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Objectives We investigated clinical determinants of disease burden and vulnerability using optical coherence tomography (OCT) co-registered with intravascular ultrasound (IVUS) in a large cohort of patients. Methods A total of 704 patients [44.5% with acute coronary syndromes (ACS)] underwent coronary intervention. IVUS plaque burden and OCT lipid, macrophage and calcium indices and the presence of thrombus, plaque rupture and thin-cap fibroatheroma (TCFA) were analyzed. Results Median patient age was 66 years with 81.8% men, 34.4% with diabetes mellitus and 15.5% with preadmission statins. Median lesion length was 25.7 mm, and 33.0% had a TCFA. Adjusted models indicated (1) older patient age was related to more calcium, but fewer macrophages; (2) men were related to more thrombus with plaque rupture while women had more thrombus without plaque rupture; (3) ACS presentation was related to morphological acute thrombotic events (more thrombus with/without rupture) and plaque vulnerability (more TCFA, more lipid and macrophages and larger plaque burden); (4) diabetes mellitus was related to a greater atherosclerotic disease burden (more lipid and calcium and larger plaque burden) and more thrombus without rupture; (5) hypertension was related to more macrophages; (6) current smoking was related to less calcium; and (7) renal insufficiency and preadmission statin therapy were not independently associated with IVUS or OCT plaque morphology. Conclusion Patient characteristics, especially diabetes mellitus and aging, affect underlying atherosclerotic burden, among which a greater lipidic burden along with sex differences influence local thrombotic morphology that affects clinical presentation.

Genetic studies have revealed a critical role of the distal-less homeobox gene 5 (Dlx5) in the pathogenesis of ovarian cancer, lung cancer, and T-cell lymphoma; however, the role and underlying mechanisms of Dlx5 in oral squamous cell carcinoma (OSCC) are largely unknown. In this study, we demonstrated that Dlx5 is up-regulated in OSCC tissues and cell lines, compared with their control groups. The results from our immunohistochemistry (IHC) analyses show that high expression levels of Dlx5 correlated with advanced TNM stages (P = 0.0001), lymph node metastasis (P = 0.0049), poor cellular differentiation (P = 0.0491), location of the tumors (P = 0.0132), and poor prognosis for the patient. We also demonstrated that knockdown of Dlx5 inhibited the viability, proliferation, and colony formation of OSCC cell lines CAL-27 and WSU-HN6 cells, probably by blocking cell cycle in the G1 phase. Furthermore, we revealed that Dlx5 exerts its biological functions via direct regulation of CCND1 in CAL-27 and WSU-HN6 cells. Ultimately, we have demonstrated that silencing of Dlx5 inhibits the growth of xenograft tumors in vivo, and that Dlx5 affects the progression of OSCC both in vitro and in vivo via directly regulating CCND1, providing a potential diagnostic biomarker and therapeutic target for OSCC.

In virtue of the essential role in controlling polarized light, outstanding ultraviolet (UV) and deep-ultraviolet (DUV) birefringent crystals are imperative in many advanced optical instruments. To design the UV and DUV crystals with large birefringence, we paid more attention to combining the excellent gene, π-conjugated [BO3] unit and metal cations beneficial to blue-shift the cutoff edge; finally, two rare-earth borates Li3La2(BO3)3 and Li1.75Na1.25La2(BO3)3 have been synthesized using the high-temperature solution method. Compared with Na3La2(BO3)3, Li3La2(BO3)3 and Li1.75Na1.25La2(BO3)3 are isostructural, and the isolated [BO3] units are arranged nearly parallel to each other in the structure, which is conducive to generating a larger birefringence. The structural comparison between the two crystals and Na3La2(BO3)3 indicates that the various coordination environments of alkali metal cations play an important role in the evolution of the crystal structure from Li3La2(BO3)3 and Li1.75Na1.25La2(BO3)3 to Na3La2(BO3)3. This work can contribute to a better understanding of the enhancement in birefringence from Na3La2(BO3)3 (0.023 @ 1064 nm) to Li3La2(BO3)3 (0.078 @ 1064 nm) with the perspective of structure-property relationships. Meanwhile, the two title crystals possess the DUV cutoff edge (

BACKGROUND Syncope presents with diagnostic challenges and is associated with high healthcare costs. Neurogenic orthostatic hypotension (nOH) as one cause of syncope is not well established. We review a case of syncope caused by nOH in a patient with Parkinson's disease. CASE SUMMARY We describe a case of syncope caused by nOH in Parkinson's disease and review the literature. A 70-year-old man with Parkinson's disease had uncontrolled blood pressure for 1 mo, with blood pressure ranging from 70/40 to 220/112 mmHg, and once lost consciousness lasting for several minutes after getting up. Ambulatory blood pressure monitoring indicated nocturnal hypertension (up to 217/110 mmHg) and morning orthostatic hypotension (as low as 73/45 mmHg). Seated-to-standing blood pressure measurement showed that the blood pressure dropped from 173/96 mmHg to 95/68 mmHg after standing for 3 min from supine position. A diagnosis of nOH with supine hypertension was made. During the course of treatment, Midodrine could not improve the symptoms. Finally, the patient's blood pressure stabilized with simple strategies by strengthening exercises, reducing the duration of lying in bed in the daytime, and consuming water intake before getting up. CONCLUSION nOH is one of the causes of syncope. Ambulatory blood pressure monitoring is a cost-effective method for its diagnosis, and non-pharmacological measures are still the primary management methods.

BACKGROUND Coronary artery disease (CAD) is one of the leading causes of death and disease burden in China and worldwide. A practical and reliable prediction scoring system for CAD risk and severity evaluation is urgently needed for primary prevention. AIM To examine whether the prediction for atherosclerotic cardiovascular disease risk in China (China-PAR) scoring system could be used for this purpose. METHODS A total of 6813 consecutive patients who underwent diagnostic coronary angiography were enrolled. The China-PAR score was calculated for each patient and CAD severity was assessed by the Gensini score (GS). RESULTS Correlation analysis demonstrated a significant relationship between China-PAR and GS (r = 0.266, P < 0.001). In receiver operating characteristic curve analysis, the cut-off values of China-PAR for predicting the presence and the severity of CAD were 7.55% with a sensitivity of 55.8% and specificity of 71.8% [area under the curve (AUC) = 0.693, 95% confidence interval: 0.681 to 0.706, P < 0.001], and 7.45% with a sensitivity of 58.8% and specificity of 67.2% (AUC = 0.680, 95% confidence interval: 0.665 to 0.694, P < 0.001), respectively. CONCLUSION The China-PAR scoring system may be useful in predicting the presence and severity of CAD.

Congestive heart failure (HF) is a known risk factor of contrast-induced acute kidney injury (CI-AKI). However, the relationship of the classification and severity of HF with CI-AKI remains under-explored. From January 2009 to April 2019, we recruited patients undergoing elective PCI who had complete pre- and post-operative creatinine data. According to the levels of ejection fraction (EF), HF was classified as HF with reduced EF (HFrEF) [EF p value p value p value p value = 0.031). Additionally, lower levels of EF were risk factors for CI-AKI in the HFrEF and HFmrEF groups, but not in the HFpEF group. NT-proBNP was an independent risk factor for CI-AKI in the HFrEF, HFmrEF and HFpEF groups. Elevated levels of NT-proBNP are independent risk factors for CI-AKI irrespective of the classification of HF. Lower levels of EF were risk factors for CI-AKI in the HFrEF and HFmrEF groups, but not in the HFpEF group.

