ObjectiveTo reproduce a clinically relevant two-hit model of sepsis complicated by pneumonia and to explore the correlation between two-hit and immune state.Methods Eighty-one male Sprague-Dawley ( SD ) rats were divided into groups according to the random number table. Forty-five male rats were assigned respectively to sepsis-alone group, pneumonia 4 days and 7 days after sepsis groups, respectively. Survival rate of each group was observed. Another group of 36 male rats were divided into normal control group, sepsis-alone for 1, 4 and 7 days groups, and sepsis complicated by pneumonia for 4 days and 7 days after sepsis groups, each group consisted of 6 rats. Cecal ligation and puncture (CLP) was done in rats, andStreptococcus pneumoniae suspension (bacteria count 1×1010 cfu/mL) was injected via the nose on the 4th day or 7th day after CLP. Rats were sacrificed at corresponding time points, and 1 day after challenge ofStreptococcus pneumoniae on the 4 days or 7 days post CLP for the collection of blood and tissue samples to make bacterial count of the blood, splenocyte count, biochemical indices, cytokines concentration, pathological changes in spleen and apoptotic cells.Results① Compared with the rats of sepsis-alone group, the rats in pneumonia 4 days after CLP group had poor survival rate (4 vs. 11,χ2 = 6.533,P = 0.011), while no difference was found between pneumonia 7 days after CLP group and sepsis-alone group (9 vs. 11,χ2 = 0.600,P = 0.439).② The blood bacterial count and all the biochemical indexes were sharply increased on 1 day post-CLP in the rats of sepsis-alone group, and then they gradually lowered. Compared with the rats of 1 day post-CLP, the proportion of splenocytes were decreased on the 4th day post-CLP [dendritic cells (DC): (0.69±0.09)% vs. (0.87±0.31)%, CD4+T cells: (21.05±2.89)% vs. (24.84±4.59)%, CD8+ T cells: (10.62±1.79)% vs. (13.40±1.31)%, allP< 0.05], but T-regulatory cell (Treg) count was higher on the 4th day after CLP compared with sepsis-alone rats [(3.14±0.74 )% vs. (2.87±1.08)%,P< 0.05]. The biochemical indices, including alanine transaminase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), and serum creatinine (SCr) were obviously lowered on 7 days post-CLP compared with 1 day after CLP [ALT (U/L): 35.33±11.52 vs. 81.00±38.40, AST (U/L): 70.33±42.16 vs. 156.00±28.11, BUN (mmol/L): 5.30±2.27 vs. 9.13±4.04, SCr (μmol/L): 55.33±10.67 vs. 96.67±45.79, allP< 0.05]. The serum levels of tumor necrosis factor-α (TNF-α) and interleukins (IL-6, IL-1β) peaked on the 1st day after CLP [TNF-α:(18.03±2.88) ng/L, IL-6: (10.37±4.20) ng/L, IL-1β: (102.44±51.46) ng/L], and high mobility group box-1 (HMGB1) peaked on the 4th day after CLP [(1.76±0.71)μg/L]. The levels of anti-inflammatory cytokines transforming growth factor-β1 (TGF-β1 ) and soluble tumor necrosis factor receptor-Ⅰ (sTNFR-Ⅰ) maintained at high levels [7 days post-CLP: TGF-β1 was (0.90±0.56) ng/L, sTNFR-Ⅰ was (1.56±0.39) ng/L]. The spleen pathology became more marked with the time in the group of sepsis-alone, meanwhile the number of apoptotic spleencytes increased 4 days post-CLP as compared with that of the 1st day post-CLP (cells/HP: 52.99±20.79 vs. 16.05±3.28,P< 0.05).③ Compared with the same period of sepsis-alone group, the rats with pneumonia 4 days post-CLP group showed a higher blood bacterial count (log cfu/mL: 1.78±0.54 vs. 0.25±0.18,P< 0.05), while no difference was found between 7-day of post-CLP pneumonia group and sepsis-alone group (log cfu/mL: 0.57±0.46 vs. 0.13±0.12,P> 0.05). The same trend of changes, with slight reduction in splenocytes and biochemical indices were found between the groups of sepsis followed by pneumonia and sepsis-alone, but no significant difference was found. The level of HMGB1 in the 4-day group of sepsis with complication of pneumonia was further decreased compared with sepsis-alone group (μg/L:1.17±0.74 vs. 1.76±0.71,P< 0.05), and IL-1β in the 7-day group of sepsis complicated pneumonia was further higher than those of sepsis-alone group in the same period (ng/L: 105.73±25.06 vs. 61.04±31.29,P< 0.05), while there were no differences in levels of other cytokines between two-hit group and sepsis-alone group. Apoptosis of spleencytes in the 4-day group of sepsis complicated pneumonia was more marked than that of sepsis-alone group at the same period (cells/HP: 74.48±22.47 vs. 52.99±20.79,P< 0.05), while no difference was found between the 7-day groups of sepsis complicated pneumonia and the sepsis-alone group (cells/HP: 28.70±4.13 vs. 30.43±14.55, P> 0.05).Conclusions The mortality of this two-hit model with complication of pneumonia 4 days after CLP was significantly higher than that of single sepsis model. The ability of bacteria clearance was decreased, and immunocyte apoptosis was exacerbated. These findings may be with the result of the occurrence of immunoparalysis in the mid stage of sepsis. The two-hit model reproduced on 7 days after CLP might suggest reconstruction of host immune function, and maybe associated with the recovery of immune response.

