Biomarkers, signaling pathways, and programmed cell death in acute lung injury and its treatment with Traditional Chinese Medicine: a narrative review.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are common life-threatening, high-mortality lung diseases associated with acute and severe inflammation of the lungs. However, research on diagnostic markers and signaling pathways associated with ALI/ARDS is lacking, and no specific drug therapy is available for ALI/ARDS. Therefore, in this study, biomarkers and signaling pathways associated with ALI/ARDS were summarized to provide a reference for future clinical and research work. A review of Traditional Chinese Medicine for the treatment or prevention of ALI/ARDS is also presented to provide a reference for further development of Traditional Chinese Medicine. In summary, this review will help raise awareness of ALI/ARDS and provide insight into the future exploitation of Traditional Chinese Medicine.

[Evaluation of spinopelvic alignment according to Roussouly classification can predict the occurrence of adjacent segment disease after lumbar fusion].

Objective: To investigate the correlation of spinopelvic alignment according to Roussouly classification on the occurrence of adjacent segment disease (ASD) in the patients undergoing fusion surgery for lumbar degenerative diseases. Methods: A cross-sectional study. Clinical data of 166 consecutive patients who had undergone lumbar fusion between January 2009 and January 2019 in the Affiliated Changzhou Second People's Hospital of Nanjing Medical University and Affiliated Drum Tower Hospital of Medical School of Nanjing University were retrospectively reviewed. There were 59 males and 107 females, with an average age of (58.6±9.5) years (ranged 41-78 years). Fusion length averagely spanned (1.7±0.7) levels (ranged 1-3 levels). The patients were classified by both "theoretical" (based on pelvic incidence (PI)) and "current"(based on sacral slope (SS)) Roussouly types. The patients were classified as "matched" if their "current" shape matched the "theoretical" type and otherwise as "unmatched". Multivariate logistic regression analysis of the variables recruited from univariate analyses was performed to identify the factors independently associated with the development of ASD after lumbar fusion. Results: The average follow-up duration after initial surgery was (49.2±20.7) months (ranged 25 to 134 months). Thirty (18.1%, 30/166) patients were diagnosed as ASD. Postoperatively, two thirds of the patients who suffered ASD after surgery were unmatched, while 36.8% (50/136) of the patients without ASD had unmatched type. Univariate analyses showed that older age, more fusion levels, float fusion, pre-and postoperative worse spinopelvic alignment, and postoperative unmatched Roussouly type were identified as risk factors of ASD. Multivariate logistic regression analysis identified postoperative Roussouly type mismatch (OR=3.310, 95%CI: 1.282-8.545, P=0.013), old age (OR=1.074, 95%CI: 1.019-1.131, P=0.008) and postoperative SS (OR=0.928, 95%CI: 0.865-0.995, P=0.036) as the independent risk factors of development of ASD after lumbar fusion. Conclusion: A significant association between postoperative sagittal malalignment and occurrence of ASD is detected, the evaluation of sagittal alignment by Roussouly classification could help predict the occurrence of ASD.

Evaluation of the efficacy of aparatinib and carrilizumab combined with transcatheter arterial chemoembolization in the treatment of primary hepatocellular carcinoma.

