Objective To explore the neuroprotective effects of osteocalcin(OCN)on an Alzheimer's disease(AD)cell model and its potential mechanisms,providing a scientific basis for new therapeutic targets for AD.Methods Human neuroblastoma cell line SH-SY5Y was treated with 40 nmol/L okadaic acid(OA)for 24 h to establish an AD cell model.The cells were divided into a normal group(untreated SH-SY5Y cells),a model group(40 nmol/L OA intervention),and an OCN intervention group(intervention with various concentrations of OCN in the AD cell model),and AKT knockout/overexpression groups(AKT-KO group and AKT-OE group),and AKT-KO OCN group and AKT-OE OCN group.CCK-8 assay was used to detect the changes in cell viability.Wright's staining was employed to observe the morphological changes of AD cells.Western blotting was utilized to detect the protein levels of Tau,p-Tau,Bax,Bcl-2,Caspase-3 and their lytic types,as well as the expression of Tau,p-Tau,mTOR,AKT and p-AKT in each group after AKT knockout/overexpression.TUNEL staining and flow cytometry were applied to detect the changes in early and late apoptotic cells and the apoptotic rate in the OCN-treated AD cell model.Results ①Compared to the normal group,the model group exhibited a significant decrease in cell viability,noticeable morphological and structural damage,upregulation of p-Tau and Caspase-3,increased early and late apoptosis,and a significantly higher apoptotic rate(P<0.05).②After treatment of different concentrations of OCN for 24 h,cell viability was increased to varying degrees compared to the AD model group,with the 100 pg/mL OCN group showing a significant increase in cell viability(P<0.01)and marked improvement in cell number and morphology(P<0.01).③ Compared to the AD cell model group,the p-Tau/Tau ratio was decreased in all OCN treatment groups,particularly in the 100 pg/mL OCN intervention group,where the p-Tau/Tau ratio was significantly lower than that of the model group(P<0.01).④ Compared to the model group,a significant concentration-dependent decrease in the Cleaved Caspase-3/Caspase-3 ratio was observed when OCN concentrations ranged from 1 to 100 pg/mL,with a significant reduction in the Bax/Bcl-2 ratio in the 100 pg/mL group(P<0.000 1).⑤ The results of TUNEL staining and flow cytometry showed that,compared to the model group,all concentrations of OCN effectively inhibited the apoptosis in the AD model cells,with a significant reduction in early and late apoptotic cells and apoptotic rate in the 100 pg/mL OCN group.⑥ Compared with the control group and the model group,the P-AKT was significantly increased in the AKT-OE group after AKT overexpression(P<0.05).The expression level of AKT protein was decreased in the AKT-KO group after AKT knockout(P<0.05).When the AKT pathway was inhibited,the expression level of p-Tau was higher in the AKT-KO group than the control group(P<0.05),and when the AKT was overexpressed,the expression level was significantly inhibited(P<0.05).Conclusion OCN may inhibit cell apoptosis and reduce p-tau protein level by regulating the ratio of Caspase-3/Caspase-3 and Bax/Bcl-2,and thereby improve the morphology of AD model cells and effectively protect nerve cells,which may be related to the regulation of the AKT/mTOR pathway.

Objective:To explore the effect of the treatment of tendinous mallet finger deformity by the minimally invasive percutaneous quantitative suture technique eight times.Methods:A retrospective analysis was performed on patients with fresh tendinous mallet fingers who underwent surgery in the Department of Hand and Foot Microsurgery of Nanjing Jiangbei Hospital from April 2021 to April 2022. During the procedure, the extensor digitalis tendon in the zone Ⅰ was sutured percutaneous with 3-0 thread monofilament sutures in the "quantitative 8-stitch method" according to the pre-marked number sequence of 1 to 8, and fixed at the base of the distal phalanx via a constructed bone tunnel. Removal of the Kirschner wire 8 weeks, the brace was used to fix the affected finger in the dorsal extension. The flexion and extension of the affected finger were gradually strengthened. The function of the affected finger was evaluated according to the Crawford standard after operation and follow-up: the active flexion and extension range of motion of each joint of the affected finger and the contralateral healthy finger was measured, and the total active ranges of motion of the finger were recorded. Finger function was evaluated according to the total active range of motion (TAM) system of the American Association of Hand Surgeons.Results:A total of 10 patients (10 digits) were enrolled, including 7 males and 3 females, and the age ranged from 20 to 52 years old, with an average age of 36.5 years old. The distance of tendon break was ≤10 mm. The operation time of the patients was 20-30 min, with an average of 24.5 min. The intraoperative blood loss was minimal. All 10 cases were followed up and the follow-up period was 6 to 12 months, with an average of 7 months. Mallet finger deformities were all corrected postoperatively, dorsal skin of fingers without a scar, there were no knot exposure, skin necrosis and other complications. At the last follow-up, the mean active range of motion of the distal interphalangeal joint was 84.4° and the mean TAM of the injured finger was 265.6°. According to TAM system assessment criteria: 8 cases were excellent, and 2 cases were good.Conclusions:Satisfactory therapeutic outcome for the treatment of tendinous mallet finger deformity can be achieved by the minimally invasive percutaneous quantitative suture technique eight times. It is a simple, safe, and effective method with minimal invasion.

