Thermodynamics Evaluation of Selective Hydride Reduction for α,ß-Unsaturated Carbonyl Compounds.

The selective reduction of α,ß-unsaturated carbonyl compounds is one of the core reactions and also a difficult task for organic synthesis. We have been attempting to study the thermodynamic data of these compounds to create a theoretical basis for organic synthesis and computational chemistry. By electrochemical measurement method and titration calorimetry, in acetonitrile at 298 K, the hydride affinity of two types of unsaturated bonds in α,ß-unsaturated carbonyl compounds, their single-electron reduction potential, and the single-electron reduction potential of the corresponding radical intermediate are determined. Their hydrogen atom affinity, along with the hydrogen atom affinity and proton affinity of the corresponding radical anion, is also derived separately based on thermodynamic cycles. The above data are used to establish the corresponding "Molecule ID Card" (Molecule identity card) and analyze the reduction mechanism of unsaturated carbonyl compounds. Primarily, the mixture of any carbonyl hydride ions and Ac-tempo+ will stimulate hydride transfer process and create corresponding α,ß-unsaturated carbonyl compounds and Ac-tempoH from a thermodynamic point of view.

Evaluation of Copper Levels in Dental Calculus of OSF Patients with Chewing Dried Areca-Nut Quids in Hunan Province of Mainland China.

Dental calculus is a potential material that can be used for assessing chronic exposure to trace heavy metals in oral cavity as it is a long-term reservoir. The aim of this study was to investigate the correlation between dental calculus copper levels and risk of oral submucous fibrosis (OSF) due to chewing dried areca-nut quids in Mainland China. This study included 34 OSF (grade 1) sufferers with dried areca-nut quids chewing as the patient group and 23 healthy individuals without areca-nut chewing as the control group. The dental calculus sample was obtained from all 57 participants and evaluated by inductively coupled plasma mass spectrometry (ICP-MS) for dental calculus level of copper. This work revealed that the mean copper level of dental calculus was significantly higher in OSF (grade 1) sufferers with areca-nut chewing than those in healthy individuals without areca-nut chewing (p < 0.001). This work provided an evidence to support that there may be a positive correlation between elevated levels of copper in dental calculus caused by chewing dried areca-nut quids and an increased risk of developing OSF in Mainland China.

PCBP-1 Regulates the Transcription and Alternative Splicing of Inflammation and Ubiquitination-Related Genes in PC12 Cell.

PCBP-1, a multifunctional RNA binding protein, is expressed in various human cell/tissue types and involved in post-transcriptional gene regulation. PCBP-1 has important roles in cellular Iron homeostasis, mitochondrial stability, and other cellular activities involved in the pathophysiological process of neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS) and Huntington's disease (HD). However, it remains enigmatic whether PCPB-1 is associated with the pathogenesis of PD. In this study, we cloned and constitutively overexpressed PCBP-1 in rat PC12 cells (PC12 cell is the common cell line studying neurodegenerative disease include PD). RNA-seq was performed to analyze PCBP-1-regulated differentially expressed genes (DEGs) and alternative splicing events (ASEs) between control and PCBP1-overexpressed cells. GO and KEGG pathway analyses were performed to identify functional DEGs and alternatively spliced genes. Consequently, we validated PCBP-1-regulated genes using RT-qPCR. Finally, we downloaded CLIP-seq data from GEO (GSE84700) to analyze the mechanisms of PCBP-1's regulation of gene expression and ASEs by revealing the binding profile of PCBP-1 on its target pre-mRNAs. Overexpression of PCBP-1 partially regulated the ASE and expression of genes enriched in neuroinflammation and protein ubiquitination, which were also associated with PD pathogenesis. Moreover, RT-qPCR assay verified the PCBP-1-modulated expression of neuroinflammatory genes, like LCN-2, and alternative splicing (AS) of ubiquitination-related gene WWP-2. Finally, CLIP-seq data analysis indicated that the first UC motif was the critical site for PCBP-1 binding to its targets. In this study, we provided evidence that PCBP-1 could regulate the expression of LCN-2 gene expression associated with neuroinflammation and AS of WWP-2 in relation to protein ubiquitination. These findings thus provided novel insights into the potential application of PCBP-1 as the disease pathophysiological or therapeutic target for neurodegenerative disease.

Quantitative Proteomics Reveals the Development of HBV-Associated Glomerulonephritis Triggered by the Downregulation of SLC7A7.

