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Purpose: To discuss effects of vitexin glucolone (VG) to radiosensitivity of NSCLC (Non-small cell lung cancer) cell lines (A549 and H1299). Methods: Treating A549 and H1299 cells by VG with or without X-radiation. Cell viability was calculated by CCK8. Apoptosis rate was measured by flow cytometry and Western blot to expressions of protein. Subsequently, cells were transferred with TAK1 siRNA, cell viability and apoptosis were measured. Results: VG decreased the viability of Huh7 cells and inhibited effects of VG was more strengthen than radiotherapy in concentrations of 20 μmol/L and 40 μmol/L. Meanwhile, VG sensitized HCC exposed to radiation therapy to apoptosis as demonstrated by increased Bax/Bcl-2 ratio. In addition, VG enhanced the promotive effects of X-radiation on the expressions of TAK1, AMPKα1 and PPARγ. Furthermore, silence the expression of TAK1 partly reversed the effects of VG on HCC and radiosensitivity of NSCLC. Conclusion: VG enhances radiosensitivity of NSCLC via TAK1/AMPK pathway.

Effective classifiers for the prediction of individual adjuvant chemotherapy (AC) benefits are scarce.This study aimed to construct a useful classifier to predict the AC benefit and recurrence hazard based on preoperative hematological indices through a multicenter database.Multivariate analysis revealing GCRF (comprehensive deep learning classifier) as an independent prognostic factor associated with overall survival (OS) and disease-free survival (DFS). Locally advanced gastric cancer (LAGC) patients are categorized into the high-risk group (HRG) and low-risk group (LRG). In HRG, OS and DFS of the AC group are significantly higher than those of the non-AC group (all p˂0.05), whereas in LRG, OS and DFS of the AC group are comparable to those of the non-AC group (all p gt; 0.05). Furthermore, combined GCRF with 8th AJCC TNM staging system, only 650 (51.1%) patients can benefit most from AC among 1273 patients with pStage II-III. From the perspective of recurrence pattern, the recurrence rate of HRG is significantly higher than that of LRG in any recurrence type, including local recurrence, peritoneal recurrence, and distant recurrence (all p˂0.05). Furthermore, the mean time to peritoneal recurrence and lung metastasis in HRG is earlier than that in the LRG (p = 0.028 and 0.011, respectively).In summary, our novel classifier based on deep learning preoperative hematological indices can predict not only the AC benefit of LAGC patients, but also the recurrence hazard after surgery. This classifier is expected to be an effective supplement to the 8th AJCC TNM staging system for the prediction of AC benefits and is helpful for clinical decision in AC individual administration. Further large-scale western studies are warranted.

Few studies have reported the association between the pattern and time point of recurrence in different groups stratified by age in postoperative survival of patients with gastric cancer.The clinicopathological data and recurrence data of 2028 patients with GC who underwent curative surgery from January 2010 to March 2015 were enrolled in this study. Patients were grouped according to age: young group (YG) (≤45 years old) (n = 180) and non-young group (OG) (gt;45 years old) (n = 1848).A total of 2028 patients were enrolled. The young group had better 5-year OS and DFS than the non-young group. In peritoneal recurrence, the cumulative incidence of recurrence in YG was higher than that in OG (P lt; 0.001). In distant recurrence, the cumulative incidence of recurrence YG was always lower than that of OG (P = 0.004). Recurrence hazard function varied over time between the two groups:in the peritoneal metastasis, the recurrence hazard for YG was higher and earlier than that of OG and the YG was observed during five years after surgery with two recurrence peaks in 8.5 months and in 41.5 months. In distant recurrence, the recurrence hazard for OG had an earlier and higher single peak than that of YG (6.0 months).The recurrence characteristics of patients with gastric cancer after curative resection between young group and older group are different. Personalized follow-up strategies should be developed according to the age and time point after operation for the early detection of recurrence and making decision for further treatment.