Objective To investigate the value of serum cholinesterase (S-ChE) levels in judgment of severity and prognosis in patients with severe pneumonia. Methods The clinical data of patients with severe pneumonia, who were admitted to the Department of Internal Medicine in the First Affiliated Hospital of Sun Yat-sen University, or the Department of Neurology in the Third People's Hospital of Foshan from May 2011 to May 2015, whose hospital time was longer than 24 hours, were retrospectively analyzed. They were divided into survival group and death group according to the final outcome. Lab data, acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score, multiple organ dysfunction syndrome (MODS) score, the improved pneumonia score of British Thoracic Society (confusion, uremia, respiratory, blood pressure, age 65 years, CURB-65), and S-ChE levels of all patients were collected after they were hospitalized into the intensive care unit (ICU) within 24 hours. Independent risk factors for prognosis were analyzed by binary logistic regression analysis, and receiver operating characteristic curve (ROC) was plotted. Best truncation point analysis was used to compare their estimated value for prognosis of patients with severe pneumonia. Results Eighty-six patients with severe pneumonia were studied. Among them 46 patients survived, and 40 patients died. By the single factor analysis, the following lab data in the death group were found significantly lower than those in the survival group: S-ChE levels (kU/L: 2.748±0.826 vs. 4.489±1.360, t' = 7.274, P = 0.000), arterial partial pressure of oxygen [PaO2 (mmHg, 1 mmHg = 0.133 kPa): 52.55±18.29 vs. 60.83±16.65, t = 2.196, P = 0.031], oxygenation index (mmHg: 114.20±48.01 vs. 167.10±69.68, t' = 4.229, P = 0.000), and carbon dioxide combining power [CO2-CP (mmol/L): 22.85±5.44 vs. 26.00±7.63, t' = 2.225, P = 0.029]. The following clinical data were significantly higher in the death group than those in the survival group, namely body temperature (℃: 38.67±1.18 vs. 37.74±1.18, t = -3.627, P = 0.000), pulse (bpm: 130.65±15.72 vs. 107.26±19.61, t' = -6.133, P = 0.000), the ratio of concomitant chronic lung disease [45.0% (18/40) vs. 13.0% (6/46), χ2 = 10.860, P = 0.001], fraction of inspired oxygen [FiO2: 0.495 (0.410, 0.600) vs. 0.380 (0.290, 0.500), Z = -3.265, P = 0.001], APACHE Ⅱ score (25.80±5.07 vs. 16.39±5.12, t =-8.540, P = 0.000), CURB-65 score [3 (3, 4) vs. 2 (1, 2), Z = -5.562, P = 0.000], MODS score (8.15±2.49 vs. 4.35±2.01, t = -7.832, P = 0.000), international normalized ratio [INR: 1.22 (1.08, 1.31) vs. 1.07 (1.00, 1.10), Z = -4.231, P = 0.000], and activated partial thromboplastin time [APTT (s): 33.80 (32.13, 38.75) vs. 28.50 (25.70, 36.00), Z = -3.482, P = 0.000]. Binary logistic regression analysis showed that, S-ChE levels, APACHE Ⅱ score and MODS score were found to be the independent risk factors for prognosis in the patients with severe pneumonia, respectively [S-ChE: odds ratio (OR) = 0.084, 95% confidence interval (95%CI) = 0.017-0.424, P = 0.003; APACHE Ⅱ score: OR = 1.675, 95%CI = 1.098-2.556, P = 0.017; MODS score: OR = 2.189, 95%CI = 1.262-3.800, P = 0.005]. The area under ROC (AUC) for S-ChE levels, APACHE Ⅱ score and MODS score were 0.874±0.036, 0.889±0.033 and 0.884±0.035, respectively (all P > 0.05 as compared between any two means). At the best truncation points of S-ChE levels, APACHE Ⅱ score and MODS score were 3.372 kU/L, 19.5 score, and 6.5 score respectively. The sensitivity, specificity, positive predictive value and negative predictive value in predicting death risk in patients with severe pneumonia were (80.0%, 78.0%, 76.19% and 81.82%), (95.0%, 70.0%, 73.08% and 94.12%) and (70.0%, 91.0%, 87.50%, 77.78%), respectively. If S-ChE levels was combined with APACHE Ⅱ score or combined with MODS score, the sensitivity, specificity, positive predictive value and negative predictive value [S-ChE levels combined APACHE Ⅱ score: 100%, 92.0%, 93.75% and 100%; S-ChE levels combined MODS score: all 100%] were higher than single power of S-ChE levels, APACHE Ⅱ score or MODS score. Conclusions S-ChE levels can be considered as an effective and practical index to estimate the severity and prognosis in patients with severe pneumonia. The combined application of S-ChE levels and APACHE Ⅱ score or MODS score can obviously improve the prognostic power in patients with severe pneumonia.