Background and Aims Serum uric acid (SUA) levels have been reported to be associated with an increased risk of coronary artery disease (CAD) among patients with diabetes in observational study. Whether this relationship is causal remains unclear. The current study aimed to explore the causal association between SUA and the risk of CAD in patients with diabetes. Methods and Results A two-sample Mendelian randomization (MR) approach was employed to evaluate the causal effect of SUA on the risk of CAD in patients with diabetes. A total of 28 single nucleotide polymorphisms (SNPs) related to SUA were identified as instruments. Genetic association with CAD were obtained from a recently published genome-wide association study (GWAS) of 15,666 patients with diabetes (3,968 CAD cases and 11,696 controls). The fixed-effects inverse variance-weighted method was employed to estimate the causal effect for the primary analysis, and other robust methods were employed for sensitivity analyses. In addition, the whole analyses were repeated using 9 non-pleiotropic SNPs. Genetic determined SUA levels were not significantly associated with the risk of CAD in patients with diabetes in the primary analysis (odds ratio = 1.13, 95% confidence interval: 0.98 - 1.16, P = 0.09). Consistent results were observed in the sensitivity analyses using various robust methods. In addition, this finding was confirmed by the repeated analyses using 9 non-pleiotropic SNPs. Conclusions This two-sample MR study does not support a causal effect of genetically predicted SUA levels on the risk of CAD in patients with diabetes.

Motor imagery (MI) EEG signal classification is a critical issue for brain–computer interface (BCI) systems. In traditional MI EEG machine learning algorithms, feature extraction and classification often have different objective functions, thus resulting in information loss. To solve this problem, a novel spatial-frequency-temporal (SFT) 3D CNN model is proposed. Specifically, the energies of EEG signals located in multiple local SFT ranges are extracted to obtain a novel 3D MI EEG feature representation, and a novel 3D CNN model is designed to simultaneously learn the complex MI EEG features in the entire SFT domains and carry out classification. An extensive experimental study is implemented on two public EEG datasets to evaluate the effectiveness of our method. For BCI Competition III Dataset IVa, the average accuracy rate of five subjects obtained by the proposed method reaches 86.6% and yields 4.1% improvement over the state-of-the-art filter band common spatial pattern (FBCSP) method. For BCI Competition III dataset IIIa, by achieving an average accuracy rate of 91.85%, the proposed method outperforms the state-of-the-art dictionary pair learning (DPL) method by 4.44%.

Background and Purpose. Patients with early-stage Parkinson’s disease (PD) have gait impairments, and gait parameters may act as diagnostic biomarkers. We aimed to (1) comprehensively quantify gait impairments in early-stage PD and (2) evaluate the diagnostic value of gait parameters for early-stage PD. Methods. 32 patients with early-stage PD and 30 healthy control subjects (HC) were enrolled. All participants completed the instrumented stand and walk test, and gait data was collected using wearable sensors. Results. We observed increased variability of stride length (SL) ( P < 0.001 ), stance phase time (StPT) ( P = 0.004 ), and swing phase time (SwPT) ( P = 0.011 ) in PD. There were decreased heel strike (HS) ( P = 0.001 ), range of motion of knee ( P = 0.036 ), and hip joints ( P < 0.001 ) in PD. In symmetry analysis, no difference was found in any of the assessed gait parameters between HC and PD. Only total steps ( AUC = 0.763 , P < 0.001 ), SL ( AUC = 0.701 , P = 0.007 ), SL variability ( AUC = 0.769 , P < 0.001 ), StPT variability ( AUC = 0.712 , P = 0.004 ), and SwPT variability ( AUC = 0.688 , P = 0.011 ) had potential diagnostic value. When these five gait parameters were combined, the predictive power was found to increase, with the highest AUC of 0.802 ( P < 0.001 ). Conclusions. Patients with early-stage PD presented increased variability but still symmetrical gait pattern. Some specific gait parameters can be applied to diagnose early-stage PD which may increase diagnosis accuracy. Our findings are helpful to improve patient’s quality of life.

Objective. Rapid eye movement (REM) sleep behavior disorder (RBD) is a common symptom in Parkinson’s disease (PD), and patients with PD-RBD tend to have an increased risk of cognitive decline and have the tendency to be akinetic/rigidity predominant. At the same time, the mechanisms of RBD in patients with PD remain unclear. Therefore, this study aimed to detect the structural and functional differences in patients with PD-RBD and PD without RBD (PD-nRBD). Methods. Twenty-four polysomnography-confirmed patients with PD-RBD, 26 patients with PD-nRBD, and 26 healthy controls were enrolled. Structural and functional patterns were analyzed based on voxel-based morphometry and seed-based functional connectivity (FC). Correlations between altered gray matter volume (GMV)/FC values and cognitive scores and motor impairment scores in PD subgroups were assessed. Results. Compared with patients with PD-nRBD, patients with PD-RBD showed relatively high GMV in the cerebellar vermis IV/V and low GMV in the right superior occipital gyrus (SOG). For the FC, patients with PD-RBD displayed lower FC between the right SOG and the posterior regions (left fusiform gyrus, left calcarine sulcus, and left superior parietal gyrus) compared with the patients with PD-nRBD. The GMV values in the right SOG were negatively correlated with the Unified PD Rating Scale-III scores in patients with PD-RBD but positively correlated with delayed memory scores. The GMV values in the cerebellar vermis IV/V were positively correlated with the tonic chin EMG density scores. There were positive correlations between the FC values in the right SOG-left superior parietal gyrus and MoCA and visuospatial skills/executive function scores and in the right SOG-left calcarine sulcus and delayed memory scores. Conclusion. Higher GMV in the cerebellum may be linked with the abnormal motor behaviors during REM sleep in patients with PD-RBD, and lower GMV and FC in the posterior regions may indicate that PD-RBD correspond to more serious neurodegeneration, especially the visuospatial–executive function impairment and delayed memory impairment. These findings provided new insights to learn more about the complicated characteristics in patients with PD-RBD.