ImportanceThe survival benefit of laparoscopic total gastrectomy combined with spleen-preserving splenic hilar lymphadenectomy (LSTG) for locally advanced proximal gastric cancer (APGC) without invasion into the greater curvature remains uncertain.ObjectiveTo compare the long-term and short-term efficacy of LSTG (D2 + No. 10 group) and conventional laparoscopic total gastrectomy (D2 group) for patients with APGC that has not invaded the greater curvature.Design, Setting, and ParticipantsIn this open-label, prospective randomized clinical trial, a total of 536 patients with clinical stage cT2 to 4a/N0 to 3/M0 APGC without invasion into the greater curvature were enrolled from January 2015 to October 2018. The final follow-up was on October 31, 2021. Data were analyzed from December 2021 to February 2022.InterventionsEligible patients were randomized to the D2 + No. 10 group or the D2 group.Main Outcomes and MeasuresThe primary outcome was 3-year disease-free survival (DFS). The secondary outcomes were 3-year overall survival (OS) and morbidity and mortality within 30 days after surgery.ResultsOf 526 included patients, 392 (74.5%) were men, and the mean (SD) age was 60.6 (9.6) years. A total of 263 patients were included in the D2 + No. 10 group, and 263 were included in the D2 group. The 3-year DFS was 70.3% (95% CI, 64.8-75.8) for the D2 + No. 10 group and 64.3% (95% CI, 58.4-70.2; P = .11) for the D2 group, and the 3-year OS in the D2 + No. 10 group was better than that in the D2 group (75.7% [95% CI, 70.6-80.8] vs 66.5% [95% CI, 60.8-72.2]; P = .02). Multivariate analysis revealed that splenic hilar lymphadenectomy was not an independent protective factor for DFS (hazard ratio [HR], 0.86; 95% CI, 0.63-1.16) or OS (HR, 0.81; 95% CI, 0.59-1.12). Stratification analysis showed that patients with advanced posterior gastric cancer in the D2 + No. 10 group had better 3-year DFS (92.9% vs 39.3%; P P Conclusions and RelevanceAlthough LSTG could not significantly improve the 3-year DFS of patients with APGC without invasion into the greater curvature, patients with APGC located posterior gastric wall may benefit from LSTG.Trial RegistrationClinicalTrials.gov Identifier: NCT02333721

Background Preoperative imaging examination is the primary method for diagnosing metastatic gastrointestinal stromal tumor (GIST), but it is associated with a high rate of missed diagnosis. Therefore, it is important to establish an accurate model for predicting occult peritoneal metastasis (PM) of GIST. Patients and methods GIST patients seen between April 2002 and December 2018 were selected from an institutional database. Using multivariate logistic regression analyses, we created a nomogram to predict occult PM of GIST and validated it with an independent cohort from the same center. The concordance index (C-index), decision curve analysis (DCA) and a clinical impact curve (CIC) were used to evaluate its predictive ability. Results A total of 522 eligible GIST patients were enrolled in this study and divided into training (n=350) and validation cohorts (n=172). Factors associated with occult PM were included in the model: tumor size (odds ratio [OR] 1.194 95% confidence interval [CI], 1.034-1.378; p=0.016), primary location (OR 7.365 95% CI, 2.192-24.746; p=0.001), tumor capsule (OR 4.282 95% CI, 1.209-15.166; p=0.024), Alb (OR 0.813 95% CI, 0.693-0.954; p=0.011) and FIB (OR 2.322 95% CI, 1.410-3.823; p=0.001). The C-index was 0.951 (95% CI, 0.917-0.985) in the training cohort and 0.946 (95% CI, 0.900-0.992) in the validation cohort. In the training cohort, the prediction model had a sensitivity of 82.8%, a specificity of 93.8%, a positive predictive value of 54.7%, and a negative predictive value of 98.4%; the validation cohort values were 94.7%, 85.0%, 43.9% and 99.2%, respectively. DCA and CIC results showed that the nomogram had clinical value in predicting occult PM in GIST patients. Conclusion Imaging and inflammatory indexes are significantly associated with microscopic metastases of GIST. A nomogram including these factors would have an excellent ability to predict occult PM.

