Evaluation of brain iron deposition in different cerebral arteries of acute ischaemic stroke patients using quantitative susceptibility mapping.

AIM: To investigate differences in iron deposition between infarct and normal cerebral arterial regions in acute ischaemic stroke (AIS) patients using quantitative susceptibility mapping (QSM). MATERIALS AND METHODS: Forty healthy controls and 40 AIS patients were recruited, and their QSM images were obtained. There were seven regions of interest (ROIs) in AIS patients, including the infarct regions of responsible arteries (R1), the non-infarct regions of responsible arteries (R2), the contralateral symmetrical sites of lesions (R3), and the non-responsible cerebral arterial regions (R4, R5, R6, R7). For the healthy controls, the cerebral arterial regions corresponding to the AIS patient group were selected as ROIs. The differences in corresponding ROI susceptibilities between AIS patients and healthy controls and the differences in susceptibilities between infarcted and non-infarct regions in AIS patients were compared. RESULTS: The susceptibilities of infarct regions in AIS patients were significantly higher than those in healthy controls (p<0.0001). There was no significant difference in non-infarct regions between the two groups (p>0.05). The susceptibility of the infarct regions in AIS patients was significantly higher than those of the non-infarct region of responsible artery and non-responsible cerebral arterial regions (p<0.01). CONCLUSIONS: Abnormal iron deposition detected by QSM in the infarct regions of AIS patients may not affect iron levels in the non-infarct regions of responsible arteries and normal cerebral arteries, which may open the door for potential new diagnostic and treatment strategies.

Sudomotor dysfunction is associated with impaired left ventricular diastolic function in persons with type 2 diabetes: a cross-sectional study.

BACKGROUND: The incidence of preserved ejection fraction heart failure has significantly increased in persons with type 2 diabetes mellitus (T2DM). Left ventricular (LV) diastolic dysfunction is an early and important manifestation of preserved ejection fraction heart failure. The onset of heart failure in persons with diabetes is associated with diabetic neuropathy. However, the relationship among sudomotor function, which is an early manifestation of small fiber neuropathy, and LV diastolic function remains unclear. This study aimed to explore the association between sudomotor function and LV diastolic function in persons with T2DM. METHODS: In total, 699 persons with T2DM were enrolled and divided into three groups according to electrochemical skin conductance (ESC) assessed using the SUDOSCAN device: "no dysfunction" group (NSF), "moderate dysfunction" group (MDF), and "severe dysfunction" group (SDF). LV diastolic function was assessed using Doppler echocardiography. To evaluate the relationship between ESC and echocardiographic parameters, Pearson's correlation analysis was performed. Additionally, logistic regression analysis was used to determine the association between LV diastolic function and ESC. A receiver operating characteristic (ROC) curve was constructed to evaluate the performance of sudomotor function indicators in detecting impaired cardiac diastolic function. RESULTS: There were 301 persons (43.06%) in the NSF group, 232 (33.19%) in the MDF group, and 166 (23.75%) in the SDF group. Compared to the NSF group, the MDF and SDF groups had higher A and E/e' and lower e' values (all p < 0.05). Pearson's correlation analysis showed that A and E/e' were negatively associated with foot ESC (FESC) and hand ESC (HESC), whereas e' was positively associated with FESC and HESC (all p < 0.05). After adjusting for confounding factors, binary logistic regression analysis showed that ESC was independently associated with impaired LV diastolic function (p = 0.003). The area under the ROC curve values for FESC and HESC were 0.621 and 0.635, respectively (both p < 0.05). CONCLUSIONS: Deteriorating sudomotor function was associated with reduced diastolic function indicators. ESC can be used as a biomarker for detecting LV diastolic impairment.

[Primary antibody deficiencies and respiratory manifestations in adults].

Primary antibody deficiencies (PAD) are a group of congenital disorders caused by genetic defects that affect the development and function of the body's immune defence mechanisms. Patients with PAD may present with recurrent infections, lymphoproliferation, autoimmune diseases, autoinflammation, or malignancies. Respiratory system manifestations may include bronchiectasis, bronchial asthma, and interstitial lung disease, among others. A comprehensive understanding of PADs will help to distinguish these covert cases from more common respiratory diseases.

[Research advances on the mechanism of immune regulation of interferon in Aspergillus infection].