Objective To investigate the clinical efficacy and safety of transcatheter arterial chemoemblization (TACE) using raltitrexed and lobaplatin in treating advanced hepatocellular carcinoma (HCC).Methods From March 2009 to November 2014,95 cases were treated by raltitrexed combined with lobaplatin (raltitrexed group) through TACE and 124 cases by fluorouracil combined with oxaliplatin (fluorouracil group) through TACE.Disease control rate (DCR),median progression-free survival (mPFS) time and median overall survival (mOS) time were compared between the two groups.Survival rate were analyzed using Kaplan-Meier method and Log-rank analysis in SPSS 16.0.Results The disease control rate of raltitrexed group was 91.6％ (87/95),compared with fluorouracil group of 84.6％ (105/124) in fluorouracil group (x2 =2.505,P =0.474).The mPFS of raltitrexed group was 6.8 months and that of fluorouracil group was 5.9 months (x2 =5.542,P =0.019);mOS of raltitrexed group was 13.6 months and fluorouracil group was 11.4 months (x2 =5.953,P =0.015).The main adverse reactions in the two groups were not statistically significant (P ＞ 0.05).Conclusions TACE using rahitrexed and oxaliplatin prolongs the progression free survival and overall survival time of patients with advanced hepatic carcinoma.

Objective To study the outcomes and influencing factors of the conversion from normal glucose tolerance -hyperinsulinemia (NCT-HINS) to diabetes in the population of a community in Beijing.Methods All the subjects investigated received 75 g oral glucose tolerance test (OGTT) for diabetes screening carried out in May, 2006 and May, 2008. Data were calculated to analyze the outcomes and influencing factors of the conversion. HINS was diagnosed if fasting serum insulin & 15 mIU/L and/or 2-hour serum insulin after glucose loading ≥ 80 mIU/L Results The prevalence of NGT-HINS in the community in 2006 and 2008 was 5.28% and 8.67% (P<0.01) respectively and that of diabetes mellitus (DM) and impaired glucose regulation (IGR) was 3.52% , 6.56% in 2006 and 4.42% ,6.47% in 2008.The probability of the conversion from NGT-HINS to IGR and DM was 18.6% and 2.3% , being much higher than that from normal glucose tolerance- normoinsulinemia (NGT-NINS) (5.4% and 0.7% , P <0.01). However, the probability of the conversion from NGT-HINS to DM was 2.3% , which was much lower than that from IGR (26.3% , P <0.01). The reason might be that individuals with NGT-HINS had a higher waist circumference, BMI, fasting plasma glucose, 2 h plasma glucose and TG but a lower HDL-C than individuals with NGT-NINS in 2006. The HOMA β-cell function index/HOMA insulin resistance index (HBCI/IR) of individuals with NGT-HINS was much lower than that of individuals with NGT-NINS, but much higher than that of individuals with IGR. Logistic regression analysis showed that age, TG and HBCI/IR were the major influencing factors of the conversion from NGT to glucose metabolic disorders.Conclusions The probability of conversion from NGT to DM was increased remarkably when HINS was diagnosed. The reason might be that individuals with NGT-HINS suffered more metabolic risk factors and had a decreased β-cell function. Therefore, individuals with NGT-HINS should be paid attention to in diabetes prevention study.

