Objective To investigate the balance between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in the lung tissue in a rat model of ventilator-induced lung injury. Methods Thirty healthy male SD rats weighing 200-250g were randomly divided into 3 groups( n = 10 each) : group A spontaneous breathing; group B small tidal volume (VT = 7 ml?kg-1, RR = 40 bpm, FiO2=0.21) and group C large tidal volume (VT = 40 ml?kg-1, RR = 20 bpm, FiO2=0.21). The animals were mechanically ventilated for 4 h in group B and C. The lung injury was assessed by measurement of PaO2 /FiO2 . At the end of the experiment the animals were killed and the lungs were removed. The right lung was used for determination of the expression of mRNAs of MMP-2, MMP-9, TIMP-1 and TTMP-2 using RT-PCR and histologic examination. The left lung was weighed and then lavaged. The broncho-alveolar lavage fluid (BALF) was collected for total WBC and neutrophil counts and determination of total protein content and gelatinase activity. After lavage the left lung was heated at 60℃. The W/D lung weight ratio was calculated. Results PaO2/FiO2 was significantly lower after 4h mechanical ventilation in group C than in group A and B. The total WBC count and total protein content in BALF were significantly higher in group C than in group A and B. The W/D ratio of the left lung was significantly higher in group C than in group A and B. Microscopic examination showed that there were marked WBC infiltration and destructive changes of alveolar walls in group C. The levels of gelatinase (MMP-2 and MMP-9) activities in BALF were significantly higher in group C than in group A and B. The expression of the mRNA of MMP-2 and MMP-9 was significantly higher in group C than in group A and B, but there was no significant difference in the expression of the mRNA of TIMP-1 and TIMP-2 between group C and group A and B. Conclusion Large tidal volume ventilation can induce acute lung injury. MMP-2 and MMP-9 play an important role in the development of ventilator induced lung injury and the imbalance between MMPs and TIMPs contributes to the mechanism of ventilator-induced lung injury.

Objective To investigate the efficacy of small interfering RNA against Pseudomonos aeruginosa expressing MexA-MexB-OprM multidrug efflux pump in vivo.Methods Two short hairpin (sh)RNA expression vectors targeting the MexB gene,and negative controls,were designed,synthesized,and electrotransformed into the P.aeruginosa strain PAO1.The in vivo therapeutic efficacy of the MexB small interfering (si)RNAs was determined by infecting a murine model of chronic P.aeruginosa lung infection (1 × 107 CFU/ml).The mice were killed on day 3,5 and 7 after infection with the Pseudomonas aeruginosa strains.Results In the murine infection model,treatment with MexB-siRNAs led to significantly reduced bacteria burden of the bellows by day 5 and 7 post-infection,and reduced the P.aeruginosa-induced pathological changes.In addition,MexB-siRNA2 treatment enhanced neutrophil recruitment and production of inflammatory cytokines (IL-1β,IL-12) in the early infection stage (day 3) (P＜0.05),both of which decreased by day 7.Conclusion MexB-siRNA could inhibit both mRNA expression and the activity of P.aeruginosa in vitro.siRNA was effective in reducing the bacterial load in a murine model of chronic lung infection.Targeting of MexB with siRNA appears to be a novel strategy for treating P.aeruginosa infections.