Pulmonary aspergillosis is a serious pulmonary fungal infectious disease. It is difficult to manage and has limited treatment options. Existing anti-aspergillus medications have high rates of treatment failure and increased drug resistance, making it difficult to meet the clinical requirements. Therefore, the development of new, effective treatment programs is critical. According to research, interferons play an important role in the body's immune response to bacterial and viral infectious diseases. Inadequate interferon expression or dysfunction can put the body at risk for certain infectious diseases. Interferon has been used in clinical trials to prevent or treat infectious diseases. In recent years, researchers have focused on the immunological role of interferon in Aspergillus infections and its potential for clinical application. This review summarized the most recent advances in the immunoregulatory mechanisms of interferon and its clinical application in Aspergillus infections.

Circ_0124055 promotes the progression of thyroid cancer cells through the miR-486-3p/MTA1 axis.

BACKGROUND: Thyroid cancer is one of the malignancy cancers. CircRNA, a non-coding RNA, plays an important role in the development of cancer. The relationship and roles of circ_0124055, miR-486-3p and MTA1 in thyroid cancer have not been reported. METHODS: Real-time quantitative polymerase chain reaction (RT-qPCR) was performed to analyze the RNA levels of circ_0124055, miR-486-3p and MTA1. Western blot was conducted to analyze the protein levels of MTA1, Epithelial cadherin (E-cadherin) and Neuro cadherin (N-cadherin). Subcellular localization assay was used to analyze circ_0124055 location in thyroid cancer cells. Colony formation assay and 5-Ethynyl-2'-deoxyuridine (EdU) assay were carried out to analyze cell proliferation. Cell migration and invasion were analyzed by wound-healing assay and transwell assay. Flow cytometry assay was performed to investigate cell apoptosis. Dual-luciferase reporter assay and RIP assay were employed to analyze the interactions among circ_0124055, miR-486-3p and MTA1. Immunohistochemical (IHC) assay was performed to assess the expression of Ki67, MTA1 and E-cadherin in tumor tissues. Thyroid cancer tumor growth in vivo was evaluated by tumor xenograft mouse model assay. RESULTS: The expression of circ_0124055 was up-regulated in tumor tissues and cells. Knockdown of circ_0124055 could inhibit thyroid cancer cell proliferation, migration and invasion and promote cell apoptosis, accompanied by the dysregulation of E-cadherin and N-cadherin expression. Circ_0124055 could target miR-486-3p, and miR-486-3p could target MTA1. MiR-486-3p inhibitor could restore the effect of circ_0124055 knockdown in the progression of thyroid cancer. Moreover, MTA1 overexpression weakened the inhibitory effects of miR-486-3p mimics on the progression of thyroid cancer. Further, circ_0124055 could influence tumor growth in vivo. CONCLUSION: Circ_0124055 promoted the progression of thyroid cancer cells through the miR-486-3p /MTA1 axis.

[Effect of different respiratory motion correction methods on PET image quality in chest PET/MRI].

Objective: To investigate the effect of different respiratory motion correction methods on PET images during chest PET/MRI scans. Methods: The data of 35 patients (24 males and 11 females, aged from 29 to 84 year) of pulmonary lesions with significantly high uptake in thoracic PET/MRI scan were retrospective collected from Jingling Hospital. Four different methods were used to reconstruct the PET data. Group A was the full-time 20 min without respiratory motion correction static acquisition (Static) as a control, group B was the end-expiration static collection (Q.Static), and group C was the multi-bins respiratory gating (Gated-Respiratory). In addition, the influence of the time being considered, group D was added for reconstruction in the first 1/3 period (6 min 40 s) of group A. Then, the maximum value (L-SUVmax) and the mean value (L-SUVmean) of the SUV of the lesion, the mean value (B-SUVmean) and the standard deviation (B-SUVsd) of the SUV of the background under each reconstruction results were measured, and for each lesion the signal-to-noise ratio (L-SNR) was calculated. In order to exclude the interference of the background, the mean of the relative SUV (L-dSUVmean) of the L-SUVmean relative to the B-SUVmean was also calculated. Finally, One-Way Repeated Measures ANOVA was used, and the post-hoc pairwise comparison between groups was tested by Bonferroni's modified test. Results: There was statistically significant difference among group B or group C compared to group A and group D in L-SUVmax, L-SUVmean and L-dSUVmean [L-SUVmax:group B vs group A or group D was 8.06±3.57 vs 7.73±3.45 or 7.61±3.50, group C vs group A or group D was 8.04±3.56 vs 7.73±3.45 or 7.61±3.50 (all P<0.05); L-SUVmean: group B vs group A or group D was 4.12±1.78 vs 3.98±1.72 or 3.91±1.71, group C vs group A or group D was 4.13±1.78 vs 3.98±1.72 or 3.91±1.71 (all P<0.05); L-dSUVmean: group B vs group A or group D was 3.52±0.16 vs 3.39±0.18 or 3.31±0.18, group C vs group A or group D was 3.53±0.18 vs 3.39±0.18 or 3.31±0.18 (all P<0.05)], but there was no statistically significant difference between group B and group C (all P>0.05). There were statistically significant differences between group D and group A in B-SUVsd (0.07±0.00 vs 0.07±0.00, P=0.023) and L-SNR (69.80±44.57 vs 85.35±68.98, P=0.001). There was no statistically significant difference between group D and group A in L-SUVmax, L-SUVmean, B-SUVmean and L-dSUVmean (all P>0.05). Conclusions: There was no significant difference in PET image quality between the Q.static and Gated-Respiratory group, both of the two groups were better than the Static group which with no Gated-Respiratory motion correction. If non-respiratory gated Static is used, the PET acquisition time is recommended to be 6 min 40 s.

