The Chinese version of the Ohkuma questionnaire: reliability analysis and diagnostic value.

BACKGROUND: While the Ohkuma questionnaire is a simple, reliable, and easy-to-use tool to assess dysphagia, none of its versions can be used by the Chinese population. OBJECTIVE: The purpose of this study was to evaluate the internal consistency, reliability and clinical validity of a newly made Chinese version of the Ohkuma questionnaire, and to provide some objective basis for its application in screening dysphagia. MATERIALS AND METHODS: From September 21 to June 2022, 96 patients with dysphagia and 89 asymptomatic subjects were recruited from three hospitals in China to form an observation and a control group, respectively. All subjects completed the Ohkuma questionnaire, Eating Assessment Tool-10, and a Video Fluoroscopy Study of Swallowing. RESULTS: The Cronbach's α coefficient measured in the questionnaire was 0.867, indicating acceptable internal reliability. The analysis of variance generated four main factors to be assessed, showing a good aggregation effectiveness of the questionnaire. The AVE square root values of three factors were greater than the maximum absolute value of the correlation coefficients between factors, indicating good differentiation effectiveness. The sensitivity and specificity scores, together with the positive and negative likelihood as well as diagnostic odds ratios indicate a good reactivity of the questionnaire. Lastly, after adjusting for age and sex, the results of the stepwise linear regression analysis showed that there was a significant positive correlation between the Ohkuma questionnaire and the penetration aspiration scale. CONCLUSIONS: The Chinese version of the Ohkuma questionnaire has good reliability and validity, and can be used as a rapid and effective screening tool for dysphagia.

Paper-based material with hydrophobic and antimicrobial properties: Advanced packaging materials for food applications.

The environmental challenges posed by plastic pollution have prompted the exploration of eco-friendly alternatives to disposable plastic packaging and utensils. Paper-based materials, derived from renewable resources such as wood pulp, non-wood pulp (bamboo pulp, straw pulp, reed pulp, etc.), and recycled paper fibers, are distinguished by their recyclability and biodegradability, making them promising substitutes in the field of plastic food packaging. Despite their merits, challenges like porosity, hydrophilicity, limited barrier properties, and a lack of functionality have restricted their packaging potential. To address these constraints, researchers have introduced antimicrobial agents, hydrophobic substances, and other functional components to improve both physical and functional properties. This enhancement has resulted in notable improvements in food preservation outcomes in real-world scenarios. This paper offers a comprehensive review of recent progress in hydrophobic antimicrobial paper-based materials. In addition to outlining the characteristics and functions of commonly used antimicrobial substances in food packaging, it consolidates the current research landscape and preparation techniques for hydrophobic paper. Furthermore, the paper explores the practical applications of hydrophobic antimicrobial paper-based materials in agricultural produce, meat, and seafood, as well as ready-to-eat food packaging. Finally, challenges in production, application, and recycling processes are outlined to ensure safety and efficacy, and prospects for the future development of antimicrobial hydrophobic paper-based materials are discussed. Overall, the emergence of hydrophobic antimicrobial paper-based materials stands out as a robust alternative to plastic food packaging, offering a compelling solution with superior food preservation capabilities. In the future, paper-based materials with antimicrobial and hydrophobic functionalities are expected to further enhance food safety as promising packaging materials.

Determination of iodine in workplace air by inductively coupled plasma mass spectrometry / 中国职业医学

