for the prognosis of patients with stage Ⅰa2-Ⅱa2 cervical cancer. For patients without LNM or UCI, LRH through VC could reduce the intraperitoneal recurrence rate, while it is not enough to improve 5-year DFS and OS of patients. Low proportion of intraperitoneal recurrence, intra-operative tumor cells spillage to vagina stump and pelvic cavity might be the explanation.

Objective To analyze the correlation of interferon-induced protein with tetratricopeptide repeats 1(IFIT1)with immune infiltration and prognosis of ovarian cancer(OC).Methods GEO database was employed to select the tumor immune related genes,and Kaplan-Meier and Prognoscan databases were used to identify the genes significantly associated with OC prognosis.The differential expression of IFIT1 between OC tissue and normal tissue were confirmed with GEPIA,Human Protein Atlas,and Timer databases.The expression level of IFIT1 in OC tissues with different grades and stages were analyzed in the UALCAN database.In addition,based on David database,GO enrichment analysis was used to analyze the interacting genes and proteins of IFIT1 in the String and Genemania databases.Timer and Tisidb databases verified the correlation between IFIT1 and immune cells mutually.Finally,after IFIT1 knockdown xenograft model was constructed based on lentiviral vector of IFIT1 shRNA,the tumor growth was observed in the transplanted nude mice,and infiltration of neutrophils was observed with immunohistochemical assay.Results FIT1,a tumor immune gene,selected from the GEO database,Kaplan-Meier and Prognoscan databases,was negatively correlated with the OC prognosis.GEPIA,Human Protein Atlas,Timer database,and UALCAN database indicated that the expression level of IFIT1 was significantly higher in the OC tissues than the normal ovarian tissues,and had no obvious correlation with tumor stage and grade.Analysis in String,Genemania,and David database found the interaction genes and proteins of IFIT1 were enriched in activation of 2'-5'oligonucleotide synthase,virus defense,and innate immunity,and other processes.The Timer database presented that IFIT1 was positively correlated with the infiltration of CD8+T cells,B cells,dendritic cells,neutrophils,and macrophage in OC,with neutrophils having the most significant correlation.Tisidb and GSCA also confirmed the positive correlation between IFIT1 and neutrophil infiltration in OC(P＜0.05).RT-qPCR and Western blotting confirmed that IFIT1 knockdown resulted in suppressed tumor growth in OC cells xenograft nude mice(P＜0.05)and reduced neutrophil infiltration in the xenograft tissues.Conclusion IFIT1 may influence the malignant progression of OC by promoting neutrophil infiltration.

Objective:To compare the results of thinned latissimus dorsi muscle flap combined with skin grafting and dorsal free flaps in repairing traumatic dorsal foot defects.Methods:From January 2005 to December 2019, 41 patients with large soft tissue defects in the dorsum of the foot were admitted to our department. Inclusion criteria: unilateral dorsal foot and ankle soft tissue defects, accompanied by tendon and/or bone exposure, cannot be repaired by simple methods such as skin grafting and local flaps, and the affected area has blood vessels that can be used for anastomosis. Exclusion criteria: primary or secondary vascular diseases, systemic conditions intolerant to prolonged surgery. According to the patient’s choices, the latissimus dorsi flap or the scapular flap were used for repair, namely the traditional flap group. Or latissimus dorsi muscle flap was used to fill and cover the defect, and then the surface of the muscle flap was sealed with split-thickness or full-thickness skin grafting, which is the combined transplantation group. Postoperative follow-up was mainly focused on the recovery of foot function, whether the shoes were worn normally, the appearance of the flap, and the rate of second operation.Results:A total of 41 patients were included in this study. All the flaps survived without infection and tissue necrosis. Twenty three cases, 16 males and 7 females, age from 6 to 52 years with an average of 27.6 years, were repaired with latissimus dorsi flap or scapula flap. The area of soft tissue defects was from 5.5 cm×8.0 cm to 19.5 cm×23.0 cm, with an average areaof 10.1 cm×16.2 cm. The follow-up time was from 6 to 24 months with an average of 9.7 months. All walking function of the foot was basically restored, and the texture of the flap was good. Eighteen patients had bloated flap appearance, 15 of which affected shoe-wearing, and 14 had debulking surgery, 2 had developed hypertrophic scar. Eighteen cases, 14 males and 4 females, age from 19 to 49 years with an average of 30.7 years, were repaired with latissimus dorsimuscle flap combined with split-thickness or full-thickness skin grafts. The area of soft tissue defects was from 4.0 cm×6.5 cm to 20.5 cm×23.0 cm, and the average area was 11.7 cm × 17.3 cm. All donor-site incisions are sutured in one stage without skin grafting. The follow-up time was from 4 to 20 months with an average of 8.3 months. The walking function of all operative feet, with good shape and without bloating, was basically restored. The contour and curve was similar to the healthy side and no skin injury and ulcer was observed. All patients were satisfied with wearing shoes and walking function, and no secondary surgery was required. However, 9 patients had developed hypertrophic scar.Conclusions:Compared with the traditional flap, the free latissimus dorsi muscle flap combined with skin grafting can effectively cover large area of soft tissue defect on the dorsal foot, without bloated flap appearance and secondary surgery. However, the risk of scar hyperplasia after combined transplantation increased.