Effect of Curcumin on Cognitive Behavior and Pathological Characteristics of the Hippocampus in Mice with Inherent Alzheimer's Disease.

This study examined the effect of curcumin on pathological manifestations and clearance of amyloid ß peptide (Aß) in the hippocampus of 8-month-old transgenic APP/PS1 mice with inherent Alzheimer's disease. APP/PS1 mice and the age-matched wild-type controls were subjected to 3 behavioral tests: open field, new object recognition, and Morris water maze. Expression of Aß, APP, CTF, BACE1, IDE, NEP, and LRP1 proteins in the extracted hippocampal tissue was evaluated by Western blotting. The distribution and the quantity of amyloid plaques and the spread of microglia in the hippocampus were determined by immunofluorescence. The contents of Aß40 and Aß42 in the hippocampus were assayed and analyzed on Simoa HD-1 analyzer. The proteins interacting with Aß in the hippocampus of APP/PS1 mice were detected by co-immunoprecipitation. Curcumin significantly reduced motor hyperactivity in the open-field test, improved short-term recognition memory, spatial learning, and reference memory in APP/PS1 mice. In the hippocampus of APP/PS1 mice, curcumin significantly diminished the elevated Aß levels and inhibited microglia proliferation. At the same time, curcumin had no effect on Aß production, extracellular enzymatic hydrolysis, and LRP1-mediated outward transport, but enhanced Aß clearance by activation of the intracellular ubiquitin-proteasome system and related peripheral mechanisms. Thus, curcumin improves the learning and memory abilities of APP/PS1 mice and reduces the pathological accumulation of Aß in the brain.

[Molecular epidemiology and clinical characteristics of six cases of CA-MRSA pneumonia after influenza].

Objective: To summarize and analyze the strains' molecular epidemiology and clinical characteristics of 6 strains of post-influenza community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) pneumonia. Methods: Six cases of CA-MRSA pneumonia after influenza from 2014 to 2022 were retrospectively collected and CA-MRSA strains from each patient were cultured. Then, SCCmec typing, MLST typing, and spa typing were performed on the samples, which also included the procedures for the detection of virulence factors. Antibiotic susceptibility test was then performed on all 6 strains. Results: ST59-t437-Ⅳ was the predominant type in all the strains of CA-MRSA(2/6). Leukocidin (PVL) was detected in 5 cases, and hemolysin α (HLAα) and phenol soluble regulatory protein α (PSMα) were detected in 6 cases. Five of the cases included in this study were diagnosed with severe pneumonia. In terms of treatment, 4 cases received antiviral therapy, and 5 patients with severe pneumonia received anti-infection treatment with vancomycin as the first choice and were discharged after improvement of their condition. Conclusions: The molecular types and virulence factors of CA-MRSA after influenza infection could vary considerably. Our experiments also showed that secondary CA-MRSA infection after influenza was more common in young people with no underlying diseases and could cause severe pneumonia. Vancomycin and linezolid were the first-line drugs for treating CA-MRSA infection and were highly effective in improving the condition of diagnosed patients. We highlighted the importance of referring patients with severe pneumonia after influenza for etiological tests to determine whether they had CA-MRSA infection, so that they could be properly treated with anti-influenza agents and receive appropriate anti-CA-MRSA infection treatment.

