A small proton charge radius from an electron-proton scattering experiment.

Elastic electron-proton scattering (e-p) and the spectroscopy of hydrogen atoms are the two methods traditionally used to determine the proton charge radius, rp. In 2010, a new method using muonic hydrogen atoms1 found a substantial discrepancy compared with previous results2, which became known as the 'proton radius puzzle'. Despite experimental and theoretical efforts, the puzzle remains unresolved. In fact, there is a discrepancy between the two most recent spectroscopic measurements conducted on ordinary hydrogen3,4. Here we report on the proton charge radius experiment at Jefferson Laboratory (PRad), a high-precision e-p experiment that was established after the discrepancy was identified. We used a magnetic-spectrometer-free method along with a windowless hydrogen gas target, which overcame several limitations of previous e-p experiments and enabled measurements at very small forward-scattering angles. Our result, rp = 0.831 ± 0.007stat ± 0.012syst femtometres, is smaller than the most recent high-precision e-p measurement5 and 2.7 standard deviations smaller than the average of all e-p experimental results6. The smaller rp we have now measured supports the value found by two previous muonic hydrogen experiments1,7. In addition, our finding agrees with the revised value (announced in 2019) for the Rydberg constant8-one of the most accurately evaluated fundamental constants in physics.

Chemo-Enzymatic Synthesis of Isomeric I-branched Polylactosamines Using Traceless Blocking Groups.

Poly-N-acetyl lactosamines (polyLacNAc) are common structural motifs of N- and O-linked glycan, glycosphingolipids and human milk oligosaccharides. They can be branched by the addition of ß1,6-linked N-acetyl-glucosamine (GlcNAc) moieties to internal galactoside (Gal) residues by the I-branching enzyme beta-1,6-N-acetylglucosaminyltransferase 2 (GCNT2). I-branching has been implicated in many biological processes and is also associated with various diseases such as cancer progression. Currently, there is a lack of methods that can install, in a regioselective manner, I-branches and allows the preparation of isomeric poly-LacNAc derivatives. Here, we described a chemo-enzymatic strategy that addresses this deficiency and is based on the enzymatic assembly of an oligo-LacNAc chain that at specific positions is modified by a GlcNTFA moiety. Replacement of the trifluoroacetyl (TFA) moiety by tert-butyloxycarbonyl (Boc) gives compounds in which the galactoside at the proximal site is blocked from modification by GCNT2. After elaboration of the antennae, the Boc group can be removed, and the resulting amine acetylated to give natural I-branched structures. It is also shown that fucosides can function as a traceless blocking group that can provide complementary I-branched structures from a single precursor. The methodology made it possible to synthesize a library of polyLacNAc chains having various topologies.

Notch signaling regulates Th17 cells differentiation through PI3K/AKT/mTORC1 pathway and involves in the thyroid injury of autoimmune thyroiditis.

PURPOSE: Autoimmune Thyroiditis (AIT) is the most common thyroid disease; however, there were no measures to prevent the progression of the disease. The present study attempts to identify that Notch signaling regulates the differentiation of T helper 17 (Th17) cells by activating downstream Phosphatidylinositol-3 kinase/protein kinase/mechanistic target of rapamycin complex 1 (PI3K/AKT/mTORC1) pathway participating in the thyroid injury of the experimental autoimmune thyroiditis (EAT). METHODS: In vivo experiments, mice were randomly divided into 4 groups: a control group, an EAT group, and two groups with LY294002 treatment (pTg plus 25 mg/kg or 50 mg/kg LY294002, respectively). The degrees of thyroiditis were evaluated, and the percentage of Th17 cells, expression of interleukin-17A (IL-17A), and the main components of the Notch-PI3K signaling pathway were detected in different groups. In vitro experiments, two different dosages of LY294002 (25 and 50 µM) were used to intervene splenic mononuclear cells (SMCs) from EAT mice to further evaluate the regulatory effect of Notch-PI3K pathway on Th17 cells. RESULTS: Our data demonstrate that the infiltration of Th17 cells and the expressions of IL-17A, Notch, hairy and split 1 (Hes1), p­AKT (Ser473), p­AKT (Thr308), p­mTOR (Ser2448), S6K1, and S6K2 increased remarkably in EAT mice. After PI3K pathway was blocked, the degrees of thyroiditis were significantly alleviated, and the proportion of Th17 cells, the expression of IL-17A, and the above Notch-PI3K pathway-related molecules decreased in a dose-dependent manner. Additionally, the proportion of Th17 cells was positively correlated with the concentration of serum thyroglobulin antibody (TgAb), IL-17A, and Notch-PI3K pathway-related molecules mRNA levels. CONCLUSIONS: Notch signal promotes the secretion of IL-17A from Th17 cells by regulating the downstream PI3K/AKT/mTORC1 pathway through Hes-Phosphatase and tensin homolog (PTEN) and participates in thyroid autoimmune damage, and the PI3K pathway inhibitor may play important effects on AIT by affecting Th17 cells differentiation.