OBJECTIVETo investigate the absorption characteristic of borneol.

METHODUsing single pass perfusion model, the active ingredient of borneol were detected by GC. The drug concentration, perfusion rate and pH value on the absorption of borneol were studied.

RESULTPerfusion rate on the absorption rate constants (Ka) had significant effects. Drug concentration and pH value on the absorption rate constants had no significant impact.

CONCLUSIONthe absorption of borneol is good by nasal. The absorption rate constants of borneol have no effected by drug concentration. The absorption of borneol is via a simple diffusion.

Absorption ; Administration, Intranasal ; methods ; Animals ; Bornanes ; administration & dosage ; pharmacokinetics ; Drugs, Chinese Herbal ; administration & dosage ; pharmacokinetics ; Perfusion ; methods ; Rats

Objective: To observe the activation of microglia and the changing rule of inflammatory cytokine as IL-6, IL-10 and nuclear factor-κB (NF-κB) in experimental rabbits after spinal cord ischemia reperfusion (SCIR) injury in order to provide theoretical basis for post-conditioning time. Methods: Rabbit SCIR injury model was established by thoracic aorta balloon occlusion. 54 New Zealand male adult white rabbits were divided into 9 groups: Sham group (the animals received balloon implantation without occlusion), SCIR-0h group (reperfusion was conducted at 0 hour of spinal cord ischemia), SCIR-1h, -2h, -3h, -8h, -24h,-48h and -72h groups. n=6 in each group. The number of normal and apoptosis neurons, the levels of Iba-1, IL-6, IL-10 and NF-κB in spinal tissue were examined and compared among different groups respectively. Results: The number of normal neuron was decreasing with the extended reperfusion time, TUNEL-positive neuron began to increasing in SCIR-8h group and the peak was reached in SCIR-24h group. The expression of Iba-1 began to elevating in SCIR-2h group and the peak was obtained in SCIR-8h group; NF-κB began to rising in SCIR-3h group and the peak was observed in SCIR-8h group; both IL-6 and IL-10 arrived the peak in SCIR-24h group. The expressions of NF-κB, IL-6 and IL-10 were positively related to Iba-1 level. Conclusion: Microglia activation had dynamic changes in experimental SCIR rabbits and the expression levels of NF-κB, IL-6 and IL-10 were positively to microglia activation; post-conditioning time at front and back to microglia activation may reduce neuron injury.

