ObjectiveTo investigate the role and mechanism of Lck/Yes-related novel protein tyrosine kinase （Lyn） on lipopolysaccharide （LPS）-induced M1-type polarization of macrophage. MethodsThe LentiCRISPR-V2 plasmid was digested with the restriction endonuclease BSMBI-V2， and the digested DNA fragments were recovered. The digested plasmid was ligated with Lyn-sgRNA using T4 ligase to generate the Lenti-Lyn-gRNA lentivirus. THP-1 cells were infected with the Lenti-Lyn-gRNA lentivirus to obtain a stable cell line with Lyn knockout， and a monoclonal THP-1 cell line with complete Lyn knockout （Lyn^⁻/⁻） was established subsequently. Wild-type Lyn （Lyn^WT） and Lyn^⁻/⁻ THP-1 cells were induced with 100 ng/mL phorbol myristate acetate （PMA） for 48 h to differentiate into M0 macrophages， which were further polarized into M1 macrophages by stimulation with 100 ng/mL LPS for 24 h. Quantitative real-time polymerase chain reaction （qPCR） was performed to detect the expression of M0 macrophage markers， including integrin αM （CD11b）， macrophage antigen （CD68）， and monocyte differentiation antigen （CD14）. The expression of Lyn in M1 macrophages differentiated from wild-type THP-1 cells （Lyn^WT-M1） was measured by qPCR， and the ratio of phosphorylated Lyn to total Lyn （P-Lyn/Lyn） in Lyn^WT-M1 cells was determined by Western blot. In M1 macrophages differentiated from Lyn-knockout THP-1 cells （Lyn^⁻/⁻-M1）， qPCR was used to detect the mRNA expression of inducible nitric oxide synthase （iNOS）， interleukin-6 （IL-6）， and chemokine （C-X-C motif） ligand 10 （CXCL-10）. Western blot was conducted to assess the protein expression of iNOS， as well as the protein levels of molecules related to the Janus kinase 1 （JAK1）-signal transducer and activator of transcription 1 （STAT1）signaling pathway， including JAK1， phosphorylated JAK1 （P-JAK1）， STAT1， and phosphorylated STAT1 （P-STAT1）. Additionally， the expression of the M1 macrophage marker cluster of differentiation 80 （CD80） was analyzed by flow cytometry. ResultsThe Lyn^-/- monoclonal cell line was successfully constructed. The expression of CD11b was significantly elevated in Lyn^-/- M0 macrophages， and the differentiation of M1 macrophages was successful. Knockdown of Lyn inhibited mRNA expression of iNOS， IL⁃6， CXCL⁃10， protein expression of iNOS and CD80 expression in M1 macrophages （P<0.05）. Western blot assay showed that Lyn knockdown inhibited protein expression of JAK1 and P-STAT1 （P<0.01）. ConclusionAfter CRISPR/Cas9-mediated Lyn knockout， the expression levels of JAK1 and P-STAT1， the key molecules in the JAK/STAT signaling pathway of M1 macrophages， are significantly downregulated； concomitantly， the expression of M1 macrophage-specific secretory factors （iNOS， IL⁃6， CXCL⁃10 mRNA） and CD80 is also downregulated， which may be achieved via targeted regulation of the JAK1/P-STAT1-mediated JAK/STAT signaling pathway.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Compared with normal tissue, interstitial extracellular pH of tumor cells is acidic. The reverse transmembrane pH gradient around tumor cells is closely related to its uncontrolled progression, angiogenesis and metastasis. Changes in urinary pH have an impact on the occurrence, progression and treatment of bladder cancer by regulating the microenvironment of bladder cancer cells. Relevant studies have shown that urinary pH value is an important factor in predicting the final clinical efficacy of bladder cancer patients combined with alkalization agents, which helps to reflect the acid-base balance and immune defense system in the body. Continuous monitoring of urinary pH can provide guidance and decision-making for the prognosis of bladder cancer patients.

