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Carotid atherosclerosis is an important cause of ischemic stroke. Lipids play a key role in the progression of atherosclerosis. To date, the spatial lipid profile of carotid atherosclerotic plaques related to histology has not been systematically investigated.Carotid atherosclerosis samples from 12 patients were obtained and classified into four classical pathological stages (preatheroma, atheroma, fibroatheroma and complicated lesion) by histological staining. Desorption electrospray ionization-mass spectrometry imaging (DESI-MSI) was used to investigate the lipid profile of carotid atherosclerosis, and correlated it with histological information. Bioinformatics technology was used to process MSI data among different pathological stages of atherosclerosis lesions.A total of 55 lipids (26 throughout cross-section regions [TCSRs], 13 in lipid-rich regions [LRRs], and 16 in collagen-rich regions [CRRs]) were initially identified in carotid plaque from one patient. Subsequently, 32 of 55 lipids (12 in TCSRs, eight in LRRs, and 12 in CRRs) were further screened in 11 patients. Pathway enrichment analysis showed that multiple metabolic pathways, such as fat digestion and absorption, cholesterol metabolism, lipid and atherosclerosis, were enriched in TCSRs; sphingolipid signaling pathway, necroptosis pathway were enriched in LRRs; and glycerophospholipid metabolism, ether lipid metabolism pathway were mainly enriched in CRRs.This study comprehensively showed the spatial lipid metabolism footprint in human carotid atherosclerotic plaques. The lipid profiles and related metabolism pathways in three regions of plaque with disease progression were different markedly, suggesting that the different metabolic mechanisms in these regions of carotid plaque may be critical in atherosclerosis progression.

Previous research has shown that T-2 toxin can damage cartilage, resulting in a disease phenotype similar to osteoarthritis. The precise molecular mechanism by which T-2 toxin causes chondrocyte injury, however, is unknown. The purpose of this study was to look into the role of YAP in T-2 toxin-induced rat chondrocyte injury. Based on research results, T-2 toxin decreased the levels of collagen II and PCNA while increasing the expression of matrix metalloproteinase MMP13. These findings supported the T-2 toxin's detrimental effect on chondrocytes. YAP's role in T-2 toxin-induced chondrocyte injury was also investigated. Total YAP and related nuclear proteins were found to decrease as the concentration of T-2 toxin increased. While PYAP expression was not significantly altered in response to T-2 toxin, the PYAP/YAP ratio decreased as the T-2 toxin concentration increased, implying that the HIPPO signaling pathway was activated. Furthermore, the YAP-specific inhibitor Verteporfin was used to investigate the role of YAP in T-2 toxin-induced chondrocyte injury. YAP inhibition increased MMP13 expression while decreasing COL2 and PCNA levels. In summary, the current study found that T-2 toxin decreased the levels of COL2 and PCNA while increasing the expression of MMP13 in chondrocytes after inhibiting YAP, providing a new insight into the mechanism of T-2 toxin-induced cartilage damage.

Background: In cancer patients, surgery is an essential part of the multimodality treatment to remove solid tumors and nearly 50% of the cancer patients underwent surgery for the treatment of cancer usually experienced post-operative delirium (POD). Currently, screening for delirium in the surgical wards at many cancer hospitals in China isn’t the component of everyday clinical care. Objectives: This study aims to examine the existing situation of suspected post-operative delirium in cancer patients undergoing surgery during the first 72 hours after surgery, and to identify the risk factors associated with postoperative delirium (POD). Study Design: Prospective/observational study Place and Duration: Hunan cancer Hospital. 1st December 2019 and 31st December 2019 Methods: Chinese Cancer patients scheduled for surgery, aged 18 years or elders were prospectively observed by bedside nurses for 03 consecutive postoperative days for the presence of delirium by using Nursing delirium screening scale (Nu-DESC Chinese version). Results: Among the 319 included cancer patients, 39 (12.2%) developed suspected POD. Univariate analysis showed that cancer surgical patient with comorbidity of hypertension and chronic hepatitis, surgical specialty, duration of surgery >3 hours, post-operative use of benzodiazepine and opioids to be significantly associated with suspected POD. Binary logistic regression model showed hypertension (OR 7.857 95% CI 3.484–17.718 p=3 hours (OR 2.908 95% CI 1.285–6.580 p=0.01), to be independent risk factors for occurrence of suspected POD. Conclusion: The 12.2% incidence of suspected postoperative delirium (POD) in cancer patients is significant. Recognizing of cancer patients by the nurses and clinicians who may be at risk for developing POD and addressing the modifiable risk factors are extremely essential to lower the risk of its developing. Keywords: Delirium; Postoperative delirium; Cancer; risk factors; Nu-DESC