Objective To investigate the clinical efficacy of endoscopic variceal ligation (EVL) in the treatment of type 1 gastroesophageal varices (GOV1).Methods From July 2016 to May 2017,at the First Affiliated Hospital of Anhui Medical University,NO.2 People's Hospital of Fuyang City and the Sixth People's Hospital of Shenyang,the efficacy of EVL in the treatment of patients with GOV1 were retrospectively analyzed.The number of ligation rings,emergency (bleeding within 24 hours) hemostasis,successful hemostasis,early rebleeding (from 72 hours to six weeks after operation),delayed rebleeding (at six weeks after operation) and disappearance of gastroesophageal varices were observed.Patients were followed up for six to 16 months and postoperative complications of EVL were evaluated.Results There were 61 patients with GOV1 (40 males and 21 females),and the mean age was (50.9±10.9) years.The number of ligation during EVL operation was one to six (mean 3.8 ± 1.9).Seven patients with active bleeding were all successfully achieved emergency hemostasis.One case had rebleeding in 72 hours after operation,and the hemostatic rate was 98.3 ％ (60/61).The early rebleeding rate was 11.5 ％ (7/61),the delayed rebleeding rate was 4.9％ (3/61),and the total rebleeding rate was 16.4％ (10/61).The disappearance rate of gastroesophageal varices was 85.2％ (52/61).The complication rate was 21.3％ (13/61).No post-ligation ulcer bleeding,spontaneous bacterial peritonitis and perforation were observed in all patients.Conclusions EVL can effectively control the acute hemmorrhage of GOV1 type gastric varices.The postoperative rebleeding rate and complication rate are low.However,the disappearance rate of varices is high.

Objective:To investigate the risk factors for delirium after intertrochanteric fracture surgery in the elderly.Methods:The data of 423 elderly patients with femoral intertrochanteric fracture were retrospectively analyzed who had been treated by closed reduction and internal fixation with proximal femoral nail antirotation (PFNA) at Department of Orthopedics, The Second Central Hospital of Baoding from December 2010 to April 2018. They were 205 males and 218 females, aged from 70 to 98 years (mean, 78.6 years). By AO classification, 239 fractures were type 31-A1, 141 ones type 31-A2, and 43 ones type 31-A3. Of them, 362 were complicated with disease of internal medicine. The interval from injury to surgery ranged from 4 to 72 hours with an average of 46.6 hours. The incidence of postoperative delirium was recorded. The risk factors were screened by univariate analysis from the hidden blood loss, gender, age, body mass index, complications, anesthesia method, preoperative preparation time and electrolyte disturbance; multivariate logistic regression analysis was used to determine the independent risk factors from the factors with P< 0.05. Results:Post-operative delirium occurred in 49 of the 423 patients (11.58%) (29 cases on the first postoperative day and 20 ones on the second postoperative day). It was not observed in the other 374 (88.42%) patients. Univariate analysis showed significant differences in the interval from injury to surgery, hidden blood loss and electrolyte disturbance between the patients with and without postoperative delirium ( P<0.05). Multivariate logistic regression analysis showed that the interval from injury to surgery >48 hours ( OR=3.386, 95% CI: 1.362 to 6.638), hidden blood loss>600 mL ( OR=10.292, 95% CI: 1.244 to 35.091) and electrolyte disturbance ( OR=4.157, 95% CI: 1.595 to 7.626) were the independent risk factors for postoperative delirium in elderly patients with intertrochanteric fracture. Conclusion:Long preoperative preparation, a large amount of hidden blood loss and postoperative electrolyte disturbance may be the risk factors for post-operative delirium in elderly patients with intertrochanteric fracture afterinternal fixation.