As a hepadnavirus, hepatitis B virus (HBV) can cause damage to extrahepatic organs. The kidney is one of the organs that is more susceptible to damage. Research studies on HBV-associated glomerulonephritis (HBV-GN) have been going on for decades. However, the underlying molecular mechanism remains obscure. Here, we applied a tandem mass tag (TMT) isobaric labeling-based method to quantitatively profile the kidney proteome of HBV transgenic mice to illustrate the pathological mechanisms of HBV-GN. Weighted correlation network analysis, a clustering method for gene expression, is used to cluster proteins. Totally, we identified 127 proteins that were highly associated with HBV expression out of a total of 5169 quantified proteins. Among them, the downregulated solute carrier (SLC) family proteins are involved in the process of HBV-GN. We also found that IL1B was upregulated in the kidney tissue of HBV transgenic mice. These findings suggest that HBV disrupts the small molecule transport network of the kidney, which contributes to the occurrence of HBV-GN. The transporter, particularly SLC family 7 member 7 (SLC7A7), is involved in this process, which might serve as an intervention target for HBV-GN. All MS data have been deposited to the ProteomeXchange Consortium via the iProX partner repository with the data set identifier PXD016450.

Chronic hepatitis B virus infection is associated with a poorer prognosis in diffuse large B-cell lymphoma: a meta-analysis and systemic review.

Accumulating evidence from clinical trials indicates chronic hepatitis B virus (HBV) infection is associated with the incidence of diffuse large B-cell lymphoma (DLBCL) and may be associated with the prognosis of DLBCL, though this suggestion remains controversial. We performed a meta-analysis to assess whether HBV infection is associated with prognosis and response to chemotherapy in DLBCL. After a strict literature search strategy, a total of 809 HBV surface antigen (HBsAg) seropositive patients with DLBCL and 2849 HBsAg seronegative patients with DLBCL from twelve trials were included. DLBCL patients with chronic HBV infection had significantly poorer 2- and 5-year overall survival (OS) (HR 1.54, 95% CI 1.23-1.92, P<0.001 and 1.79, 1.48-2.17, P<0.001) and 2- and 5-year progression-free survival (PFS) (HR 1.44, 95% CI 1.14-1.81, P=0.002 and HR 1.34, 95% CI 1.02-1.75, P=0.03). HBsAg-seronegative patients also had a lower complete response (CR) rate (OR 0.48, 95% CI 0.34-0.68, P<0.001), higher progressive disease (PD) rate (OR 2.08, 95% CI 1.34-3.24, P=0.001), and more advanced clinical features. This meta-analysis indicates HBV infection leads to a poorer prognosis and poorer response to standard chemotherapy.

Incidence and mortality risk factors of acute kidney injury in critical ill pregnancies: a single center retrospective analysis / 中华危重病急救医学

Objective To evaluate the incidence and mortality risk factors of pregnancy-related acute kidney injury (PR-AKI) in intensive care unit (ICU). Methods A retrospective analysis was conducted. Critically ill pregnancies admitted to ICU of Shandong University Affiliated Provincial Hospital from January 1st, 2012 to December 31st, 2016 were enrolled. Based on the Kidney Disease: Improving Global Outcomes (KDIGO)-acute kidney injury (AKI) criteria, patients were divided into two groups: PR-AKI group and non-PR-AKI group. Clinical characteristics and laboratory data of two groups were compared. Risk factors of incidence and mortality of PR-AKI patients were analyzed, and the receiver operating characteristic (ROC) curve was drawn to evaluate the value of these risk factors in predicting mortality of PR-AKI patients in ICU. Results ①A total of 219 pregnancies in ICU were included in the analysis, 85 cases (38.8％) were diagnosed with PR-AKI, with 29.4％ in AKI stage 1, 27.1％ in AKI stage 2 and 43.5％ in AKI stage 3. ②Nineteen of 219 critically ill pregnancies died in ICU, the total ICU mortality was 8.7％. The mortality of PR-AKI group was higher than non-PR-AKI group (16.5％ vs. 3.7％, P = 0.003). The mortality was worsened with increasing severity of AKI (4.0％ for AKI stage 1, 4.3％ for AKI stage 2, 32.4％ for AKI stage 3). ③Acute fatty liver of pregnancy (AFLP) and lactate (Lac) were the independent risk factors for PR-AKI [AFLP: odds ratio (OR) = 6.081, 95％ confidence interval (95％CI) was 1.587-23.308, P = 0.008; Lac: OR = 1.460, 95％CI was 1.078-1.977, P = 0.014]. ④ Age, Lac, acute physiology and chronic health evaluation Ⅱ(APACHEⅡ) and sequential organ failure assessment (SOFA) were the independent risk factors associated with the mortality of PR-AKI patients in ICU (age: OR = 1.130, 95％CI was 1.022-1.249, P = 0.017; Lac: OR = 1.198, 95％CI was 1.009-2.421, P = 0.039; APACHEⅡ: OR = 1.211, 95％CI was 1.102-1.330, P < 0.001; SOFA: OR = 1.411, 95％CI was 1.193-1.669, P < 0.001). ⑤ ROC curve analysis showed that age, Lac, APACHEⅡscore and SOFA score all had good predictive values for in-hospital mortality among PR-AKI patients in ICU, the cut-off value was 29 years old, 3.8 mmol/L, 16 and 8, respectively, and the AUC was 0.751, 0.757, 0.892 and 0.919, respectively (all P < 0.01). Conclusions The incidence and mortality of PR-AKI of critically ill pregnancies in ICU are high. Increased age, Lac, APACHEⅡ score and SOFA score are independent risk factors associated with the mortality of PR-AKI patients in ICU, and have good predictive values for prognosis.