[Investigation on a case of Amanita neoovoidea poisoning].

This paper reported a case of poisoning caused by ingestion of Amanita neoovoidea. The patient experienced nausea, vomiting, oliguria, acute renal function injury, and was discharged after symptomatic support treatment and blood purification treatment. Given the different toxicity of different mushrooms, species identification of poisonous mushrooms can help clinicians in diagnosis and treatment.

[The research of liver failure in Banna miniature pigs caused by amanita exitialis].

Objective: To explore the characteristics of Banna miniature pig liver failure induced by amanita exitialis. Methods: From September to October 2020, a reverse high performance liquid chromatography (RP-HPLC) method was used to determine the toxin content of amanita exitialis solution, and 2.0 mg/kg amanita exitialis solution (α-amanitins+ß-amanitins) was administered orally to Banna miniature pigs. Toxic symptoms, blood biochemical indexes and histopathological changes of liver, heart and kidney were observed at each time point. Results: All Banna miniature pigs died within 76 h of exposure, and different degrees of digestive tract symptoms such as nausea, vomiting and diarrhea appeared between 6 and 36 h. The biochemical indexes of alanine aminotransferase, aspartate aminotransferase, total bilirubin, lactate dehydrogenase, myoglobin, creatine kinase isoenzyme, blood urea nitrogen and creatinine increased significantly at 52 h after exposure, and the differences were statistically significant compared with 0 h (P<0.05). The bleeding of liver and heart was obvious under macroscopic and microscopic observation, hepatocyte necrosis, renal tubule epithelial cell swelling. Conclusion: Large dose of amanita exitialis can cause acute liver failure of Banna miniature pigs, which is in line with the pathophysiological characteristics of acute liver failure, and lays a foundation for further research on the toxic mechanism and detoxification drugs of amanita exitialis induced liver failure.

A novel kinase subverts aluminium resistance by boosting ornithine decarboxylase-dependent putrescine biosynthesis.

Rice, as one of the most aluminium (Al)-resistant cereal crops, has developed more complicated Al resistance mechanisms than others. By using forward genetic screening from a rice ethyl methanesulfonate mutant library, we obtained a mutant showing specifically high sensitivity to Al. Through MutMap analysis followed by a complementation test, we identified the causal gene, Al-related Protein Kinase (ArPK) for Al-sensitivity. ArPK expression was induced by a relatively longer exposure to high Al concentration in the roots. The result of RNA-sequencing indicated the functional disorder in arginine metabolism pathway with downregulation of N-acetylornithine deacetylase (NAOD) expression and upregulation of Ornithine decarboxylase1 (ODC1) expression in arpk mutant. Al specifically and rapidly upregulated ODC1 expression and causes overaccumulation of putrescine (Put), whereas the ODC inhibitor difluoromethylornithine reverted Al-sensitive phenotype of arpk, suggesting that overaccumulation of endogenous Put might be harmful for root growth, and that ArPK seems to act as an endogenous inhibitor of ODC1 action to maintain suitable endogenous Put level under Al treatment. Overall, we identified ArPK and its putative repressive role in controlling a novel ODC-dependent Put biosynthesis pathway specifically affecting rice Al resistance, thus enriching the fundamental understanding of plant Al resistance.

Evidence of a shared binding site for Bacillus thuringiensis Cry1Ac and Cry2Aa toxins in Cnaphalocrocis medinalis cadherin.

Insect midgut cadherins function as receptors and play critical roles as protein receptors of insecticidal Bacillus thuringiensis (Bt) toxins used as biopesticides and in Bt transgenic crops worldwide. Here, we cloned and characterized the full-length midgut cadherin (CmCad) cDNA from the rice leaffolder (Cnaphalocrocis medinalis), a destructive pest of rice in many Asian countries. Expression of recombinant proteins corresponding to the extracellular domain of CmCad allowed testing binding of Cry proteins. Results from in vitro ligand blotting and enzyme-linked immunosorbent assays supported that the extracellular domain of CmCad contains regions recognized by both Cry1Ac and Cry2Aa. Molecular modelling and docking simulations indicated that binding to both Cry1Ac and Cry2Aa is localized primarily within a CmCad motif corresponding to residues T1417-D1435. A recombinant CmCad protein produced without residues T1417-D1435 lacked binding to Cry1Ac and Cry2Aa, confirmed our modelling predictions that CmCad has a shared Cry1Ac and Cry2Aa binding site. The potential existence of a shared binding region in CmCad suggests that caution should be taken when using combinations of Cry1Ac and Cry2Aa in pyramided transgenic rice, as their combined use could speed the evolution of resistance to both toxins.