Brain structural and functional MRI alterations and their predictive value for the visual outcome at 3 years in clinically isolated optic neuritis.

AIM: To investigate the structural and functional magnetic resonance imaging (MRI) alterations and their clinical significance for predicting visual outcomes at 3 years in clinically isolated optic neuritis (CION). MATERIALS AND METHODS: Forty-three CION patients and 44 matched healthy controls (HC) underwent a three dimensional (3D) T1-weighted and resting-state functional MRI using a 3 T MRI system. Grey-matter volume (GMV) and functional MRI measures were compared among HC and CION patients with good and poor outcomes. The correlations between MRI measures and visual outcomes were investigated, and a binary logistic regression model was performed to predict the visual outcome. RESULTS: CION patients with good and poor outcomes showed similar patterns of decreased GMV and increased functional MRI activities compared to HC. Compared to patients with good visual recovery, CION patients with poor visual recovery showed significantly reduced GMV in the insula and superior temporal gyrus (STG), decreased amplitude of low-frequency fluctuation (ALFF) in the inferior frontal gyrus (IFG), and increased functional activities in the middle frontal gyrus (MFG) and middle temporal gyrus (MTG). Binary logistic regression analysis predicted poor visual recovery, including decreased GMV in the bilateral insula (right insula: odds ratio [OR] = 17.46, p<0.001; left insula: OR=10.538, p=0.001; respectively) and STG (OR=16.551, p<0.001) and increased ALFF (OR=17.148, p<0.001) and regional homogeneity (OR=10.068, p=0.002) in the left MTG. CONCLUSION: CION patients showed decreased GMV and increased functional activities predominantly located in visual- and cognition-related areas. Decreased GMV and increased ALFF or regional homogeneity in the high-order visual regions (insula, STG, and MTG) are promising imaging markers predicting poor visual outcomes at the 3-year follow-up.

[Changes of serum calcium and bone turnover markers in maintenance hemodialysis patients treated with denosumab].

A total of 20 patients (8 males and 12 females) aged (64.8±13.9) years who underwent regular hemodialysis and had bone loss or osteoporosis in Peking University People's Hospital from July to December 2021 were recruited. Sixty milligrams of denosumab were given subcutaneously. The average serum calcium decreased by 0.31 mmol/L and 40% (8/20) of the patients had hypocalcemia one month after treatment. The markers of bone turnover began to decrease 3 days after treatment, and continued to decrease until 5 months after denosumab medication. Multivariate logistic regression analysis failed to detect any independent risk factor for hypocalcemia (R2=0.516, P=0.021). Therefore, denosumab can significantly inhibit bone turnover in hemodialysis patients, however, patients with denosumab medication are more prone to hypocalcemia.

[Comparative analysis of clinical diagnosis application of two intrauterine adhesion scoring criteria].

Objective: To explore the similarities and differences of China Society of Gynecology Endoscopy (CSGE) and American Fertility Society (AFS) intrauterine adhesion (IUA) scoring criteria on IUA grading and their predictive value of reproductive prognosis. Methods: From January 2016 to January 2019, a total of 1 249 patients were diagnosed with IUA by hysteroscopy at Beijing Obstetrics and Gynecology Hospital. Totally, 378 patients with complete clinical data were enrolled, and the results diagnosed by CSGT and AFS scoring criteria were compared and analyzed.And follow-up for 2 years, the pregnancy rate and live birth rate were statistical analysis. Results: (1) The grade of IUA according to AFS and CSGE scoring criteria was less consistent (κ=0.295, P<0.001). Compared with AFS, the proportion of severe IUA cases diagnosed by CSGE was significantly lower [45.8% (173/378) vs 15.1% (57/378); RR=0.22, 95%CI: 0.15-0.30, P<0.01); the proportions of both mild and moderate IUA cases were significantly higher (RR=4.16, 95%CI: 2.38-7.14; RR=2.38, 95%CI: 1.75-3.23; both P<0.01). (2) The pregnancy rates of mild, moderate and severe IUA diagnosed according to CSGE were 11/13, 64.5% (147/228), 31.8% (7/22), live birth rates were 11/13, 54.8% (125/228) and 22.7% (5/22), respectively; there were statistically significant differences between the groups (all P<0.01). The pregnancy rates of mild, moderate and severe IUA diagnosed based on AFS were 3/3, 66.9% (97/145) and 56.5% (65/115), respectively, with no statistically significant difference between the groups (P>0.05). (3) IUA grades based on both CSGE and AFS criteria were significantly negatively correlated with pregnancy rates and live birth rates (CSGE: r=-0.210, r=-0.226; AFS: r=-0.130, r=-0.147; all P<0.05). Univariate logistic regression analysis showed that CSGE had higher OR for both pregnancy rates and live birth rates compared to AFS (3.889 vs 1.657, 3.983 vs 1.554, respectrvely). Conclusions: Compared with AFS, the IUA grade based on CSGE is better related with reproductive prognosis, suggesting that the CSGE standard might be more objective and comprehensive and has better predictive value for reproductive prognosis, thus avoiding overdiagnosis and overtreatment.