OBJECTIVE: The study aimed to analyze the efficacy of aparatinib and carrilizumab combined with transcatheter arterial chemoembolization (TACE) in the treatment of primary hepatocellular carcinoma (HCC). PATIENTS AND METHODS: A total of 150 patients with primary HCC admitted to our hospital from March 1, 2019, to March 1, 2022 was chosen and randomized as the control and treatment group. The control group went through TACE treatment, and the treatment group experienced apatinib + karilizumab + TACE treatment. The near and long-term efficacy of the two groups were compared. The total survival time (OS), time to progression (TTP), and hospital costs were compared between the two groups. Fasting venous blood was collected before and one month after treatment in the two groups, and liver and kidney functions were tested using automatic biochemical analyzer. The levels of CD3+, CD4+ and CD8+ were detected by flow cytometry, and CD4+/CD8+ was calculated. The levels of cysteinyl aspartate specific protease-8 (Caspase-8), vascular endothelial growth factor (VEGF) and alpha fetoprotein (AFP) were detected by enzyme-linked immunosorbent assay (ELISA). The patients' conditions were closely observed and the adverse reaction rates of diarrhea, hand foot syndrome, bone marrow suppression, proteinuria, fever and pain were compared between the two groups. RESULTS: The disease control rate (DCR) of short-term treatment in the treatment group was 97.33%, which was much higher than 88.00% in the control group. The survival ratios of the treatment group in September and December were 65.33% and 42.67% respectively, which were also much higher than 48.00% and 20.00% in the control group (p < 0.05). The TTP and OS of patients in the treatment group were significantly longer than those in the control group (p < 0.05), and the hospital expenses were significantly higher than those in the control group (p < 0.05). The levels of liver function indicators such as alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBIL) were largely decreased in both groups after treatment, and more significant difference was detected in the treatment group (p < 0.05). Renal function between the two groups had no significant difference after treatment (p > 0.05). After treatment, the levels AFP and VEGF were strongly decreased and the level of Caspase-8 was markedly increased in both groups, and the treatment group had lower levels of AFP and VEGF and higher level of Caspase-8 than the control group (p < 0.05). The CD3+ and CD4+/CD8+ levels in two groups were dramatically elevated after treatment, and the treatment group had much higher CD3+ and CD4+/CD8+ levels than the control group (p < 0.05). There was no statistically significant difference in the rates of adverse reactions such as diarrhea, hand-foot syndrome, bone marrow suppression, proteinuria, fever, and pain between the two groups (p > 0.05). CONCLUSIONS: The combination of apatinib and carrilizumab with TACE had better near- and long-term efficacy in the treatment of primary HCC by effectively inhibiting tumor vascular regeneration, inducing tumor cell apoptosis, and improving patients' liver function and immune function with higher safety, which could be widely used in clinical practice.

Epidemiologic and clinical characteristics of 91 hospitalized patients with COVID-19 in Zhejiang, China: a retrospective, multi-centre case series.

BACKGROUND: Recent studies have focused on initial clinical and epidemiological characteristics of the coronavirus disease 2019 (COVID-19), which is the mainly revealing situation in Wuhan, Hubei. AIM: This study aims to reveal more data on the epidemiological and clinical characteristics of COVID-19 patients outside of Wuhan, Zhejiang, China. DESIGN: This study was a retrospective case series. METHODS: Eighty-eight cases of laboratory-confirmed and three cases of clinically confirmed COVID-19 were admitted to five hospitals in Zhejiang province, China. Data were collected from 20 January 2020 to 11 February 2020. RESULTS AND DISCUSSION: Of all 91 patients, 88 (96.70%) were laboratory-confirmed COVID-19 with throat swab samples that tested positive for SARS-Cov-2, three (3.30%) cases were clinically diagnosed. The median age of the patients was 50 (36.5-57) years, and female accounted for 59.34%. In this sample, 40 (43.96%) patients had contracted the disease from local cases, 31 (34.07%) patients had been to Wuhan/Hubei, eight (8.79%) patients had contacted with people from Wuhan, and 11 (12.09%) patients were diagnosed after having flown together in the same flight with no passenger that could later be identified as the source of infection. In particular within the city of Ningbo, 60.52% cases can be traced back to an event held in a temple. The most common symptoms were fever (71.43%), cough (60.44%) and fatigue (43.96%). The median of incubation period was 6 (interquartile range 3-8) days and the median time from the first visit to a doctor to the confirmed diagnosis was 1 (1-2) days. According to the chest computed tomography scans, 67.03% cases had bilateral pneumonia. CONCLUSIONS: Social activity cluster, family cluster and flying alongside with persons already infected with COVID-19 were how people got infected with COVID-19 in Zhejiang.

