Thromboembolic diseases are major health problems worldwide,and remain the leading cause of mortality and disabil-ity at present.Bleeding is the most important complication of an-tithrombotic therapy for thromboembolism,therefore research and development of new antithrombotic drugs with lowered bleeding risk is a significant medical need.The data that elevated plasma levels of FXI are associated with thromboembolic diseases,se-vere FXI deficiency reduced incidence of DVT and ischemic stroke,and FXI deficiency or inhibition in animals shows protec-tive effects against thrombus formation supporting FXI as a novel antithrombotic target with lowered bleeding risk.This paper re-views the progress on FXI as a novel antithrombotic target and the inhibitors target FXI.

Objective:To investigate the knowledge of hand-cleaning in student nurses,cultivate their awareness of washing hands,improve their submitting of washing hands and standardize their washing procedure,so as to reduce the hospital-acquired infection via hands.Methods: A self-designed questionnaire on hand-cleaning-related knowledge was used to survey 100 student nurses in their clinical practice in our hospital.Results:In the 100 questionnaires,some student nurses have poor-mastering of the signs of hand-cleaning,and have indefinite concepts of the time,position and frequency of hand-cleaning.The most frequently forgotten part of hands cleaning is finger(42%),the second is wrist(29%).Lots of student nurses(92%) mistakingly thought that washing hands with warm water was much better.Conclusion:The student nurses had relatively poor knowledge on hand-cleaning,much more attention should be paid on the education of this aspect by nursing department,in order to improve self-protection and control of hospital-acquired infection effectively.

Background Interleukin-6 (IL-6) is a pleiotropic cytokine involving in inflammation and wound healing.Previous report found that IL-6 increases phosphorylated STAT3 (p-STAT3) level and promotes corneal epithelial wound healing by stimulating migration.However,the essential role of IL-6 in corneal epithelial wound healing and the expression changes in diabetic mellitus remains unknown.Objective This study was to explore the roles of IL-6 in corneal epithelial proliferation and wound healing in both normal and diabetic mice.Methods Fifty-two normal C57BL/6 mice were randomized into normal control group (32 mice) and diabetic group (20 mice).Type 1 diabetic mellitus was induced by intraperitoneal injections of 50 mg/kg streptozotocin once per day for consecutive 5 days in the mice of the diabetic group.Whole corneal epithelium was scraped in all mice,and the corneal epithelial defect area was examined by fluorescein staining in 24,48 and 72 hours after corneal epithelium removal.Recombinant mouse IL-6 or anti-IL-6 blocking antibody of 5 μl were subconjunctivally injected according to the grouping and contrasted with PBS injection group or isotype control antibody group,respectively.TKE2 cells,a mouse corneal epithelial stem/progenitor cell line,were trypsinized and incubated in the KSFM with different concentrations of IL-6 or without IL-6,and colony formation efficency (CFE) was examined by crystal violet staining.The expressions of △NP63 and Ki67,specific makers of stem cells,were detected by immunofluorescine technology.The expressions of △NP63,Ki67 and p-STAT3 proteins were assayed in the cells by Western blot,respectively.The expression of IL-6 mRNA and protein in the regenerated corneal epithelium was detected by real time quantitative PCR and ELISA.The use and care of the mice complied with the Statement of Association for Research in Vision and Ophthalmology.Results The percentage of residual corneal epithelium defect area with initial detect area was gradually shrinked over time after PBS and IL-6 injection in both normal control mice and diabetic mice,and the percentage of residual corneal epithelium defect area was significantly reduced in the IL-6 injected group compared with the PBS injected group (normal control group:Fgroup =19.982,P ＜ 0.01;Ftime =589.350,P ＜ 0.01;Diabetic group:Fgroup =25.411,P＜0.01;Ftime =334.807,P＜0.01).The CFE was (13.23± 1.12)％,(15.87± 1.30)％,(21.69±1.62)％,(25.33±1.28)％ and (18.67±1.54)％ in the blank control group and 10,20,50,100 ng/ml IL-6-treated groups,respectively,showing a gradual increase of CFE dependent upon IL-6 concetrations (F =35.547,P＜0.01).The expressions of △NP63,Ki67,p-STAT3 proteins in the cells were gradually increased over time after 50 ng/ml IL-6 treated for 5,10,15,30 and 60 minutes,and the relative expression level of the cytokines was significnatly higher in the IL-6 cultured groups than that without IL-6 culture group (all at P＜0.05).The relative expression of IL-6 mRNA in the regenerated corneal epithelilum was 0.45±0.21 and 1.00±0.16 in the diabetic group and normal control group,respectively,and compared with the normal control group,the expression of IL-6 mRNA reduced by 56％ (t=3.42,P=0.03).The content of IL-6 protein in regenerated corneal epithelium of the diabetic group was (257±12) ng/μl,which was significantly lower than (323 ± 17) ng/μl of the normal control group (t =5.60,P＜0.01).Conclusions IL-6 promotes the proliferation and regeneration of corneal limbal stem cells to repair defected corneal epithelium by activating STAT3 signaling pathway in both normal and diabetic mice,while the blocking of endogenous IL-6 impairs the corneal epithelial cell activation and wound healing.