COVID-19 vaccine safety and side effects in children aged 5-11 years: a cross-sectional study.

INTRODUCTION: The COVID-19 pandemic has prompted a global drive for vaccination, including children. Despite the urgency, understanding the safety and side effects remains crucial. Our study aimed to evaluate the safety of the Pfizer- BioNTech (BNT162b2) vaccine in children by determining the proportion of vaccinated children who experienced side effects and identifying factors associated with postvaccination side effects. MATERIALS AND METHODS: A cross-sectional study was conducted among children who received the COVID-19 vaccine between 3 February and 8 May 2022. Data were collected using a self-administered questionnaire filled out by the parent or legal guardian. RESULTS: The mean age of the study participants was 9 years old and 43.1% were males. Out of the 195 participants in the study, 62 (31.8%) reported side effects after vaccination. The most frequently reported side effects were pain at the injection site (29.7%, n=58), fever (15.9%, n=31), localised inflammation (10.8%, n=21) and arthralgia/myalgia (9.2%, n=18). There were no reported severe adverse events such as anaphylaxis or myocarditis. Most side effects occurred within the first two days post-vaccination. There was a higher proportion of side effects among children with underlying co-morbidities. No significant differences were observed based on age, weight, ethnicity and the presence of allergies, or the use of premedication. CONCLUSION: The BNT162b2 vaccine was generally welltolerated in children, with most side effects being mild and self-limiting. These findings support the safety of the COVID-19 vaccine and would guide healthcare professionals, parents and policy-makers in making informed decisions about COVID-19 vaccination, especially among high-risk groups.

Adverse events following BNT162b2 mRNA COVID-19 vaccination among healthcare workers: A single-centre experience in Malaysia.

INTRODUCTION: The COVID-19 pandemic is a global health crisis that has resulted in a massive disease burden worldwide. Mass vaccination plays an important role in controlling the spread and severity of COVID-19 infections worldwide. MATERIALS AND METHODS: A cross-sectional study was conducted in Hospital Tuanku Ja'afar Seremban between 1 March 2021 and 4 May 2021 to describe the adverse events (AE) following BNT162b2 (Pfizer-BioNTech) vaccination. Healthcare personnel who received at least one dose of the vaccine were invited to complete an online questionnaire. RESULTS: Of 2282 analysed samples, AE were experienced in up to 64.5% (n=1472) of the study participants. Most AE were encountered after the second dose (56.5%, n=832). Pain at the injection site (41.5%, n=944), fever (35.1%, n=798) and lethargy (34.8%, n=792) were the most commonly reported AE. Severe AEFI were reported in a minority (2.9%, n=68). There were no documented anaphylaxis, vaccine-induced thrombosis, or myocarditis. The proportion of female recipients and recipients with a history of allergy were higher in the AE group compared to the non-AE group. CONCLUSION: Our study reinforces the safety of the BNT162b2 mRNA vaccine in the local population. The main adverse events were mild, although they occurred in most patients.

[Observation of microstructure and vessel density changes in the superficial retinal layer in buried optic disc drusen patients].

Objective: To investigate the changes of the microstructure and vascular density in the superficial retinal layer of buried optic disc drusen (ODD) patients. Methods: Retrospective case-control study. A total of 36 ODD eyes (20 patients) and 26 normal control eyes were recruited in Beijing Union Medical College Hospital from January 2018 to July 2020. Measurement of best corrected visual acuity (BCVA), intraocular pressure, slit lamp, fundus examination and visual field examination were performed. The images and data of spectral domain-optical coherence tomography (SD-OCT) and optical coherence tomography angiography (OCTA) were analyzed and summarized. The differences of nasal retinal nerve fiber layer (RNFL), ganglion cell complex (GCC) thickness and macular superficial vascular density (VD) between ODD patients and normal controls were compared by independent sample t-test or Mann Whitney U test (the right eye was selected in bilateral ODD patients). Results: The 20 ODD patients and 26 normal controls were all female. There was no significant difference in age between the two groups (P>0.05). The BCVA and visual field examination was normal in all ODD patients. The SD-OCT examination showed an oval low signal shadow under the nasal outer nuclear layer of the optic disc, or local accumulation like a medium signal shadow with a clear boundary, and a high signal capsule in ODD patients. The RNFL in the upper nasal side of the ODD group was significantly different from the normal control group [(102.6±19.1) µm vs. (119.0±13.8) µm; t=-2.81; P<0.01]. Compared with normal control group [101.0 (100.0, 102.0) µm], the average GCC thickness in the ODD group [97.0 (89.3, 99.8) µm] was significantly different (U=48.50; P<0.01). The OCTA en-face scan showed that the vascular network in the macular area of the affected eyes was sparser than that of the control eyes. There was significant difference in superficial macular VD beteeen the ODD group (48.5%±2.8%) and the control group (51.0%±2.3%) (t=-2.63; P<0.05). Conclusions: There is thinning in the RNFL upper nasal side and GCC layer of the macular region in buried ODD patients, and the superficial VD of the macular region in buried ODD patients is lower than that in the normal controls.