[Analysis of silica dust detection results in workplace air of somewhere in enterprise].

Objective: To understand the occupational hazard and distribution of silica dust (free SiO(2)≥10%) in the workplace environment of the enterprises in Fengxian District, and to provide scientific basis for improving the working environment and protecting the physical and mental health of the workers. Methods: Individual sampling monitoring and on-site labor hygiene investigation were conducted on 421 workers involved in 87 silicon dust enterprises in the jurisdiction from 2014 to 2018, and measured concentration-time weighted average (C(TWA)) . Results: The results showed that the range of the C(TWA) was (0.021~17.000) mg/m(3), the median was 1.600 mg/m(3), and the qualified rate of 30.88%. The difference of total dust concentration was statistically significant in different years (Z=38.831, P<0.05) . The qualified rate of small-scale enterprises is higher than that of medium-scale enterprises (χ(2)=9.472, P<0.05) . The qualified rate of other domestic enterprises is higher than that of private enterprises and foreign enterprises (χ(2)=10.089, P<0.05) . The acceptance rate of metal products manufacturing is lower than that of general equipment manufacturing and other manufacturing enterprises (χ(2)=64.626, P<0.05) . The qualification rate of natural ventilation is higher than that of mechanical ventilation (χ(2)=6.278, P<0.05) . Conclusion: The enterprises involved in silicon production in Fengxian District need to further strengthen the production process reform and improve the ventilation and dust removal protection measures. Widely carry out the publicity of occupational disease prevention and control law, conduct targeted pre-job training, improve workers' awareness of self-protection, and protect the occupational health of workers in many ways.

Carbon content-tuned martensite transformation in low-alloy TRIP steels.

Ultrahigh strength and good ductility are obtained for two low-alloy transformation-induced-plasticity steels fabricated by the quenching and partitioning (Q&P) processing, respectively. Compared to 0.19 wt.% C steel in which γ → α'-martensite transformation is the dominant mechanism under deformation, the relatively high C content of austenite in 0.47 wt.% C steel is responsible for the transformation from γ to ε-martensite, suggesting that the transformation is not solely determined by the stacking fault energy. The study shows that during the Q&P process, strong and ductile steels with specific transformation procedures can be obtained by adjusting volume fraction and carbon content of the retained austenite.

[Development and Optimization of Therapeutic Analogues of Anti-TNFα Antibody Infliximab].

Previously, we have reported the crystal structures of Fab fragment of Infliximab in complex with TNFα. The structurally identified epitope on TNFα revealed the mechanism of TNFα inhibition by partially overlapping with the TNFα-receptor interface and the possibility to optimize the binding affinity. In this study, we launched a screen of a phage display library to isolate novel anti-TNFα antibodies based on the infliximab epitope. To develop novel anti-TNFα antibodies, structural analysis, the phage display antibody isolation, step by step antibody optimization, CDR residues random mutagenesis, and binding affinity characterization were performed. One of the novel antibodies generated on the backbone of infliximab, Inf3D6, has the superior binding affinity to TNFα, thus, demonstrating the potential for structure guided optimization for improvement of existing antibody-based therapeutics.

[Clinical analysis of lung transplantation in eight patients with obstructive bronchiolitis syndrome after hematopoietic stem cell transplantation].

Objective: To investigate the efficacy and prognosis of lung transplantation (LT) for end-stage bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: The clinical data of eight cases with end-stage BOS after allo-HSCT who were treated by LT in our hospital were retrospectively analyzed. Results: Eight patients with hematological malignancy underwent allo-HSCT, and the median age was 23 (12-40) years. The donors are parents or siblings. Severe BOS occurred in 8 patients after allo-HSCT, the median age for LT was 27.5 (13-47) years. The median interval between allo-HSCT and LT was 69 (21-132) months. The median follow-up time for 8 patients after LT was 15 (6-63) months, 7 patients survived, 1 patient died of pulmonary hemorrhage 15 months after LT treatment. Of the survivors, three had BOS again, and one of them received reduplicated lung transplantation. Conclusion: LT is an effective treatment for patients with severe BOS after HSCT.