Incidence and mortality risk factors of acute kidney injury in critical ill pregnancies: a single center retrospective analysis / 中华危重病急救医学

Objective@#To evaluate the incidence and mortality risk factors of pregnancy-related acute kidney injury (PR-AKI) in intensive care unit (ICU).@*Methods@#A retrospective analysis was conducted. Critically ill pregnancies admitted to ICU of Shandong University Affiliated Provincial Hospital from January 1st, 2012 to December 31st, 2016 were enrolled. Based on the Kidney Disease: Improving Global Outcomes (KDIGO)-acute kidney injury (AKI) criteria, patients were divided into two groups: PR-AKI group and non-PR-AKI group. Clinical characteristics and laboratory data of two groups were compared. Risk factors of incidence and mortality of PR-AKI patients were analyzed, and the receiver operating characteristic (ROC) curve was drawn to evaluate the value of these risk factors in predicting mortality of PR-AKI patients in ICU.@*Results@#①A total of 219 pregnancies in ICU were included in the analysis, 85 cases (38.8%) were diagnosed with PR-AKI, with 29.4% in AKI stage 1, 27.1% in AKI stage 2 and 43.5% in AKI stage 3. ②Nineteen of 219 critically ill pregnancies died in ICU, the total ICU mortality was 8.7%. The mortality of PR-AKI group was higher than non-PR-AKI group (16.5% vs. 3.7%, P = 0.003). The mortality was worsened with increasing severity of AKI (4.0% for AKI stage 1, 4.3% for AKI stage 2, 32.4% for AKI stage 3). ③Acute fatty liver of pregnancy (AFLP) and lactate (Lac) were the independent risk factors for PR-AKI [AFLP: odds ratio (OR) = 6.081, 95% confidence interval (95%CI) was 1.587-23.308, P = 0.008; Lac: OR = 1.460, 95%CI was 1.078-1.977, P = 0.014]. ④ Age, Lac, acute physiology and chronic health evaluation Ⅱ(APACHEⅡ) and sequential organ failure assessment (SOFA) were the independent risk factors associated with the mortality of PR-AKI patients in ICU (age: OR = 1.130, 95%CI was 1.022-1.249, P = 0.017; Lac: OR = 1.198, 95%CI was 1.009-2.421, P = 0.039; APACHEⅡ: OR = 1.211, 95%CI was 1.102-1.330, P < 0.001; SOFA: OR = 1.411, 95%CI was 1.193-1.669, P < 0.001). ⑤ ROC curve analysis showed that age, Lac, APACHEⅡscore and SOFA score all had good predictive values for in-hospital mortality among PR-AKI patients in ICU, the cut-off value was 29 years old, 3.8 mmol/L, 16 and 8, respectively, and the AUC was 0.751, 0.757, 0.892 and 0.919, respectively (all P < 0.01).@*Conclusions@#The incidence and mortality of PR-AKI of critically ill pregnancies in ICU are high. Increased age, Lac, APACHEⅡ score and SOFA score are independent risk factors associated with the mortality of PR-AKI patients in ICU, and have good predictive values for prognosis.