Phage therapy holds great promise for resolving the ever-worsening crisis of antibiotic resistance, but it also faces many challenges. One of the issues hampering phage therapy is the short blood residence time of bacteriophages. We have previously identified, through in vivo phage display, a blood circulation-prolonging peptide (BCP1) that was capable of significantly prolonging the blood retention time of a doxorubicin-loaded human ferritin nanocage, leading to enhanced therapeutic efficacy against tumors. Herein, we aimed to extend the application of BCP1 to anti-bacterial phage therapy. Methods: A genetically engineered M13 phage, BCP1-BGL, that displayed the BCP-1 peptide and expressed the restriction endonuclease Bgl II, was constructed. Taking advantage of the fact that BCP1 harbors an RGD motif (a three amino-acid sequence Arg-Gly-Asp with the ability to bind to integrins) and exerts its circulation-prolonging activity primarily through interaction with platelets, we further designed and fabricated a biomimetic phage-platelet hybrid nanoparticle (PPHN) via the physical binding of the BCP1-BGL phage to the platelet membrane nanoparticles derived via a repeated freeze-thaw procedure. A series of experiments in vitro and in vivo were conducted to reveal the long circulation and anti-bacterial capacities of BCP1-BGL phages and PPHNs. Results: The resulting PPHNs possessed a hydrodynamic size of 368 nm in deionized water, with each spherical membranous nanoparticle harboring approximately 12 rod-shaped phage particles stably bound to its surface. PPHNs, which were superior to the BCP1-BGL phages that displayed significantly prolonged anti-bacterial action in vivo against Escherichia coli infection, exhibited further extended blood retention time and optimal anti-bacterial performance in both the prophylactic and treatment approaches. Conclusion: Our work demonstrated a novel strategy in engineering biomimetic phage-based nanoparticles with improved blood retention and anti-bacterial performance and may have implications in phage therapy.

Background and Purpose Little is known about non-motor symptoms (NMSs) associated with the postural instability and gait difficulty (PIGD) phenotype, especially in de novo Parkinson’s disease (PD) patients. The aims of this study were to compare NMSs between the tremor dominant (TD) and PIGD phenotypes in de novo PD patients and to determine factors that are associated with the PIGD subtype. Patients and Methods In a cross-sectional study conducted at our single center, 226 de novo PD patients with a median disease duration of 2 years were recruited. Data, including comprehensive demographics, motor subtypes and NMSs were obtained. Motor subtypes were classified as PIGD and non-PIGD (TD and indeterminate) by Jankovic’s method. NMSs were evaluated by the non-motor symptoms questionnaire (NMSQuest). Results We identified 73 (32.3%), 34 (15.0%) and 119 (52.7%) patients with TD, intermediate and PIGD subtypes, respectively. Patients with the PIGD subtype had poorer ADL, motor, depression, anxiety, sleep, and non-motor scores compared with those with the TD subtype. In the NMSQuest, the prevalence of cardiovascular, sleep, mood/cognitive and miscellaneous domains was increased in patients with the PIGD subtype compared with patients with the TD subtype. Multivariable forward stepwise logistic regression revealed that the Hamilton Depression Scale (HAMD) [odds ratio (OR), 1.059; 95% confidence interval (CI), 1.016–1.104, p = 0.007] and pain (OR, 3.175; 95% CI, 1.695–5.947, p < 0.001) exhibit significant discriminative power in differentiating PIGD and non-PIGD groups. Conclusion The PIGD group had more severe cardiovascular symptoms, sleep impairments, mood disturbances and pain. We demonstrated for the first time that pain was associated with the PIGD phenotype. Prompt detection and early treatment of NMSs related to the PIGD phenotype may improve patient outcomes.

Aims Observational studies have reported that homocysteine (Hcy) is associated with an increased risk of coronary artery disease (CAD) in individuals with diabetes, though controversy remains. The present study aimed to investigate the causal association between Hcy and CAD in individuals with diabetes. Methods A 2-sample Mendelian randomization (MR) study was designed to infer causality. Genetic summary data on the association of single nucleotide polymorphisms (SNPs) with Hcy were extracted from the hitherto largest genome-wide association study (GWAS) of up to 44,147 individuals of European ancestry. SNP-CAD data were obtained from another recently published GWAS which included 15,666 individuals with diabetes (3,968 CAD cases, 11,696 controls). The fixed-effects inverse variance-weighted method was employed to calculate the effect estimates. Other robust methods and leave-one-out analyses were used in the follow-up sensitivity analyses. Potential pleiotropy was assessed with the MR-Egger intercept test. Results The 2-sample MR analysis suggested no evidence of an association between genetically predicted plasma Hcy levels and CAD risk in individuals with diabetes (odds ratio = 1.14, 95% confidence interval: 0.82–1.58, p = 0.43) using 9 SNPs as instrumental variables. Similar results were observed in the follow-up sensitivity analyses. The MR-Egger intercept test indicated no evidence of directional pleiotropy (intercept = 0.03, 95% confidence interval: − 0.08–0.03, p = 0.35). Conclusion This 2-sample MR analysis found no evidence of a causal association between plasma Hcy levels and CAD risk in individuals with diabetes.

Purpose Gait impairment is a common clinical symptom of patients with Parkinson’s disease (PD). Detecting specific gait parameters’ changes in order to guide clinical intervention is at present lacking. The present study aimed to (1) quantify gait impairments in different PD subtypes and (2) explore whether the results of quantitative gait analysis are beneficial to clinical treatment. Patients and Methods We enrolled 86 patients with PD (48 men, and 38 women) from the Department of Geriatrics of the Affiliated Brain Hospital of Nanjing Medical University. Unified Parkinson’s Disease Rating Scale (UPDRS) and Hoehn-Yahr Scale were used to evaluate the motor symptoms of PD. All patients stopped anti-Parkinsonian medication for 24 hours (72 hours for controlled release medicine). The patients were divided into two subtypes, namely, postural instability gait difficulty (PIGD; n=56) and tremor dominant (TD; n=30) subtypes according to UPDRS. All patients completed the instrumented stand and walk test, and a set of JiBuEn gait analysis system was used in gait data collection. Results We observed a shorter stride length (p=0.021), a longer stride time (p=0.036), a faster cadence (p=0.036), and a more variable stride length (p=0.012) in the PIGD group compared with the TD group. In addition, compared with the TD group, we found that the toe-off angle (p=0.005) and the range of motion of ankle joint (p=0.009) decreased in the PIGD group. Conclusion Our study demonstrated that the gait performance of patients with PIGD is worse than those with TD from the perspective of quantitative gait analysis. We extended previous research and found the PIGD group exhibited severe gait impairments in some specific spatiotemporal and kinematic gait parameters. The different manifestations of these gait impairments may guide in choosing appropriate treatment of patients with different PD subtypes.

Background The fact that each inflammatory indicator has a forecasting capacity on the occurrence of periprocedural myocardial infarction (PMI) has a controversial existence. The purpose of this study was to explore the role of inflammation biological indicators on PMI in a group of patients undergoing selective percutaneous coronary intervention (PCI). Methods The study was carried out both in a retrospective and prospective manner in 7,413 and 1,189 subjects, respectively. In the retrospective cohort study, the association between inflammation biomarkers and PMI was assessed by univariate and multivariate logistic regression. WBC, CRP, and NLR were distributed using k-means clustering into a virtual variable "Inflammatory Trend", and multivariate logistic regression and subgroup analysis were performed. In the prospective cohort study, the endpoints were PMI, cardiovascular death or cardiac arrest. The chi-square test was performed to calculate the relative risk (RR). Results In the retrospective cohort study, except WBC, CRP, NLR and virtual variable "Inflammatory trend" were independent risk factors for PMI. The subgroup analysis revealed that CRP can serve as the most stable predictor. In the prospective cohort study, WBC (RR =1.134, P=0.416) has no effect on the incidence of PMI. However, an elevation in the incidence of PMI was observed with an increase of NLR (RR =1.354, P=0.041) and CRP (RR =1.412, P=0.025). Conclusions In patients with elective PCI for single-vessel lesions, high CRP increases the risk for PMI. The increase of NLR was an independent risk factor for PMI, especially for patients with hypertension and under the age of 70. WBC has no influence on the occurrence of PMI.