Purpose Gastrointestinal stromal tumors (GISTs) are commonly known to be derived from the gastrointestinal (GI) tract, but recently there have been more and more literature describing lesions with similar pathological and immunohistochemical resembling GISTs but located outside the GI tract, and they have been termed as extra-GISTs (eGISTs). However, due to the rare incidence of eGISTs, its association with survival outcomes is poorly understood, especially in the Chinese population. Here, we aimed to identify the risk factors of eGISTs and to assess their association with overall survival (OS) and disease-free survival (DFS). Patients and methods Data of pathologically confirmed eGISTs cases, without radiological and perioperative evidence of other primary lesions, and with no microscopically identified adhesion between the tumor and the gastrointestinal serosa, which were surgically treated between January 2006 and September 2017 were retrieved from the database of four high-volume hospitals. Immunohistochemical and genetic testing were performed on the postoperative lesions and were staged using the National Institutes of Health (NIH) criteria. Results A total of 55 cases were retrieved. eGISTs were identified from the retroperitoneum (36.4%), mesocolon (25.5%), small bowel mesentery (12.7%), abdominopelvic cavity (12.7%), lesser omental sac (5.5%), ovary (3.6%), pancreatic capsule (1.8%), or urinary bladder (1.8%). Based on the NIH risk classification, majority of the lesion were classified as high risk (85.5%). KIT 11 was the most common mutation site (76.5%) and 25.0% of the cases were wild-type eGISTs. Multivariate analyses showed that tumor location and size were independent factors affecting prognoses. Patients with tumors in the retroperitoneum had significantly poorer OS and DFS as compared to those in the non-retroperitoneum (HR [95% CI] for OS and DFS: 2.546 [1.023-6.337] [P = 0.037] and 2.475 [0.975-6.273] [P = 0.049], respectively). Similar findings were found for tumors of size >15 cm, compared to ≤15 cm (HR [95% CI] for OS and DFS: 5.350 [2.022-14.156] [P Conclusion eGISTs were predominantly found from the retroperitoneum and mostly classified as high risk. Those located in the retroperitoneum and of size >15 cm had the poorer OS and DFS as compared to those in the non-retroperitoneum and of size

Purpose The potential additive influence of adjuvant chemotherapy (AC) on prognosis of patients with stage II/III gastric cancer (GC) who experienced complications after radical surgery is unclear.Methods The whole group was divided into a postoperative complication (PC) group and a postoperative non-complication (NPC) group, and the overall survival (OS) rate, recurrence-free survival (RFS) rate and recurrence rate were compared between the two groups of patients. Results A total of 1563 patients between January 2010 and December 2015 in our center were included in this analysis. There were 268 patients (17.14%) in the PC group and 1295 patients (82.86%) in the NPC group. The 5-year OS rate of the PC group was 55.2%, the NPC group was 63.3%; and the 5-year RFS rate of the PC group was 53.7%, the non-PC group was 58.8%. Recurrence patterns showed no significant difference between the two group (all p>0.05). Adjuvant chemotherapy (AC) significantly improved the OS and RFS rates of patients with and without PCs (both p 0.05). Stratified analysis showed that AC only improve the OS or RFS rates of stage III patients (both pConclusion AC can abolish the negative effect of PCs on the long-term survival of patients with stage III GC; for stage II patients, the above offset effect is affected by the TI. Delaying AC initiation after 6 weeks may not improve the survival of patients experienced stage II GC with complications.

D-dimer (DDI) and albumin are prognostic markers for numerous cancers; however, the predictive value of the preoperative DDI-to-albumin ratio (DAR) on the survival and recurrence patterns of gastric cancer (GC) remains unclear.The aim of this study was to explore the prognostic value of the DAR in GC.Our study included 1766 patients with GC, divided into training and testing cohorts at a ratio of 7:3. Patients were classified into either a high-DAR group (0.0145) or low-DAR group (≤ 0.0145) according to the cut-off value of receiver operating characteristic (ROC) curve analysis. The relationship between the DAR and recurrence pattern was analyzed in stage II/III patients.Eight preoperative hematological factors were included and 17 composite inflammatory markers were constructed. ROC and random forest analyses indicated that among 17 markers, DAR was the best predictor for overall survival (OS) in GC (p 0.01). High DAR was significantly associated with poor OS (hazard ratio [HR] 1.89, p 0.001) and recurrence-free survival (RFS; HR 1.85, p 0.001). Subgroup analysis showed no differences in OS and RFS between the high- and low-DAR groups in stage I or pT1/2 or pN0/1 patients; however, in stage II/III or pT3/4 or pN2/3 patients, the high-DAR group had shorter OS and RFS rates than the low-DAR group (p 0.001). Similar results were found in the testing cohort. According to the multivariate analysis based on the training cohort, five indices, including DAR, cT stage, cN stage, age and body mass index (BMI), were incorporated to establish a nomogram model to predict the long-term prognosis of GC. The model showed comparable forecast performance in predicting OS (C-index: 0.773 vs. 0.786) and RFS (C-index: 0.788 vs. 0.795) compared with pTNM. Recurrence pattern analysis in stage II/III patients showed that the high-DAR group had a higher incidence of peritoneal implantation and early recurrence (ER) than the low-DAR group, and the post-recurrence survival in the high-DAR group was significantly shorter than that in the low-DAR group (p = 0.016).The preoperative DAR is a new biomarker for the long-term survival prediction of GC. In advanced GC, a preoperative DAR0.0145 aids the timely detection of ER and peritoneal recurrence after surgery, thus guiding individual follow-up strategies.