Expression profile of eukaryotic translation initiation factor and matrix metalloproteinase 9 in endometrial cancer tissue.

The aim of the present study was to provide a novel method for the diagnosis, prevention and treatment of endometrial cancer by the determination of the characteristic expression of the eukaryotic translation initiation factor 4E (eIF4E) and the enzyme matrix metalloproteinase 9 (MMP9) in endometrial cancer tissue. Three types of endometrial tissue specimens were selected (including 20 cases of normal endometrial tissue specimens, 15 cases of hyperplastic endometrial tissue specimens and 45 cases of endometrial cancer tissue specimens). The expression of eIF4E and MMP9 in the specimens was examined by immunohistochemistry and their corresponding levels were statistically analyzed. The positive expression rates of eIF4E and MMP9 in endometrial cancer specimens were 64.44% and 66.67% respectively, which were higher than those noted in hyperplastic endometrial tissue specimens and normal endometrial tissue specimens (p less than 0.05). The comparisons between the groups indicated that the expression levels of eIF4E and MMP9 in the endometrial cancer specimens were increased compared with those noted in the normal endometrial tissue specimens (p less than 0.0167). In endometrial cancer specimens, the positive expression rates of eIF4E and MMP9 were related to the endometrial cancer stages as determined by the International Federation of Gynecology and Obstetrics (FIGO), tumor cell differentiation degree and lymphatic metastasis (p less than 0.05) classifications. eIF4E expression was positively related to MMP9 expression in endometrial cancer specimens. High expression levels of eIF4E and MMP9 proteins were noted in endometrial cancer specimens, which were correlated with FIGO stages, histological grade and degree of lymphatic metastasis. Thus, endometrial cancer and malignant biological behavior may be connected to the high expression of eIF4E and MMP9. The positive correlation between eIF4E and MMP9 expression in endometrial cancer specimens suggests their potential up-regulation during carcinogenesis.

[Distribution and drug resistance of pathogens at hematology department of Jiangsu Province from 2014 to 2015: results from a multicenter, retrospective study].

Objective: To describe the distribution and drug resistance of pathogens at hematology department of Jiangsu Province from 2014 to 2015 to provide reference for empirical anti-infection treatment. Methods: Pathogens were from hematology department of 26 tertiary hospitals in Jiangsu Province from 2014 to 2015. Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or agar dilution method. Collection of drug susceptibility results and corresponding patient data were analyzed. Results: The separated pathogens amounted to 4 306. Gram-negative bacteria accounted for 64.26%, while the proportions of gram-positive bacteria and funguses were 26.99% and 8.75% respectively. Common gram-negative bacteria were Escherichia coli (20.48%) , Klebsiella pneumonia (15.40%) , Pseudomonas aeruginosa (8.50%) , Acinetobacter baumannii (5.04%) and Stenotropho-monas maltophilia (3.41%) respectively. CRE amounted to 123 (6.68%) . Common gram-positive bacteria were Staphylococcus aureus (4.92%) , Staphylococcus hominis (4.88%) and Staphylococcus epidermidis (4.71%) respectively. Candida albicans were the main fungus which accounted for 5.43%. The rates of Escherichia coli and Klebsiella pneumonia resistant to carbapenems were 3.5%-6.1% and 5.0%-6.3% respectively. The rates of Pseudomonas aeruginosa resistant to tobramycin and amikacin were 3.2% and 3.3% respectively. The resistant rates of Acinetobacter baumannii towards tobramycin and cefoperazone/sulbactam were both 19.2%. The rates of Stenotrophomonas maltophilia resistant to minocycline and sulfamethoxazole were 3.5% and 9.3% respectively. The rates of Staphylococcus aureus, Enterococcus faecium and Enterococcus faecalis resistant wards vancomycin were 0, 6.4% and 1.4% respectively; also, the rates of them resistant to linezolid were 1.2%, 0 and 1.6% respectively; in addition, the rates of them resistant to teicoplanin were 2.8%, 14.3% and 8.0% respectively. Furthermore, MRSA accounted for 39.15% (83/212) . Conclusions: Pathogens were mainly gram-negative bacteria. CRE accounted for 6.68%. The rates of Escherichia coli and Klebsiella pneumonia resistant to carbapenems were lower compared with other antibacterial agents. The rates of gram-positive bacteria resistant to vancomycin, linezolid and teicoplanin were still low. MRSA accounted for 39.15%.