Radiotherapy is a standard treatment for head and neck tumors that significantly increases patients' long-term survival rates. However, late cerebrovascular complications, especially carotid artery stenosis (CAS), have gained increasing attention. Investigation of biomarkers of radiation-induced CAS may help to elucidate the mechanism by which radiation induces damage to blood vessels and identify possible preventive measures against such damage.In this study, we used lipidomics strategy to characterize the lipids present in 8 radiation-induced carotid plaques (RICPs) and 12 atherosclerotic carotid plaques (ASCPs). We also used desorption electrospray ionization-mass spectrometry imaging (DESI-MSI) to map the spatial distribution of the screened lipids from 2 RICPs samples and 2 ASCPs samples.The results showed that 31 metabolites in RICPs were significantly higher than that in ASCPs, 24 of which were triglycerides (TGs). We used four machine learning models to select potential indicators from the 31 metabolites. Six TGs [TG(17:2/17:2/18:0), TG(17:1/17:2/18:0), TG(17:0/17:2/18:0), TG(17:2/17:2/20:0), TG(17:1/17:2/20:0), TG(15:0/22:0/22:2)] were found to be the potential markers for distinguishing RICPs and ASCPs (AUC = 0.83). The DESI-MSI results suggested that the 6 TGs were localized in the collagen fiber regions and confirmed the differences of these TGs between the two kinds of plaques.The 6 TGs primarily localized in the collagen fiber regions of plaques are likely to be potential indicators for the differentiation of RICPs from ASCPs which may have implications in the mechanisms and possible preventive measures against RICPs.

Background Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease with neuronal cell inclusions composed of neurofilaments and other abnormal aggregative proteins as pathological hallmarks. Approximately 90% of patients have sporadic cases (sALS), and at least 4 genes, i.e. C9orf72, SOD1, FUS and TARDBP, have been identified as the main causative genes, while many others have been proposed as potential risk genes. However, these mutations could explain only ~ 10% of sALS cases. The neurofilament polypeptides encoded by NEFH, NEFM, and NEFL are promising protein biomarkers for ALS and other degenerative diseases. However, whether the genetic variants of these genes were associated with ALS remain ambiguous. Methods Here, we used PCR-Sanger to sequence the exons of these three genes in a cohort of 371 sALS patients and 711 healthy controls (Phase I) and validated the risk variant in another 300 sALS patients and 1076 controls (Phase II). Results A total of 92 variants were identified, including 36 rare heterozygous variants in NEFH, 27 in NEFM, and 16 in NEFL, and only rs568759161 (p.Ser787Arg) in NEFH reached nominal statistical power (P = 0.02 at Phase I, P = 0.009 at Phase II) in the case–control comparison. Together, the Phase I and II studies showed the significantly higher frequency of the variant in cases (9/1342, 0.67%) than in controls (2/3574, 0.07%) (OR 12.06; 95% CI 2.60–55.88; P = 0.0003). No variants passed multiple testing in the discovery cohort, but rs568759161 was associated with ALS in a replication cohort. Conclusions Our results confirmed that NEFH Ser787Arg is a novel sALS risk variant in Chinese subjects, but NEFM and NEFL were not associated with sALS. These data may have implications for genetic counselling and for understanding the pathogenesis of sALS.

Monolithic Nd: YAG lasers pumped by laser diodes have been widely used in precision measurement fields due to its low frequency noise and intensity noise. Previously, people found that the intensity noise of the pump laser would affect the frequency noise of the Nd: YAG lasers, but the cause has not been well explained so far. In this paper, we propose that this effect is thermally induced. The experimental results agreed well with the theoretical model predictions in up to 60 kHz frequency range. The finding can provide ideas for further reducing the frequency noise of Nd: YAG lasers. We get about 300 Hz linewidth in NPRO laser pumped by single laser diode.