Objective:To explore the effect of the treatment of tendinous mallet finger deformity by the minimally invasive percutaneous quantitative suture technique eight times.Methods:A retrospective analysis was performed on patients with fresh tendinous mallet fingers who underwent surgery in the Department of Hand and Foot Microsurgery of Nanjing Jiangbei Hospital from April 2021 to April 2022. During the procedure, the extensor digitalis tendon in the zone Ⅰ was sutured percutaneous with 3-0 thread monofilament sutures in the "quantitative 8-stitch method" according to the pre-marked number sequence of 1 to 8, and fixed at the base of the distal phalanx via a constructed bone tunnel. Removal of the Kirschner wire 8 weeks, the brace was used to fix the affected finger in the dorsal extension. The flexion and extension of the affected finger were gradually strengthened. The function of the affected finger was evaluated according to the Crawford standard after operation and follow-up: the active flexion and extension range of motion of each joint of the affected finger and the contralateral healthy finger was measured, and the total active ranges of motion of the finger were recorded. Finger function was evaluated according to the total active range of motion (TAM) system of the American Association of Hand Surgeons.Results:A total of 10 patients (10 digits) were enrolled, including 7 males and 3 females, and the age ranged from 20 to 52 years old, with an average age of 36.5 years old. The distance of tendon break was ≤10 mm. The operation time of the patients was 20-30 min, with an average of 24.5 min. The intraoperative blood loss was minimal. All 10 cases were followed up and the follow-up period was 6 to 12 months, with an average of 7 months. Mallet finger deformities were all corrected postoperatively, dorsal skin of fingers without a scar, there were no knot exposure, skin necrosis and other complications. At the last follow-up, the mean active range of motion of the distal interphalangeal joint was 84.4° and the mean TAM of the injured finger was 265.6°. According to TAM system assessment criteria: 8 cases were excellent, and 2 cases were good.Conclusions:Satisfactory therapeutic outcome for the treatment of tendinous mallet finger deformity can be achieved by the minimally invasive percutaneous quantitative suture technique eight times. It is a simple, safe, and effective method with minimal invasion.

Objective:To investigate the efficacy and safety of different dosage regimens of levosimendan in elderly patients with severe heart failure.Methods:Thirty-two patients 75 years or older were randomly divided into a loading dose group (16 cases) in which levosimendan was maintained at 0.1 μg·kg -1·min -1 for 24 h after loaded with 6 μg/kg, and a maintenance dose group (16 cases) with same schedule without loading dose. The amino-terminal brain natriuretic peptide (NT-proBNP) before and after treatment was detected. Left ventricular ejection fraction (LVEF), stroke volume (SV), stroke volume index (SVI) by echocardiograph were monitored. Adverse events, the length of stay in ICU and 28-day mortality were recorded. Results:The NT-proBNP level in loading group after treatment was 1 950 (922,6 481)ng/L, which was improved than that before treatment [4 018(2 716,9 637)ng/L, P<0.05]. The result was similar in maintenance group [1 390 (599,3 297)ng/L vs. 4 576 (2 681,10 682)ng/L, P<0.05]. LVEF in loading group before and after treatment was (39.4±8.8) % vs. (48.9±9.2) % respectively, while in maintenance group it was (40.4±8.8) % vs. (48.7±12.0) % (both P<0.05). SV were also improved after treatment in both groups compared with baseline levels ( P<0.05). NT-proBNP started to decline on day 3 in the loading group, while on day 7 in the maintenance group. SVI recovered on day 14 in the loading group [ (29.4±6.5) ml/m 2 vs. (27.3±6.7) ml/m 2, P<0.05], while it did not change much in the maintenance group. There was no significant differences as to the length of stay in ICU [ (11.1±4.4) d in loading group vs. (9.6±3.5) d in maintenance group] and 28-day mortality rates were comparable (2/16 in loading group vs. 1/16 in maintenance group) . The adverse events were 7 vs. 2 cases in loading group and maintenance group respectively, which were mild and all alleviated. Conclusion:The application of levosimendan only with maintenance dose improves cardiac function in very elderly patients with severe heart failure. Adverse events are mild and manageable.