[The prevalence and influence factors of work-related musculoskeletal disorders of dental nurse].

Objective: To investigate the prevalence and Influence factors of work-related musculoskeletal disorders (WMSDs) among dental nurses in tertiary stomatology hospitals. Methods: From June to July 2020, 1321 dental nurses from 18 tertiary stomatology hospitals in 18 provinces of China were enrolled as research subjects through a phased sampling method. The cross-sectional study was performed with validated instruments including the basic information questionnaire, Effort-Reward Imbalance Questionnaire, Nurse-Physician Collaboration Scale, and Chinese Musculoskeletal Questionnaire, so as to get the information about the social demography information, nursing-physician cooperation, work stress and the incidence of WMSDs. The influenang factors of WMSDs was analyzed. Results: The past prevalence, annual prevalence, and weekly prevalence of WMSDs were 80.8% (1067/1321) , 68.7% and 43.7% (575/1321) . 58.4% (771/1321) of nurses had WMSDs in three or more body parts. Neck (51.4%) , waist (42.2%) and shoulder (41.6%) were the top three body regions in the past year. The absenteeism rate due to musculoskeletal disorders ranged from 3.5% to 9.0%, waist (8.9%) and neck (8.0%) were the top two body regions. Working more than 40 hours per week (OR=1.74, P<0.001) and effect/reward>1 (OR=1.50, P=0.002) were risk factors of WMSDs (OR=1.74, 95% CI: 1.32~2.30; OR=1.50, 95%CI: 1.17~1.92, P<0.05) , while regular physical exercise every week (≥30 min per times) was the protective factor (OR=0.74, 95%CI: 0.56~0.97, P=0.030) . Conclusion: The prevalence rate of WMSDs of dental nurses in China was high, and most of the nurses suffered with many body parts. Thus, we should reduce controllable occupational stresso, ensuring adequate rest and strengthening physical exercise to reduce the incidence of WMSDs.

Study on a new manner of the magnetization switching actuated by a unidirectional pulse current.

A new writing scheme with a unidirectional pulse current is proposed for spin transfer torque (STT) based magnetic random-access memory (MRAM). To investigate the feasibility of the writing scheme, bilayered nano-pillars composed of a soft layer with small in-plane shape anisotropy and a hard layer with either large perpendicular anisotropy (PMA) or in-plane anisotropy (IMA) are designed and their switching behaviors are studied. It is found that in either type of bilayered nano-pillars, with the aid of the attached hard layer, the magnetization of the soft layer can be switched back and forth under a unidirectional pulse current. In an IMA/IMA nano-pillar, the magnetization of the free layer (FL) can achieve excellent alignment, which is in contrast to the IMA/PMA nano-pillar. By optimizing the dimensions and magnetic parameters of the IMA/IMA nano-pillar, a decently low switching current density (4.3 × 1011A m-2) and ultrashort switching time (<1 ns) can be reached. Based on these results, the unidirectional writing scheme is practical if an IMA/IMA bilayer is used to replace the FL in a magnetic tunnel junction. Considering that a unidirectional writing scheme can enable the application of materials with high spin polarization such as half metals, and avoid the injection of writing current into junction using a special design, it may be very promising for STT-MRAM.

Engagement among physicians fighting COVID-19: the mediating role of autonomy.

BACKGROUND: Keeping and improving work engagement among physicians fighting COVID-19 is important to healthy medical systems. In line with the job demands-resources model, optimism was expected to positively relate with job resources, leading to higher work engagement. However, the underlying mechanism between optimism, autonomy and work engagement has not been explored. AIMS: To examine whether optimism has a positive impact on work engagement via autonomy among physicians fighting COVID-19 in China. METHODS: This study was conducted among physicians in March 2020. A convenience sample was used to recruit physicians from the Wuhan Leishenshan Hospital and Wuhan Jinyintan Hospital. One hundred and four Chinese physicians working in the COVID-19 epidemic completed a survey measuring levels of autonomy, optimism and work engagement. The PROCESS macro (model 4) was used to test hypotheses about mediation. RESULTS: This current study found that optimism was related to increased autonomy, and autonomy was related to increased work engagement. The results of the bias-corrected bootstrap method suggested the indirect effect of optimism on work engagement via autonomy (Effect = 0.16, SE = 0.08, lower level confidence interval = 0.04, upper level confidence interval = 0.37), indicating a mediated relationship, in which autonomy is one mechanism to explain the link between optimism and increased work engagement. CONCLUSIONS: This study follows an observational design, with in-depth analysis of the relationship between optimism, autonomy and work engagement. When management implements strategies to improve work engagement among physicians working in the COVID-19 epidemic, the mediating impact of autonomy on the association between optimism and work engagement should be considered.