ObjectiveTo investigate the early clinical risk factors of severe acute inhaled organic fluorine poisoning.Methods The clinical data of patients with acute poisoning of organic fluorine inhalation admitted since 2004 in Northern Jiangsu People's Hospital were retrospectively analyzed. According toDiagnostic Criteria of Occupational Acute Fluorohydrocarbon Poisoning(GBZ66-2002), all the patients were divided into three groups: mild, moderate and severe poisoning groups, the severe cases were included in the intensive group, and the others were grouped in the non-intensive group. The contents in the survey were as follows: gender, age, vital signs on admission (body temperature, pulse rate, respiratory rate, systolic blood pressure), arterial blood gas analysis record〔arterial oxygen saturation(SaO2), oxygenation index(PaO2/FiO2), lactic acid(Lac) and arterial partial pressure of carbon dioxide(PaCO2), pH value(pH)〕. Before treatment, the white blood cell(WBC) count, platelet(PLT) count, levels of alanine transaminase(ALT), creatinine(Cr), blood glucose, electrolytes(potassium, sodium, chloride, calcium), creatine kinase isoenzyme(CK-MB), etc. were examined and recorded. All the patients were immediately arranged for bedside chest X-ray examination, and the chest X-ray lung injury scores were recorded. By univariate and multivariate logistic regression analyses, the receiver operating characteristic curve(ROC curve) was drawn to evaluate the diagnostic value of the clinical risk factors.Results Sixty-two cases consisting with the standard criteria of enrollment were collected in the study, 36 cases being in intensive group and 26 cases in non-intensive group. The univariate analysis showed that the differences in pulse rate, respiratory rate, PaO2/FiO2, WBC, SaO2, Lac, pH, and lung injury score were statistically significant(P<0.05 orP<0.01). Logistic multiple regression analysis showed that PaO2/FiO2, WBC, Lac and chest X-ray lung injury score were the four indexes for predicting the independent risk factors of severe acute inhaled organic fluorine poisoning. The area under ROC curve(AUC) of PaO2/FiO2 was the highest(0.884), 95% confidence interval(95%CI) was 0.784 - 0.984, the critical value was 96.5 mmHg(1 mmHg=0.133 kPa), with the sensitivity of 75.6%, specificity of 95.2%, positive predictive value(PPV) of 92.3% and the negative predictive value(NPV) of 71.4%, in sequence, the rest were WBC(AUC 0.846, 95%CI 0.728 - 0.965, the criticalvalue 12.15×109/L), Lac(AUC 0.800, 95%CI 0.662 - 0.938, the critical value 4.2 mmol/L), chest X-ray lung injury score(AUC 0.795, 95%CI 0.652 - 0.938, the critical value 2.50), the sensitivity of the above three items was 90.2%, 83.6%, 88.5%, specificity was 90.2%, 83.6%, 88.5%, the PPV was 86.7%, 82.4%, 85.8% and NPV was 72.0%, 73.9%, 69.2% respectively.ConclusionThe blood WBC count, Lac, PaO2/FiO2 and chest X-ray lung injury score can be used as the early clinical risk factors of severe acute inhaled organic fluorine poisoning.

Objective To investigate the expression change of LRP16 in endometrial cancer tissues and its influence on the pro-liferation of human endometrial carcinoma HEC-1-B cells .Methods HEC-1-B cells were transfected with LRP16 .RT-PCR was used to examine the expression of LRP16 in 26 normal endometrium specimens ,10 endometrial cancer specimens .RT-PCR was used for verifying the transfection success .WES-T was used to observe the proliferation change of HEC-1-B cells .Results The positive expression rate and level of LRP16 mRNA in the endometrial cancer tissues were 83 .33% and 0 .82 ± 0 .21 ,which were significantly higher than 30 .00% ,0 .47 ± 0 .18 in the normal endometrium tissues(P<0 .05) .The RT-PCR detection results revealed that the expression of LRP16 mRNA after transfection was significantly increased .HEC-1-B cells in the transfection group could continued to proliferate in vitro ,but the proliferation capacity was not increased .Conclusion The expression abnormality of LRP16 may be closely related to the occurrence and progress of endometrial cancer ,LRP16 gene may have potential value for the endometrial canc-er gene therapy .

OBJECTIVETo compare the susceptibility of Porphyromonas gingivalis to metronidazole at different planktonic cell densities and in biofilm, and to evaluate the role of cell density in antibiotic drug resistance in Porphyromonas gingivalis biofilm.

METHODSThe minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) of metronidazole against Porphyromonas gingivalis were detected by a broth dilution method under a final inocula of 10(6) CFU x mL(-1) and 10(9) CFU x mL(-1) (cell number equal to biofilm). After the initial biofilm formed in the microtiter plate wells, the MIC and MBC of metronidazole to the intact and succedent resuspended biofilm were determined.