Background The intracavitary electrocardiogram (IC-ECG) method has been used for the tip location of central venous access devices for the advantage of being safe, accurate and highly cost effective. However, long-term follow-up is rare. This randomized clinical trial aimed to evaluate the long-term complications of peripherally inserted central catheters (PICCs) positioned by the IC-ECG method. Methods We randomized 2250 patients who needed PICC placement to either a landmark length estimation supplemented by IC-ECG positioned group (ECG group) or the traditional landmark length estimation alone group (control group) in a 2:1 allocation. Post-procedural chest X-rays were applied to confirm tip position. Follow-up was performed monthly to six months. Standard statistics analyses were performed with the SAS 9.13 software, and p Results As evaluated by post-procedural chest X-ray, tip location in the ECG group had a first-attempt success (catheter tip located at optimal position) of 91.7% (95% confidence interval (CI): 90.3%–93.1%), significantly higher than 78.9% (95% CI: 76.0%–81.9%) observed in the control group (p 0.05), phlebitis (1.1%, p > 0.05), deep venous thrombosis (1.2%, p > 0.05), liquid extravasation (2.4%, p > 0.05) and mechanical failure (1.2%, p > 0.05). In the univariable logistic regression analysis, ECG method, other diseases and upper arms were the independent protective factors, and the number of adjustment procedures (n ≥ 2) were the independent risk factors of the complications. Conclusions The intra-procedural tip location by IC-ECG is more safe and accurate than the traditional method of verifying tip location only post-procedurally, by chest X-ray.

Posterior cortical atrophy (PCA) is widely considered as an atypical variant of Alzheimer disease and is characterized by a progressive decline in visual function. PCA has been investigated from the standpoints of brain structure and metabolism, but tau deposition and its relationship to disease severity still remain unclear. Here, we used a novel tau ligand, [18F]PI2620, to visualize tau deposition in a PCA patient. The results showed that high [18F]PI2620 uptake in posterior cortical regions was associated with clinical manifestations, morphologic changes in the brain observed by magnetic resonance imaging (MRI), and hypometabolism detected by [18F] fluorodeoxyglucose (FDG) positron emission tomography (PET). This is the first report demonstrating a clinical anatomical correspondence between [18F]PI2620 PET results, clinical manifestations, MRI, and [18F]FDG PET findings in a Chinese patient with PCA. The results also support the utility of [18F]PI2620 for visualizing tau aggregation in PCA.

Spastic paraplegias (SPGs) are a group of clinically and genetically heterogeneous neurodegenerative diseases. Mutations in 78 genes have been identified in autosomal dominant hereditary SPG (AD-HSP) and autosomal recessive hereditary SPG (AR-HSP). Compared to familial HSP, much less is known about the genetic and clinical profiles of sporadic SPGs. In this study, we have screened mutations for 18 sporadic SPGs or AR-HSP patients (mainly Northern Chinese) by whole-exome sequencing. We identified 12 mutations in five genes in 9 (50%) patients, including 9 novel ones: SPG5A/CYP7B1 (c.851C > A; c.122 + 2 T > G), SPG11/KIAA1840 (c.1735 + 3_ 1735 + 6del AAGT); SPG7/SPG7 (c.1454G > A; c.1892_ 1906dup GAGGACGGGCCTCGG); SPG39/PNPLA6 (c.1591G > A; c. 2990C > T); SPG15/ ZFYVE26 (c. 4804C > T; c. 4278 G > A). Among all the mutations, 7 were detected in the SPG5A and SPG11. Age at onset was significantly younger in cases with mutations (15.45 ± 6.78 years) than those without mutations (25.56 ± 10.90 years) (P = 0.03). Except for two cases with the SPG5A mutations, all cases presented with complicated SPGs. Three cases carrying mutations in SPG7, SPG15, SPG39 showed symptoms and signs of ataxia. One case carrying the homozygous c.259 + 2 T > C mutation in CYP7B1 showed serum parameters indicating liver impairment. Magnetic resonance imaging showed significantly thinned corpus callosum in cases with SPG11 and SPG15, but not in those with SPG5A, SPG7 or SPG39. In contrast, cerebellar atrophy was prominent in the SPG7 and SPG39 cases. These findings expand the spectrum of genetic, clinical and imaging features of sporadic SPG and AR-HSP, and have important implications in genetic counselling, molecular mechanisms and precise diagnosis of the disease.