Objective To investigate the effect of levosimendan on cardiac function and prognosis in elderly patients with septic myocardial contractility impairment.Methods A prospective,randomized,controlled study was conducted.The elderly patients with septic myocardial contractility impairment who were admitted to Intensive Care Unit in Zhejiang Hospital were consecutively enrolled from January 2017 to September 2017.The key inclusive criterion was left ventricular ejection fraction (LVEF) ≤ 50％ after fluid resuscitation.A total of 30 patients were randomly assigned to levosimendan group (n=15) and dobutamine group (n=15).Based onconventional treatment,intravenous dobutamine (5 μg per kilogram of body weight per minute) or levosimendan (0.2 μg per kilogram of body weight per minute)were continuously administrated for 24 hours in two groups.At 0 h,24 h,48 h,72 h after injection,the following parameters or values were recorded including serum lactic acid (Lac),and echocardiographic parameters such as LVEF,stroke volume (SV).The time of mechanical ventilation,length of stay in ICU and 28-day mortality were compared in two groups.Results Compared with dobutamine group,blood Lac at 24 h [(1.97±1.10)mmol/L vs.(2.73 ± 2.06) mmol/L,P=0.002] decreased significantlyin levosimendan group.LVEF and SV were significantly higher in levosimendan group at 24 h [LVEF:(47.93±5.01)％ vs.(45.60±5.47)％,P=0.004;SV:(47.73 ± 14.01) ml vs.(44.80±16.89) ml,P=0.035;respectively],48 h [LVEF:(51.07 ± 5.05)％ vs.(46.73 ± 6.34)％,P=0.004;SV:(49.87 ± 14.15) ml vs.(45.07± 16.94) ml,P=0.005;respectively] and 72 h [LVEF:(53.20±5.92)％ vs.(47.70±6.71)％,P=0.002;SV:(51.27±14.98) ml vs.(45.73±17.34) ml,P=0.010].The time of mechanical ventilation,length of stay in ICU and 28-day mortality were comparable between two groups (P＞0.05).Conclusions Levosimendan improves cardiac systolic function and tissue perfusion in elderly patients with septic myocardial contractility impairment.However,cardiac diastolic function,liver and kidney function are not further improved by levosimendan compare with dubutamine.Time of mechanical ventilation,length of stay in ICU and 28-day mortality in two groups are similar.