[Effects of the Veterinary Antibiotic Sulfamethazine on Ammonia Volatilization from a Paddy Field Treated with Conventional Synthetic Fertilizer and Manure].

Veterinary antibiotics have been widely detected in croplands due to the application of animal excrements as fertilizer. However, their effects on ammonia (NH3) volatilization remain unclear. A field experiment was conducted to evaluate the effect of sulfamethazine on NH3 volatilization from a paddy field when conventional synthetic fertilizer or manure was applied as basal fertilizer. Five different treatments were conducted in this study: without application of fertilizers and antibiotics (CK), compound fertilizer used as basal fertilizer with and without the addition of sulfamethazine (CF+SD and CF respectively), and pig manure used as base fertilizer with and without the addition of sulfamethazine (CM+SD and CM respectively). Urea was used for topdressing in the CF, CF+SD, CM, and CM+SD treatments. The results showed that regardless of the fertilizer type applied, sulfamethazine did not affect the seasonal pattern of NH3volatilization. However, it promoted the NH3 volatilization rate in the topdressing stage significantly (P<0.01). During the observation period, the proportions of applied N lost as NH3-N in the CF+SD and CM+SD treatments were 1.65 and 2.78 times higher than those in the CF and CM treatments, respectively. The promoting effect of sulfamethazine was more obvious in the pig manure treatment than in the compound fertilizer treatment. Sulfamethazine significantly increased the soil urease activity (P<0.05). Furthermore, the NH3 volatilization rate was positively correlated with urease activity and soil ammonia nitrogen content (P<0.05). This indicates that sulfamethazine can increase the NH3 volatilization rate by changing the soil urease activity and inorganic nitrogen content. Controlling the misuse of veterinary antibiotics and environmental and ecological risks posed by the antibiotic residues in farmland excrements are urgent problems in China that need to be solved.

[Characteristics and Source Analysis of Atmospheric Carbonaceous Aerosols in the Cities of Hangzhou and Ningbo].

To investigate the seasonal variations and sources of carbonaceous aerosols in the cities of Hangzhou and Ningbo, field PM2.5 sampling was conducted at four representative sites (two urban, one suburban, and one rural) in this region from December 2014 to November 2015. A thermal/optical carbon analyzer was employed to analyze both organic carbon (OC) and elemental carbon (EC) contents in PM2.5 by identifying eight different carbon fractions, including OC1, OC2, OC3, OC4+OPC, EC1-OPC, EC2, and EC3. Based on these fractions, OC and EC were defined as OC1+OC2+OC3+OC4+OPC and EC1+EC2+EC3-OPC, respectively; total carbon (TC) was calculated as the sum of OC and EC; and total carbonaceous aerosols (TCAs) were quantified via the sum of organic aerosols (OAs; converted from OC) and EC. The results showed the following. ①The annual average level of TC in this region was (14.3±4.1) µg·m-3, accounting for (26.2±6.5)% of the annual average PM2.5 concentration. The annual average OC and EC concentrations were (11.3±3.4) µg·m-3 and (3.0±0.9) µg·m-3, respectively. The highest TC level was observed in winter among the four seasons. ②The annual average TCA concentration in this region was (25.6±7.5) µg·m-3, contributing (42.2±10.0)% of PM2.5. In addition, secondary organic carbon (SOC) was also estimated by the commonly applied EC method. It was found that SOC contributed (41.1±5.5)% to OC on an annual average basis. ③The sources of carbonaceous aerosols were determined using the correlation between OC and EC, OC/EC mass ratio, and different carbon fraction characteristics. The annual average OC/EC ratio in this region was 4.7±1.7, which falls in the diagnostic ratio range for vehicular emissions, coal combustion, and biomass burning, indicating these sources are probably the major contributors of the regional carbonaceous aerosols. Moreover, a higher char-EC/soot-EC ratio was observed during winter and autumn at all sites, possibly implying the enhanced biomass burning activities during these two seasons.

Prevalence and multi-locus genotyping of Giardia duodenalis from goats in Shaanxi province, northwestern China.