RESULTSThe MIC and MBC of metronidazole against 10(6) CFU x mL(-1) planktonic Porphyromonas gingivalis were 0.063, 0.125 mg x L(-1) respectively. However, those against 10(9) CFU x mL(-1) planktonic Porphyromonas gingivalis were 25, 50 mg x L(-1). Against intact Porphyromonas gingivalis biofilm, the MIC was 25 mg x L(-1) and MBC was higher than 125 mg x L(-1), those against resuspended biofilm was 25, 125 mg x L(-1) respectively.

CONCLUSIONThe resistance of Porphyromonas gingivalis to metronidazole increases along with the augment of the bacterial density. Cell density plays an important role in the resistance of biofilm. However, extracellular matrix and the integrity of biofilm may be the other influence factors for the biofilm resistance.

Anti-Bacterial Agents ; Biofilms ; Cell Count ; Metronidazole ; Microbial Sensitivity Tests ; Porphyromonas gingivalis

Objective To observe the effect of different airway pressure on ventilation, organ perfusion and return of spontaneous circulation (ROSC) of cardiac arrest (CA) pigs during cardiopulmonary resuscitation (CPR), and to explore the possible beneficial mechanism of positive airway pressure during CPR. Methods Twenty healthy landrace pigs of clean grade were divided into low airway pressure group (LP group, n = 10) and high airway pressure group (HP group, n = 10) with random number table. The model of ventricular fibrillation (VF) was reproduced by electrical stimulation, and mechanical chest compressions and mechanical ventilation (volume-controlled mode, tidal volume 7 mL/kg, frequency 10 times/min) were performed after 8 minutes of untreated VF. Positive end expiratory pressure (PEEP) in LP group and HP group was set to 0 cmH2O and 6 cmH2O (1 cmH2O = 0.098 kPa) respectively. Up to three times of 100 J biphasic defibrillation was delivered after 10 minutes of CPR. The ROSC of animals were observed, and the respiratory parameters, arterial and venous blood gas and hemodynamic parameters were recorded at baseline, 5 minutes and 10 minutes of CPR. Results The number of animals with ROSC in the HP group was significantly more than that in the LP group (8 vs. 3, P < 0.05). Intrathoracic pressure during chest compression relaxation was negative in the HP group, and its absolute value was significantly lower than that in LP group at the same time [intrathoracic negative pressure peak (cmH2O): -4.7±2.2 vs. -10.8±3.5 at 5 minutes, -3.9±2.8 vs. -6.5±3.4 at 10 minutes], however, there was significantly difference only at 5 minutes of CPR (P < 0.01). Intrathoracic pressure variation during CPR period in the HP group were significantly higher than those in the LP group (cmH2O: 22.5±7.9 vs. 14.2±4.4 at 5 minutes, 23.1±6.4 vs. 12.9±5.1 at 10 minutes, both P < 0.01). Compared to the LP group, arterial partial pressure of oxygen [PaO2 (mmHg, 1 mmHg = 0.133 kPa): 81.5±10.7 vs. 68.0±12.1], venous oxygen saturation (SvO2: 0.493±0.109 vs. 0.394±0.061) at 5 minutes of CPR, and PaO2 (mmHg: 77.5±13.4 vs. 63.3±10.5), arterial pH (7.28±0.09 vs 7.23±0.11), SvO2 (0.458±0.096 vs. 0.352±0.078), aortic blood pressure [AoP (mmHg): 39.7±9.5 vs. 34.0±6.9], coronary perfusion pressure [CPP (mmHg): 25.2±9.6 vs. 19.0±7.6], and carotid artery flow (mL/min:44±16 vs. 37±14) at 10 minutes of CPR in the HP group were significantly higher (all P < 0.05). Arterial partial pressure of carbon dioxide (PaCO2) in the HP group was significantly lower than that in the LP group at 10 minutes of CPR (mmHg: 60.1±9.7 vs. 67.8±8.6, P < 0.05). Conclusions Compared to low airway pressure, a certain degree of positive airway pressure can still maintain the negative intrathoracic pressure during relaxation of chest compressions of CPR, while increase the degree of intrathoracic pressure variation. Positive airway pressure can improve oxygenation and hemodynamics during CPR, and is helpful to ROSC.