Objective To establish a solvent desorption inductively coupled plasma-mass spectrometry (ICP-MS) method for determination of iodine in workplace air. Methods Iodine in workplace air was collected with alkaline activated carbon tube and desorbed with 10.0 mL pure water or 20 mmol/L sodium bicarbonate solution. Rhenium-185 was used as an internal standard for quantification. The sample was determined in standard mode and kinetic energy discrimination collision (KED) mode by ICP-MS. Results In standard mode, iodine showed a good linear range in the concentration of 9.0 to 1 100.0 μg/L, with a correlation coefficient of 0.999 3 and a detection limit of 2.7 μg/L. In KED mode, iodine showed a good linear range in the concentration of 24.3 to 800.0 μg/L, with a correlation coefficient of 0.999 1 and a detection limit of 7.3 μg/L. The average desorption efficiency using pure water ranged from 99.1% to 106.7%, with within-run relative standard deviation (RSD) of 3.1% to 8.0% and between-run RSD of 4.9% to 9.3%. The average desorption efficiency using sodium bicarbonate solution ranged from 96.5% to 105.3%, with within-run RSD of 4.9% to 8.6% and between-run RSD of 2.5% to 9.9%. There were no statistical significant differences in the main effects of desorption solution, ICP-MS detection mode, their interaction on average desorption efficiency and within-run RSD (all P>0.05). Samples could be stored at room temperature for at least 7 days. Conclusion This method is highly sensitive, accurate, and suitable for the determination of iodine in workplace air. The sample pretreatment is simple and rapid.

Stable Angina Pectoris with Sleep Disorders Treated by Modified Tongmai Anshen Formula （通脉安神方加减）： An Clinical Observation of 74 Cases / 中医杂志

ObjectiveTo observe the clinical efficacy of the Modified Tongmai Anshen Formula （通脉安神方加减， MTAF） in the treatment of stable angina pectoris （SAP） with sleep disorders. MethodsA total of 148 patients suffering from SAP with sleep disorder were included and randomly divided into control group and treatment group， with 74 patients in each group. The control group received conventional western medicine， and the treatment group additionally received MTAF （1 dose per day）， both for 4 weeks. The changes in angina pectoris symptoms， traditional Chinese medicine （TCM） syndromes， sleep quality， quality of life， serological indicators including serum intercellular adhesion molecule-1 （ICAM-1） and vascular cell adhesion molecule-1 （VCAM-1）， brain-derived nerve growth factor （BDNF） and tyrosine kinase receptor B （TrkB） were compared between groups before and after treatment， and the safety was evaluated. ResultsIn the treatment group and the control group， the total effective rates of TCM syndromes（82.43% vs 52.70%）， angina pectoris （79.73% vs 64.86%） and sleep （89.19% vs 68.92%） showing significant difference （P＜0.001）. After treatment， the total TCM syndrome score， primary symptom score， secondary symptom score， and secondary symptoms sleeplessness， restlessness， tiredness and fatigue individual score， angina pectoris score， PSQI total score and each item score were all significantly reduced in both groups， while the SF-36 single item score significantly increased （P＜0.05）. The total TCM syndromes and primary symptom scores， secon-dary symptoms sleeplessness， restlessness， tiredness and fatigue individual score， angina pectoris score， time to fall asleep， sleep quality， hypnotic medication， sleep disturbance， daytime dysfunction score and PSQI total score were significantly lower in the treatment group than those in the control group after treatment （P＜0.05）， while the somatic pain， general health status， social functioning， emotional functioning， mental health， and health change were significantly higher in the treatment group （P＜0.05）. After treatment， ICAM-1 and VCAM-1 level significantly decreased （P＜0.05）， and BDNF and TrkB levels increased （P＜0.05） in the treatment group， while BDNF level significantly decreased in the control group （P＜0.05）. The TrkB level was significantly higher in the treatment group compared to the control group after treatment （P＜0.05）. A total of four adverse events occurred during the treatment， none of which were considered to be related to this study. ConclusionMTAF can significantly improve angina pectoris symptoms， TCM syndromes， sleep quality and quality of life in patients suffering from SAP with sleep disorders， the mechanism of which may be related to the protection of vascular endothelial function and central neurons.