ObjectiveTo investigate the correlation between stroke volume variation (SVV) and blood volume during hypovolemia.MethodsTwenty ASA Ⅰ or Ⅱ patients,aged 20-64 yr,with body mass index 20-30 kg/m2,scheduled for elective orthopedic operation,were studied.Anesthesia was induced with dexamethasone,midazolam,propofol,fentanyl and cisatracurium and maintained with sevoflurane,fentanyl and cisatracurium.The patients were tracheal intubated and mechanically ventilated.HR,MAP,CVP,arterial pressure-based cardiac output (APCO),SVV,systemic vascular resistance (SVR) and cardiac index (CI) were recorded 5 min after tracheal intubation.Blood was taken from central vein at a rate of 30-50 ml/min,the volume was 5％ of the whole blood volume and the haemodynamic parameters mentioned above were recorded after the haemodynamics was kept stable for 5 min.Blood was taken again as the method mentioned above and the haemodynamic parameters were recorded.6％ HES 130/0.4 was then infused at 50-70 ml/min via right internal jugular vein,the volume was equal to 5 ％ of the whole blood volume and the haemodynamic parameters were recorded after the haemodynamics was kept stable for 5 min.Fluid replacement was performed again using the method mentioned above and the haemodynamic parameters were recorded.Linear correlation of the change in blood volume (difference between the blood volume at each time point and the baseline value) with dSVV (difference between the value monitored at each time point and the baseline value) was analyzed.ResultsThere was significant change in SVV,APCO and CI after each change in blood volume ( P ＜ 0.05 or 0.01),while there was not always significant change in HR,MAP,CVP and SVR after each change in blood volume.The change in blood volume was negatively correlated with dSVV ( r =- 0.875,P ＜ 0.01 ).ConclusionThere is high correlation between SVV and blood volume during hypovolemia and SVV can reflect the change in blood volume accurately and be used for volume therapy during hypovolemia.

Objective To investigate the correlation between stroke volume variation (SVV) and blood volume during hypovolemia.Methods Twenty ASA Ⅰ or Ⅱ patients,aged 20-64 years,with body mass index (BMI) of 20-30 kg/m2,scheduled for elective orthopedic operation were enrolled in this study.Anesthesia was induced with dexamethasone,midazolam,propofol,fentanyl and cisatracurium,and maintained with sevoflurane,fentanyl and cisatracurium.Then the patients received endotracheal intubation and mechanical ventilation.Heart rate (HR),mean arterial blood pressure (MAP),central venous pressure (CVP),arterial pressure-based cardiac output (APCO),SW,systemic vascular resistance (SVR) and cardiac index (Cl) were recorded 5 minutes after endotracheal intubation.Blood was taken from the central vein at a rate of 30-50 ml/min and the volume was 5％ of the whole blood volume,and then haemodynamic parameters mentioned above were recorded after the haemodynamics were kept stable for 5 minutes.Blood was taken again with the method mentioned above and the haemodynamic parameters were recorded.Then 6％ hydroxyethyl starch (HES) 130/0.4 was infused at 50-70 ml/min via the right internal jugular vein,and the volume was equal to 5％ of the whole blood volume,and then haemodynamic parameters were recorded after the haemodynamics was kept stable for 5 minutes.Fluid replacement was performed again using the method mentioned above and the haemodynamic parameters were recorded.Linear correlation of the changes in blood volume (difference between the blood volume at each time point and the baseline value) with dSVV (difference between the value monitored at each time point and the baseline value) was analyzed.Results Significant changes were found in SW,APCO and Cl after each change in blood volume (P ＜ 0.05 or 0.01),while no significant changes were found in HR,MAP,CVP and SVR after each change in blood volume.The change in blood volume was negatively correlated with dSVV (r =-0.875,P ＜ 0.01).Conclusion There is high correlation between SVV and blood volume during hypovolemia.And SVV can reflect the changes in blood volume accurately and can be used for volume therapy during hypovolemia.