Giardia duodenalis (syn. Giardia lamblia, Giardia intestinalis) is an important zoonotic parasite that parasitizes the gastro-intestines of humans and animals, with diarrhea as the most common clinical symptom. The goat has been indicated as one of the most important reservoirs of G. duodenalis for humans. In the present study, we investigated the prevalence and genetic diversity of G. duodenalis in goats in Shaanxi province, northwestern China. A total of 1311 faecal specimens were examined, and the overall prevalence was 7.1% (93/1311). Although all the meat, cashmere and dairy goats were positive for infection, the highest prevalence was found in cashmere goats (10.2%), followed by dairy (9.4%) and meat goats (2.0%). Negative correlation between age and prevalence was also observed, and the highest prevalence was detected in 0-2-month goats. Genetic analysis showed the presence of three assemblages, including two zoonotic (A and B) and one animal-adapted assemblage E, with E as the prevalent assemblage found in all breeds of positive goats. The zoonotic assemblage A was found in Guanzhong dairy and Shanbei cashmere goats, but B was only detected in Boar goats. Additionally, mixed assemblages E and A were also identified in two cashmere goats. Multi-locus genotyping (MLST) using the gene loci of the triosephosphate isomerase (tpi), b-giardin (bg) and glutamate dehydrogenase (gdh) identified four novel multi-locus genotypes (MLGs), including two assemblage E MLGs and two assemblage A MLGs. These results suggested that Boar, Guanzhong dairy and Shanbei cashmere goats in Shaanxi province would be potential reservoirs for human infections in this area, and this study also provided basic data for controlling G. duodenalis infection in goats as well as other hosts.

Luteolin-7-O-Glucoside Present in Lettuce Extracts Inhibits Hepatitis B Surface Antigen Production and Viral Replication by Human Hepatoma Cells in Vitro.

Hepatitis B virus (HBV) infection is endemic in Asia and chronic hepatitis B (CHB) is a major public health issue worldwide. Current treatment strategies for CHB are not satisfactory as they induce a low rate of hepatitis B surface antigen (HBsAg) loss. Extracts were prepared from lettuce hydroponically cultivated in solutions containing glycine or nitrate as nitrogen sources. The lettuce extracts exerted potent anti-HBV effects in HepG2 cell lines in vitro, including significant HBsAg inhibition, HBV replication and transcription inhibition, without exerting cytotoxic effects. When used in combination interferon-alpha 2b (IFNα-2b) or lamivudine (3TC), the lettuce extracts synergistically inhibited HBsAg expression and HBV replication. By using differential metabolomics analysis, Luteolin-7-O-glucoside was identified and confirmed as a functional component of the lettuce extracts and exhibited similar anti-HBV activity as the lettuce extracts in vitro. The inhibition rate on HBsAg was up to 77.4%. Moreover, both the lettuce extracts and luteolin-7-O-glucoside functioned as organic antioxidants and, significantly attenuated HBV-induced intracellular reactive oxygen species (ROS) accumulation. Luteolin-7-O-glucoside also normalized ROS-induced mitochondrial membrane potential damage, which suggests luteolin-7-O-glucoside inhibits HBsAg and HBV replication via a mechanism involving the mitochondria. Our findings suggest luteolin-7-O-glucoside may have potential value for clinical application in CHB and may enhance HBsAg and HBV clearance when used as a combination therapy.

Temporal and spatial variation in major ion chemistry and source identification of secondary inorganic aerosols in Northern Zhejiang Province, China.

To investigate the seasonal and spatial variations of ion chemistry of fine particles in Northern Zhejiang Province (NZP), China, one year-long field sampling was conducted at four representative sites (two urban, one suburb, and one rural sites) in both cities of Hangzhou and Ningbo from December 2014 to November 2015. Twelve water soluble inorganic ions (WSII) were characterized in this comprehensive study. The annual average of PM2.5 concentration in NZP as overall was 66.2 ± 37.7 µg m-3, and urban sites in NZP were observed with more severe PM2.5 pollution than the suburban and rural sites. The annual average concentration of total WSII at four sampling sites in NZP was 29.1 ± 19.9 µg m-3, dominated by SO42- (10.3 µg m-3), and followed by NO3- (8.9 µg m-3), NH4+ (6.6 µg m-3), Cl- (1.3 µg m-3) and K+ (0.7 µg m-3). Among all cations, NH4+ was the predominant neutralizing ion with the highest neutralization factor (NF), while the remaining cations showed limited neutralization capacity. The highest and lowest sulfur oxidation ratio (SOR) values in this region were found in summer and winter, respectively; while the seasonal patterns for nitrogen oxidation ratio (NOR) were opposite to that of SOR. Principal component analysis (PCA) showed that the significant sources of WSII in NZP were industrial emissions, biomass burning, and formation of secondary inorganic aerosols. In addition, contribution from transboundary transport of polluted aerosols was also confirmed from the assessment through air mass backward trajectory analysis.

