Nonadiabatic Charge Transfer within Photoexcited Nickel Porphyrins.

Metalloporphyrins with open d-shell ions can drive biochemical energy cycles. However, their utilization in photoconversion is hampered by rapid deactivation. Mapping the relaxation pathways is essential for elaborating strategies that can favorably alter the charge dynamics through chemical design and photoexcitation conditions. Here, we combine transient optical absorption spectroscopy and transient X-ray emission spectroscopy with femtosecond resolution to probe directly the coupled electronic and spin dynamics within a photoexcited nickel porphyrin in solution. Measurements and calculations reveal that a state with charge-transfer character mediates the formation of the thermalized excited state, thereby advancing the description of the photocycle for this important representative molecule. More generally, establishing that intramolecular charge-transfer steps play a role in the photoinduced dynamics of metalloporphyrins with open d-shell sets a conceptual ground for their development as building blocks capable of boosting nonadiabatic photoconversion in functional architectures through "hot" charge transfer down to the attosecond time scale.

A study on the perioperative effects of obesity on minimally invasive coronary artery bypass grafting and its surgical techniques.

OBJECTIVES: The aim of this study was to discuss the perioperative effects of obesity on minimally invasive coronary artery bypass grafting (CABG) and its surgical techniques. METHODS: A total of 582 patients with multivessel lesion who underwent off-pump CABG by our medical group of Beijing Anzhen Hospital between January 2017 and January 2021 were divided into the minimally invasive cardiac surgery (MICS) group and the conventional group (median sternotomy) according to the surgical method used. The body mass index of the patients was calculated, based on which both groups were divided into obese (≥28 kg/m2) and non-obese subgroups (<28 kg/m2). First, the perioperative data of the obese subgroups of both MICS and conventional groups were compared. Second, the obese and non-obese subgroups were compared in the MICS group. RESULTS: Despite a higher proportion of diabetes in the MICS group, there was no significant difference in preoperative baseline nor in the incidence of major complications within 30 days after surgery between obese subgroups of the MICS and conventional groups. The MICS group had a significantly lower rate of poor wound healing, along with a higher predischarge Barthel Index. Also, the preoperative baseline between the obese and non-obese subgroups of the MICS group exhibited no statistical differences. The obese subgroup had longer postoperative ventilator assistance, while other intraoperative data and postoperative observation indexes exhibited no significant differences. CONCLUSIONS: MICS CABG method is safe and feasible for obese patients with multivessel lesion. Minimally invasive surgery is beneficial to wound healing in obese patients. However, it requires a thorough preoperative evaluation and adequate surgical experience and skills.

A Web-Based Prediction Model for Estimating the Probability of Post-hepatectomy Major Complications in Patients with Hepatocellular Carcinoma: A Multicenter Study from a Hepatitis B Virus-Endemic Area.

BACKGROUND: The identification of patients at high risk of developing postoperative complications is important to improve surgical safety. We sought to develop an individualized tool to predict post-hepatectomy major complications in hepatitis B virus (HBV)-infected patients with hepatocellular carcinoma (HCC). METHODS: A multicenter database of patients undergoing hepatectomy for HCC were analyzed; 2/3 and 1/3 of patients were assigned to the training and validation cohorts, respectively. Independent risks of postoperative 30-day major complications (Clavien-Dindo grades III-V) were identified and used to construct a web-based prediction model, which predictive accuracy was assessed using C-index and calibration curves, which was further validated by the validation cohort and compared with conventional scores. RESULTS: Among 2762 patients, 391 (14.2%) developed major complications after hepatectomy. Diabetes mellitus, concurrent hepatitis C virus infection, HCC beyond the Milan criteria, cirrhosis, preoperative HBV-DNA level, albumin-bilirubin (ALBI), and aspartate transaminase to platelet ratio index (APRI) were identified as independent predictors of developing major complications, which were used to construct the online calculator ( http://www.asapcalculate.top/Cal11_en.html ). This model demonstrated good calibration and discrimination, with the C-indexes of 0.752 and 0.743 in the training and validation cohorts, respectively, which were significantly higher than those conventional scores (the training and validation cohorts: 0.565 ~ 0.650 and 0.568 ~ 0.614, all P < 0.001). CONCLUSIONS: A web-based prediction model was developed to predict the probability of post-hepatectomy major complications in an individual HBV-infected patient with HCC. It can be used easily in the real-world clinical setting to help management-related decision-making and early warning, especially in areas with endemic HBV infection.