Feasibility Study of Beam Angle Optimization Based on Scripts in Automated-planning for Liver Cancer / 中国医疗器械杂志

OBJECTIVE@#To study the feasibility and potential benefits of beam angle optimization (BAO) to automated planning in liver cancer.@*METHODS@#An approach of beam angle sampling is proposed to implement BAO along with the module Auto-planning in treatment planning system (TPS) Pinnacle. An in-house developed plan quality metric (PQM) is taken as the preferred evaluating method during the sampling. The process is driven automatically by in-house made Pinnacle scripts both in sampling and scoring. In addition, dosimetry analysis and physician's opinion are also performed as the supplementary and compared with the result of PQM.@*RESULTS@#It is revealed by the numerical analysis of PQM scores that only 15% patients whose superior trials evaluated by PQM are also the initial trials. Gantry optimization can bring benefit to plan quality along with auto-planning in liver cancer. Similar results are provided by both dose comparison and physician's opinion.@*CONCLUSIONS@#It is possible to introduce a full automated approach of beam angle optimization to automated planning process. The advantages of this procedure can be observed both in numerical analysis and physician's opinion.

The engagement of histone lysine methyltransferases with nucleosomes: structural basis, regulatory mechanisms, and therapeutic implications

Histone lysine methyltransferases (HKMTs) deposit methyl groups onto lysine residues on histones and play important roles in regulating chromatin structure and gene expression. The structures and functions of HKMTs have been extensively investigated in recent decades, significantly advancing our understanding of the dynamic regulation of histone methylation. Here, we review the recent progress in structural studies of representative HKMTs in complex with nucleosomes (H3K4, H3K27, H3K36, H3K79, and H4K20 methyltransferases), with emphasis on the molecular mechanisms of nucleosome recognition and trans-histone crosstalk by these HKMTs. These structural studies inform HKMTs' roles in tumorigenesis and provide the foundations for developing new therapeutic approaches targeting HKMTs in cancers.

Cardiac rehabilitation program for patients undergoing small incision aortic valve replacement / 中华胸心血管外科杂志

Objective:To study the effect of cardiac rehabilitation program on recovery of patients after small incision aortic valve replacement.Methods:600 patients who underwent small incision aortic valve replacement in our hospital from January 2015 to January 2020 were retrospectively collected and divided into Cardiac rehabilitation group(CR) and control group by propensity matching analysis. Clinical data of CR group and control group were collected 6 months and 12 months after the beginning of Cardiac rehabilitation program. The primary outcome measures were the peak oxygen uptake(VO 2 Peak) of cardiopulmonary function test and the number of patients attending cardiovascular specialty in tertiary hospitals after the rehabilitation program began. The secondary outcome measures were 6-minute Walk test(6-MWT), psychological evaluation, and assessment of cardiovascular disease risk factors. Results:After 6 months and 12 months of cardiac rehabilitation program, the VO2 peak in CR group was statistically significant compared with the control group, and the 6-MWT index after 12 months was statistically significant.The cardiovascular specialist visits in tertiary hospitals in the two groups were statistically significant. The comparison of psychological self-rating scale and cardiovascular disease risk factors between the two groups was statistically significant after propensity matching analysis.Conclusion:Cardiac rehabilitation has a positive effect on postoperative recovery after small incision aortic valve replacement, and can improve patients’ motor ability.

Application status of generalized periodic discharges in continuous electroencephalography monitoring in hypoxic-ischemic encephalopathy / 中华神经科杂志

In the electroencephalography (EEG) monitoring of patients with hypoxic-ischemic encephalopathy, generalized periodic discharges are often monitored abnormal waveforms. When there are some features of generalized periodic discharges (e.g., frequency≥1.5 Hz or plus), it indicates that the patient is at high risk for seizures or has a poor prognosis. Compared with conventional EEG, the time of continuous EEG monitoring is longer, so the detection rate of these waveforms is higher. At present, scholars at home and abroad have studied these waveforms, but there is controversy about the significance of these waveforms. In this paper, the definition and characteristics of these waveforms and their significance in determining prognosis and guiding treatment in patients with hypoxic-ischemic encephalopathy are reviewed.