Relation between cervical squamous cancer lesion among Uighur and Han ethnic women in Xinjiang with expression of PI3K,ERK,IGF-1R and ER protein / 重庆医学

Objective To observe the expression levels of PI3K ,ERK ,IGF‐1R and ER in cervicitis and cervical squamous cancer tissues among Uighur and Han ethnic patients and their correlation .Methods The 90 paraffin embedding samples of cervici‐tis tissue( 46 cases for Han and 44 cases for Uighur) and 224 paraffin embedding samples of cervical squamous cancer tissue (36 ca‐ses for Han and 188 cases for Uighur) were collected and detected the protein expression levels by using immunohistochemistry .Re‐sults The positive expression rates of IGF‐1R and PI3K in cervical squamous cancer were 58 .04% and 92 .41% respectively ,which were higher than 13 .33% and 57 .78% in cervicitis tissue ,the positive expression rates of ER and ERK in cervical squamous cancer were 22 .32% and 68 .30% respectively ,which were lower than 63 .33% and 95 .56% in cervicitis tissue ;the positive expression rate of IGF‐1R and PI3K of cervical squamous cancer in Han and Uighur were 69 .44% ,88 .89% and 55 .85% ,93 .09% respective‐ly ,which were higher than 15 .22% ,54 .35% and 11 .36% ,61 .36% of cervicitis tissue ;the positive expression rate of ER and ERK of cervical squamous cancer in Han and Uighur were 13 .89% ,83 .33% and 23 .94% ,65 .43% respectively ,which were lower than 65 .22% ,93 .48% and 61 .36% ,97 .73% of cervicitis tissue respectively ;the expression of ERK in Uighur cervical squamous carci‐noma tissue was 65 .43% ,which was lower than 83 .33% in Han ,the difference was statistically significant (P<0 .01) .Conclusion PI3K ,ERK ,IGF‐1R and ER protein expression positive or deficiency is closely related to the occurrence of cervical cancer ,which may serve as the important biological indicators for detecting cervical cancer ,and the ethnic difference of ERK protein expression exists in cervical cancer .

Effects of inhibition of AMP-activated protein kinase on cytochrome c expression in the cortex and hippocampus after focal cerebral ischemia-reperfusion in mice / 国际脑血管病杂志

Objective To investigate the effects of of inhibition of AMP-activated protein kinase (AMPK) on cytochrome c (CytC) expression in the cortex and hippocampus after focal cerebral ischemia-reperfusion in mice. Methods Thirty-six male C57BL/6 mice were randomly divided into 3 groups: a sham operation group, an ischemia-reperfusion group, and a compound C group (n = 12 in each group). The mice of the compound C group were intraperitonealy injected an AMPK specific inhibitor compound C (20 mg/kg) at the time of ischemia. A model of middle cerebral artery occlusion was induced by a modified suture method. After 24 h of reperfusion, Western blot was used to detect the expression levels of AMPK, phosphorylated-AMPK (p-AMPK), and cytoplasm CytC in the cortex and hippocampus in the ischemic side. Results p-AMPK/MPK levels in the cortex in the sham operation group, ischemia-reperfusion group, and compound C group were 0. 701 ± 0. 197, 1. 408 ± 0. 322, and 0. 930 ± 0. 229, respectively (F = 12. 000, P =0. 001); p-AMPK/MPK levels in the hippocampus were 0. 685 ± 0. 228, 1. 507 ± 0. 418, and 0. 964 ± 0. 378, respectively ( F = 8. 530, P = 0. 003 ); p-AMPK/AMPK levels both in the cortex ( P < 0. 001 ) and hippocampus (P = 0. 001) in the ischemia-reperfusion group were significantly higher than those in the sham operation group, p-AMPK/AMPK levels both in the cortex (P = 0. 005) and hippocampus (P = 0. 017) in the compound C group were significantly lower than those in the ischemia-reperfusion group. CytC levels in the cortex in the sham operation group, ischemia-reperfusion group, and compound C group were 0. 496 ±0. 278, 1. 461 ± 0. 321, and 1. 018 ± 0. 175, respectively (F = 19. 915, P < 0. 001); CytC levels in the hippocampus were 0. 511 ± 0. 257, 1. 610 ± 0. 441, and 0. 921 ± 0. 228 (F = 17. 795, P < 0. 001); CytC levels both in the cortex (P < 0. 001) and hippocampus (P < 0. 001) in the ischemia-reperfusion group were significantly higher than those in the sham operation group, while CytC levels both in the cortex (P = 0. 011) and hippocampus (P = 0. 002) in the compound C group were significantly lower than those in the ischemia-reperfusion group. Conclusion Inhibition of the AMPK may down-regulate the cytoplasm CytC expression in the cortex and hippocampus after cerebral ischemia-reperfusion in mice.