Objective To explore the clinical effect of tension-free repair in the treatment of inguinal hernia in elderly patient.Methods A total of 124 elderly patients with inguinal hernia admitted in our hospital in 2016 were randomly divided into a study group(n=62)and a control group (n=62).The control group was treated with open tension-free inguinal hernia repair,whereas with laparoscopic tension-free inguinal hernia repair in the study group.The operation time,intraoperative blood loss,the postoperative pain relief-time,mean days of hospitalization,postoperative recurrence rate,and complications rates were compared between the two groups.Results The more significant improvements were found in study group versus control group in the intraoperative bleeding volume [(19.9±2.0)ml vs.(36.8±-2.5)ml,t=41.564,P=0.000],in the mean hours of postoperative pain [(22.1 ± 4.2) h vs.(35.3 ± 7.0) h,t =12.732,P =0.000],in mean days of hospitalization [(5.5 ± 1.0)d vs.(9.2±1.9)d,t=13.569,P=0.000],in incidence rate of postoperative recurrence(0.0％ vs.6.5％,x2 =4.133,P=0.042),and in postoperative complications rate(3.2％ vs.12.9％,x2 =3.916,P=0.048).Nevertheless,the operation time was longer in the study group than in the control group[(87.0±5.0)min vs.(55.5±4.2)min,t=-37.984,=0.000],Conclusions As compared with open tension-free repair,the clinical efficacy of laparoscopic tension-free hernia repair is exactly sure in the treatment of inguinal hernia,with shorter postoperative hospitalization time and lower incidence of complications.

Objective To investigate the relationship between intelligence impairment and interictal epileptiform discharges spreading in mesial temporal lobe epilepsy(mTLE)patients. Method We assessed 145 patients diagnosed as mTLE and their general materials, analyzed the relationship between intelligence impairment and interictal epileptiform discharges spreading. Results ①Patients with mTLE with longer disease course and higher frequencies of epilepsy tended to have a severe impairment in the total intelligence quotient (IQ), verbal intelligence quotient (vIQ) and performance intelligence quotient (pIQ). ② IQ of was negatively correlated with the condition that interictal epileptiform discharges spreading to the ipsilateral central and parietal region in patients with left lesion; pIQ was negatively correlated with the condition that interictal epileptiform discharges spreading to the ipsilateral frontal region, while positively correlated with the condition that interictal epileptiform discharges spreading to the ipsilateral occipital region in patients with right lesion. Conclusion ①Intelligence impairment of mTLE patients is related with courses and frequencies.②Total IQ is more severely impaired by interictal epileptiform discharges spreading to the ipsilateral central and parietal region in left mTLE patients, and the pIQ is more severely impaired by interictal epileptiform discharges spreading to the ipsilateral frontal region in right mTLE patients.

Objective To explore the effect of probucol on the inflammatory response in rabbits with arteriosclerosis obliterans.Methods SPF male new zealand white rabbits were subjected to incomplete right femoral artery ligation model of arteriosclerosis obliterans.The model rabbits were divided into experimental group and control group.The rabbits in experimental group were treated by probucol.After treatment for 4 weeks,HE staining was used to evaluate the injury severity of right femoral artery in rabbits;ELISA was used to measure the levels of IL-1,IL-6,TNF-α and CRP;Realtime PCR was used to detect the expressions of IL-1,TNF-α in right femoral artery;Western blot was used to measured the nucleus accumulations of NF-κB,and the phosphorylation of IκB.Results Compared with control group,the degree of pathological injury of right femoral artery was significantly atteunated,the levels of IL-1 、IL-6 、TNF-α and CRP in plasma,the mRNA expressions of IL-1 、TNF-α and the nucleus accumulations of NF-κB,and the phosphorylation of IκB in right femoral artery decreased significantly.Conclusion Probucol attenuates the inflammatory response in rabbits with arteriosclerosis obliterans significantly.