Barriers to research in interventional radiology within the UK.

AIM: To identify these barriers to research within interventional radiology (IR) and suggest potential solutions to support IR academia within the UK and beyond. MATERIALS AND METHODS: An electronic survey was compiled using Google Forms and distributed to the British Society of Interventional Radiology (BSIR) members by email and through social media (Twitter). The survey was open between 15 October 2021 and 15 December 2021. Questions included prior research experience and qualifications, research interests and barriers to research development. The data were analysed in Microsoft Excel 365. RESULTS: One hundred and six responses were received with the majority from junior (42.5%) and senior radiology trainees (25.5%). Eight-three percent had not undertaken formal research qualifications with 56.4% stating they would like to undertake a PhD or MD; 81.1% stated they planned to be involved in research. The most common perceived barriers were lack of time (64.2%), lack of research experience (61.3%), and lack of senior supervision (58.5%). CONCLUSION: Developing and supporting the academic IR infrastructure is vital to ensure the future of IR. Radiology trainees have shown interest in being involved with IR research and undertaking formal research training. Additional support from local hospitals, national societies, and the Royal College of Radiologists are required.

An integrated analysis of herpes virus infections from eight randomized clinical studies of baricitinib in adults with moderate-to-severe atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is associated with an increased risk for viral infections including those caused by herpes simplex virus and varicella zoster virus. OBJECTIVES: This study examined treatment-emergent (TE) herpes simplex infection including eczema herpeticum (EH), and herpes zoster (HZ), in adult patients with AD receiving ≥1 dose of baricitinib (BARI), an oral selective inhibitor of Janus kinase 1/2. METHODS: We evaluated data from six double-blinded, randomized, placebo-controlled (PC) trials and two long-term extension studies, within three analysis sets: PC, 2-4-mg BARI extended and All-BARI-AD. Frequency, incidence rate (IR)/100 person-years (PYs) and clinical characteristics of TE-herpes simplex, EH and HZ were reported. RESULTS: In the All-BARI-AD dataset (n = 2531; 2247 PYs), herpes simplex was reported in 8.9% of patients (n = 224; IR = 10.3). Most herpes simplex events were rated as mild or moderate (93.3%), rarely led to permanent discontinuation (2.2%) and presented mostly as oral/perioral herpes simplex (51.3%). TE-EH occurred at a low frequency (All-BARI-AD 1.7% n = 43; IR = 2.0) and were reported in 0.5%, 0.2% and 1.4% of patients receiving placebo, 2-mg or 4-mg BARI respectively. In the All-BARI-AD dataset, most events were investigator-rated as mild/moderate (79.1%), affected ≤2% of the body surface area (74.2%) and occurred as single events (88.4%). Serious TE-EH (n = 11) occurred exclusively in patients with poor disease control (vIGA-AD™ score ≥3) at infection onset. TE-HZ was reported in 2.1% of BARI patients (n = 53; IR = 2.3), without a dose relationship during the PC period (IR = 2.7 and IR = 0.0) or the extended dataset (IR = 3.7 and IR = 1.7) for 2- or 4-mg BARI respectively. CONCLUSIONS: TE-herpes simplex was common, while occurrence of EH was uncommon. Most events of EH were localized with involvement of a small BSA and were linked to poor disease control. Events of HZ were rare in the PC dataset and without a dose dependent increase in frequency.

[A review: drug-drug interactions of epithelial growth factor receptor-tyrosine kinase inhibitors].