[Effects of (+)-catechin and epigallocatechin gallate on alcoholic fatty liver in mice models].

Objective: To investigate the effects of (+)-catechin and epigallocatechin gallate (EGCG) on alcoholic fatty liver in mice models. Methods: Alcohol and high-fat diet were used to construct the model of alcoholic fatty liver disease, and treated the model with (+)-catechin and EGCG. The effects of (+)-catechin and EGCG were analyzed by detecting the contents of TG, TC, MDA, SOD, ALT and AST in serum and pathological changes of liver. Results: (+)-catechin and EGCG could effectively reduce the contents of TG, TC, MDA, ALT and AST, increase the content of SOD in serum of mice with alcoholic fatty liver disease, improve the degree of liver cell edema and reduce the formation of lipid droplets. Conclusion: (+)-catechin and EGCG could repair liver injury and regulate lipid metabolism of hepatocytes in alcoholic fatty liver disease mice models.

[GPCR48 promotes invasion and metastasis by inducing epithelial-mesenchymal transition in hepatocellular carcinoma cells].

Objective: To observe the G protein-coupled receptor 48 (GPCR48) expression in hepatocellular carcinoma (HCC) cell lines with different metastatic potential and its characteristics effect on the invasion and metastasis of Huh7 hepatoma cells via epithelial-mesenchymal transition (EMT). Methods: Western blot was used to detect the protein expression level of GPCR48 in HCC cells with different metastatic potential. The lentivirus vector expressing GPCR48 gene was constructed. GPCR48 was overexpressed in Huh7 hepatoma cells. The GPCR48 overexpression level was detected by real-time PCR and Western blot. Transwell invasion and migration assay was used to detect the Huh7 hepatoma cells invasion and migration ability in the Control, Mock and GPCR48 overexpression group. Real-time PCR and Western blot were used to detect Huh7 hepatoma cells mRNA and protein expression levels of the EMT related markers (E-cadherin, N-cadherin, vimentin, and γ catenin) in the Control, Mock and GPCR48 overexpression groups, respectively. Analysis of variance was used to compare the differences between data sets. Results: GPCR48 protein expression level in metastatic HCC cell lines was significantly higher than non-metastatic HCC cell lines (P < 0.05). The lentivirus vector expressing the GPCR48 gene had effectively transfected the Huh7 hepatoma cells and stably expressed the GPCR48mRNA and protein. Compared with the Mock and the Control group, Huh7 hepatoma cells invasion and migration ability in the GPCR48 overexpression group was significantly enhanced (F≥5.54, P < 0.05), and the mRNA and protein expression levels of epithelial phenotypic markers E-cadherin and γ-catenin were decreased (P < 0.05). The mRNA and protein expression levels of the mesenchymal phenotypic markers N-cadherin and Vimentin were increased (P < 0.05), indicating that EMT changes occurred in Huh7 hepatoma cells had overexpressed GPCR48. Conclusion: GPCR48 expression level is positively correlated with the metastatic potential of HCC cells. GPCR48 overexpression can down-regulate the expression of epithelial phenotypic markers and up-regulate the expression of mesenchymal phenotypic markers, and induce EMT changes in HCC cells, thus promoting HCC cells invasion and migration.

[Veracity of using a visual chart with a testing distance of 2.5 meters for measurement of distance visual acuity in teenagers].