Background. Previous studies found levodopa could improve the activity of the ankle joints of patients with Parkinson’s disease (PD). But ankle joint movement is composed of four motion ranges. The specific changes of four motion ranges in PD remain unknown. Objective. The purpose of this study was to decompose the complex ankle joint movement, measure ankle joint changes before and after the acute levodopa challenge test (ALCT), and investigate the effects of these parameters on gait performance. Methods. 29 PD patients and 30 healthy control subjects (HC) completed the Instrumented Stand and Walk (ISAW) test and gait parameters were collected by the JiBuEn gait analysis system. The percentage of improvement of gait data and the UPDRS III in the on-drug condition (ON) were determined with respect to the off-drug condition (OFF). Results. We observed a reduction in the heel strike angle (HS), 3-plantarflexion (3-PF) angle, and 4-dorsiflexion (4-DF) angle of ankle joints. We did not find significant difference in the toe-off angle (TO), 1-plantarflexion (1-PF) angle, and 2-dorsiflexion (2-DF) angle among three groups. Stride length improvement rate was significantly correlated with HS (rs = 0.616, P<0.001) and 3-PF (rs = 0.639, P<0.001) improvement rates. The improvement in the sum of rigidity items (UPDRS motor subsection item 22) was also correlated with HS (rs = 0.389, P=0.037) and 3-PF (rs = 0.373, P=0.046) improvement rates. Conclusions. Exogenous levodopa supplementation can significantly reduce the rigidity of patients with PD, improve their 3-PF and 4-DF of ankle joint kinematic parameters, and ultimately enhance their gait.

Objective. The aim of this work was to investigate whether there are differences in the executive control network (ECN) between patients with Parkinson’s disease (PD) before and after deep brain stimulation (DBS) surgery and to explore how deep brain stimulation (DBS) surgery affects ECN connectivity in patients with PD. Methods. Resting-state magnetic resonance imaging (MRI) data were obtained from 23 patients with Parkinson’s disease preoperatively (pre-PD) and postoperatively (post-PD) and 14 normal controls (CN). The right dorsolateral prefrontal cortex (DLPFC) was used as the seed region of interest (ROI) to study the characteristics of the functional connectivity of the ECN in these subjects. Results. There were differences in the ECN among PD patients before and after surgery and between the CN. Compared with the CN group, the pre-PD patients showed significantly reduced functional connectivity (FC) between the DLPFC and the left inferior frontal gyrus, left precuneus, left cerebellum posterior lobe, right middle frontal gyrus, right inferior parietal gyrus, right posterior central gyrus, right precuneus, and right inferior frontal gyrus. Compared to the CN group, the post-PD patients showed significantly reduced FC between the DLPFC and left inferior frontal gyrus, left precuneus, left cerebellum posterior lobe, right middle frontal gyrus, right inferior frontal gyrus, and right parietal lobule. There is no difference in the ECN between the pre-PD patients and the post-PD patients. Conclusions. The FC of ECN in PD patients was different from that in normal controls, but the FC of the ECN in patients with PD may not be altered by DBS. This suggests that the ECN may be considered an imaging biomarker for the identification of PD but may not be a good imaging biomarker for the evaluation of DBS efficacy.

Hyperglycemia caused by diabetes mellitus could increase the risk of diabetic cardiomyopathy. However, to the best of our knowledge, the underlying mechanism of this process is still not fully explored. Thus, developing ways to prevent hyperglycemia can be beneficial for diabetic patients. The present study was designed to investigate the influence of metoprolol and bisoprolol on the cardiomyocytic hypertrophy of neonatal rat cardiomyocytes. Cardiomyocytes were cultured in two types of media: One with low glucose levels and one with high glucose levels. Cardiomyocytes cultured in high glucose were further treated with the following: A protein kinase C (PKC) inhibitor, an NF-κB inhibitor, metoprolol or bisoprolol. The pulsatile frequency, cellular diameter and surface area of cardiomyocytes were measured. Protein content and [3H]-leucine incorporation were determined, atrial natriuretic peptide (ANP), α-myosin heavy chain (α-MHC) and β-myosin heavy chain (β-MHC) mRNA levels were calculated by reverse transcription-quantitative PCR, while the expression and activation of PKC-α, PKC-β2, NF-κB, tumor necrosis factor-α (TNF-α), and c-fos were detected by western blotting. Metoprolol or bisoprolol were also used in combination with PKC inhibitor or NF-κB inhibitor to determine whether the hypertrophic response would be attenuated to a lower extent compared with metroprolol or bisoprolol alone. Cardiomyocytes cultured in high glucose presented increased pulsatile frequency, cellular diameter, surface area, and protein content and synthesis, higher expression of ANP and β-MHC, and lower α-MHC expression. High glucose levels also upregulated the expression and activation of PKC-α, PKC-β2, NF-κB, TNF-α and c-fos. Metoprolol and bisoprolol partly reversed the above changes, while combined use of metoprolol or bisoprolol with PKC inhibitor or NF-κB inhibitor further ameliorated the hypertrophic response mentioned above to lower levels compared with using metroprolol or bisoprolol alone. In conclusion, metoprolol and bisoprolol could prevent hypertrophy of cardiomyocytes cultured in high glucose by the inhibition of the total and phospho-PKC-α, which could further influence the PKC-α/NF-κB/c-fos signaling pathway.

Objective: To evaluate the influence of the variability of Lipoprotein a (Lp(a)) and Non-high-density lipoprotein cholesterol (non-HDL-C) on the neutrophil to lymphocyte ratio (NLR) during the follow-up period in patients with coronary heart disease (CHD) after elective coronary intervention.Methods: A total of 3320 consecutive patients with CHD after percutaneous coronary intervention (PCI) in a multi-center from January 2010 to January 2019 were enrolled. The baseline demographic data were Analyzed, and the NLR levels in tertile groups according to the baseline Lp(a) and non-HDL-C levels were compared. Linear regression is used to analyze the association of the variation rate of Lp(a) and non-HDL-C with NLR; and subgroup analysis of the relevant factors were found. All verifications are verified by SD, CV, and VIM triple methods.Results: The NLR is significantly different among tertile Lp(a) variation groups in SD, CV and VIM methods, which is consistent in non-HDL-C variation rate except SD method. Multiple linear regression indicated that Lp(a) variability, age, gender, BMI, hypertension, eGFR were related to NLR, which was verified in age, gender, hypertension and non-diabetic subgroups. Non-HDL-C variability, age, gender, BMI, eGFR, statins, follow-up HDL-C and non-HDL-C were also related to NLR, and established in the above subgroups.Conclusion: The variation rate of Lp(a) and non-HDL-C are independent positive predictors of NLR after elective PCI.