Objective To investigate the expression and clinical significance of platelet activating factor [PAC]-1, CD62P and TPP hi severe sepsis. Method Patients with severe sepsis who were admitted into the EICU of Subei People's Hospital from April 2007 to March 2008 were included. Patients with severe sepsis (Group Ⅲ)were treated according to the treatment guidelines for severe sepsis, and were divided, according to their clinical records, into those who survived and those who died within 28 days of admission. Patients admitted during the same period with symptoms of infection but without severe sepsis were included as the General Infected Group (Group Ⅱ). A Control Group (Group Ⅰ) comprised patients who visited the hospital over the same period for physical examination or the healthy volunteers. The group members were all included randomly, and the gender and sex of patients in all three groups were similar. Patients with acute brain infarction, acute coronary syndrome,serious diabetes, hyperlipidemia, malignant tumor, leukemia, primary liver, renal and hematopoietic system dis-eases,long-term bedridden patients, pregnant women, and patients taking hormone treatment or hranunosuppres-sants were excluded from the study. Morning venous blood was collected and ELISA and Flow Cytometry performed on the fwst day of admission for Groups Ⅰ- and Ⅱ, and on the first, third and fifth day after admission for Group Ⅲ, to determine the TpP,PAC-1 and CD62P respectively; and the Marshall score was determined. Data were ana-lyzed by SPSS 12.0 software. For continuous variables, comparisons among groups were analyzed by ANOVA.Levene's and LSD test were applied to assess homogeneity. Bivariate test is applied to Correlation Analysis. P<0.05 was regarded as a statistically significant difference. Results There were a total of 20 patients each in GroupⅠ-and GroupⅡ, and 30 in Group Ⅲ; of these, 19 were classed as survivors and 11 died during the 28-day peri-od. On the first day of admission, there were no significant differences in PAC-1, CD62P or TpP expression between Groups Ⅰ- and Ⅱ(P>0.05); however, Group Ⅲ was significantly different compared with both Group Ⅰ and Group Ⅱ (both:P<0.05). The expression of PAC-1, CD62P and TpP tended to decline in the survivor group,and became normal with the treatment process, while the expression of PAC-1 ,CD62P and TpP in the patients who died remained high, and even increased significantly over time. On the first day, the expression of CD62P and TpP in the patients who survived and in those who died was not significantly different (P>0.05); on the third day,however, a significant difference appeared with values of (2.89±1.48) % vs. (5.04±2.57) % (P<0.01) for CD62P, and (5.24±2.22) mg/L vs. (9.20±1.93) mg/L (P<0.01) for TpP. The expression of PAC-1 was significantly different between the two subgroups on the first day, with values of (3.15±0.42)% vs. (5.30±.48)% (P<0.01). The Marshall score of the two groups showed similar changes. Correlation analysis showed that PAC-1, CD62P and TpP were significantly correlated with the Marshall score. Conclusions Platelet activation and microthrombosis existing in the early stage of severe sepsis work together in the early hypercoagulable state.They both play important roles in disease development and progression. The dynamic detection of CD62P and TpP is beneficial to the diagnosis and prognosis of severe sepsis.PAC-1 appears to hold a risk stratification effect, as pa-tients with high expression of PAC-1 in the early stage show poor prognosis. Therefore, PAC-1 could be used as a marker of severe sepsis and poor prognsis.

OBJECTIVETo explore the quantitative relationship between the intensity of psychosocial stress and the degree of overall health damages.

METHODSA multi-group case-control study was designed and implemented. The cases included two groups of out-patients (177) and in-patients (214) in a hospital in Jianyang city, and controls (587) were from the follow-up cohort in the same city. Three groups were studied on the following contents: general demographic characteristics, psychosocial factors and the degree of health damages including mental, physical, and social status. Major statistical analyses were as follows: ranks test, ANOVA, cluster analysis, multinomial logistic regression and ordered-logit regression.

RESULTSOrdered-logit regression model showed that the odds ratio of negative life-events on degree of health damages was 1.335 (P < 0.01). This result showed that there was a positive dose-effect relationship between the negative life-events score and overall health damages. The utility of social support to overall health had protective effect (OR = 0.513).