Fluorescence spectroscopy (FS) has been used to characterize tissue fluorophores in vivo for the diagnosis of precancers in the uterine cervix. In this study, a two-step curve fitting process is established to extract the intrinsic fluorescence intensity and spectrum of fluorophores including NADH and FAD in the epithelium and collagen crosslinks in the stroma. Forward Monte Carlo (MC) models of diffuse reflectance spectroscopy (DRS) and FS are replaced by artificial neuron networks to improve the computation speed. First, absorption and scattering coefficients of the two tissue layers and the epithelial thickness are estimated from DRS data. Second, the genetic algorithm is used to find the best set of intrinsic fluorescence parameters of the three fluorophores that best fit measured FS data. Results suggest that the two-layered tissue model outperforms conventional homogeneous tissue models in extracted tissue optical properties. Intrinsic fluorescence parameters are extracted from in-vivo spectra measured on 31 subjects.

It remains inconclusive whether laparoscopic gastrectomy (LG) has better long-term outcomes when compared with open gastrectomy (OG) for elderly gastric cancer (EGC). We attempted to explore the influence of the immune prognostic index (IPI) on the prognosis of EGCs treated by LG or OG to identify a population among EGC who may benefit from LG. We included 1539 EGCs treated with radical gastrectomy from January 2007 to December 2016. Propensity score matching was applied at a ratio of 1:1 to compare the LG and OG groups. The IPI based on dNLR ≥ cut-off value (dNLR) and sLDH ≥ cut-off value (sLDH) was developed, characterizing two groups (IPI = 0, good, 0 factors; IPI = 1, poor, 1 or 2 factors). Of the 528 EGCs (LG: 264 and OG: 264), 271 were in the IPI = 0 group, and 257 were in the IPI = 1 group. In the entire cohort, the IPI = 0 group was associated with good 5-year overall survival (OS) (p = 0.001) and progression-free survival (PFS) (p = 0.003) compared to the IPI = 1 group; no significant differences in 5-year OS and PFS between the LG and OG groups were observed. In the IPI = 1 cohort, there was no significant difference in OS or PFS between the LG and OG groups across all tumor stages. However, in the IPI = 0 cohort, LG was associated with longer OS (p = 0.015) and PFS (p = 0.018) than OG in stage II EGC, but not in stage I or III EGC. Multivariate analysis showed that IPI = 0 was an independent protective factor for stage II EGC receiving LG, but not for those receiving OG. The IPI is related to the long-term prognosis of EGC. Compared with OG, LG may improve the 5-year survival rate of stage II EGC with a good IPI score. This hypothesis needs to be further confirmed by prospective studies.

In this paper, a novel design of a tunable narrow band-pass LC FSS resonating at Ka-band frequencies, with a 3 dB bandwidth closed to 4.3% of its center frequency that has simulated numerically is reported.