Background: Metoprolol is the most used cardiac selective β-blocker and has been recommended as a mainstay drug in the management of acute myocardial infarction (AMI). However, the evidence supporting this regimen in periprocedural myocardial infarction (PMI) is limited.Methods: This study identified 860 individuals who suffered PMI following percutaneous coronary intervention (PCI) procedure and median followed up for 3.2 years. Subjects were dichotomized according to whether they received chronic oral sustained-release metoprolol succinate following PMI. After inverse probability of treatment weighting (IPTW) adjustment, logistic regression analysis, Kaplan-Meier curve, and Cox regression analysis were performed to estimate the effects of metoprolol on major adverse cardiovascular events (MACEs) which composed of cardiac death, myocardial infarction (MI), stroke, and revascularization. Moreover, an exploratory analysis was performed according to hypertension, cardiac troponin I (cTnI) elevation, and cardiac function. A double robust adjustment was used for sensitivity analysis.Results: Among enrolled PMI subjects, 456 (53%) patients received metoprolol treatment and 404 (47%) patients received observation. After IPTW adjustment, receiving metoprolol was found to reduce the subsequent 3-year risk of MACEs by nearly 7.1% [15 vs. 22.1%, absolute risk difference (ARD) = 0.07, number needed to treat (NNT) = 14, relative risk (RR) = 0.682]. In IPTW-adjusted Cox regression analyses, receiving metoprolol was related to a reduced risk of MACEs (hazard ratio [HR] = 0.588, 95%CI [0.385–0.898], P = 0.014) and revascularization (HR = 0.538, 95%CI [0.326–0.89], P = 0.016). Additionally, IPTW-adjusted logistic regression analysis showed that receiving metoprolol reduced the risk of MI at the third year (odds ratio [OR] = 0.972, 95% CI [0.948–997], P = 0.029). Exploratory analysis showed that the protective effect of metoprolol was more pronounced in subgroups of hypertension and cTnI elevation ≥1,000%, and was remained in patients without cardiac dysfunction. The benefits above were consistent when double robust adjustments were performed.Conclusion: In the real-world setting, receiving metoprolol treatment following PCI-related PMI has decreased the subsequent risk of MACEs, particularly the risk of recurrent MI and revascularization.

Background: Dyslipidemia is one of the risks of coronary atherosclerosis disease (CAD). Intensive-dose statins or combining with ezetimibe are widely used to improve the lipid-lowering efficacy in the clinic. Recently, lipid variability has gradually gained attention to be a more reliable predictor of cardiovascular events. We aimed to investigate the variability in plasma lipids in the above two lipid-lowering strategy.Methods: It was a multicenter retrospective study, a total of 1275 patients with CAD from January 2009 to April 2019 were divided into 2 groups: intensive statins (atorvastatin 40 mg/d or rosuvastatin 20 mg/d) group and conventional-dose statins (atorvastatin 20 mg/d or rosuvastatin 10 mg/d) combined with ezetimibe group. All patients were followed up for at least 1-year. Multiple linear regression was used to analyze the association of two lipid-lowering regimens with plasma lipids variability; and subgroup analyses of the relevant factors were applied. All verifications are verified by standard deviation (SD), coefficient of variation (CV), and variability independent of mean (VIM) triple methods.Results: In the overall participants, the mean age was 62.3±10.4 years old, and 72.8% was male. Multivariate linear regression indicated that intensive statins group had lower variability in total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and non-high-density lipoprotein cholesterol (non-HDL-C) in all SD, CV, and VIM triple methods than statins combined with ezetimibe group (p for all Conclusions: Intensive statins therapy has lower variability in TC, LDL-C, and non-HDL-C, that is, better lipids stability than statins combined with ezetimibe therapy in patients with CAD.

Background. Patients with Parkinson’s disease (PD) undergoing deep brain electrode implantation experience a temporary improvement in motor symptoms before the electrical stimulation begins. We usually call this the microlesion effect (MLE), but the mechanism behind it is not clear. Purpose. This study aimed to assess the alterations in brain functions at the regional and whole-brain levels, using regional homogeneity (ReHo) and functional connectivity (FC), during the postoperative microlesion period after deep brain stimulation (DBS) in PD patients. Method. Resting-state functional MRI data were collected from 27 PD patients before and after the first day of DBS and 12 healthy controls (HCs) in this study. The ReHo in combination with FC analysis was used to investigate the alterations of regional brain activity in all the subjects. Results. There were increased ReHo in the basal ganglia-thalamocortical circuit (left supplementary motor area and bilateral paracentral lobule), whereas decreased ReHo in the default mode network (DMN) (left angular gyrus, bilateral precuneus), prefrontal cortex (bilateral middle frontal gyrus), and the cerebello-thalamocortical (CTC) circuit (Cerebellum_crus2/1_L) after DBS. In addition, we also found abnormal FC in the lingual gyrus, cerebellum, and DMN. Conclusion. Microlesion of the thalamus caused by electrode implantation can alter the activity of the basal ganglia-thalamocortical circuit, prefrontal cortex, DMN, and CTC circuit and induce abnormal FC in the lingual gyrus, cerebellum, prefrontal cortex, and DMN among PD patients. The findings of this study contribute to the understanding of the mechanism of MLE.

Glioblastoma multiforme (GBM) is one of the deadliest cancers in brain. There have been few treatment advances for GBM despite increasing scientific understanding of this disease. β-hexosaminidase (Hex) is an important enzyme system in human body, encoded by two genes, HEXA and HEXB, are closely related to central nervous system (CNS) diseases such as Sandhoff disease (SD) and Tay-Sachs disease (TSD). However, the expression pattern and function of HEXA and HEXB in GBM remains unclear. Here, we found that both the mRNA and protein expression levels of HEXA and HEXB were significantly upregulated in GBM patient samples. The results from single-cell RNA-sequencing (scRNA-seq) database and double immunostaining showed that HEXA and HEXB were specifically expressed in microglia in GBM patient samples. Furthermore, our in vitro experiments revealed that conditioned media from HEXA and HEXB knockdown-microglia cells could inhibit the proliferation and migration of GBM cells. Finally, according to survival analysis based on online database, higher expression of HEXA and HEXB was associated with poor prognosis in GBM patients. In conclusion, these results suggest that microglial HEXA and HEXB play fundamental role in GBM progression, and they will be potential biomarkers for GBM.