Objective To investigate the influence of left ventricular-arterial coupling(VAC) on clinical prognosis of elderly patients with septic shock.Methods A total of 56 elderly septic shoek patients were enrolled in this study,all of whom were admitted to Department of Intensive Care Unit in Zhejiang Hospital from August 2014 to October 2015.The patients were divided into two groups according to the status of left ventricular-arterial coupling when septic shock was diagnosed,which were left ventricular-arterial uncoupling group(UC group) and left ventricular-arterial coupling group(C group).Various parameters were recorded,including blood lactate level,central venous oxygen saturation(ScvO2),serum level of N-terminal pro-brain natriuretic peptide(NT-proBNP) and cardiac troponin Ⅰ (cTN Ⅰ),dose of vasoactive drugs,the total fluid volume and urine volume per hour within 24 hours.The 28-day survival rate was a key index of prognosis.Multivariate logistic regression was taken to analyze risk factors related to death within 28 day.Results Compared with C group,UC group had lower values of left ventricular ejection fraction[(42.43 ±4.76)％ vs (53.17±3.01)％;P＜0.01] and cardiac index[(2.36±0.68) L· min-1 · m 2vs (2.93±0.45)L · min-1 · m-2;P ＜0.01].Yet serum levels of NT-proBNP[lg NT-proBNP 3.93 ±0.53 vs 3.40 ±0.63;P =0.004] and cTN Ⅰ [lg cTN Ⅰ-0.16 ± 0.68 vs-1.03 ± 0.69;P ＜ 0.001] in UC group were higher than those in C group.Moreover,the total fluid volume within 24 hours [(3 806.3 ± 831.4) ml vs (3 142.0±770.0) ml;P =0.016],blood lactate level[(5.61 ±2.68) mmol/L vs (3.93 ± 1.59)mmol/L;P =0.043] and dose of norepinephrine[(0.630 ±0.300) μg · kg-1 · min-1 vs (0.292 ±0.234)μg · kg-1 · min-1;P =0.001] in UC group were greater than those in C group,while ScvO2 [(60.75 ±2.91)％ vs (64.42 ±2.19)％;P＜0.001] and urine volume per hour[(0.518 ±0.358) ml vs (0.926 ±0.678) ml;P =0.007] were less than those in C group.Compared with C group,UC group had a lower 28-day survival rate [43.2％ (19/44) vs 9/12;P =0.049].Ea/Ees ratio was negatively correlated with LVEF,ScvO2 (r =-0.686,P ＜ 0.001;r =-0.411,P =0.002),positively correlated with NT-proBNP,cTN Ⅰ (r =0.294,P =0.028;r =0.363,P =0.006),yet no obvious correlation was noticed with blood lactate level (r =0.170,P =0.21).Multiple logistic regression analysis showed that VAC(OR =11.187,95％ CI 2.489-50.285;P =0.002),lactate level (OR =1.727,95 ％ CI 1.164-2.563;P =0.007) and lg cTN Ⅰ (OR =0.247,95 ％ CI 0.079-0.779;P =0.017) were independent risk factors affecting 28-day mortality.Conclutions In elderly patients with septic shock,left ventricular-arterial uncoupling indicates a lower 28-day survival rate,worse cardiac function and tissue perfusion.Ea/Ees ratio might sever as a predictive indicator of 28-day mortality.

BACKGROUNDSevere sepsis and septic shock are the leading causes of morbidity and mortality in hospitalized patients. This study aimed to investigate the association of poly (ADP-ribose) polymerase-1 (PARP-1) activity in circulating mononuclear cells with myocardial dysfunction in patients with septic shock.

METHODSA total of 64 patients with septic shock were divided into the survival group (n = 41) and the nonsurvival group (n = 23) according to mortality at 28 days after enrollments. PARP-1 activity in circulating mononuclear cells, brain natriuretic peptide, Acute Physiology and Chronic Health Evaluation II score, the cardiac index (CI), the cardiac function index (CFI), global ejection fraction (GEF), and the left ventricular contractility index (dp/dt max) were measured after admission to the intensive care unit.

RESULTSPARP-1 activity in circulating mononuclear cells of nonsurvival patients with septic shock was significantly higher than that in survival patients. PARP-1 activity in circulating mononuclear cells was strongly, negatively correlated with the CI, the CFI, GEF, and dp/dt max. Multiple Logistic regression analysis showed that PARP-1 activity in circulating mononuclear cells was an independent risk factor of myocardial dysfunction. The optimal cutoff point of PARP-1 activity for predicting 28-day mortality was 942 nmol/L with a sensibility of 78.2% and specificity of 65.1%.

CONCLUSIONPARP-1 activity in circulating mononuclear cells is significantly associated with myocardial dysfunction and may have prognostic value in patients with septic shock.

Aged ; Aged, 80 and over ; Female ; Humans ; Leukocytes, Mononuclear ; enzymology ; Male ; Middle Aged ; Poly(ADP-ribose) Polymerases ; metabolism ; Shock, Septic ; enzymology

Objective To investigate the role of damaged mitochondria in cardiac cell apoptosis in septic rats and the possible mechanism involved.Methods Seventy-two Sprague-Dawley rats were randomly (random number) divided into negative control group (n =18) and septic group (further divided into three groups as per rats sacrificed 6 h,12 h,and 24 h after endotoxin injection intra-peritoneally,n =18).The hearts of rats were taken.The changes of cardiac morphology were observed under light microscope and scanning electron microscope.Cell apoptosis in situ were examined by using terminal transferase-mediated dUTP nick end-labeling assay and nuclear factor-kappa B (NF-κB) activation in myocardium was detected by using Western blotting to estimate myocardial cell apoptosis.Mitochondrial lipid and protein oxidation were measured to assess oxidative stress,and mitochondrial superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities were determined to estimate antioxidant defense.Results Septic induced inflammatory cells infiltration,myocardium degeneration and effusion in a time-dependent manner.A remarkable expansion of capillaries could be observed in the hearts of infected rats at post-challenge of 24 h.Compared with sham-treated rats,the percentage of apoptosis increased in a time-dependent manner in the hearts of infected rats at 6 h,12 h,24 h of post-injection (P ＜0.05).The concentration of NF-κB p65 in the cytosol decreased gradually and increased in the nucleus during sepsis in a time-dependent manner (P ＜0.05),indicating that septic challenge provoked progressive activation of NF-κB.Mitochondrial cristae disappeared in 6 h of challenge,and significant mitochondrial cristae disappearance,vacuolization,and rupture of mitochondria membrane became markedly obvious 12 and 24 h later.Both SOD and GPx activities decreased,while mitochondrial lipid and protein oxidation increased in a time-dependent manner after 6-24 h of challenge (P ＜ 0.05).Conclusions Septic challenge induced myocardial apoptosis and mitochondrial damage.Further,damaged mitochondria might play an important role by means of alteration of defenses against reactive oxygen species in myocardial cell apoptosis during sepsis.