Objective To investigate the value of ADC histogram of tumor volume measurement in the diagnosis of prostate cancer,and to screen out the best diagnostic parameter value.Methods 31 cases of prostate cancer and 35 cases of benign prostatic hyperplasia confirmed by biopsy or surgical pathology were analyzed retrospectively.DWI examination was performed on all patients before treatment,and b value of 0 and 1500 s/mm2 was selected.The total tumor ADC histogram parameters were measured respectively,including the average value of ADC (ADCmean ),the median ADC (ADCmedian ),the tenth percentile ADC (ADC10th),the twenty-fifth percentile ADC (ADC25th), the fiftieth percentile ADC (ADC50th),the seventy-fifth percentile ADC (ADC75th),the ninetieth percentile ADC (ADC90th), skewness and kurtosis.The histogram parameters of the two groups of patinents and their diagnostic efficacy were analyzed and compared.Results ADCmean ,ADCmedian ,ADC10th,ADC25th,ADC50th,ADC75th and ADC90th in the prostate cancer group were statistically lower than those of benign prostatic hyperplasia group (P <0.01),and there was no significant difference in the skewness and kurtosis between the two groups of diseases (P > 0.05 ).ADCmean ,ADCmedian ,ADC10th,ADC25th,ADC50th,ADC75th and ADC90th diagnosing prostate cancer in the area under ROC curves (AUC)were more than 0.78.ADC10th had the best diagnostic efficacy and its AUC was 0.82, with the optimal cut-off value for 0.27 × 10 -3 mm2/s,with sensitivity and specificity for 78.4％ and 83.3％.Conclusion The ADC histogram of the total tumor volume measurement is of great value in the diagnosis of prostate cancer,among which ADC10th is the most effective parameter.It can accurately distinguish between prostate cancer and prostatic hyperplasia nodules.

Inhibition of NEDD8 activating enzyme (NAE),the rate limiting enzyme in Neddylation,can suppress the activity of ubiquitin-proteasome system (UPS) pathway and decrease degradations of related proteins,resulting in cell apoptosis.Compared with the proteasome inhibitors,NAE inhibitors can interfere with cellular homeostasis with more specificity.With the rapid development of the research on NAE,a variety of NAE inhibitors have been reported.According to the structure characteristics,NAE inhibitors can be divided into the AMP analogues,double flavonoids deoxidization duckbill alkali ketone derivatives and metal rhodium complex classes,etc.The process of ubiquitinated modified Neddylation,NAE and physiological role of tumor has been introduced in this paper,and the latest progress of NAE inhibitors also has been summarized.