Background Preoperative imaging examination is the primary method for diagnosing metastatic gastrointestinal stromal tumor (GIST), but it is associated with a high rate of missed diagnosis. Therefore, it is important to establish an accurate model for predicting occult peritoneal metastasis (PM) of GIST. Patients and Methods GIST patients seen between April 2002 and December 2018 were selected from an institutional database. Using multivariate logistic regression analyses, we created a nomogram to predict occult PM of GIST and validated it with an independent cohort from the same center. The concordance index (C-index), decision curve analysis (DCA) and a clinical impact curve (CIC) were used to evaluate its predictive ability. Results A total of 522 eligible GIST patients were enrolled in this study and divided into training (n=350) and validation cohorts (n=172). Factors associated with occult PM were included in the model: tumor size (odds ratio [OR] 1.194 95% confidence interval [CI], 1.034–1.378; p=0.016), primary location (OR 7.365 95% CI, 2.192–24.746; p=0.001), tumor capsule (OR 4.282 95% CI, 1.209–15.166; p=0.024), Alb (OR 0.813 95% CI, 0.693–0.954; p=0.011) and FIB (OR 2.322 95% CI, 1.410–3.823; p=0.001). The C-index was 0.951 (95% CI, 0.917–0.985) in the training cohort and 0.946 (95% CI, 0.900–0.992) in the validation cohort. In the training cohort, the prediction model had a sensitivity of 82.8%, a specificity of 93.8%, a positive predictive value of 54.7%, and a negative predictive value of 98.4%; the validation cohort values were 94.7%, 85.0%, 43.9% and 99.2%, respectively. DCA and CIC results showed that the nomogram had clinical value in predicting occult PM in GIST patients. Conclusion Imaging and inflammatory indexes are significantly associated with microscopic metastases of GIST. A nomogram including these factors would have an excellent ability to predict occult PM.

This letter proposes the use of carbon black film in absorbing high-frequency power. This low-cost material can be obtained easily using a low-cost fabrication process (i.e., screen printer). The 70 wt% carbon black film is 0.055-mm thick, with sheet resistance of $162~\Omega $ /sq and conductivity of 113.6 S/m. Results show that carbon black film absorbs high-frequency signal, and the power loss reaches 70% at 3 GHz. Moreover, the starting suppression frequency could be controlled by adjusting the proportion of carbon black.

In this paper, Al-doped ZnO (AZO) films are deposited on glasses substrate by RF magnetron sputtering. The optical, electrical and morphological properties of AZO films textured by wet-etching with different etchants, H3PO4, HCl, and HNO3 are studied. It is found that the textured structure could enhance the light scattering and light trapping ability of amorphous silicon solar cells. The textured AZO film etched with HNO3 exhibits optimized optical properties (T% ≧ 80% over entire wavelength, haze ratio > 40% at 550 nm wavelength) and excellent electrical properties (ρ = 5.86 × 10−4 Ωcm). Scanning electron microscopy and Atomic force microscopy are used to observe surface morphology and average roughness of each textured AZO films. Finally, the textured AZO films etched by H3PO4, HCl and HNO3 were applied to front electrode layer for p–i–n amorphous silicon solar cells. The highest conversion efficiency of amorphous silicon solar cell fabricated on HNO3-etched AZO film was 7.08% with open-circuit voltage, short-circuit current density and fill factor of 895 mV, 14.92 mA/cm2 and 0.56, respectively. It shows a significantly enhancement in the short-circuit current density and conversion efficiency by 16.2% and 20.2%, respectively, compared with the solar cell fabricated on as-grown AZO film.

As a result of the growing use of wireless communication devices, high-frequency noise issues are becoming increasingly important. In this study, a graphene film is utilized as a high-frequency power absorber. Epoxy is mixed with the graphene to adjust its conductivity. The graphene film is deposited onto a microstrip line of FR4 substrates via screen printing technology. Experimental results show that graphene film is with a sheet resistance of 114 Ω/sq and a conductivity of 973 S/m and its power loss reaches 70% at 1.35 GHz.

A novel compact multiband planar antenna fed by a microstrip line structure is presented. The proposed antenna is developed for wireless communication applications of the global system for mobile (GSM) communication and long-term evolution (LTE) in different service bands of 900, 1800, 1900, 2300, and 2500 MHz. The antenna has five bands, and the structure is a combination of a monopole antenna and a coupled ground line fabricated on an FR4 substrate. The proposed antenna can be embedded in mobile phones for GSM and LTE applications. The measured peak gains are ∼2.12 and 3.82 dBi for the GSM and LTE bands, respectively.