CONCLUSIONNegative life-events were the major risk factors to overall health, and there was a dose-effect relationship between negative events and health damages. Function of social support played a protective factor for health.

Analysis of Variance ; Case-Control Studies ; Cohort Studies ; Educational Status ; Health Status ; Humans ; Marital Status ; Social Class ; Stress, Psychological ; psychology

Objective To explore the effect of fish oil fat emulsion as perioperative nutritional support on patients with liver cirrhosis and portal hypertension.Methods Randomized controlled clinical trial was performed between September 2011 and September 2017 in patients with liver cirrhosis and portal hypertension who underwent pericardial devascularization and splenectomy.Hypocaloric total parenteral nutritional support (TPN) started from the first day after the operation for 5 consecutive days.Patients were divided into experimental group and control group according to thetype of fat emulsion used.43 patients in experimental group were applied for fish oil fat emulsion injection (10％ Omegaven) + medium long chain structure fat emulsion (20％STG) and 42 patients in control group were applied for medium long chain structure fat emulsion (20％STG).Liver function (total bilirubin and alanine aminotransferase),nutrition index (serum albumin and prealbumin),inflammatory mediators (TNF-α,IL-6 and IL-10) were measured before and after the operation,and the clinical outcomes were observed.Results There was no statistically significant difference in liver function and nutritional indices between the experimental group and the control group (P＞0.05).The inflammatory mediators like TNF-u,IL-6 and IL-10 on the first day after surgery were significantly higher than those before surgery in both groups [experiment group:(225.54±54.78) vs.(61.49±16.47),(74.94±6.36) vs.(39.84±2.77),(77.53±11.4) vs.(46.05±6.13) ng/L;control group:(229.26±62.15) vs.(63.48±13.76),(77.23±7.83)vs.(40.64±3.34),(73.89±7.97)vs.(44.88±5.72) ng/L;P＜ 0.01].With the progress of time,the proinflammatory factors like TNF-α and IL-6 decreased after the operation and the range of decrease was higher in experiment group than in control group [d4-d 1:(-56.88± 31.63) vs.(-35.96±20.02),(-13.52±5.20) vs.(-6.38±2.84) ng/L;d7-d1:(-150.67±42.58) vs.(-132.79±53.35),(-27.04±8.97) vs.(-20.85±6.38) ng/L;P＜ 0.05].The range of increase in anti-inflammatory media IL-10 was higher in experiment group than in the control group (d4-d1:(14.22±13.08) vs.(5.64±3.58) ng/L;d7-d1:(17.78±5.58) vs.(-37.96±11.43) ng/L;P＜0.05).The incidence of grade Ⅲ complications and total complications (4.7％ vs.21.4％,23.3％ vs.45.2％) and hospitalization time [(10.12 ±1.48) vs.(12.33±2.04) d] in the experimental group were significantly lower than those in the control group (P＜0.05).Conclusions In patients with liver cirrhosis and portal hypertension,perioperative nutritional support of fish oil fat emulsion can reduce systemic inflammatory response and operative complications and promote rapid recovery through its two-way regulation of inflammatory mediators.

OBJECTIVE: To investigate the clinical and genetic characteristics of a patient with STISS syndrome due to variant of PSMD12 gene. METHODS: Clinical data and result of genetic testing of a patient who was admitted to Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine on October 4, 2020 were analyzed, together with a review of relevant literature. RESULTS: The patient was found to harbor a heterozygous c.601C>T (p.Arg201*) nonsense variant of the PSMD12 gene, which was unreported previously. Clinically, the height of the patient has differed significantly from reported in the literature. An extremely rare case of STISS syndrome due to variant of the PSMD12 gene has been diagnosed. CONCLUSION Whether the severely short stature is part of the clinical spectrum for PSMD12 gene variants needs to be further explored, and the efficacy and safety of growth hormone therapy has yet to be determined.
Child ; Humans ; China ; Dwarfism ; Genetic Testing ; Heterozygote ; Syndrome