Objective: To compare the results of visual acuity testing for teenagers with visual acuity charts designed at 2.5-meter and 5-meter distances, and to investigate the accuracy of the 2.5-meter visual acuity chart. Methods: It was a self-control study. A total of 227 teenagers (454 eyes) with ametropia who came to the ophthalmic clinic of Peking Union Medical College Hospital from March 2019 to September 2019 were included. There were 123 males and 104 females aged (11.74±3.26) years. The vision examiners were trained in the same testing environment and passed the consistency test. Distance visual acuity of all participants was tested with charts designed at 2.5 meters and 5 meters in a 10-minute interval. According to the age (7-9, 10-12, 13-15 and 16-18 years old) and visual acuity (1.00-0.52, 0.40-0.30 and 0.22-0.10), the results of two kinds of visual acuity charts were compared. The testing order of the two visual charts was randomly determined. The visual acuity results were converted into logMAR values and compared. Paried t-student test was used to compare the difference between two charts, and Pearson correlation test was used to explore the correlation between the results of two charts. Results: The visual acuity of the right eye was 0.37±0.24 (logMAR) at 2.5 meters and 0.50±0.26 (logMAR) at 5 meters. The distance visual acuity measured with the 2.5-meter visual acuity chart was better (t=16.19, P<0.01). The visual acuity of the left eye was 0.36±0.23 (logMAR) at 2.5 meters and 0.45±0.23 (logMAR) at 5 meters (t=11.71, P<0.01). The differences between two charts were larger among teenagers with lower visual acuity (r=0.387,P<0.01). Conclusion: Under the same test conditions, the distance visual acuity measured with a 2.5-meter chart was significantly better than a 5-meter chart. The visual acuity chart designed at 2.5 meters was not an appropriate tool to measure distance vision in adolescents. (Chin J Ophthalmol, 2021, 57: 122-125).

[Peripapillary and macular vessel density in eyes with different phases of thyroid-associated ophthalmopathy].

Objective: To analyze the characteristics of vessel density in the optic disc and macular area of patients with different phases of thyroid-associated ophthalmopathy (TAO) and their correlation with visual function. Methods: This case-control study was conducted at the Department of Ophthalmology of Peking Union Medical College Hospital between June 2019 and September 2019. TAO patients and healthy volunteers were included in the study. Patients with a clinical activity score greater than or equal to 3 points were categorized as active TAO. Dysthyroid optic neuropathy (DON) patients with a course less than 6 months were categorized as acute phase of DON, and those more than 6 months were in the chronic group. Healthy volunteers were in the control group. Each group included 12 subjects, with right eyes for analysis. There were 6 males and 6 females in each group. All participants underwent comprehensive ophthalmic examination including best corrected visual acuity and visual field examination for the mean defect (MD). Best corrected visual acuity was subsequently converted to logarithm of minimum angle of resolution (logMAR). Optical coherence tomography was used to measure the thickness of the retinal nerve fiber layer (RNFL) and retinal ganglion cell complex (GCC). Optical coherence tomography angiography was used to the peripapillary and macular vessel density. The differences in the vessel densities in the optic disc and macular area between groups and their correlation with different factors were analyzed. Analysis of variance, non-parametric Mann-Whitney U test and Spearman coefficient were conducted for statistical analysis. Results: There was no significant difference in age among the four groups (P>0.05). The logMAR of the acute DON group was 0.1 (0.0, 0.2), worse than the control group, which was 0.0 (0.0, 0.0) (U=114.000, P<0.05). The overall vessel densities of the optic disc in acute DON and chronic DON were significantly lower than the control group (54.70%±2.31% and 54.31%±3.65% vs. 57.54%±2.17%; t=3.104, 2.636; both P<0.05). The overall superficial vessel densities of the macular area in active TAO, acute DON and chronic DON were significantly lower than the control group (46.07%±3.06% and 42.26%±5.05% and 45.63%±3.87% vs. 49.34%±3.08%), and the differences were statistically significant (t=2.614, 4.147, 2.603; all P<0.05). There was no statistically significant difference in the size of the foveal avascular zone or the density of deep blood vessels in the macular area among the four groups (all P>0.05). In the active TAO period, there was no correlation between the MD value, RNFL thickness, GCC thickness and the vessel densities of the optic disc and macular area (all P>0.05). The vascular density of the whole layer of the optic disc in acute DON was negatively correlated with the MD value (r=-0.591, P<0.05) and positively correlated with the RNFL thickness and GCC thickness (r=0.595, 0.693; both P<0.05). In chronic DON, the overall capillary density of the optic disc was negatively correlated with the MD value (r=-0.673, P<0.05); the superficial overall blood vessel density of the macular area was positively correlated with the thickness of RNFL and GCC (r=0.732, 0.712;both P<0.01). Conclusions: In active TAO, only the blood supply to the superficial layer of the macular area is decreased. In the acute and chronic phases of DON, the blood supply to the superficial layer of the macular area and the optic disc is both reduced; the smaller the blood vessel density, the more severe the visual field defect, and the thinner the RNFL and GCC. (Chin J Ophthalmol, 2020, 56:824-831).

Adenosine stress CMR perfusion imaging of the temporal evolution of perfusion defects in a porcine model of progressive obstructive coronary artery occlusion.