Nanoscale spheroidized cementite induced ultrahigh strength-ductility combination in innovatively processed ultrafine-grained low alloy medium-carbon steel.

We describe here innovative processing of low alloy medium-carbon steel with a duplex microstructure composed of nanoscale spheroidized cementite (Fe3C) in an ultrafine-grained (UFG) ferritic steel. After multi-pass rolling and intermittent annealing at 550 °C for 300 s, the obtained UFG-1 steel showed an average ferrite grain size of ~430 nm, containing nanoscale spheroidized cementite (Fe3C) particles with an average size of ~70 nm. On annealing at 600 °C for 300 s, the average size of ferritic grains was increased to ~680 nm and the average size of spheroidized Fe3C particles increased to ~90 nm, referred as UFG-2 steel. Tensile tests indicated that UFG-1 steel had high yield strength (σ y) of 1260 MPa, and ultimate tensile strength (σ UTS) of 1400 MPa. These values are higher than that of UFG-2 steel (σ y = 1080 MPa and σ UTS = 1200 MPa), suggesting that the strengthening contribution is a cumulative effect of decrease in ferrite grain size and nanoscale cementite. The incoherent interfaces between nanosized particles and the matrix acted as a strong barrier to dislocation motion. The study underscores that nanosized precipitates not only provide strength but also contribute to ductility, which is very encouraging for improving the ductility of medium-carbon steels.

Success of dental implants in vascularised fibular osteoseptocutaneous flaps used as onlay grafts after marginal mandibulectomy.

We have evaluated the survival of dental implants placed in vascularised fibular flap onlay grafts placed over marginal mandibulectomies and the effects on marginal bone loss of different types of soft tissue around implants under functional loading. From 2001-2009 we studied a total of 11 patients (1 woman and10 men), three of whom had had ameloblastoma and eight who had had squamous cell carcinomas resected. A total of 38 dental implants were placed either at the time of transfer of the vascularised fibular ostoseptocutaneous flaps (nine patients with 30 implants) or secondarily (two patients with eight implants). Four patients were given palatal mucosal grafts to replace intraoral skin flaps around the dental implants (n=13), and the other seven had the skin flaps around the dental implants thinned (n=25) at the second stage of implantation of the osteointegrated teeth. All vascularised fibular osteoseptocutaneous flaps were successfully transferred, and all implants survived a mean (range) of 73 (33-113) months after occlusal functional loading. The mean (SD) marginal bone loss was 0.5 (0.3) mm on both mesial and distal sides in patients who had palatal mucosal grafts, but 1.8 (1.6) mm, and 1.7 (1.5) mm, respectively, on the mesial and distal sides in the patients who had had thinning of their skin flaps. This difference is significant (p=0.008) with less resorption of bone in the group who had palatal mucosal grafts. Palatal mucosa around the implants helps to reduce resorption of bone after functional loading of implants.

[Protective effect of glucagon-like peptide-1 analogue on cardiomyocytes injury induced by hypoxia/reoxygenation].