Introduction: Ultrasound-guided venipuncture and tip location by intracavitary electrocardiogram have many advantages during the insertion of peripherally inserted central catheters, both in terms of safety and cost-effectiveness. Recently, a new tip-conductive peripherally inserted central catheters and new Doppler ultrasound device integrated with intracavitary electrocardiogram have been introduced into clinical practice in China. A randomized multicenter study (clinical trial no. NCT03230357) was performed to verify the feasibility and accuracy of intracavitary electrocardiogram, as performed with this new peripherally inserted central catheters and device. Methods: Our study enrolled a total of 2250 adult patients in 10 different Chinese hospitals. The patients were randomly assigned to either the study group (intracavitary electrocardiogram) or the control group (anatomical landmark guidance) in a 2:1 allocation. Ultrasound was used in both groups for venipuncture and tip navigation. All patients underwent chest X-ray after the procedure to verify the position of the catheter tip. Results: No insertion-related complications were reported in either group. In the study group, first-attempt successful tip location was 91.7% (95% confidence interval: 90.3%–93.1%), significantly higher than 78.9% (95% confidence interval: 76.0%–81.9%) observed in the control group (p Conclusion: These results indicated that during peripherally inserted central catheters insertion in adult patients, tip location with intracavitary electrocardiogram guidance, as carried out by a new tip-conductive peripherally inserted central catheters and intracavitary electrocardiogram integrated ultrasound device, was more effective and more accurate than tip location using anatomical landmarks.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. Over 90% of cases are sporadic (sALS) and 5%-10% are familial (fALS). So far, more than 20 genes/loci have been linked to ALS. C9orf72, SOD1, TARDBP, and FUS are noted as the most common ALS genes; however, mutations of these genes explain10% of sALS cases. Recently, Rho guanine nucleotide exchange factor, encoded by ARHGEF28, has been linked to the ALS pathogenesis, possibly by binding low-molecular-weight neurofilament mRNA and affects its stability. However, a systemic screening of ARHGEF28 mutations in ALS is lacking. In this study, we sequenced the entire coding sequence of ARHGEF28 in a Chinese cohort of 399 sporadic ALS and 327 elderly controls. A total of 73 coding variants were identified, including 26 synonymous and 47 nonsynonymous. Among the nonsynonymous variants, 33 were rare (minor allele frequency [MAF]0.01), in which 18 were only identified in cases and 12 were only in controls. Three loss-of-function mutations were identified, including 2 truncations (p.Arg231Ter and p.Ser561Ter) and a frameshift deletion (p.Lys1070fs) in 2 cases and 1 control subject. The frequency of total and case-only rare variants was 7.5% (30/399) and 5.0% (20/399), respectively, in the patients. SKAT-O test suggested that the novel coding variants were marginally enriched in the cases (p = 0.049). Single-variant analysis suggested that the p.Asn1046Ser variant had a higher frequency in cases (8/399, 0.02) than in controls (1/327, 0.003) (OR: 6.67, 95% CI: 0.83-53.61; p = 0.046). By contrast, none of the low-frequency (MAF: 0.01-0.05) or common (MAF0.05) variants was associated with ALS (p0.05). Among all patients, 9 (2.3%) carried rare variants predicted to be deleterious, and the age at onset of these carriers (45.6 ± 10.9 years) was marginally younger than noncarriers (51.9 ± 10.7 years) (p = 0.11). Our results supported a possible genetic contribution of rare but not low-frequency and common coding variants to ALS. These data may have implications in the mechanisms and genetic counseling of the disease.

Neuronal hemoglobin (nHb) plays a critical role in maintaining normal mitochondrial functioning in the brain. However, in aging and Parkinson's disease (PD) brains, mitochondrial nHb levels are greatly reduced in neurons that accumulate α-synuclein (α-syn), suggesting a link between the two proteins. In this study, we demonstrate that α-syn and Hb can form a complex in both brain tissue and peripheral red blood cells (RBCs) in aging cynomolgus monkeys. nHb-α-syn complex levels in the mitochondrial fraction of the striatum decreased with age; this was negatively correlated with levels in the cytoplasmic fraction and in RBCs and was accompanied by a reduction in mitochondrial free nHb. In contrast, no changes in nHb-α-syn complex formation or free nHb levels were detected in the cerebellum. In vitro studies using a cultured dopaminergic cell line showed that intracellular accumulation of α-syn caused an elevation in nHb-α-syn complex levels in both mitochondrial and cytoplasmic fractions as well as a reduction in mitochondrial free nHb. nHb overexpression increased free nHb levels in mitochondria, stabilized mitochondrial membrane potential, and reduced α-syn-induced apoptosis. The above results suggest that α-syn forms a complex with nHb in selected regions of the aging brain, thereby decreasing mitochondrial function and increasing the risk of PD.

Mesostructured nickel phosphate (MW-NiPO-2) was rapidly synthesized in the presence of cationic sur- factant by a microwave assisted hydrothermal process. The synthesis parameters, microwave irradiation temperature and time, OH - /P and Ni/P molar ratios of the precursor, were systematically investigated and optimized. The charac- terizations of the materials obtained by the two different procedures, Sol-Gel method and microwave assisted hydro- thermal process, were carried out by ICP, FT-IR, TEM and N2 physisorption. The results show that MW-NiPO-2 can be obtained at relatively low temperature (60℃). When the microwave radiation temperature was 100℃, the mesostruc- tured phase formed in an extremely short period about 0.25 h. Ordered MW-NiPO-2 can be obtained under micro- wave irradiation for 1 h at 100℃, when OH − /P and the Ni/P molar ratios of the precursor are 2.0 and 0.7, respectively. In contrast, it took at least 24 h for completion via Sol-Gel method. MW-NiPO-2 and SG-NiPO-2 possess similar structure and composition while MW-NiPO-2 exhibites a worm-like appearance other than piled nanotubes. In com- parison with the sample synthesized via Sol-Gel method, MW-NiPO-2 possesses a relatively high BET surface area (334.4 m 2 /g) and pore volume (0.318 cm 3 /g).