Mutations in the epithelial growth factor receptor (EGFR) is a driving factor that causes non-small cell lung carcinoma (NSCLC). The epithelial growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) is a crucial discovery in the treatment of lung cancer, particularly the efficacy of EGFR-TKIs is superior to that of the standard chemotherapy for patients with EGFR mutation-positive advanced NSCLC. Patients with NSCLC use EGFR-TKIs and other medications simultaneously is commonly seen, especially among those with comorbidities, which increases the risk of drug-drug interactions (DDIs) of EGFR-TKIs. The most common mechanisms underlying the DDIs of EGFR-TKIs are modulations of cytochrome P450 (CYP) and drug transporters [including P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP)], as well as gastrointestinal acid-inhibitory drugs [proton pump inhibitors (PPIs) and H(2) receptor antagonists (H(2)RA)]. Inhibitors or inducers of CYP enzymes and drug transporters can inhibit or accelerate the metabolism of EGFR-TKIs, which increase or reduce the exposure of EGFR-TKIs, thereby affect the efficacy and safety of EGFR-TKIs. In addition, PPIs or H(2)RA can decrease the solubility, bioavailability and efficacy of EGFR-TKIs. This review summarizes the mechanisms of DDIs of gefitinib, erlotinib, icotinib, afatinib, dacomitinib and osimertinib; the management recommendations for DDIs of those EGFR-TKIs from the Chinese and global guideline, as well as from the recent pre-clinical and clinical studies, which provide the reference and evidence for managing the combination therapies of EGFR-TKIs and other medications in clinics.

[Application of multiple post labeling delay time arterial spin labeling imaging in the quantitative blood flow analysis of brain subregions in healthy adults].

Objective: To explore the normal ranges of perfusion parameters between cerebral hemisphere, cerebellar hemisphere and brain anatomical subregions (56 pairs) in different gender and age groups with multiple post labeling delay time (Multi-PLD) arterial spin labeling (ASL) imaging. Methods: From November 2020 to December 2020, 42 healthy adult volunteers (Male 25, Female 17) were recruited to perform 7 PLD ASL imaging, including 21 young adults (15 males and 6 females, aged 23-35 years) and 21 seniors (10 males and 11 females, aged 36-74 years). The data was processed offline by Cereflow software to obtain arterial arrival time (ATT) and corrected cerebral blood flow (CBF) and cerebral blood volume (CBV) perfusion parameters. SimpleITK standardization function was used to standardize the calculated perfusion image according to the anatomical automatic labeling (AAL) template. Therefore, CBF, ATT, CBV perfusion values of brain subregions were obtained. Paired samples t test, Wilcoxon rank sum test, independent samples t test and Mann-Whitney U test were used to compare the differences of perfusion parameters in the cerebral hemisphere, the cerebellar hemisphere, brain subregions depending on side, gender and age. Pearson correlation analysis was used to compare the correlations of perfusion parameters with age. Results: CBF in 62.5% (35/56) subregions and CBV in 44.6% (25/56) subregions were higher in right side than those in left side. ATT in most brain anatomical subregions (16/56) were higher in left side. The CBF [(35.30±8.31) vs. (34.34±7.53) ml·100g-1·min-1, P=0.021], CBV [(0.47±0.11) vs. (0.45±0.09) ml/100g, P<0.001], ATT [(1.30±0.10) vs. (1.24±0.11) s, P<0.001] in left cerebellar hemisphere were higher than that of right side. The CBF (28/56) of cerebral hemisphere, cerebellar hemisphere and brain subregions was higher in females than that in males, while ATT in 83.9% (47/56) subregions was lower than that in males (all P<0.05). CBV in female subjects was higher only in 5 brain regions (superior occipital gyrus, middle occipital gyrus, inferior occipital gyrus, superior parietal gyrus and cerebelum_7b) (all P<0.05). In young subjects, CBF in 44.6% (25/56) subregions and CBV in 33.9% (19/56) subregions were higher than those in the senior group (all P<0.05). The ATT in most subregions in young group were lower than those in senior group, but the difference was statistically significant only in rectus gyrus (P=0.026) and paracentral lobule (P=0.006). The CBF (r=-0.430, P=0.005) and CBV (r=-0.327, P=0.035) of cerebral hemisphere were negatively correlated with age. The CBF (24/25, r range:-0.497 --0.343, all P<0.05) and CBV (16/19, r range:-0.474 --0.322, all P<0.05) in most subregions were negatively correlated with age, while ATT was positively correlated (gyrus rectus: r=0.311, P=0.045; paracentral lobule: r=0.392, P=0.010). Conclusions: Multi-PLD ASL imaging could be applied for quantitative analysis of brain perfusion. The perfusion parameters of anatomical subregions are different depending on side, gender, and age.