Objective: To investigate the role of "Hong′s single-stitch duct to mucosa pancreaticojejunostomy(HSDMP)" in laparoscopic pancreaticoduodenectomy (LPD). Methods: The clinical data including perioperative and short-term outcomes of 51 cases of LPD with HSDMP which performed in Zhejiang Provincial People′s Hospital(33 cases) and Frist Clinical Hospital of Jilin University(18 cases) between April and October 2016 were reviewed retrospectively. There were 31 male patients and 20 female patients. The mean age was(59±11)years. Body mass index (BMI) was 18 to 28 kg/m² and the average BMI was (23.2±4.4)kg/m². Preoperative diagnosis: 18 cases with pancreatic mass, 26 cases with peri-ampullary tumor, 3 cases with intra-ductal papillary mucinous neoplasms, 2 cases with duodenal carcinoma, 2 cases with serous cystadenoma. Results: Fifty-one patients accepted LPD using HSDMP. One patient underwent LPD combined with resection of superior mesentery vein. The mean operation time was (307±69)minutes, the mean diameter of pancreatic duct for reconstruction was (3.1±1.1)mm.The mean operation time for HSDMP was (34±5) minutes, the estimated blood loss was (170±127)ml. Twelve cases(23.5%) had pancreatic fistula according to International Study Group definition, including 9 cases(17.6%) of grade A and 3 cases (5.9%) of grade B. Five cases(9.8%) had delayed gastric empty, 5 cases(9.8%) had bile leakage and 2 cases(3.9%) had pulmonary infection postoperative.All these complications were treated by non-surgical strategies. One patient(2.0%) suffered from postoperative intra-abdominal bleeding and recovered after reoperation. Pathologic results showed pancreatic ductal adenocarcinomas in 20 cases(39.2%), non-pancreatic original peri-ampullary tumors in 23 cases(45.1%), intra-ductal papillary mucinous neoplasms in 3 cases(5.9%), duodenal carcinoma in 2 cases(3.9%), serous cystadenoma in 2 cases(3.9%) and neuroendocrine tumors in one case(2.0%). Conclusions HSDMP could not only reduce the incidence of clinical pancreatic fistula, but also save operation time. It is a feasible and safe method for pancreaticojejunostomy.

BACKGROUND:Exosomes play a role in all stages of wound repair,and there is currently a large body of research on exosomes in skin wound repair,which has been shown to have great potential for clinical applications. OBJECTIVE:To summarize and discuss the main mechanisms and clinical applications of exosomes in the treatment of skin wounds,in order to promote the clinical translation of exosomes. METHODS:PubMed,clinicaltrials.gov,China National Knowledge Infrastructure,Food and Drug Administration database,and Chinese Clinical Trial Register were searched from inception to March 2023.The English search terms were"exosomes,wound healing,stem cells,chronic wound,immunoregulation,inflammation,skin,therapeutic use,isolation,characterization,infections".The Chinese search terms were"exosomes,wound healing,stem cells,immunomodulation,clinical applications".A total of 79 articles were included for the summary. RESULTS AND CONCLUSION:(1)Exosomes can improve and accelerate wound healing through inflammation regulation,immune protection,angiogenesis,cell proliferation and migration,and collagen remodeling.(2)Exosomes derived from stem cells have mature preparation techniques and related mechanism research,which is currently the mainstream research direction.Non-stem cell-derived exosomes have the advantages of convenience,economy,and easy production,and can be used as a supplement for clinical applications.(3)The clinical application of exosomes is still in its infancy,but has great potential for application.Various exosome modification techniques have laid the foundation for the future development of clinically personalized services and require further research.(4)The clinical translation of exosomes faces many challenges,such as low yield,high heterogeneity,lack of unified standards for isolation,purification,and quality control,and difficulties in storage.

Objective:To investigate the effect of vagus nerve stimulation (VNS) on serum cytokines and neurotransmitters in epilepsy patients with depression.Methods:From March 2015 to 2018, 13 patients with epilepsy combined with depression undergoing VNS surgery in Brain Hospital of Hunan Province were selected as the research objects. The surgical efficacy, depression degree, serum cytokines and neurotransmitter changes before operation, 6 months and 12 months after operation were compared.Results:The effective rate of epilepsy treatment at 6 and 12 months after VNS were 61.5%(8/13) and 76.9%(10/13), respectively. After 6 months and 12 months, Hamiton Depression scale (HAMD) and self-rating depression scale (SDS) scores were significantly lower than those before operation ( P<0.05 or P<0.01). At 6 months after operation, serum 5-hydroxytryptamine (5-HT) level was significantly higher than that before operation, while serum interleukin (IL)-1α, IL-6 and tumor necrosis factor α (TNF- α) were significantly lower than those before operation ( P<0.05 or P<0.01). At 12 months after operation, 5-HT and dopamine (DA) were significantly increased, while IL-1 α, IL-2, IL-6 and TNF -α were significantly decreased ( P<0.05 or P<0.01). Conclusions:VNS may can improve epilepsy and depression by regulating the level of neurotransmitter and serum cytokines.