Adenosine stress CMR perfusion imaging can quantify absolute perfusion and myocardial perfusion reserve (MPR) in coronary artery disease (CAD) with higher spatial resolution than positron emission tomography, the only clinically available technique for quantitative myocardial perfusion imaging. While porcine models of CAD are excellent for studying perfusion abnormalities in chronic CAD, to date there are a limited number of studies that use quantitative perfusion for evaluation. Therefore, we developed an adenosine stress CMR protocol to evaluate the temporal evolution of perfusion defects in a porcine model of progressive obstructive CAD. 10 Yucatan minipigs underwent placement of an ameroid occluder around the left circumflex artery (LCX) to induce a progressive chronic coronary obstruction. Four animals underwent a hemodynamic dose range experiment to determine the adenosine dose inducing maximal hyperemia. Each animal had a CMR examination, including stress/rest spiral quantitative perfusion imaging at baseline and 1, 3, and 6 weeks. Late gadolinium enhancement images determined the presence of myocardial infarction, if any existed. Pixelwise quantitative perfusion maps were generated using Fermi deconvolution. The results were statistically analyzed with a repeated mixed measures model to block for physiological variation between the animals. Five animals developed myocardial infarction by 3 weeks, while three developed ischemia without an infarction. The perfusion defects were located in the inferolateral myocardium in the perfusion territory of the LCX. Stress perfusion values were higher in remote segments than both the infarcted and ischemic segments (p < 0.01). MPR values were significantly greater in the remote segments than infarcted and ischemic segments (p < 0.01). While the MPR decreased in all segments, the MPR recovered by the sixth week in the remote regions. We developed a model of progressive CAD and evaluated the temporal evolution of the development of quantitative perfusion defects. This model will serve as a platform for understanding the development of perfusion abnormalities in chronic occlusive CAD.

First Measurement of Near-Threshold J/ψ Exclusive Photoproduction off the Proton.

We report on the measurement of the γp→J/ψp cross section from E_{γ}=11.8 GeV down to the threshold at 8.2 GeV using a tagged photon beam with the GlueX experiment. We find that the total cross section falls toward the threshold less steeply than expected from two-gluon exchange models. The differential cross section dσ/dt has an exponential slope of 1.67±0.39 GeV^{-2} at 10.7 GeV average energy. The LHCb pentaquark candidates P_{c}^{+} can be produced in the s channel of this reaction. We see no evidence for them and set model-dependent upper limits on their branching fractions B(P_{c}^{+}→J/ψp) and cross sections σ(γp→P_{c}^{+})×B(P_{c}^{+}→J/ψp).

[Effects of different drugs on bronchial stenosis by TGF-ß/mTOR signaling pathway in rabbit model].

Objective: To investigate the effect of different drugs on tracheal stenosis caused by transforming growth factor-ß/rapamycin target protein (TGF-ß/mTOR) signaling pathway. Methods: Thirty rabbits were randomly divided into normal control group, normal saline group, penicillin group, budesonide group and erythromycin group. The normal control group was not treated,and tracheal stenosis models were established in the other groups. From the 1st to 10th day after modeling, each group was respectively administered with normal saline (0.75 ml/kg, 2 times/d), intramuscular injection of penicillin (40 000 U/kg, 2 times/d), gastric administration of erythromycin (12.5 mg/kg, 2 times/d), inhalation of budesonide (0.05 mg/kg, 2 times/d). Rabbits were sacrificed on the 11th day after surgery, and tracheal specimens were collected to measure the degree of tracheal stenosis. Relative mRNA expression level of interleukin-6 (IL-6), transforming growth factor-ß (TGF-ß), Type Ⅰ collagen (COL-1), Type Ⅲ collagen (COL-3), and Sirtuin 1 (SIRT-1) were detected by Real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR); protein expression of mTOR, phosphorylated protein kinase B (p-AKT), vascular endothelial growth factor (VEGF),SIRT-1 were detected by immunohistochemical analysis; protein expression of nuclear factor κB (NF-κB),phosphorylated nuclear factor κB (p-NF-κB),protein kinase B (AKT),p-AKT,mTOR were detected by Western blotting. Results: The degree of stenosis of normal control group was (14.02±2.86)%, saline group was (64.14±3.21)%, penicillin group was (49.11±2.96)%, budesonide group was (39.52±2.09)%, erythromycin group was (32.60±4.27)%. The differences between any two groups were statistically significant (all P<0.05). Except between erythromycin group and normal control group, the differences in relative expression of IL-6 mRNA between any two groups (1.00±0.00, 9.02±1.50, 4.25±0.87, 2.53±0.17, 1.31±0.56) was statistically significant (all P<0.05), and the differences in relative expression of TGF-ß mRNA among all groups (1.00±0.00, 6.92±0.84, 3.83±0.44, 2.13±0.25, 1.40±0.15) were statistically significant (all P<0.05). The relative expression of SIRT-1 mRNA among all the groups (1.000±0.000, 0.209±0.042, 0.375±0.034, 0.555±0.028, 0.667±0.032) was statistically significant different (all P<0.05); except between erythromycin group and budesonide group,the protein levels of SIRT-1 among all other groups (16.93±2.28, 4.77±1.45, 7.70±0.61, 10.76±1.04, 11.03±1.10) were statistically significant different (all P<0.05). The protein levels of mTOR (9.28±4.56, 58.18±8.12, 44.75±5.56, 32.82±5.99, 24.73±3.56) and p-AKT (16.57±4.86, 61.79±6.66, 42.98±5.99, 32.79±5.34, 24.00±4.40) determined through immunohistochemistry of all groups were statistically significant different (all P<0.05). The protein levels of NF-κB, p-NF-κB, AKT, p-AKT and mTOR determined through Western blotting had the same trend as that of determined through immunohistochemistry. The protein expression of NF-κB,AKT and mTOR in saline group were significantly higher than other groups; those protein expression of erythromycin group was lower than budesonide group and penicillin group. Except between the erythromycin group and the normal control group, the protein expression of mTOR in other groups was statistically significant different (all P<0.05). Conclusion: Penicillin,erythromycin and budesonide can alleviate inflammation by increasing SIRT-1, alleviate tracheal scar hyperplasia induced by TGF-beta/mTOR pathway, and reduce the degree of tracheal stenosis in rabbits.