[Application of cold flowable gutta-percha in root canal obturation after apexification].

OBJECTIVE: To evaluate the clinical effect of root canal obturation therapy using cold flowable gutta-percha on young permanent teeth after apexification. METHODS: Ninety cases of young permanent teeth with pulp necrosis or periapical periodontitis treated by apexification were randomly divided into two groups. The cases in each group were divided into single root canal and multiple root canal according to the number of the root canal, and divided into classifications Ⅰ, and Ⅱ/Ⅲ/Ⅳ according to Frank's classification of root development after apexification. Cold flowable gutta-percha and warm gutta-percha obturation techniques were used for root canal obturation of the two groups. The operation time was recorded, and the patients' therapy pain degree was evaluated by visual analog scale (VAS) immediately after operation. Periapical X-ray was performed after operation to evaluate the effect of the root canal filling. The total length of the root was divided into equal three parts on the X-ray film, and three-dimensional tightness of the apical, middle, and coronal region of the root canals were statistically analyzed respectively. Clinical examinations and X-ray examination were performed 6 and 12 months after the operation to evaluate the treatment success rate. RESULTS: The operation time of cold flowable gutta-percha group was significantly lower than that of the control group, which were 51 s and 74 s (P < 0.05); The percentages of pain and discomfort in the two groups were 26.67% and 40.00%, respectively. There were two cases of underfilling and no overfilling in both groups. The percentages of proper filling and tight three-dimensional obturation in the experimental and control groups were 71.11% and 60.00% respectively; and the percentages of tight three-dimensional obturation in the apical third areas were 86.67% and 66.67%, the difference was significant (P < 0.05). There was no significant difference in the three-dimensional tightness between the two groups in the middle and coronal third areas. The percentages of tight three-dimensional obturation in classification Ⅰ groups were 86.67%, 83.33%, 93.33% and 76.67%, 90.00%, 96.67% in experimental and control group, respectively; The percentages of classification Ⅱ/Ⅲ/Ⅳ groups were 86.67%, 86.67%, 100.00% and 46.67%, 86.67%, 100.00%, respectively, and the difference was significant (P < 0.05). There were no apical lesions that occurred in either group during the one-year review period. CONCLUSION: The application of cold flowable gutta-percha on young permanent teeth root canal obturation after apexification can achieve good obturation effect. The root obturation effect in the apical third area is significantly better than that of warm gutta-percha obturation techniques. Cold flowable gutta-percha can shorten the clinical treatment time and ameliorate the patients' therapy comfort.

[Efficacy of combined application of glycine powder air-polishing in non-surgical treatment of peri-implant diseases].

OBJECTIVE: To compare the clinical efficacy of combined application of glycine powder air-polishing and mechanical submucosal debridement in non-surgical treatment of peri-implant diseases. METHODS: A randomized controlled clinical study was carried out on patients diagnosed with peri-implant diseases in the Department of Periodontology, Peking University School and Hospital of Stomatology, between May of 2020 and June of 2021.Twenty-eight patients with totally sixty-two implants were enrolled.The patients were randomly divided into the test group and control group. The patients in the test group (13 subjects/32 implants) received mechanical submucosal debridement using titanium curettes combined with application of glycine powder air-polishing, while the control group (15 subjects/30 implants) received mechanical submucosal debridement using titanium only. Clinical parameters, such as plaque index (PLI), pocket probing depth (PPD), bleeding index (BI) and the percentage of suppuration on probing on implants' level (SoP%) were measured at baseline and 8 weeks after non-surgical intervention. Changes and group differences of clinical parameters of the implants before and 8 weeks after non-surgical intervention were compared. RESULTS: Mean PLI, PPD, BI of both the test group and control group significantly reduced 8 weeks after non-surgical intervention (P < 0.05). Compared with the control group, the test group achieved lower BI (2.7±0.8 vs. 2.2±0.7, P < 0.05), more reduction of BI (0.6±0.7 vs. 1.1±0.6, P < 0.01) and more reduction of SoP% (21.9% vs. 10%, P < 0.05) after non-surgical intervention. Both the control and test groups exhibited comparable PLI and PPD reductions (P>0.05). For the implants diagnosed with peri-implant mucositis, the test group revealed more signi-ficant reduction in BI and SoP% than the control group (1.0±0.7 vs. 0.4±0.7, P=0.02; 6.3% vs. 0, P=0.012). There was no significant difference existing in PLI and PD improvement between the control group and test group (P>0.05). For the implants diagnosed with peri-implantitis, there was no significant difference existing in PLI, PPD, BI and SoP% improvement values between the test and control groups (P>0.05). No complications or discomforts were reported during the study. CONCLUSION: Both treatment procedures could relieve the inflammation of peri-implant soft tissue. Non-surgical mechanical submucosal debridement combined application of glycine powder air-polishing is associated with significant reduction of soft tissue bleeding and suppuration on probing especially in the implants diagnosed with peri-implant mucositis.