Comparing patient outcomes following minimally invasive coronary artery bypass grafting surgery vs. coronary artery bypass grafting: a single-center retrospective cohort study.

Background: This present research was designed for comparing coronary artery disease (CAD) patient outcomes following minimally invasive coronary artery bypass grafting surgery (MICS) or coronary artery bypass grafting (CABG). Methods: From 2014-2017, 679 CAD patients underwent MICS (n=281) or CABG (n=398) and were evaluated for the present study. Patient data were analyzed using 1:1 propensity score-matched assessment and a multivariate Cox proportional hazards regression model, and primary study achievements comprised major adverse cardiac and cerebrovascular events (MACCEs), myocardial infarction (MI), cardiac death, heart failure (HF), revascularization, and stroke. The median follow-up period was 2.68 years. Results: CABG patients exhibited a trend towards higher cumulative overall rates of MACCEs at 2 years (CABG: 6.2% vs. MICS: 3.8%) and 4 years (CABG: 9.3% vs. MICS: 7.6%) [adjusted hazard ratio (HR): 1.33; 95% confidence interval (CI): 0.33-5.39 for CABG vs. MICS; P=0.687], although this difference was not significant. No significant differences in 2- or 4-year cardiac death rates were observed between groups (CABG: 3.5%, 5.6% vs. MICS 2.8%, 2.8%; adjusted HR: 0.23; 95% CI: 0.03-1.81 for CABG vs. MICS; P=0.160). Further, there existed no discrepancies in rates of MI (P=1.000), HF (adjusted HR: 4.76; 95% CI: 0.01-6.40 for CABG vs. MICS; P=0.996), stroke (adjusted HR: 9.58; 95% CI: 0.11-25.24 for CABG vs. MICS; P=0.320), or repeated revascularization (adjusted HR: 1.71; 95% CI: 0.01-7.21 for CABG vs. MICS; P=0.631) when comparing these patient groups. In a multivariable Cox proportional hazards regression analysis, patients that were male (adjusted HR: 5.28; 95% CI: 1.48-18.83; P=0.010) and cases with a history of previous MI epsiodes (adjusted HR: 3.20; 95% CI: 1.09-9.37; P=0.034) were found to be at a higher risk of MACCEs. Conclusions: Follow-up data indicated that the MICS and CABG treatments could achieve similar outcomes.

Risk factors and long-term prognosis of beyond-Milan recurrence after hepatectomy for BCLC stage 0/A hepatocellular carcinoma: A large-scale multicenter study.