OBJECTIVE: To investigate the effect of glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide on hypoxia/reoxygenation (H/R)-induced cardiomyocytes death under high glucose condition and the potential mechanisms. METHODS: H9C2 cardiomyocytes were divided into 4 groups: normal glucose (N, 5 mmol/L), high glucose (G, 20 mmol/L), high glucose in combination with liraglutide (L, 100 nmol/L), high glucose in combination with liraglutide and wortmannin (W, 25 nmol/L). The apoptosis of H9C2 was detected by TUNEL assay. Nitric oxide synthetase(eNOS), nitric oxide (NO) and reactive oxygen(ROS) in supernatants were measured by enzymatic analysis. p-PI3K, PI3K, p-Akt, Akt, Bcl-2, caspase-3 were examined by western blotting. RESULTS: Compared with cells in N group, the apoptosis of H9C2 cells induced by H/R was markedly increased [(15.79±3.92)% vs (9.74±1.14)%, P=0.028] in G group. The same was true for ROS [(489.63±21.01) U/ml vs (338.50±43.60) U/ml, P<0.001] and caspase-3 levels (1.87±0.03 vs 1.15±0.04, P<0.001), but not for Bcl-2 protein expression (1.79±0.06 vs 1.89±0.03, P=0.047). Pretreatment of cells with liraglutide (100 nmol/L) prevented the cell death induced by high glucose and H/R together with decrease of ROS and caspase-3 levels and increase of Bcl-1 expression. Moreover, treatment of cells with liraglutide also significantly increased phosphorylation of PI3K and Akt (p-PI3K/PI3K: 0.87±0.07 vs 0.59±0.09, P=0.002; p-Akt/Akt: 0.34±0.01 vs 0.08±0.01, P<0.001), eNOS[(41.29±0.56)µmpl/L vs (37.20±0.52)µmpl/L, P<0.001)and NO [(31.24±0.40)µmpl/L vs (26.66±0.53)µmpl/L, P<0.001)levels. Furthermore, addition of PI3K/Akt inhibitor wortmanin markedly inhibited the expression of p-PI3K/PI3K, p-Akt/Akt, reversed the changes of eNOS, NO, caspase-3 and Bcl-2 by liraglutide, and abolished the protective effect of liraglutide on cell apoptosis. CONCLUSIONS: GLP-1 receptor agonist liraglutide treatment could alleviate cardiomyocytes apoptosis induced by high glucose and H/R through the activation of PI3K-Akt-eNOS-NO signaling pathway and inhibition of oxidative stress.

Nanoscale precipitates strengthened lanthanum-bearing Mg-3Sn-1Mn alloys through continuous rheo-rolling.

We elucidate the effect of lanthanum (La) on the microstructure and mechanical properties of Mg-3Sn-1Mn-xLa (wt.%) alloy plates processed through continuous rheo-rolling for the first time. At x = 0.2 wt.%, La dissolved completely in the α-Mg matrix. As the La content was increased to 0.6 wt.%, a new plate-shaped three-phase compound composed of La5Sn3, Mg2Sn and Mg17La2 phases was formed with an average length of 380 ± 10 nm and an average width of 110 ± 5 nm. This compound had a pinning effect on the α-Mg grain boundary and on dislocations. With further increase in La-content to 1.0 wt.%, the length of the plate-shaped compound increased to an average length of 560 ± 10 nm, while the width was reduced to 90 ± 5 nm. The particle size of Mg2Sn decreased from 100 nm to 50 nm with increase in La-content from 0.2 to 1.4 wt.%. At La content of 1.0 wt.%, the tensile strength and elongation of the alloy was maximum, with 29% and 32% increase, respectively, compared to the Mg-3Sn-1Mn (wt.%) alloy, and 37% and 89% increase, in comparison to the Mg-3Sn-1Mn-0.87 Ce (wt.%) alloy.

The change of plasma pituitary adenylate cyclase-activating polypeptide levels after aneurysmal subarachnoid hemorrhage.