Objective To explore the therapeutic mechanism of compound Yuye Decoction against diabetic cardiomyopathy(DCM).Methods Drugbank,Gene Cards,OMIM and PharmGKb databases were used to obtain DCM-related targets,and the core targets were identified and functionally annotated by protein-protein interaction network analysis followed by GO and KEGG enrichment analysis.The"Traditional Chinese Medicine-Key Component-Key Target-Key Pathway"network was constructed using Cytoscape 3.9.1,and molecular docking was carried out for the key components and the core targets.In the animal experiment,Wistar rat models of DCM were treated with normal saline or Yuye Decoction by gavage at low(0.29 g/kg)and high(1.15 g/kg)doses for 8 weeks,and the changes in cardiac electrophysiology and histopathology were evaluated.The changes in serum levels of LDH,CK,and CK-MB were examined,and myocardial expressions of PI3K,P-PI3K,Akt,P-AKT,BAX,IL-6,and TNF-α were detected using Western blotting.Results We identified 61 active compounds in Yuye Decoction with 1057 targets,3682 DCM-related disease targets,and 551 common targets between them.Enrichment of the core targets suggested that apoptosis,inflammation and the PI3K/Akt pathways were the key signaling pathways for DCM treatment.Molecular docking studies showed that the active components in Yuye Decoction including gold amidohydroxyethyl ester and kaempferol had strong binding activities with AKT1 and PIK3R1.In DCM rat models,treatment with Yuye Decoction significantly alleviated myocardial pathologies,reduced serum levels of LDH,CK and CK-MB,lowered myocardial expressions of BAX,IL-6 and TNF-α,and increased the expressions of P-PI3K and P-AKT.Conclusion The therapeutic effect of compound Yuye Decoction against DCM is mediated by its multiple active components that act on multiple targets and pathways to inhibit cardiomyocyte apoptosis and inflammatory response by regulating the PI3K/Akt signaling pathway.

Objective To explore the therapeutic mechanism of compound Yuye Decoction against diabetic cardiomyopathy(DCM).Methods Drugbank,Gene Cards,OMIM and PharmGKb databases were used to obtain DCM-related targets,and the core targets were identified and functionally annotated by protein-protein interaction network analysis followed by GO and KEGG enrichment analysis.The"Traditional Chinese Medicine-Key Component-Key Target-Key Pathway"network was constructed using Cytoscape 3.9.1,and molecular docking was carried out for the key components and the core targets.In the animal experiment,Wistar rat models of DCM were treated with normal saline or Yuye Decoction by gavage at low(0.29 g/kg)and high(1.15 g/kg)doses for 8 weeks,and the changes in cardiac electrophysiology and histopathology were evaluated.The changes in serum levels of LDH,CK,and CK-MB were examined,and myocardial expressions of PI3K,P-PI3K,Akt,P-AKT,BAX,IL-6,and TNF-α were detected using Western blotting.Results We identified 61 active compounds in Yuye Decoction with 1057 targets,3682 DCM-related disease targets,and 551 common targets between them.Enrichment of the core targets suggested that apoptosis,inflammation and the PI3K/Akt pathways were the key signaling pathways for DCM treatment.Molecular docking studies showed that the active components in Yuye Decoction including gold amidohydroxyethyl ester and kaempferol had strong binding activities with AKT1 and PIK3R1.In DCM rat models,treatment with Yuye Decoction significantly alleviated myocardial pathologies,reduced serum levels of LDH,CK and CK-MB,lowered myocardial expressions of BAX,IL-6 and TNF-α,and increased the expressions of P-PI3K and P-AKT.Conclusion The therapeutic effect of compound Yuye Decoction against DCM is mediated by its multiple active components that act on multiple targets and pathways to inhibit cardiomyocyte apoptosis and inflammatory response by regulating the PI3K/Akt signaling pathway.