BACKGROUND: Data on recurrence are important to inform surveillance and improve long-term surgical outcomes for patients with hepatocellular carcinoma. We sought to identify risk factors and long-term prognosis among patients who experienced beyond-Milan recurrence after hepatectomy for early-stage hepatocellular carcinoma. METHODS: Patients who underwent hepatectomy for Barcelona Clinic Liver Cancer stage 0/A hepatocellular carcinoma were identified from a multi-institutional database. Predictors of beyond-Milan recurrence and risk factors associated with post-recurrence survival among patients with beyond-Milan recurrence were assessed using univariate and multivariate Cox regression analyses. RESULTS: Among 753 patients (median follow-up, 51.8 months), 138 (18.3%) developed beyond-Milan recurrence. Regular surveillance (interval follow-up ≤3 months within 1 year and ≤6 months in subsequent years after surgery) was not carried out for 53 (38.4%) patients who developed beyond-Milan recurrence. On multivariate analysis, increased risk of beyond-Milan recurrence was independently associated with preoperative alpha-fetoprotein level >400 ng/mL, tumor size >5.0 cm, multifocal disease, microvascular invasion, and no/irregular recurrence surveillance. Median post-recurrence survival among patients with beyond-Milan recurrence was only 8.4 months (95% confidence interval: 7.0-9.8 months). Among patients who developed beyond-Milan recurrence, Child-Pugh grade B/C, early recurrence within 1 year after surgery, macrovascular invasion/distant metastasis, and noncurative treatment of recurrence were independent risk factors associated with worse post-recurrence survival. CONCLUSION: Nearly 1 in 5 patients developed beyond-Milan recurrence after hepatectomy for early-stage hepatocellular carcinoma. Patients with beyond-Milan recurrence had a median survival of less than 1 year after diagnosis of the recurrence. Regular surveillance is an important and actionable measure to decrease beyond-Milan recurrence and, in turn, improve long-term survival among patients treated with hepatectomy for hepatocellular carcinoma.

Comparison of early outcomes associated with coronary artery bypass grafting for multi-vessel disease conducted using minimally invasive or conventional off-pump techniques: a propensity-matched study based on SYNTAX score.

BACKGROUND: This study was designed to compare early outcomes associated with coronary artery bypass grafting for multi-vessel disease conducted using either minimally invasive or conventional off-pump techniques. METHODS: From January 2017 through January 2021, 582 patients with multi-vessel lesion coronary artery disease underwent either minimally invasive cardiac surgery coronary artery bypass grafting (MICS CABG) or conventional off-pump coronary artery bypass grafting (OPCABG) treatment by our team at Anzhen Hospital. Patients in the MICS CABG group were propensity score-matched with those in the OPCABG at a 1:1 ratio (MICS CABG = 172; OPCABG = 172), using epidemiological data, preoperative clinical characteristics, and SYNTAX score as covariates. Perioperative outcomes and 6-month computed tomography angiography findings were compared between these groups. RESULTS: No significant differences between groups were observed with respect to 30-day postoperative mortality, myocardial infarction, and stroke incidence. Surgical data indicated that the MICS CABG procedure was able to cover all three main arterial territories with a relatively low need for circulatory assistance. The MICS CABG procedure was associated with a longer operative duration, but was also associated with higher postoperative hemoglobin and activities of daily living index values as well as a shorter duration of postoperative hospitalization (P < 0.05). No differences in 6-month graft patency were observed between groups. CONCLUSIONS: MICS CABG is a safe, less invasive alternative to OPCABG when performing complete revascularization provided patients are properly selected, yielding similar in-hospital outcomes and 6-month graft patency rates together with an earlier return of physical function.

circ­Grm1 promotes pulmonary artery smooth muscle cell proliferation and migration via suppression of GRM1 expression by FUS.

Pulmonary arterial hypertension is a progressive and fatal disease. Recent studies suggest that circular RNA (circRNAs/circs) can regulate various biological processes, including cell proliferation. Therefore, it is possible that circRNA may have important roles in pulmonary artery smooth muscle cell proliferation in hypoxic pulmonary hypertension (HPH). The aim of the present study was to determine the role and mechanism of circRNA­glutamate metabotropic receptor 1 (circ­Grm1; mmu_circ_0001907) in pulmonary artery smooth muscle cell (PASMC) proliferation and migration in HPH. High­throughput transcriptome sequencing was used to screen circRNAs and targeted genes involved in HPH. Cell Counting Kit­8 (CCK­8), 5­ethynyl­2­deoxyuridine and wound healing assays were employed to assess cell viability and migration. Reverse transcription­quantitative PCR and western blotting were used to detect target gene expression in different groups. Bioinformatical approaches were used to predict the interaction probabilities of circ­Grm1 and Grm1 with FUS RNA binding protein (FUS). The interactions of circ­Grm1, Grm1 and FUS were evaluated using RNA silencing and RNA immunoprecipitation assays. The results demonstrated that circ­Grm1 was upregulated in hypoxic PASMCs. Further experiments revealed that the knockdown of circ­Grm1 could suppress the proliferation and migration of hypoxic PASMCs. Transcriptome sequencing revealed that Grm1 could be the target gene of circ­Grm1. It was found that circ­Grm1 could competitively bind to FUS and consequently downregulate Grm1. Moreover, Grm1 could inhibit the function of circ­Grm1 by promoting the proliferative and migratory abilities of hypoxic PASMCs. The results also demonstrated that circ­Grm1 influenced the biological functions of PASMCs via the Rap1/ERK pathway by regulating Grm1. Overall, the current results suggested that circ­Grm1 was associated with HPH and promoted the proliferation and migration of PASMCs via suppression of Grm1 expression through FUS.