[A case of mild Zellweger spectrum disorder first diagnosed as Usher syndrome].

A 5-year-old female patient, presented with"night blindness and poor hearing for 1 year"whose first diagnosis was Usher syndrome due to retinitis pigmentosa accompanied by sensorineural deafness. Compound heterozygous variants (c.5G>A, p.W2*/c.3022C>T, p.P1008S) of PEX1, the causative gene for Zellweger spectrum disorder was confirmed by targeted exome sequencing analysis. Permanent tooth enamel dysplasia, nail leukoplakia, and biochemical abnormalities of peroxisome which is consistent with mild Zellweger spectrum disorder were found when she followed up.

[Metagenomic data-analysis reveals enrichment of lipopolysaccharide synthesis in the gut microbiota of atrial fibrillation patients].

Objective: To investigate the functional changes of key gut microbiota (GM) that produce lipopolysaccharide (LPS) in atrial fibrillation (AF) patients and to explore their potential role in the pathogenesis of AF. Methods: This was a prospective cross-sectional study. Patients with AF admitted to Beijing Chaoyang Hospital of Capital Medical University were enrolled from March 2016 to December 2018. Subjects with matched genetic backgrounds undergoing physical examination during the same period were selected as controls. Clinical baseline data and fecal samples were collected. Bacterial DNA was extracted and metagenomic sequencing was performed by using Illumina Novaseq. Based on metagenomic data, the relative abundances of KEGG Orthology (KO), enzymatic genes and species that harbored enzymatic genes were acquired. The key features were selected via the least absolute shrinkage and selection operator (LASSO) analysis. The role of GM-derived LPS biosynthetic feature in the development of AF was assessed by receiver operating characteristic (ROC) curve, partial least squares structural equation modeling (PLS-SEM) and logistic regression analysis. Results: Fifty nonvalvular AF patients (mean age: 66.0 (57.0, 71.3), 32 males(64%)) were enrolled as AF group. Fifty individuals (mean age 55.0 (50.5, 57.5), 41 males(82%)) were recruited as controls. Compared with the controls, AF patients showed a marked difference in the GM genes underlying LPS-biosynthesis, including 20 potential LPS-synthesis KO, 7 LPS-biosynthesis enzymatic genes and 89 species that were assigned as taxa harbored nine LPS-enzymatic genes. LASSO regression analysis showed that 5 KO, 3 enzymatic genes and 9 species could be selected to construct the KO, enzyme and species scoring system. Genes enriched in AF group included 2 KO (K02851 and K00972), 3 enzymatic genes (LpxH, LpxC and LpxK) and 7 species (Intestinibacter bartlettii、Ruminococcus sp. JC304、Coprococcus catus、uncultured Eubacterium sp.、Eubacterium sp. CAG:251、Anaerostipes hadrus、Dorea longicatena). ROC curve analysis revealed the predictive capacity of differential GM-derived LPS signatures to distinguish AF patients in terms of above KO, enzymatic and species scores: area under curve (AUC)=0.957, 95%CI: 0.918-0.995, AUC=0.940, 95%CI 0.889-0.991, AUC=0.972, 95%CI 0.948-0.997. PLS-SEM showed that changes in lipopolysaccharide-producing bacteria could be involved in the pathogenesis of AF. The key KO mediated 35.17% of the total effect of key bacteria on AF. After incorporating the clinical factors of AF, the KO score was positively associated with the significantly increased risk of AF (OR<0.001, 95%CI:<0.001-0.021, P<0.001). Conclusion: Microbes involved in LPS synthesis are enriched in the gut of AF patients, accompanied with up-regulated LPS synthesis function by encoding the LPS-enzymatic biosynthesis gene.