Dynamic alterations of connexin43, matrix metalloproteinase-2 and tissue inhibitor of matrix metalloproteinase-2 during ventricular fibrillation in canine.

The aim of this study is to investigate the dynamic alterations of cardiac connexin 43 (Cx43), matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-2 (TIMP-2) in the setting of different ventricular fibrillation (VF) duration. In this study, thirty-two dogs were randomly divided into sham control group, 8-min VF group, 12-min VF group, and 30-min VF group. Cx43 and phosphorylated Cx43 (p-Cx43) in tissues were detected by western blot and immunofluorescence analysis. MMP-2 and TIMP-2 were detected by western blot and immunohistochemistry analysis. The results showed that Cx43 levels in three VF groups were significantly decreased compared with sham control group. p-Cx43 levels in 12-min and 30-min VF groups were significantly reduced compared with sham control group. The ratio of p-Cx43/Cx43 was also decreased in VF groups. Compared with sham controls, no significant difference was observed between the sham control group and 8-min VF group in MMP-2 level, but MMP-2 level increased in 12-min and 30-min VF groups. The ratios of MMP-2/TIMP-2 were higher in VF groups, and were correlated with the duration of VF. A remarkable correlation was observed between the ratio of p-Cx43/Cx43 and MMP-2/TIMP-2 (r = -0.93, P < 0.01). In conclusion, the alteration of Cx43 and/or p-Cx43 levels and the imbalance of MMP-2 and TIMP-2 may contribute to the initiation and/or persistence of VF. Maneuvers managed to modulate Cx43 level or normalize the balance of MMP-2/TIMP-2 are promising to ameliorate prognosis of VF.

TP53 K351N mutation-associated platinum resistance after neoadjuvant chemotherapy in patients with advanced ovarian cancer.

OBJECTIVE: TP53 K351N mutation is associated with acquired cisplatin resistance in ovarian cancer cells following exposure to cisplatin. We investigated the effect of TP53 K351N mutation on outcome in patients with epithelial ovarian cancer (EOC) who received platinum-based chemotherapy. METHODS: We assessed TP53 K351N mutations by allele specific real-time PCR (AS-PCR) and DNA sequencing in tumor samples of 153 patients with stage IIIC/IV EOC. Clinicopathologic and follow-up data were collected by a retrospective chart review. RESULTS: TP53 K351N mutations were detected in 8 (11.27%) of 71 patients who underwent neoadjuvant chemotherapy with interval debulking surgery (NACT-IDS) but not in 82 patients who underwent primary debulking surgery (PDS) (P<0.01). In patients with relapse within 6 months, the relapse rate was 14 (19.72%) of 71 patients for NACT-IDS compared to 15 (18.29%) of 82 patients for PDS (P=0.49), and TP53 K351N mutation was observed in 8 of NACT-IDS 14 patients (57.14% P<0.01). In the patients retreated at first recurrence within 6 months, 7 with TP53 K351N mutation of 14 NACT-IDS patients exhibited progression of disease, compared to 2 of PDS 15 patients (50.00% vs. 13.33%, P=0.04). The median disease-free survival (DFS) for NACT-IDS was 13.0 months compared to 15.0 months for PDS (P=0.02). In multivariate analysis, TP53 K351N mutation is an independent factor for shorter DFS in the patients who underwent NACT-IDS (HR=19.05; P=0.01). CONCLUSIONS: TP53 K351N mutation may be associated with induction of platinum resistance after NACT in advanced EOC.

[Reinforcing and reducing method of bloodletting therapy].