Off-Pump Aortic Bypass for Hypoplastic Arch and Aortic Coarctation Via Anterolateral Thoracotomy.

We report the case of a 21-year-old woman who was referred with uncontrolled hypertension. Computed tomography angiography revealed aortic arch hypoplasia and severe aortic coarctation. An off-pump ascending-to-descending aortic bypass surgery using synthetic graft was performed via left anterolateral thoracotomy. The patient recovered well and was discharged home uneventfully after five days. This procedure was performed without touching the head vessels or any collateral vessels. We consider this a safe and less invasive alternative technique for adult coarctation patients who have aortic hypoplasia or interrupted aorta.

Is hybrid coronary revascularization really beneficial in the long term?

OBJECTIVES: This analysis aimed to compare both short- and long-term outcomes of hybrid coronary revascularization (HCR) with different techniques and coronary artery bypass grafting (CABG). METHODS: Twenty-three studies were included, covering 10 468 different patients, among whom 2403 patients underwent HCR with either simultaneous or staged method and 8065 patients underwent CABG. RESULTS: Compared with CABG, HCR had a statistically significant lower risk of stroke [odds ratio (OR) = 0.55, P = 0.049], major adverse cardiac and cerebrovascular events (OR = 0.69, P = 0.024) and blood transfusion (BT) (OR = 0.39, P < 0.001), whereas no significant differences were detected in mortality, myocardial infarction and repeat revascularization. A network meta-analysis showed that simultaneous HCR had significantly better outcomes in stroke (OR = 0.24, P = 0.01) and major adverse cardiac and cerebrovascular events (OR = 0.29, P < 0.001), and staged HCR had a significantly better outcome in BT (OR = 0.31, P < 0.001). According to the frequentist statistic results, simultaneous HCR had the highest probability of being the best treatment in terms of mortality (84%), stroke (97%), myocardial infarction (88%) and major adverse cardiac and cerebrovascular events (99%), whereas staged HCR had the highest probability of being the best in postoperative repeat revascularization (59%) and BT (83%). However, long-term results showed no significant difference between the HCR and CABG techniques. CONCLUSIONS: HCR appears to be a feasible option for multivessel coronary artery disease patients. Compared to traditional CABG, HCR had lower risk of adverse events in the short term, but in the long term, survival rate and freedom from major adverse cardiac and cerebrovascular events rate were similar between groups.

Surgical Challenges in Multi-Vessel Minimally Invasive Coronary Artery Bypass Grafting.