OBJECTIVE: Elevated circulating pituitary adenylate cyclase-activating polypeptide (PACAP) levels have been demonstrated to be associated with clinical outcomes of severe traumatic brain injury. The current study aimed to confirm whether elevated plasma PACAP levels are predictive of clinical outcomes of aneurysmal subarachnoid hemorrhage (aSAH). MATERIALS AND METHODS: One hundred and eighteen aSAH patients and 118 controls were recruited. Plasma PACAP concentrations were determined using enzyme-linked immunosorbent assay. Patients were followed up until death or completion of 6 months after aSAH. An unfavorable outcome was defined as Glasgow Outcome Scale score of 1-3. RESULTS: The admission PACAP levels were significantly elevated in all patients (296.6 ± 119.7 pg/ml) compared with controls (77.1 ± 17.9 pg/ml, P < 0.001). Plasma PACAP levels were independently associated with clinical severity indicated by World Federation of Neurological Surgeons (WFNS) score (t = 4.745, P < 0.001) and Fisher score (t = 4.239, P < 0.001) using a multivariate linear regression. PACAP was identified as an independent predictor for 6-month mortality [odds ratio (OR), 1.014; 95% confidence interval (CI), 1.005-1.030; P < 0.001] and 6-month unfavorable outcome (OR, 1.012; 95% CI, 1.006-1.028; P < 0.001) and 6-month overall survival (hazard ratio, 1.016; 95% CI, 1.008-1.023; P < 0.001) using a binary logistic regression analysis and a Cox's proportional hazard analysis, respectively. PACAP had similar predictive values compared with WFNS score and Fisher score according to the receiver operating characteristic curve analysis. CONCLUSIONS: Higher plasma PACAP levels are associated with clinical severity and long-term prognosis of aSAH patients, and PACAP has potential to be a good prognostic biomarker of aSAH.

Effect of sophoridine on Ca²âº induced Ca²âº release during heart failure.

Sophoridine is a type of alkaloid extract derived from the Chinese herb Sophora flavescens Ait (kushen) and possess a variety of pharmacological effects including anti-inflammation, anti-anaphylaxis, anti-cancer, anti-arrhythmic and so on. However, the effect of sophoridine on heart failure has not been known yet. In this study, the effect of sophoridine on heart failure was investigated using Sprague-Dawley (SD) rat model of chronic heart failure. Morphological results showed that in medium and high dose group, myofilaments were arranged orderly and closely, intermyofibrillar lysis disappeared and mitochondria contained tightly packed cristae compared with heart failure group. We investigated the Ca(2+) induced Ca(2+) transients and assessed the expression of ryanodine receptor (RyR2) and L-type Ca(2+) channel (dihydropyridine receptor, DHPR). We found that the cytosolic Ca(2+) transients were markedly increased in amplitude in medium (deltaF/F(0)=43.33+/-1.92) and high dose groups (deltaF/F(0)=47.21+/-1.25) compared with heart failure group (deltaF/F(0)=16.7+/-1.29, P<0.01), Moreover, we demonstrated that the expression of cardiac DHPR was significantly increased in medium- and high dose-group compared with heart failure rats. Our results suggest that sophoridine could improve heart failure by ameliorating cardiac Ca(2+) induced Ca(2+) transients, and that this amelioration is associated with upregulation of DHPR.

Expression of VEGF and its effect on cell proliferation in patients with chronic myeloid leukemia.