Objective To summarize the surgical experience and primary follow-up results for robotic assisted radical cystectomy ( RARC ) , as well as to evaluate the safety and feasibility of this procedure.Methods From Jan 2013 to Oct 2015, we retrospectively analysis the perioperative data and primary follow-up data from 35 patients who underwent radical cystectomy with Da VinCi robotic laparoscopic in urological institution of Changhai Hospital.The median age was 65 (ranging from 46 to 78) years.The amount of male cases were 34, the female case were 1.There were three kinds of urinary diversion, ureterocutaneostomy, Bricker operation and orthotopic neobladder, were 2, 26 and 7 respectively.We collected the parameters including operating time, estimated blood loss, blood transfusion volume, time to flatus,length of hospital stay,perioperative complication,time of recurrence,time of death and the reason of death.Results All of the related operations had been accomplished successfully, none of which had been converted to the open procedure.The estimated operating time of ureterostomy was (315.0 ±106.1) min, Ideal conduit was ( 443.2 ±93.2 ) min, Orthotopic bladder was ( 488.3 ±80.6 ) min.The estimated intraoperative blood loss was 260.0 ±108.6(100 to 500 )ml.5 cases of all patients were transfused 400ml red cell suspension, the transfusion rate was 14.2%.The mean time to flatus was 3.1 ±1.6(1 to 7) d.The estimated time to remove the gastric tube and the drainage tube was 4.2 ±2.2d(2-10d),10.8 ±5.1d(4-25d),respectively.The length of hospital stay after surgery was 12.4 ±5.17(6 to 25) d.Overall,17,8, 10,31 and 4 of these patients had

Objective To investigate feasibility and early stage postoperative complications of lapa-roscopic radical cystectomy ( LRC) . Methods We retrospectively analyzed the data of 63 consecutive pa-tents (58 males and 5 females) who underwent LRC from Oct .2011 to Oct.2013 in our institute.Of these patients, 46 patients underwent ileal conduit , 9 patients underwent ureterocutaneostomy , and 8 patients un-derwent orthotopic ileal neobladder urinary diversion .The average age and body mass index of patients were 67.7±11.1 (33-84) years and 23.3±2.1 (18.8-28.7) kg/m2, respectively.The mean hemoglobin and al-bumin of patients were (130.7±20.3) g/L and (38.9±4.1) g/L, respectively.Comorbidities of hyperten-sion, diabetes, coronary heart disease and decompensated liver cirrhosis were found in 10, 6, 2 and 1 pa-tient, respectively.10 of 61 patients had a history of abdominal surgery .The indications for cystectomy were classified as muscle invasive bladder cancer for 30 patients, unresectable superficial bladder cancer for 19 patients and recurrent bladder cancer for 14 patients.Postoperative data and early stage postoperative compli-cations within 3 months after surgery were collected . Results The median operative time for LRC and uri-nary diversion was 390 (260-480) min, with a median estimated blood loss of 400 (100-1 500) ml.This was one patient converted to open surgery .The mean postoperative hemoglobin and albumin of patients was 108.5±14.7 g/L and 29.5±3.7 g/L, respectively, both of which significantly reduced compared with pre-operative data (P<0.01).The median duration of hospital stay was 15 days.The median time for liquid in-take, abdominal drainage removal and ureteral stent removal was 4 days, 9 days and 2 months after surgery , respectively.Catheter was removed 2 weeks after laparoscopic orthotopic cystectomy .21 (33.3%) of 63 pa-tients suffered from perioperative complications .15 of 46 patients (32.6%) in ileal conduit group had com-plications including ileus ( 5, 1 of 5 need re-operation ) , lymphatic fistulas ( 5) , pulmonary infection ( 1) , pyelonephritis (1), delirium (1), anastomotic leak (1, re-operation was needed) and pneumothorax (1). 2 of 9 patients (22.2%) in ureterocutaneostomy group had complications such as ileus (1) and lymphatic fistulas (1).4 of 8 patients (50.0%) in orthotopic ileal neobladder group suffered from complications like ileus (2, 1 of 2 required re-operation), lymphatic fistulas (1) and arrhythmia (1). Conclusions LRC is technically feasible and safe .It reduces the estimated blood loss and postoperative complications .It is noteworthy to surgeons that serum albumin significantly reduced after LRC , nutrition should be kept balanced after surgery.