Objective To investigate the clinical values of central venous pressure (CVP) versus stroke volume variation (SVV) in patients with severe sepsis after early goal-directed therapy (EGDT).Methods Totally 30 mechanically ventilated patients with severe sepsis who underwent goal-achieved EGDT were enrolled and randomly divided into CVP group (study group) and SVV group (control group) according to the data detected by pulse contour continuous cardiac output (PiCCO) analysis device.The differences in 28-day survival,3-day APACHE Ⅱ score,time of ICU stay,duration of mechanical ventilation,number that need CRRT,entral venous pressure (CVP),heart end-diastolic volume index (GEDVI),intrathoracic blood volume index (ITBVI),extravascular lung water index (EVLWI),cardiac index (CI),central venous oxygen saturation (ScvO2),lactate clearance rate and APACHE Ⅱ score were compared between the 2 groups.Results The death rate had no difference between the 2 groups(x2=0.240,P=0.624).Among survival patients in the CVP group,the time of ICU stay and duration of mechanical ventilation were shorter in study group than in control group(t=2.166,P=0.041;t=2.104,P=0.046),APACHE Ⅱ score at 3th day was decreased(t=2.20,P =0.038).The values of ITBVI,GEDVI,CI,lactate clearance rate were higher in study group than in control group (t=2.759,2.146,2.199,2.654,3.362,P=0.011,0.043,0.038,0.014,0.003).EVLWI and APACHE Ⅱ score were not different (P＞0.05) between the two groups.Conclusions SVV as a recovery target for fluid resuscitation can reach a better recovery results and improvement of prognosis than CVP goal-achieved EGDT.

Objective To explore the significance of the plasma procalcitonin (PCT) level for directing antibiotic therapy in elderly patients with ventilator-associated pneumonia (VAP).Methods The 50 elderly patients with VAP were randomly separated into the regular therapy group and the PCT-directed therapy group. The regular therapy group was given regular antibiotic therapy, while the antibiotic therapy was decided according to the plasma level of PCT in the PCT-directed therapy group. The used time and utilization rate of antibiotics, as well as inflammatory indicators including white blood cells, neutrophils, C-reactive protein (CRP) and clinical pulmonary infection score (CPIS) were compared between the two groups. Results After treatment, there were no significant differences in white blood cells, neutrophils and CRP between the PCT-directed therapy group and regular therapy group [(8.9 ± 3.5 ) × 109/L vs. (9.4 ± 3.7) × 109/L, 0.62 ± 0.04 vs.0.60±0.04, (18.7±8.5) mg/Lvs. (21.6±6.0) mg/L, t=0.47, 1.84 and 1.37, allP＞0.05],but the CPIS was markedly lower in PCT-directed therapy group than in regular therapy group [(4.0± 1.4) scores vs. (4.7± 1.0) scores, t= 2. 18, P＜0.05]. The neutrophils, CRP and CPIS were significantly lower after treatment than before in the both groups. The concentration of PCT was decreased after treatment than before [(0.5 ± 0.9) mg/L vs. (1.7 ± 0.7) mg/L]. Meanwhile, the time using antibiotics was longer in regular treatment group than in PCT-directed therapy group [(8.72±1.32) d vs. (5.17±0.72) d, t=11.96, P＜0.01], the utilization rate of antibiotics was higher (95.2 % vs. 55.2 %, χ2 = 12.41, P＜0.01) in regular treatment group. Conclusions Using PCT levels for directing treatment in elderly patients with VAP can achieve better curative effect and reduce the use of antibiotics.