Many studies have examined the association between coffee consumption and risk of cardiovascular disease, but the results remain controversial. Caffeine is one of the main biologically active compounds of coffee. The aim of this study was to investigate the potential role of caffeine on myocardial ischemia/reperfusion (I/R) injury in the rats. We administered caffeine (25 mg/kg per day) or saline in rats for 4 weeks before myocardial ischemia/reperfusion operation. Compared with the sham group, caffeine treatment decreased ischemia-associated infarct size, serum creatine kinase, and lactate dehydrogenase 3-h reperfusion after 30-min ischemia. Myocardial neutrophil infiltration (assessed by myeloperoxidase activity) was significantly decreased compared with the control group. Meanwhile, caffeine reduced the myocardial apoptosis and suppressed the activation of caspase 3 during myocardial I/R. Importantly, we observed a strong poly(ADP-ribose) polymerase (PARP) activation during myocardial I/R, and caffeine administration inhibited PARP activation and attenuated the expression of PARP-related proinflammatory mediators such as inducible nitric oxide synthetase, IL-6, and TNF-α, all of which may be correlated with downregulated nuclear factor κB activity. We concluded that caffeine protected against myocardial I/R injury by inhibiting inflammation and apoptosis.

Cardiac hypertrophy, a major determinant of heart failure, is associated with heat shock proteins (HSPs). HSP75 has been reported to protect against environmental stresses; however, its roles in cardiac hypertrophy remain unclear. Here, we generated cardiac-specific inducible HSP75 transgenic mice (TG) and cardiac hypertrophy was developed at 4 weeks after aortic banding in TG mice and wild-type littermates. The results revealed that overexpression of HSP75 prevented cardiac hypertrophy and fibrosis as assessed by heart weight/body weight ratio, heart weight/tibia length ratio, echocardiographic and hemodynamic parameters, cardiomyocyte width, left ventricular collagen volume, and gene expression of hypertrophic markers. Further studies showed that overexpression of HSP75 inhibited the activation of TAK/P38, JNK, and AKT signaling pathways. Thus, HSP75 likely reduces the hypertrophy and fibrosis induced by pressure overload through blocking TAK/P38, JNK, and AKT signaling pathways.

Long Term Evolution (LTE) is the latest standard in mobile networking technology. A monopole antenna for LTE, using three resonance routes, fabricated on 0.8mm thick FR4, is proposed in this work. The radiator length, inductor circuit and coupling were tuned to get the operation frequency, and it is suitable for the LTE700/GSM900/GSM1800/GSM1900/UMTE2100/LTE2600. Simulator HFSS and vector network analyzer were used to simulate and measure frequency response of the antenna, respectively.

To investigate the effects and mechanism of verapamil preventing ischemia/reperfusion (I/R) injury by cardiac performance intracellular free [Ca(2+)](i) and L-type calcium current (I(Ca-L)) in cardiomyocytes of diabetes mellitus rats.Diabetic rats were streptozotocin-induced and received verapamil (8 mg×kg(-1)×d(-1)) from 6 - 14 weeks old. The in vitro heart models of I/R rats were randomly divided into normal control group diabetes group, verapamil control group. the changes of heart functions were observed through a Langendorff-perfusion system. The fluorescence intensity of intracellular Ca(2+) was detected with Fluo-3/AM loading by laser scanning confocal microscope. I(Ca-L) was recorded by the whole-cell technique of patch clamp in enzymatically dissociated single rat ventricular myocytes.(1) In verapamil diabetes group, the values of left ventricular developed pressure [(91.3 ± 4.6) mm Hg], diastolic end pressure [(1535 ± 280) mm Hg], the maximum rising rates of left ventricular pressure [(5833 ± 256) mm Hg/s] and coronary arterial flow [(13.7 ± 0.9) ml/min] were all significantly increased, and the maximum dropping rates of left ventricular pressure [(3504 ± 319) mm Hg/s] was obviously decreased (compared with diabetes group, P0.01, respectively). (2) The fluorescence intensities of intracellular free Ca(2+)[(155.6 ± 10.9) nmol/L] in verapamil diabetes group were significantly reduced compared with diabetes group (245.2 ± 17.5 nmol/L, P0.01). (3) When clamp voltage was -20mV, I(Ca-L) was (-6.81 ± 0.76) pA/pF in verapamil diabetes group (compared with normal group (-8.17 ± 2.07) pA/pF, P0.05, and with diabetes group (-3.21 ± 0.54) pA/pF, P0.01, and with verapamil control group (-7.14 ± 2.17) pA/pF, P0.05). The current-voltage curve was changed to the lower position with -20mV of peak clamp potential in verapamil diabetes group compared with diabetes group.A poor heart function is closely correlated with a rising [Ca(2+)]i and a declining I(Ca-L) associated with I/R injury in diabetic rats hearts. Along-term verapamil therapy may significantly improve the severe cardiac impairment. The mechanism is probably attributed to the fact that verapamil can adjust I(Ca-L) influx, normalize the balance of intercellular [Ca(2+)]i, and block the Ca(2+) overload trigger by the effects of Ca(2+)-induced Ca(2+) release in diabetic cardiomyocytes.