Through review and analysis on description of bloodletting therapy in ancient medical classics, it is found that bloodletting therapy can be classified as two categories of reinforcing and reducing. And the classification is related with many factors such as the quantity of blood, apparatus selected, depth of acupuncture, points selected and physical conditions, etc. Bloodletting therapy is not confined only in excessive syndromes, it is also applied to the treatment of complicated syndrome of excess and deficiency as well as deficiency syndrome with excessive manifestations and deficiency syndrome.

ZP123 reduces energy required for defibrillation by preventing connexin43 remodeling during prolonged ventricular fibrillation in swine.

In ventricular fibrillation, the uncoupling of gap junctions slows conduction velocity and increases action-potential dispersion, which slows and diminishes defibrillation. We studied how the peptide ZP123, a gap-junction enhancer, might lower defibrillation-energy requirements during ventricular fibrillation in live pigs. We randomly assigned 33 pigs into 3 groups: ZP123 (receiving a 1-µg/kg bolus and 10 µg/kg/hr of ZP123), control (receiving saline solution), and sham (undergoing a sham operation). After a 30-min administration of agents, ventricular fibrillation was induced and left untreated for 8 min. Biphasic defibrillation of 50 J was increased by 50-J increments as necessary. Defibrillation-energy requirements were defined as the lowest energy required to achieve defibrillation. Electrocardiographic values were obtained before and after the administration of agents. Western blot and immunofluorescence analyses were performed on ventricular myocardial samples. All but one pig survived. The ZP123 treatment did not alter electrocardiographic variables. In the ZP123 group, the average required defibrillation energy was lower than that in the control group (327.28±269.6 vs 610±192.64 J; P=0.015), and the cumulative percentage of successful defibrillation at upper energy levels was higher (P<0.05). Supraventricular rhythm occurred more often in the ZP123 group than in the control group (72.7% vs 50%, P=0.042). Western-blot and immunofluorescence results showed that ZP123 did not alter the total amount of connexin43 but did prevent its dephosphorylation. We conclude that ZP123 can reduce defibrillation-energy requirements by preventing connexin43 remodeling during prolonged ventricular fibrillation.

Imbalance between tissue inhibitor of metalloproteinase 1 and matrix metalloproteinase 9 after cardiopulmonary resuscitation.

AIMS: This study aimed to determine whether (a) there was an imbalance between matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of metalloproteinase 1 (TIMP-1) after cardiopulmonary resuscitation (CPR) in a canine model of prolonged ventricular fibrillation (VF); (b) with the duration of VF, the degree of the imbalance would be greater; and (c) there was a relationship between the level of MMP-9 or TIMP-1 and the cardiac function. METHODS AND RESULTS: Ventricular fibrillation was electrically induced in 24 dogs. The animals were randomly divided into 3 groups (sham control, n = 8; 8-minute VF, n = 8; 12-minute VF, n = 8). Echocardiographic measurement and hemodynamic variables were recorded before VF and after return of spontaneous circulation. Tissue inhibitor of metalloproteinase 1 (TIMP-1) and MMP-9 were analyzed by Western blot and immunohistochemistry. Compared with sham controls, dogs under VF and CPR showed significantly decreased level of TIMP-1 (P < .001), and with the duration of VF, the level of TIMP-1 declined (P < .01). The level of MMP-9 did not achieve statistical significance in the 3 groups (P > .05); however, they were higher in VF and longer duration VF groups. The ratios of TIMP-1/MMP-9 were lower in VF groups (P < .05). There was a negative correlation between TIMP-1 and left atrium dimension and left ventricular diastolic dimensions (r = -0.83 and r = -0.96, respectively; P < .01) and a positive correlation between TIMP-1 and left ventricular ejection fraction (r = 0.85; P < .01). CONCLUSIONS: There was an imbalance between TIMP-1 and MMP-9 after CPR. It may partly contribute to the postresuscitation cardiac dysfunction.

Reinforcing and reducing method of bloodletting therapy / 中国针灸

Through review and analysis on description of bloodletting therapy in ancient medical classics, it is found that bloodletting therapy can be classified as two categories of reinforcing and reducing. And the classification is related with many factors such as the quantity of blood, apparatus selected, depth of acupuncture, points selected and physical conditions, etc. Bloodletting therapy is not confined only in excessive syndromes, it is also applied to the treatment of complicated syndrome of excess and deficiency as well as deficiency syndrome with excessive manifestations and deficiency syndrome.