Mesostructured nickel phosphate was synthesized with urea as alkali by sol-gel method. The obtained material nominated as NiPO-3 was characterized by means of XRD, ICP, FT-IR, TEM, and N2 adsorption. In contrast to mesoporous nickel phosphate NiPO-1 and NiPO-2 we reported before, NiPO-3 exhibits relatively longer nanotubes reached up to 400~600 nm. N2 adsorption shows that NiPO-3 possesses high BET surface area (345.8 m2g-1) and pore volume (0.46 cm3g-1). The catalytic performance of NiPO-3 showed that the total selectivity of epoxycyclohexane and hexadienol was as high as 83.38%.

In the present paper, the structural, morphological and optical properties of PbI2 thick films prepared by close-spaced sublimation technique were investigated. It was found that the thickness of PbI2 films decreased from 1 000 μm to 220 μm with the increase in the sublimation source temperature. X-ray diffraction (XRD) pattern shows that the thick films are polycrystalline hexagonal structure with preferred growth orientation of (002) plane, and their grain size, dislocation density and growth stress are closely related to the source temperature. Images of scanning electron microscopy (SEM) reveal the accumulation of hexagonal plate-like particles which constitute the samples, and the particles with a diameter of 248 μm and a thickness of 32.7 μm, exhibit clearly layered structure. By spectrum fitting using Gauss function, the Raman spectra show a shift of about 147, 169, 217 and 210 cm(-1) respectively, the first three peaks correspond to the longitudinal optical vibrations (LO) mode in 4H-PbI2 crystal, while the last peak originate from a vibration pattern associated with SnO2 in substrate. Raman peak of 147 cm(-1) changes significantly with the increases in source temperature, and a dramatic decrease in peak intensity with broadening peak width occurred when the source temperature increased up to 225 degrees C or more. Under 340 nm excitation at room temperature, several weak photoluminescence peaks of PbI2 samples which associated with defects and exciton recombination near 2.25, 2.57 and 2.64 eV were observed. Given a comprehensive consideration of structural and spectral characterization results, PbI2 thick films with a thickness of about 659 μm deposited at a source temperature of 200 degrees C achieves the best crystalline quality.

To observe the effect of electroacupuncture (EA) preconditioning on cerebral ischemia and the role of cerebral neuroglobin (NgB) in EA-induced brain protection in focal cerebral ischemia and reperfusion injury (CI/RI) rats.Male SD rats were randomly assigned to sham control, CI/RI 6 h, CI/RI 24 h and CI/RI 72 h groups (n = 6) for observing changes of NgB at different time-points. Additional SD rats were randomly assigned to sham, model, and EA preconditioning (EA-PC) groups (n = 16) for observing changes of cerebral NgB positive cell counts in the ischemic penumbra region 24 h after reperfusion. EA pre-conditioning was applied to "Baihui" (GV 20) for 30 min, once daily for 5 days before CI/RI. CI/RI model was established by occlusion of the right middle cerebral artery and reperfusion for 6 h, 24 h and 72 h respectively. The neurological behavior scores (NBS) of all the rats were evaluated according to Garcia's methods. The cerebral infarct volume was determined by 2,3,5-triphenyltetrazolium chloride (TTC) staining. The number of cerebral NgB positive cells was detected by immunofluorescent staining.No infarct loci were found in the sham group. The cerebral infarction volume percentage was significantly higher in the model group than in the EA-PC group (P0.01), while the NBS was significantly lower in the model group than in the EA-PC group (P0.01). The number of cerebral NgB positive cells in the ischemic penumbra was up-regulated 6 h after CI/RI injury, peaked at 24 h and continued at 72 h. Compared with the sham group, the number of cerebral NgB positive cells of the model group was increased significantly, whereas that of the EA-PC group up-regulated further obviously in comparison with the model group (P0.01).EA pretreatment has a significant neuroprotective effect on cerebral ischemia-reperfusion, which is closely related to its effect in up-regulating NgB protein expression.