To investigate the effects of curcumin on sarcoplasmic reticulum Ca2+-ATPase in heart failure rabbits.Rabbit heart failure model was made with aortic regurgitation and abdominal aorta constriction and 40 rabbits were randomly divided into 4 groups including: (1) heart failure treated with curcumin; (2) heart failure treated with placebo; (3) healthy control treated with curcumin and (4) healthy control treated with placebo. All rabbits were administrated with curcumin capsules or placebo capsules 100 mg x kg(-1) x d(-1), respectively. All groups were sacrificed after eight weeks. Myocardial ultrastructural organization was detected by transmission electron microscope. RT-PCR and Western blot were used to measure the expression of sarcoplasmic reticulum Ca2+-ATPase in mRNA and protein levels, respectively. Malachite green colorimetric assay was used to evaluate the activity of sarcoplasmic reticulum Ca2+-ATPase.All detected parameters were similar between control curcumin group and control placebo group. Compared with the control groups (Groups 3 and 4), the heart/body weight ratio was significantly increased in the heart failure-curcumin group (Group 1) and the heart failure-placebo group (Group 2, all P0.05), but the ratio was significantly lower in heart failure-curcumin group than in heart failure-placebo group (P0.05). The degree of heart failure was decreased by curcumin. Activity and mRNA and protein expression for sarcoplasmic reticulum Ca2+-ATPase were significantly reduced in the heart failure-placebo group and which could be significantly attenuated by curcumin (all P0.05).Curcumin could improve cardiac function via upregulating the expression of sarcoplasmic reticulum Ca2+-ATPase in this model.

To investigate the influences of verapamil preconditioning on cardiac function in vitro and intracellular free Ca2+ and L-type calcium current (I(Ca-L)) in rat cardiomyocytes post ischemia-reperfusion (I/R) injury.The isolated rat hearts in control group (37 degrees C Tyrode solution perfusion for 30 min, n = 6), I/R group (no flow for 30 min followed 30 min reperfusion with 37 degrees C Tyrode solution, n = 7) and verapamil preconditioning group [37 degrees C Tyrode solution perfusion for 10 min, adding verapamil (20 micromol/L) to Tyrode solution and perfusion for another 30 min, followed then by 30 min no flow and 30 min reperfusion, n = 7] using Langendorff perfusion system. The fluorescence intensity of intracellular Ca2+ was detected with Fluo-3/AM loading by the laser scanning confocal microscope. The I(Ca-L) was recorded via whole-cell patch clamp technique in enzymatically dissociated single rat ventricular myocytes.As expected, arrhythmias and cardiac dysfunction were shown post I/R injury. The fluorescence intensities of intracellular free Ca2+ in cardiomyocytes were significantly increased compared with control group (P0.01). By voltage clamp protocol, peak current densities of I(Ca-L) was significantly reduced and I-V curve significantly elevated. Post I/R injury compared with control group (P0.01) which could be reversed by Verapamil preconditioning. Verapamil preconditioning also significantly improved diastolic and systolic functions, and reduced the incidence of arrhythmias.Myocardial I/R injury might significantly impair heart functions and induce arrhythmias via cellular Ca2+ overload. Verapamil preconditioning could prevent heart I/R injury and reduce arrhythmias by decreasing influx of I(Ca-L), thereby stabilizing cardiomyocytes in myocardial stunning and avoiding occurrence of Ca2+-induced Ca2+ release during I/R injury.