[Optic nerve morphology and vessel density in eyes with different phases of non-arteritic anterior ischemic optic neuropathy].

Objective: To compare the blood flow around the optic disc and related factors in patients with acute and chronic non-arteritic anterior ischemic optic neuropathy (NAION) and healthy volunteers with small disc cups under the same anatomical structure. Methods: This was a prospective case-control study. NAION patients with unilateral onset and healthy volunteers of the same phase were included in the study conducted at the Department of Ophthalmology of Peking Union Medical College Hospital between February 2017 and September 2018. Patients with a course of ≤ 3 months were categorized in the acute phase of NAION, and those with a course of >3 months were in the chronic phase of NAION. Healthy volunteers were in the control group. All subjects underwent the examination of best corrected visual acuity converted to logarithm of the minimum angle of resolution (LogMAR), measurement of non-contact intraocular pressure, slit lamp examination, small pupil fundus examination, and axial measurement. Optical coherence tomography was used to measure the thickness of retinal nerve fiber layers (RNFL) and retinal ganglion cell complex (GCC). Optical coherence tomography angiography was used to measure the vessel density around the optic disc. NAION patients underwent the visual field examination. Analysis of variance, non-parametric Mann-Whitney U test and Spearman coefficient was used for statistical analysis. Results: This study included 16 patients with acute phase of NAION, aged (57±9) years, 6 males and 10 females. There were 17 patients with chronic disease, aged (56±10) years, 7 males and 10 females. There were 15 healthy controls, aged (57±10) years old, 6 males and 9 females. There were no significant differences in age and gender between the groups (both P>0.05). The RNFL and the GCC in the NAION chronic phase group were significantly thinner than those in the acute phase group [(78±38) µm vs. (191±99) µm, (75±19) µm vs. (98±28) µm; t=4.389, 2.758; both P<0.05]. The cup/disc area ratio, cup/disc vertical diameter ratio and cup/disc horizontal diameter ratio in the chronic phase group were larger than those in the acute phase group [0.18 (0.11, 0.31) vs. 0.05 (0.01, 0.18), 0.45 (0.39, 0.56) vs. 0.22 (0.11, 0.41), 0.39 (0.28, 0.54) vs. 0.20 (0.07, 0.42)], and the difference was statistically significant (U=212.000, 208.000, 205.000; all P<0.05). Compared with the optic disc vessel density in the control group (53%±6%), there was a significant decrease in the acute phase group and the chronic phase group (45%±7%, 41%±8%; t=3.705, 4.940; both P<0.01). The blood vessel density in the nasal inferior of the chronic phase group was significantly lower than that in the acute phase group (36%±8% vs. 42%±7%, P=0.039), other sections didn't have significant difference (all P>0.05). There were tortuous capillaries in 8/16 of the acute phase cases, with a low blood flow density and visual field defect in relative positions. Correlation analysis showed that the whole density and peripapillary density in the NAION patients were negatively correlated with LogMAR, mean visual field defect, cup/disc area ratio, focal loss of volume of GCC and general loss of volume of GCC (r=-0.510, -0.733, -0.372, -0.532, -0.648; all P<0.01), but positively correlated with GCC and RNFL thickness (r=0.604, 0.508; both P<0.01). Conclusions: The optic disc vessel density in the acute phase and chronic phase of NAION is significantly reduced. The vessel density in the nasal area of the chronic phase is significantly reduced compared with the acute phase. The vessel density is correlated with visual acuity, visual field defect, disc indexes, thickness of RNFL and GCC. (Chin J Ophthalmol, 2019, 55: 677-686).