OBJECTIVES: Minimally invasive coronary artery bypass grafting (MICS CABG) has emerged as an alternative treatment for patients with multi-vessel coronary artery disease, but there are certain surgical challenges inherent in the adoption of this approach. The present study was conducted to provide insight regarding the outcomes associated with our first 118 cases, to discuss the surgical difficulties encountered in these patients, and to outline the potential countermeasures. METHODS: Between January 2017 and January 2020, 118 patients underwent multi-vessel MICS CABG. These patients were stratified into two groups based upon whether they did or did not experience surgical challenges, and early clinical outcomes were compared between these groups to assess the incidence of technical difficulties and associated factors. RESULTS: Surgical challenges arose in 38 of the 118 cases in this study, including 13 cases of exposure-related difficulties, 11 cases of proximal anastomosis-related difficulties, 15 cases of distal anastomosis-related difficulties, 4 cases of LITA-related difficulties, and 3 cases of lung-related difficulties. Relative to the other 80 patients, those patients for whom intraoperative technical challenges arose experience significant increases in operative duration (4.94 ± 0.89 vs. 5.59 ± 1.11 h, P=0.001), intraoperative blood loss (667 ± 313 vs. 892 ± 532 mL, P=0.005), length of the ICU admission (17.59 ± 3.51 vs. 22.59 ± 17.31 h, P=0.015), and the duration of postoperative hospitalization (5.96 ± 1.23 vs. 6.71 ± 1.92 days, P=0.012). There were no significant differences between these groups with respect to the mean graft number, major complications such as stroke or organ dysfunction, or one-year graft patency. CONCLUSIONS: There is a substantial learning curve associated with performing off-pump MICS CABG to treat multi-vessel disease. Surgical challenges encountered during this procedure may increase the operative duration, intraoperative blood loss, ICU admission, and the duration of postoperative hospitalization. However, these issues do not appear to compromise the efficacy of complete revascularization, and early clinical outcomes associated with this procedure remain acceptable.

High glucose contributes to the polarization of peritoneal macrophages to the M2 phenotype in vivo and in vitro.

Glucose is the primary osmotic medium used in most peritoneal dialysis (PD) solutions, and long­term exposure to high glucose is a major contributor to peritoneal fibrosis. Our previous study revealed that M2 macrophages participate in the development of PD­related fibrosis in a rat model. In the present study, the effects of high glucose on peritoneal macrophage polarization in vivo and in vitro were further evaluated. Continuous ambulatory PD (CAPD) patients with an overnight dwell of 1.5 or 2.5% glucose dialysate were recruited for this study. Overnight effluent samples from patients with CAPD (2,000 ml) were centrifuged to collect cells from the peritoneal cavity. J774A.1 cells (murine macrophages from ascites) were cultured in different concentrations of glucose. Macrophage phenotype markers were detected by flow cytometry. The levels of cytokines in PD effluent and the supernatant of murine macrophages were detected by enzyme­linked immunosorbent assays. The activity of arginase was determined by quantitative colorimetric analysis. In total, 107 CAPD subjects (92 patients using 1.5% glucose dialysate and 15 patients using 2.5% glucose dialysate) were recruited. The percentage of M1 macrophages (CD14­ and CCr7­positive cells) in the 1.5 and 2.5% glucose dialysate groups was 23.0±13.3 and 24.9±12.0%, respectively. The difference was not significant (P>0.05). The percentage of M2 macrophages (CD14­ and CD206­positive cells) in the 1.5% glucose dialysate group (36.2±11.4%) was significantly decreased compared to the 2.5% glucose dialysate group (43.2±7.4%) (P<0.05). Murine macrophages were cultured in a high­glucose in vitro environment, and the percentage of M1 macrophages in 138.8 mmol/l glucose medium significantly increased over time. The percentage of M2 macrophages increased in a glucose concentration­dependent and time­dependent manner. Arginase 1 in murine macrophages and the level of transforming growth factor ß1 in the supernatant increased in a glucose concentration­dependent manner. In conclusion, high glucose contributed to the polarization of peritoneal macrophages to the M2 phenotype, which may play an important role in the pathogenesis of PD­related fibrosis.

Vascular repair and anti-inflammatory effects of soluble epoxide hydrolase inhibitor.