Background: Although several observational studies have shown an association between birth weight (BW) and atrial fibrillation (AF), controversy remains. In this study, we aimed to explore the role of elevated BW on the etiology of AF.Methods: A two-sample Mendelian randomization (MR) study was designed to infer the causality. The genetic data on the associations of single-nucleotide polymorphisms (SNPs) with BW and AF were separately obtained from two large-scale genome-wide association studies with up to 321,223 and 1,030,836 individuals, respectively. SNPs were identified at a genome-wide significant level (p −8). The inverse variance-weighted (IVW) method was employed to obtain causal estimates as our primary analysis. Sensitivity analyses with various statistical methods were applied to evaluate the robustness of the results, and multivariable MR analysis was conducted to determine whether this association was mediated by the body mass index (BMI).Results: In total, 144 SNPs were identified as the genetic instrumental variables. MR analysis revealed a causal effect of elevated BW on AF (OR = 1.27, 95% CI = 1.14–1.40, p = 5.70 × 10−6). All the results in sensitivity analyses were consistent with the primary result. The effect of BW on AF was attenuated when adjusted for BMI (OR = 1.16, 95% CI = 1.01–1.33, p = 0.04).Conclusions: This study indicated that elevated BW was significantly associated with increased lifelong risk of AF, which may be partially mediated by BMI.

Iron and nitrogen co-doped two-dimensional (2D) porous carbon-flakes have been fabricated by using foam-like Medulla stachyuri (MS, the stem pith of tetrapanax papyrifer) as both carbon precursor and template and ammonium ferric citrate as iron and nitrogen precursor. The ammonium ferric citrate-impregnated foams are subsequently converted into iron and nitrogen co-doped 2D porous carbon-flakes by pyrolysis at high temperature in an inert atmosphere. The porous carbon-flakes fabricated at 900 °C (MS-Fe-900) possess high surface area (1140.9 m2 g−1) and effective Fe/N co-doping (0.22 at.% Fe and 2.02 at.% N). In comparison with Pt/C, MS-Fe-900 exhibits superior ORR activity (E0 = 968 mV; E1/2 = 830 mV vs RHE), preferable methanol/CO tolerance and better stability. Furthermore, the MS-Fe-900-based electrode presents high-rate performance (80.1% capacitance retention from 1 to 100 A g−1), and good cycling stability for over 10000 cycles in 6 M KOH electrolyte. This work takes full advantage of the unique structure of biomass and provides a feasible approach to develop cost-efficient and high performance activated carbon materials for ORR electrocatalysis and supercapacitors.

Objective Regional homogeneity (ReHo) differences in encephalic regions of Parkinson’s disease (PD) patients of different subtypes were investigated to analyze its clinical significance during disease occurrence. Methods 39 PD patients were evaluated in this study, which included 14 cases with the tremor dominant (TD) PD subtype and 23 cases with the postural instability and gait difficulty (PIGD) PD subtype, along with 28 healthy individuals, who were included as the control group. Magnetic resonance imaging (MRI) was performed for all the cases to obtain the rest-state functional magnetic resonance imaging (R-fMRI) data along with structural data. The ReHo values of the three groups were calculated and disparities in brain structures among the three groups were processed by analysis of variance. In addition, t-test analysis was used to evaluate the differences between the groups. In the end, a correlation analysis between the brain areas evaluated for ReHo differences and the clinical symptoms presented by the patients was carried out. Results Compared to the control group, brain areas with increased ReHo values in the TD PD subtype group, included the right putamen, right para-hippocampal gyrus, right inferior temporal gyrus, and right orbital superior frontal gyrus, while areas with decreased ReHo values, included the bilateral superior occipital gyrus and bilateral middle occipital gyrus. In contrast with the control group, areas like the right putamen, right superior temporal gyrus, left thalamus, and right superior parietal gyrus in the PIGD PD subtype group presented an increased in ReHo values, while a decreased in ReHo values was found in the right para-hippocampal gyrus, bilateral superior occipital gyrus, and middle occipital gyrus. Compared to the PIGD group, the TD group showed an increase in ReHo values in the right para-hippocampal gyrus. Conclusions In the present study, ReHo values increased in the TD PD subtype group of patients, indicating a compensatory performance of slow progressive cognitive decline when compared to the PIGD PD subtype group. Two subtypes of PD manifest ReHo changes in the basal ganglia, thalamus, and in several areas of the cerebral cortex, areas that are likely to correlate with non-motor symptoms, such as cognition and emotions.

Purpose The exact development process underlying traumatic heterotopic ossification of the temporomandibular joint (THO-TMJ) is largely unclear. In this study, we try to explore the histological development process of THO-TMJ. Materials and methods Condylar cartilage of one-month-old male mice was partially removed from the left joint with small scissors to induce THO-TMJ. The phenotypes were observed using gross observation, microcomputed tomography (micro-CT) scans and histological examination from one month to six months after surgery. Results The micro-CT examination results showed that the injured condyle integrated with ectopic bone tissue to form an osteophyte and that the volume and density of the osteophyte grew exponentially with time. Hematoxylin and eosin (H&E), safranin O and fast green staining of the THO-TMJ specimens revealed that the ectopic bone tissue was mainly nonmineralized fibrous tissue 1 month after surgery. This tissue gradually transformed into cartilage 3 months after surgery. Finally, the tissues transformed into mature bone tissue 6 months after surgery. Immunofluorescence staining showed VEGF-α expression in the heterotopic tissue 1 month after surgery, and the expression of Sox9 in the heterotopic tissue was obvious 3 months after surgery. Furthermore, OCN expression was evident in most of the heterotopic tissue 6 months after surgery. The results also showed clear hypoxia-inducible factor 1-alpha (Hif-1α) expression in the injured chondrocytes of the condyle, especially in the articular proliferative zone and fibrocartilaginous zone. Conclusions The THO-TMJ imaging characteristics indicated an exponential change with time. Histologically, the development process of THO-TMJ is an endochondral ossification process and includes three stages, fibroproliferative, chondrogenic and osteogenic stage. In addition, Hif-1α, which was expressed in some of the injured chondrocytes, may play an essential role in the initial THO-TMJ.

Genetic studies have revealed a critical role of Distal-homeobox (Dlx) genes in bone formation, and our previous study showed that Dlx2 overexpressing in neural crest cells leads to profound abnormalities of the craniofacial tissues. The aim of this study was to investigate the role and the underlying molecular mechanisms of Dlx2 in osteogenic differentiation of mouse bone marrow stromal cells (BMSCs) and pre-osteoblast MC3T3-E1 cells. Initially, we observed upregulation of Dlx2 during the early osteogenesis in BMSCs and MC3T3-E1 cells. Moreover, Dlx2 overexpression enhanced alkaline phosphatase (ALP) activity and extracellular matrix mineralization in BMSCs and MC3T3-E1 cell line. In addition, micro-CT of implanted tissues in nude mice confirmed that Dlx2 overexpression in BMSCs promoted bone formation in vivo. Unexpectedly, Dlx2 overexpression had little impact on the expression level of the pivotal osteogenic transcription factors Runx2, Dlx5, Msx2, and Osterix, but led to upregulation of Alp and Osteocalcin (OCN), both of which play critical roles in promoting osteoblast maturation. Importantly, luciferase analysis showed that Dlx2 overexpression stimulated both OCN and Alp promoter activity. Through chromatin-immunoprecipitation assay and site-directed mutagenesis analysis, we provide molecular evidence that Dlx2 transactivates OCN and Alp expression by directly binding to the Dlx2-response cis-acting elements in the promoter of the two genes. Based on these findings, we demonstrate that Dlx2 overexpression enhances osteogenic differentiation in vitro and accelerates bone formation in vivo via direct upregulation of the OCN and Alp gene, suggesting that Dlx2 plays a crucial role in osteogenic differentiation and bone formation., Osteogenesis: Dlx2 gene plays key role in bone development The distal-less homeobox (Dlx) gene family is related to various features of bone development, and the Dlx2 member of that family has been found to play a crucial role in bone formation. A team headed by Steve Guofang Shen at the Shanghai Jiao Tong University School of Medicine in China investigated the function of Dlx2 in osteogenic (bone development) differentiation of mouse bone marrow stromal cells (BMSCs) and MC3T3-E1 cells (precursors of osteoblasts, the major cellular component of bone). The team found that overexpression of Dlx2 promotes osteogenic differentiation in vitro and accelerates bone formation in vivo by enhancing Osteocalcin and Alp genes (both of which play critical roles in promoting osteoblast maturation). The authors conclude that their results suggest a promising future strategy for treating bone defects where BMSCs overexpress Dlx2.