To investigate the role of heterogeneous expression of calcium handling proteins and spatial heterogeneity of APD restitution in the maintenance mechanism of ventricular fibrillation.During programmed electrical simulation, APD restitution curves in the endocardium and epicardium of LV were constructed by plotting APD100 and diastolic interval. APD alternans, delayed after depolarization events were recorded simultaneously. Endocardial and epicardial myocytes were isolated from LV base and apex. Real time-PCR and Western blotting were performed to determine the relative messenger RNA and protein expression levels of calcium handling proteins.The normal hearts have spatial heterogeneity of action potential restitution property and transmural heterogeneity of calcium handling proteins. The slopes of the APD restitution curve in the endocardium were significantly steeper than those in epicardium, and the slopes of APD curve at the LV apex were significantly steeper than those in LV base. However, delayed after depolarization events with larger amplitude and earlier onset consistently occurred in the endocardium of LV base. After programmed electrical simulation, the expression of messenger RNA of RyR2, SERCA2a except for Calstabin2 significantly decreased (by 57% and 41%, respectively, P0.05) in the endocardium of the base, while the expression of RyR2, SERCA2a, Calstabin2 significantly increased (by 90%, 78%and 64%, respectively, P0.05) in the epicardium of LV base. Although transmural heterogeneity of calcium handling proteins at the LV apex were also observed after rapid pacing, there is no significant differences in the transmural heterogeneity at the LV apex compared to the LV base. The base of LV has unique calcium handling properties.It has been shown that Calcium cycling could modulate APD restitution property in the intact heart. The interaction between action potential and calcium dynamics instabilities is one of the most important reasons why simple criterion such as the APD restitution slope1 may fail to accurately predict the onset of APD alternans.

The aim of the present study was to investigate the role of anti-inflammation for MSCs transplantation in rat models of myocardial infarction. Rats with AMI induced by occlusion of the left coronary artery were randomized to MSCs transplantation group, MI group and sham operated group. The effects of MSCs transplantation on cardiac inflammation and left ventricular remodeling in non-infarcted zone were observed after 4 weeks of MI. We found that MSC transplantation (1) decreased protein production and gene expression of inflammation cytokines TNF-alpha, IL-1beta and IL-6, (2) inhibited deposition of type I and III collagen, as well as gene and protein expression of MMP-1 and TIMP-1, (3) attenuated LV cavitary dilation and transmural infarct thinning, thus prevent myocardial remodeling after myocardial infarction, and (4) increased EF, FS, LVESP and dp/dtmax (P < 0.01), decreased LVDd, LVEDV, LVEDP (P < 0.05). Anti-inflammation role for MSCs transplantation might partly account for the cardiac protective effect in ischemic heart disease.

To investigate whether autologous transplantation of adult stem cells could improve post-infarcted heart function.Bone marrow mononuclear cells (MNCs) were isolated from adult rabbits' tibias after coronary ligation. These cells were exposed to 5-azacytidine 10 micromol/L for 24 h on the third day of culture. After being labeled with bromodeoxyuridine (BrdU), the cells were auto-transplanted into bordering zone of the infarcted area at 2 weeks after injury. The animals were killed at 3 days, 2 weeks, 1 month, and 2 months after transplantation, respectively. The left ventricular functions, capillary density, and cardiac nerve density were measured and the differentiation of the engrafted cells was determined by immunostaining.BrdU-labeled MNCs were well aligned with the host cardiomyocytes. Parts of them were incorporated into capillary and arteriolar vessel walls. In addition to inducing angiogenic ligands (basic fibroblast growth factor, vascular endothelial growth factor) and inflammation cytokines (interleukin 1-beta) during the early period of MNCs implantation, MNCs induced 2.0-fold increase in capillary density as well. Moreover, GAP43-positive and TH-positive nerve density were markedly higher in the MNCs-treated groups than that in the non-treated hearts. Left ventricular ejection fraction, LV+dp/dt(max), and LV-dp/dt(max) were 47%, 67%, and 55% in MNCs-treated heart respectively, which was higher than that of the control heart, whereas left ventricular end-diastolic volume, left ventricular end-diastolic diameter, and left ventricular end-diastolic pressure were 45%, 22%, and 50% respectively in MNCs-treated heart, which was lower than that of the control heart at 2 months after cell transplantation.Autologous transplantation of MNCs induced angiogenesis and nerve sprouting and improved left ventricular diastolic function.