Kawasaki disease (KD) is the leading cause of acquired heart disease in pediatric patients in developed countries. Coronary artery aneurysms and myocardial infarction may occur if the disease remains untreated. An estimated 10-20% of KD patients do not respond to intravenous gamma globulin (IVIG), and thus, alternative treatments are currently being investigated. Epoxyeicosatrienoic acids (EETs) are natural anti-inflammatory factors and angiogenic mediators degraded by soluble epoxide hydrolase (sEH). sEH inhibitory factors have been demonstrated to stabilize EET levels, inhibit inflammation and promote vascular repair in vivo. The present study aimed to determine whether an increase in EET levels induced by treatment with the sEH inhibitor 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA) promotes vascular repair in human coronary arterial endothelial cells (HCAECs) and reduces inflammation in a mouse model of KD induced by Lactobacillus casei cell wall extract. The effect of AUDA on vascular repair in HCAECs was assessed by using cell proliferation, migration, adhesion and tube formation assays, and the anti-inflammatory effect of AUDA in the mouse model of KD was determined by detecting the expression of matrix metalloproteinase (MMP)-9, tumor necrosis factor (TNF)-α and interleukin (IL)-1ß at the protein level via ELISA. The results demonstrated that AUDA increased the proliferation, migration, adhesion and tube formation ability of HCAECs in a dose-dependent manner. Furthermore, in the mouse model of KD, AUDA reduced the protein expression of MMP-9, IL-1ß and TNF-α, indicating that AUDA may alleviate inflammatory reactions in the coronary arteries of KD model mice. The present results also indicate that these effects may be exerted through the peroxisome proliferator activated receptor γ signaling pathway. Taken together, the present study supports the potential utility of AUDA in the treatment of KD.

Twenty-four-hour urine NE level as a predictor of the therapeutic response to metoprolol in children with recurrent vasovagal syncope.

BACKGROUND: Vasovagal syncope (VVS) is a heterogeneous disorder that creates challenges for treatment. Metoprolol is an important therapeutic option for children with VVS. AIMS: The study examined the predictive value of 24-h urine norepinephrine (NE) levels in the assessment of the therapeutic efficacy of metoprolol for recurrent VVS in children. METHODS: Thirty-eight children with recurrent VVS and 20 healthy children were enrolled in our study. Twenty-four-hour urine NE levels were measured by LC-MS-MS. VVS children were diagnosed by BHUTT and/or SNHUTT, and received metoprolol treatment for 3 months. Symptom scoring was utilized to evaluate the therapeutic effect. A ROC curve was used to investigate the predictive value of 24-h urine norepinephrine levels. RESULTS: There exists significant correlation between 24-h urine NE levels and supine systolic and diastolic blood pressures. The 24-h urine NE levels of responders (40.75 ± 12.86 µg/24 h) were higher than those of nonresponders (21.48 ± 6.49 µg/24 h), and there was a significant difference between the two groups (P < 0.001). A ROC curve of the predictive value of 24 h urine NE levels revealed that the area under the curve was 0.926. A cutoff value for 24-h urine NE level of 34.84 µg/24 h produced both high sensitivity (70%) and specificity (100%) in predicting the efficacy of metoprolol therapy for VVS. CONCLUSIONS: Patients with high 24-h urine NE levels have higher supine systolic and diastolic pressures and more effective responses to metoprolol. A 24-h urine norepinephrine level of > 34.84 µg/24 h was an indicator of the effectiveness of metoprolol therapy for VVS in children.

Stem cells cardiac patch from decellularized umbilical artery improved heart function after myocardium infarction.

The construction of the high biocompatible biomaterials pretreated with MSC offers a promising strategy to improve the effects of stem cell therapy for the myocardial infarction (MI). However, assembling vascularized three-dimensional (3-D) myocardial tissues remains an enormous challenge. In this study, we optimized the decellularization protocol with the umbilical artery to construct microporous 3-D scaffold which is suitable for the stem cells (SC) proliferation. The SD rats underwent proximal left coronary ligation and a 5-mm diameter microporous SC patch was implanted directly on the infarct area (SC patch group). The LV contractile function, regional myocardial wall compliance, and tissue histology were assessed 4 weeks after patch implantation. The MSC patch integrated to the local heart tissue and the neo-vessels have been observed in the MSC patch. The vessels in the MSC patch were positive for the CD31 (marker for the mature endothelial cells). The left ventricle wall was thicker in the MSC patch group than the control group (p<0.05 vs. empty patch group). And the LVEF has been improved in the MSC patch group than empty patch group (59±6.7% vs. 31±4.5%, p<0.05). CONCLUSIONS: Our results showed that the implantation of the MSC patch improved cardiac contractile function in heart infarction rat model. The construction of artificial tissue from the decellularized umbilical artery and the MSC may open a promising perspective for the tissue therapy for MI.