Gastric cancer is the third most common cause of cancer-related deaths and is the fifth highest incidence of cancer worldwide, especially in Eastern Asia, Central and Eastern Europe, and South America. Currently, surgery is the only curative treatment for gastric cancer; however, digestive tract reconstruction after distal gastrectomy for gastric cancer is controversial due to the postoperative complications such as reflux gastritis. There is an increasing trend toward laparoscopic uncut Roux-en-Y (URY) for radical gastrectomy. However, evidence on the feasibility of this procedure in patients undergoing laparoscopic radical distal gastrectomy is still absent. Thus, a prospective randomized trial is warranted. This is a prospective, multicenter, two-arm randomized controlled trial in which 210 patients will be randomly assigned to two groups: laparoscopic URY (n=105) and laparoscopic Billroth II plus Braun anastomosis (n=105). Each participant must be pathologically diagnosed with gastric cancer and undergo laparoscopic radical gastrectomy at Xijing Hospital and other four hospitals. The laparoscopic URY procedure is based on the Billroth II gastrojejunostomy plus Braun anastomosis, and then blocked the jejunum input loop at the stump-jejunal anastomosis. The patients' demographic and pathological characteristics will be recorded. The total and oral nutritional intake, general data, total serum protein, serum albumin, blood glucose, and temperature will be recorded before surgery and at the time of hospitalization. Postoperative adverse events will also be recorded, as well as at follow-up appointments at three months and six months after surgery. The rate of reflux gastritis will represent the primary endpoint, and other secondary endpoints, which are all recorded.

Zetao Ma,1,2,&ast; Xizhi Wang,1,&ast; Qingbo Lv,1 Yingchao Gong,1 Minghong Xia,1 Lenan Zhuang,1 Xue Lu,1 Ying Yang,1 Wenbin Zhang,1 Guosheng Fu,1 Yang Ye,1 Dongwu Lai1 1Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, 310016, People’s Republic of China; 2Department of Cardiology, Zhongshan People’s Hospital, Zhongshan, Guangdong Province, 528403, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dongwu Lai; Yang YeKey Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3 East Qingchun Road, Hangzhou, Zhejiang Province, 310016, People’s Republic of ChinaTel +86-571-86006241Fax +86-571-86006246Email laidw@zju.edu.cn; yeyang1222@zju.edu.cnBackground: Considered as one of the major reasons of sudden cardiac death, hypertrophic cardiomyopathy (HCM) is a common inherited cardiovascular disease. However, effective treatment for HCM is still lacking. Identification of hub gene may be a powerful tool for discovering potential therapeutic targets and candidate biomarkers.Methods: We analysed three gene expression datasets for HCM from the Gene Expression Omnibus. Two of them were merged by “sva” package. The merged dataset was used for analysis while the other dataset was used for validation. Following this, a weighted gene coexpression network analysis (WGCNA) was performed, and the key module most related to HCM was identified. Based on the intramodular connectivity, we identified the potential hub genes. Then, a receiver operating characteristic curve analysis was performed to verify the diagnostic values of hub genes. Finally, we validated changes of hub genes, for genetic transcription and protein expression levels, in datasets of HCM patients and myocardium of transverse aortic constriction (TAC) mice.Results: In the merged dataset, a total of 455 differentially expressed genes (DEGs) were identified from normal and hypertrophic myocardium. In WGCNA, the blue module was identified as the key module and the genes in this module showed a high positive correlation with HCM. Functional enrichment analysis of DEGs and key module revealed that the extracellular matrix, fibrosis, and neurohormone pathways played important roles in HCM. FRZB, COL14A1, CRISPLD1, LUM, and sFRP4 were identified as hub genes in the key module. These genes showed a good predictive value for HCM and were significantly up-regulated in HCM patients and TAC mice. We also found protein expression of LUM and sFRP4 increased in myocardium of TAC mice.Conclusion: This study revealed that five hub genes are involved in the occurrence and development of HCM, and they are potentially to be used as therapeutic targets and biomarkers for HCM.Keywords: hypertrophic cardiomyopathy, HCM, weighted gene coexpression network analysis, WGCNA, hub gene, biomarkers, bioinformatics analysis

Based on artificial intelligence (AI), computer-assisted medical diagnosis can scientifically and efficiently deal with a large quantity of medical imaging data. AI technologies including deep learning have shown remarkable progress across medical image recognition and genome analysis. Imaging-genomics attempts to explore the associations between potential gene expression patterns and specific imaging phenotypes. These associations provide potential cellular pathophysiology information, allowing sampling of the lesion habitat with high spatial resolution. Glioblastoma (GB) poses spatial and temporal heterogeneous characteristics, challenging to current precise diagnosis and treatments for the disease. Imaging-genomics provides a powerful tool for non-invasive global assessment of GB and its response to treatment. Imaging-genomics also has the potential to advance our understanding of underlying cancer biology, gene alterations, and corresponding biological processes. This article reviews the recent progress in the utilization of the imaging-genomics analysis in GB patients, focusing on its implications and prospects in individualized diagnosis and management.

BACKGROUND: Although hyperuricemia (HU) has been reported to be related to atrial fibrillation (AF), the relationship between HU and left atrial (LA) enlargement is unclear. The aim of this study was to investigate the interaction between HU and LA enlargement in healthy adults in China. METHODS: This study retrospectively surveyed 5,392 people (3,336 males and 2,056 females) who underwent health checks. Basic data were obtained from all participants, including baseline characteristics and general health status through laboratory tests, echocardiography, and interviews. Multinomial logistic regression was used to analyze the experimental data and determine the association between HU and LA enlargement. In addition, the relationship between HU and LA enlargement in different gender groups was analyzed. RESULTS: The prevalence of HU in this study was 20.3%. Compared with the normal LA group, the prevalence of HU in the LA enlargement group was significantly higher [31.5% vs. 18.1%; P