OBJECTIVE: The aim of this study is to investigate the expression of vascular endothelial growth factor (VEGF) in the serum of patients with chronic myeloid leukemia (CML) and the effect of VEGF on cell proliferation. PATIENTS AND METHODS: Serum VEGF levels in 12 CML patients (7 chronic phase, 5 blast crisis phase) were measured using enzyme linked immunosorbent assay (ELISA). VEGF expression was interfered by transfection of K562 cells. VEGF mRNA levels in transfected K562 cells were determined using RT-PCR and the effect of VEGF on the proliferation of transfected K562 cells was investigated. RESULTS: VEGF expression levels were significantly higher in CML patients than normal controls and significantly increased during blast crisis phase than during chronic phase. Compared to controls, the proliferation of the K562 cells was suppressed when VEGF expression was inhibited. However, the inhibited proliferation of K562 cells after gene silencing of VEGF was partially abolished after introducing exogenous VEGF into the cells. CONCLUSIONS: VEGF plays an important role in the initiation and development of CML and monitoring serum VEGF assists guiding the treatment and predicting the prognosis of CML.

Molecular cloning and expression analysis of the GNAS gene in pig and porcine fibroblast cells.

The Alpha subunit of the stimulatory guanine nucleotide-binding protein (GNAS) is a complex imprinted gene. The major product of the GNAS gene is the α-subunit of the guanine nucleotide-binding protein (Gas), which plays a key role in multiple signal transduction pathways. Gas is required for the production of the receptor-stimulated intracellular cyclic adenosine monophosphate (cAMP). It has been demonstrated that an increase in the concentration of the intracellular second messenger cAMP promotes apoptosis in different tumor entities. Mutations of GNAS have also been identified in many tumors. This study aimed to investigate the expression pattern and the apoptosis effect in fibroblast cells for porcine GNAS. The results show that GNAS mRNA was detected in a wide range of tissues, especially in the longissimus dorsi muscle and thyroid gland. The developmental pattern of GNAS mRNA in the thyroid gland of Jinhua pigs was then examined; however, there was no significant difference (P > 0.05) among any of the stages. GNAS gene expression was relatively stable in the thyroid gland during the entire growth and development process. The developmental pattern of GNAS mRNA in the longissimus dorsi muscle was significantly different among the various developmental stages (P < 0.01). GNAS mRNA was strongly expressed at 60 days, 90 days, and 150 days after birth, whereas the expression level was very low during the embryo stages. Target RNA interference of GNAS in porcine fibroblast cells leads to lower mRNA expression of Bcl-2, Fas, and Caspase-3, which are recognized as apoptosis related markers.

Cerebral hyperaemia after isoflurane anaesthesia for craniotomy of patients with supratentorial brain tumour.

BACKGROUND: Few studies look into cerebral blood flow (CBF) changes during emergence from general anaesthesia for craniotomy. The purpose of this study was to assess CBF changes during emergence from general anaesthesia for craniotomy, through monitoring blood oxygen saturation of jugular vein bulb (SjvO2 ) and transcranial Doppler (TCD). METHODS: We enrolled 30 patients undergoing selective craniotomy (group C) for supratentorial brain tumour resection and 30 patients undergoing selective abdominal surgery (group A). Mean velocity of middle cerebral artery (Vmca), mean arterial pressure (MAP), SjvO2 (only measured in group C), and arterial CO2 partial pressure were measured before anaesthesia, at tracheal extubation, and 30, 60, 90, 120 min after extubation. RESULTS: Vmca of the same side of tumour was significantly higher than contralateral Vmca before anaesthesia and at all times after extubation in group C. The ipsilateral Vmca increased significantly (95.7 ± 16.9 cm/s vs. 63.7 ± 6.7 cm/s, P < 0.01) at extubation in group C, then declined but still above baseline significantly in the first 2 h after extubation. While Vmca of the right side changed only slightly (63.6 ± 7.7 cm/s vs. 61.8 ± 8.1 cm/s, P < 0.01) but significantly at extubation in group A. SjvO2 increased significantly (81.4% ± 7.4% vs. 60.9% ± 3.7%, P < 0.01) at extubation in group C, and remained above baseline significantly for 2 h. There was no significant correlation between Vmca and MAP at any time. CONCLUSIONS: Cerebral hyperaemia occurs after supratentorial brain tumour resection surgery. The hyperaemia is more pronounced on the same side as the tumour.