Tracking Co(I) Intermediate in Operando in Photocatalytic Hydrogen Evolution by X-ray Transient Absorption Spectroscopy and DFT Calculation.

X-ray transient absorption spectroscopy (XTA) and optical transient spectroscopy (OTA) were used to probe the Co(I) intermediate generated in situ from an aqueous photocatalytic hydrogen evolution system, with [RuII(bpy)3]Cl2·6H2O as the photosensitizer, ascorbic acid/ascorbate as the electron donor, and the Co-polypyridyl complex ([CoII(DPA-Bpy)Cl]Cl) as the precatalyst. Upon exposure to light, the XTA measured at Co K-edge visualizes the grow and decay of the Co(I) intermediate, and reveals its Co-N bond contraction of 0.09 ± 0.03 Å. Density functional theory (DFT) calculations support the bond contraction and illustrate that the metal-to-ligand π back-bonding greatly stabilizes the penta-coordinated Co(I) intermediate, which provides easy photon access. To the best of our knowledge, this is the first example of capturing the penta-coordinated Co(I) intermediate in operando with bond contraction by XTA, thereby providing new insights for fundamental understanding of structure-function relationship of cobalt-based molecular catalysts.

Tacrolimus Protects Podocytes from Injury in Lupus Nephritis Partly by Stabilizing the Cytoskeleton and Inhibiting Podocyte Apoptosis.

OBJECTIVE: Several studies have reported that tacrolimus (TAC) significantly reduced proteinuria in lupus nephritis (LN) patients and mouse models. However, the mechanism for this effect remains undetermined. This study explored the mechanism of how TAC protects podocytes from injury to identify new targets for protecting renal function. METHODS: MRL/lpr mice were given TAC at a dosage of 0.1 mg/kg per day by intragastric administration for 8 weeks. Urine and blood samples were collected. Kidney sections (2 µm) were stained with hematoxylin-eosin (HE), periodic acid-Schiff base (PAS) and Masson's trichrome stain. Mouse podocyte cells (MPC5) were treated with TAC and/or TGF-ß1 for 48 h. The mRNA levels and protein expression of synaptopodin and Wilms' tumor 1 (WT1) were determined by real-time PCR, Western blotting and/or immunofluorescence, respectively. Flow cytometry was used to detect cell apoptosis with annexin V. Podocyte foot processes were observed under transmission electron microscopy. IgG and C3 deposition were assessed with immunofluorescence assays and confocal microscopy. RESULTS: Synaptopodin expression significantly decreased in MRL/lpr disease control mice, accompanied by increases in 24-h proteinuria, blood urea nitrogen, and serum creatinine. TAC, however, reduced proteinuria, improved renal function, attenuated renal pathology, restored synaptopodin expression and preserved podocyte numbers. In MPC5 cells, TGF-ß1 enhanced F-actin damage in podocytes and TAC stabilized it. TAC also decreased TGF-ß1-induced podocyte apoptosis in vitro and inhibited foot process fusion in MRL/lpr mice. In addition, our results also showed TAC inhibited glomerular deposition of IgG and C3. CONCLUSION: This study demonstrated that TAC reduced proteinuria and preserved renal function in LN through protecting podocytes from injury partly by stabilizing podocyte actin cytoskeleton and inhibiting podocyte apoptosis.