BackgroundTransient improvement in motor symptoms are immediately observed in patients with Parkinson’s disease (PD) after an electrode has been implanted into the subthalamic nucleus (STN) for deep brain stimulation (DBS). This phenomenon is known as the microlesion effect (MLE). However, the underlying mechanisms of MLE is poorly understood.PurposeWe utilized resting state functional MRI (rs-fMRI) to evaluate changes in spontaneous brain activity and networks in PD patients during the microlesion period after DBS.MethodOverall, 37 PD patients and 13 gender- and age-matched healthy controls (HCs) were recruited for this study. Rs-MRI information was collected from PD patients three days before DBS and one day after DBS, whereas the HCs group was scanned once. We utilized the amplitude of low-frequency fluctuation (ALFF) method in order to analyze differences in spontaneous whole-brain activity among all subjects. Furthermore, functional connectivity (FC) was applied to investigate connections between other brain regions and brain areas with significantly different ALFF before and after surgery in PD patients.ResultRelative to the PD-Pre-DBS group, the PD-Post-DBS group had higher ALFF in the right putamen, right inferior frontal gyrus, right precentral gyrus and lower ALFF in right angular gyrus, right precuneus, right posterior cingulate gyrus (PCC), left insula, left middle temporal gyrus (MTG), bilateral middle frontal gyrus and bilateral superior frontal gyrus (dorsolateral). Functional connectivity analysis revealed that these brain regions with significantly different ALFF scores demonstrated abnormal FC, largely in the temporal, prefrontal cortices and default mode network (DMN).ConclusionThe subthalamic microlesion caused by DBS in PD was found to not only improve the activity of the basal ganglia-thalamocortical circuit, but also reduce the activity of the DMN and executive control network (ECN) related brain regions. Results from this study provide new insights into the mechanism of MLE.

Background Post-contrast acute kidney injury (PC-AKI) is a severe complication of coronary angiography (CAG) and percutaneous coronary intervention (PCI). Currently, the effect of statins on PC-AKI and its mechanism remains unclear. Methods This multicenter retrospective observational study included 4386 patients who underwent CAG or PCI from December 2006 to December 2019 in Sir Run Run Shaw Hospital and its medical consortium hospitals. Serum creatinine pre- or post-procedure within 72 h after PCI was recorded. Multivariate logical regression was used to explore whether preoperative use of statins was protective from PC-AKI. The path analysis model was then utilized to look for the mediation factors of statins. Results Four thousand three hundred eighty-six patients were enrolled totally. The median age of the study population was 68 years old, 17.9% with PC-AKI, and 83.3% on preoperative statins therapy. The incidence of PC-AKI was significantly lower in group of patients on statins therapy. Multivariate regression indicated that preoperative statins therapy was significantly associated with lower percentage of elevated creatinine (β: -0.118, P P P = 0.558). Pathway model analysis indicated a direct protective effect of preoperative statins therapy on PC-AKI (P P = 0.277) nor anti-inflammatory effect (P = 0.596). Furthermore, it was found that “low-density lipoprotein cholesterol (LDL-C)→C-reactive protein (CRP)” mediated the relationship between preoperative statins therapy and PC-AKI (P = 0.007). However, this only explained less than 1% of the preoperative protective effects of statins on PC-AKI. Conclusion Preoperative statins therapy is an independent protective factor of PC-AKI, regardless of its type. This protective effect is not achieved by lipid-lowering effect or anti-inflammatory effect. These findings underscore the potential use of statins in preventing PC-AKI among those at risk.

Both calcium-independent phospholipase A2 beta (iPLA2β) and endoplasmic reticulum (ER) stress regulate important pathophysiological processes including inflammation, calcium homeostasis and apoptosis. However, their roles in ischemic heart disease are poorly understood. Here, we show that the expression of iPLA2β is increased during myocardial ischemia/reperfusion (I/R) injury, concomitant with the induction of ER stress and the upregulation of cell death. We further show that the levels of iPLA2β in serum collected from acute myocardial infarction (AMI) patients and in samples collected from both in vivo and in vitro I/R injury models are significantly elevated. Further, iPLA2β knockout mice and siRNA mediated iPLA2β knockdown are employed to evaluate the ER stress and cell apoptosis during I/R injury. Additionally, cell surface protein biotinylation and immunofluorescence assays are used to trace and locate iPLA2β. Our data demonstrate the increase of iPLA2β augments ER stress and enhances cardiomyocyte apoptosis during I/R injury in vitro and in vivo. Inhibition of iPLA2β ameliorates ER stress and decreases cell death. Mechanistically, iPLA2β promotes ER stress and apoptosis by translocating to ER upon myocardial I/R injury. Together, our study suggests iPLA2β contributes to ER stress-induced apoptosis during myocardial I/R injury, which may serve as a potential therapeutic target against ischemic heart disease.

BackgroundAlthough several observational studies have suggested an association of elevated plasma homocysteine (Hcy) levels with increased risk of atrial fibrillation (AF), it remains unclear whether this association reflects causality. In this study, we aimed to investigate the causal association of plasma Hcy levels with AF risk.MethodsA two-sample Mendelian randomization (MR) study was designed to investigate the causal association of Hcy with AF. Summary data on association of single nucleotide polymorphisms (SNPs) with Hcy were extracted from the hitherto largest genome-wide association study (GWAS) with up to 44,147 individuals, and statistics data on association of SNPs with AF were obtained from another recently published GWAS with up to 1,030,836 individuals. SNPs were selected at a genome-wide significance threshold (p < 5 × 10–8). Fixed-effect inverse variance weighting (IVW) method was used to calculate the causal estimate. Other statistical methods and leave-one-out analysis were applied in the follow-up sensitivity analyses. MR-Egger intercept test was conducted to detect the potential directional pleiotropy.ResultsIn total, nine SNPs were identified as valid instrumental variables in our two-sample MR analysis. Fixed-effect IVW analysis indicated no evidence of causal association of genetically predicted Hcy with AF. The odds ratio (OR) and 95% confidence interval (CI) of AF per standard deviation (SD) increase in Hcy were 1.077 (0.993, 1.168), p = 0.075. Similar results were observed in the sensitivity analyses. MR-Egger intercept test suggested no evidence of potential horizonal pleiotropy.ConclusionsThis two-sample MR analysis found no evidence to support causal association of Hcy with AF.

Rabi flopping is a paradigm of two-level quantum systems in the presence of an oscillatory driving field. Different from atoms, the Rabi flopping in a molecule depends on its bond length and orientation with respect to the light polarization direction. Here we explore the Rabi flopping in the strong-field dissociation of ${\mathrm{H}}_{2}{}^{+}$ in which the two lowest electronic states are photon coupled. ${\mathrm{H}}_{2}{}^{+}$ aligned along different angles experiences different laser intensities, building the Rabi flopping with angle-dependent frequencies. During the laser-${\mathrm{H}}_{2}{}^{+}$ interaction, the electron completes different fractions of Rabi flopping for ${\mathrm{H}}_{2}{}^{+}$ aligned in different directions, leading to the angular nodes and maxima in the dissociative proton momentum distribution. Our study reveals that one-photon dissociation undergoes the alternation of absorbing and emitting one photon, instead of the one-off photon absorption. This study also provides a universal explanation for the angular distribution of the dissociative fragments in strong laser fields.