Early results of coronary endarterectomy combined with coronary artery bypass grafting in patients with diffused coronary artery disease.

BACKGROUND: It is still a challenge for the cardiac surgeons to achieve adequate revascularization for diffused coronary artery disease (CAD). Coronary endarterectomy (CE) offers an alternative choice of coronary artery reconstruction and revascularization. In this study, short-term result of CE combined with coronary artery bypass graft (CABG) was discussed in the treatment for the diffused CAD. METHODS: From January 2012 to April 2014, 221 cases of CABG were performed by the same surgeon in our unit. Among these cases, 38 cases of CE + CABG were performed, which was about 17.2% (38/221) of the cohort. All these patients were divided into two groups: CE + CABG group (Group A) and CABG alone group (Group B). All clinical data were compared between the two groups, and postoperative complications and in-hospital mortality were analyzed. The categorical and continuous variables were analyzed by Chi-square test and Student's t-test respectively. RESULTS: Diabetes mellitus, hypertension, hyperlipidemia, and peripheral vascular disease were more common in group A. In this cohort, a total of 50 vessels were endarterectomized. Among them, CE was performed on left anterior descending artery in 11 cases, on right coronary artery in 29 cases, on diagonal artery in 3 cases, on intermediate artery in 2 cases, on obtuse marginal artery in 5 cases. There was no hospital mortality in both groups. The intro-aortic balloon pump was required in 3 cases in Group A (3/38), which was more often than that in Group B (3/183). At the time of follow-up, coronary computed tomography angiogram showed all the grafts with CE were patent (50/50). There is no cardio-related mortality in both groups. All these patients were free from coronary re-intervention. CONCLUSIONS: Coronary endarterectomy + CABG can offer satisfactory result for patients with diffused CAD in a short-term after the operation.

Low-dose ionizing radiation induces direct activation of natural killer cells and provides a novel approach for adoptive cellular immunotherapy.

Recent evidence indicates that limited availability and cytotoxicity have restricted the development of natural killer (NK) cells in adoptive cellular immunotherapy (ACI). While it has been reported that low-dose ionizing radiation (LDIR) could enhance the immune response in animal studies, the influence of LDIR at the cellular level has been less well defined. In this study, the authors aim to investigate the direct effects of LDIR on NK cells and the potential mechanism, and explore the application of activation and expansion of NK cells by LDIR in ACI. The authors found that expansion and cytotoxicity of NK cells were markedly augmented by LDIR. The levels of IFN-γ and TNF-α in the supernatants of cultured NK cells were significantly increased after LDIR. Additionally, the effect of the P38 inhibitor (SB203580) significantly decreased the expanded NK cell cytotoxicity, cytokine levels, and expression levels of FasL and perforin. These findings indicate that LDIR induces a direct expansion and activation of NK cells through possibly the P38-MAPK pathway, which provides a potential mechanism for stimulation of NK cells by LDIR and a novel but simplified approach for ACI.

Highly accurate excited-state structure of [Os(bpy)2dcbpy](2+) determined by X-ray transient absorption spectroscopy.

Determining the electronic and geometric structures of photoexcited transient species with high accuracy is crucial for understanding their fundamental photochemistry and controlling their photoreactivity. We have applied X-ray transient absorption spectroscopy to measure the XANES and EXAFS spectra of a dilute (submillimolar) solution of the osmium(II) polypyridyl complex [Os(bpy)2dcbpy](PF6)2 (dcbpy = 4,4'-dicarboxy-2,2'-bipyridine) (OsL2L') in methanol at the Os LIII edge. We have obtained spectra of superb quality for both the ground state and the photoinduced (3)MLCT excited state that have allowed us not only to extract detailed information about the Os 5d orbitals but also to resolve very small differences of 0.010 ± 0.008 Å in the average Os-N bond lengths of the ground and excited states. Theoretical calculations using a recently developed DFT-based approach support the measured electronic structures and further identify the nature of the molecular orbitals that contribute to the main absorption bands in the XANES spectra.