Expression of glucose transporter 3 in cutaneous squamous cell carcinoma and its effect on the proliferation, invasion and migration of A431 cells / 中华皮肤科杂志

Objective:To determine the expression of glucose transporter 3 (GLUT3) in cutaneous squamous cell carcinoma (cSCC), and to evaluate its effect on the cSCC cell line A431.Methods:From June 2016 to December 2020, 22 paraffin-embedded tissue specimens were collected from patients with pathologically confirmed cSCC in the Department of Dermatology, Peking University Third Hospital, and 20 discarded normal skin tissues after dermatological surgeries served as controls. Immunohistochemical assay was performed to determine the GLUT3 expression in cSCC tissues and normal skin tissues. Cultured A431 cells were divided into two groups: GLUT3 overexpression group transfected with a lentiviral vector carrying the SLC2A3 gene, and negative control group transfected with an empty lentiviral vector. Real-time fluorescence-based quantitative PCR and Western blot analysis were conducted to determine the mRNA and protein expression of GLUT3 in A431 cells in different groups, the cell proliferation assay (MTS assay) was performed to estimate the cell proliferative activity, and the live-cell analysis system Incucyte S3 was used for real-time evaluation of the migratory and invasive abilities of A431 cells in different groups. The relative glucose consumption and lactic acid production in A431 cells at 48 hours were measured by using glucose and lactic acid assay kits, retrospectively. Two independent samples t-test was used for comparisons between two groups, and one-way analysis of variance was used for comparisons among multiple groups. Results:The GLUT3 expression was significantly higher in the cSCC tissues than in the normal skin tissues (immunohistochemical assay score: 9.39 ± 2.56 points vs. 2.30 ± 2.60 points; t = 8.91, P < 0.05). Compared with the negative control group, the mRNA and protein expression of GLUT3 markedly increased in the GLUT3 overexpression group. MTS assay showed significantly increased proliferative activity of A431 cells in the GLUT3 overexpression group compared with the negative control group after 24- and 96-hour treatment ( t = 2.49, 3.54, P = 0.048, 0.012, respectively); cell fusion rates in the scratched area were significantly higher in the GLUT3 overexpression group than in the negative control group in the cell migration assay at 6, 12 18, and 24 hours and cell invasion assay at 12, 18, and 24 hours (all P < 0.05). At 48 hours, the relative glucose consumption and lactic acid production in A431 cells were significantly higher in the GLUT3 overexpression group than in the negative control group ( t = 2.98, 2.20, P = 0.011, 0.038, respectively) . Conclusion:GLUT3 was highly expressed in the cSCC tissues, and may participate in the occurrence and development of cSCC by providing energy to cSCC cells via promoting glucose uptake in cells to enhance their proliferative, migratory and invasive abilities.

Biomarkers related to the treatment of melanoma with immune checkpoint inhibitors / 中华皮肤科杂志

Recently, great breakthroughs have been made in the treatment of melanoma with immune checkpoint inhibitors. However, only a small proportion of patients show a long-lasting response to immunotherapy, and risks of immune-related adverse events and drug resistance have been also increasing along with the emergence of combination treatment. This review summarizes biomarkers related to the efficacy of immune checkpoint inhibitors in the treatment of melanoma, aiming to predict and screen out patients who may benefit from immunotherapy, guide individualized clinical treatment, and reduce the occurrence of drug resistance and adverse reactions.

Gut microbiota and immune checkpoint inhibitor treatment of melanoma / 中华皮肤科杂志

A growing number of studies have shown that gut microbiota affects the development of melanoma through various mechanisms, and plays a vital role in the treatment of melanoma. This review summarizes the relationship between gut microbiota and the development of melanoma, the effect of gut microbiota on the checkpoint blockade immunotherapy of melanoma and related adverse effects.

Associations of metabolic score for insulin resistance with chronic kidney disease and albuminuria in the Chinese population / 中华内科杂志

Objective:To explore the relationship between metabolic score for insulin resistance (METS-IR) and chronic kidney disease (CKD) and albuminuria in the Chinese population.Methods:This cross-sectional study was conducted from January to December 2018 among residents aged 20 to 70 years in ten regions of eight provinces in China; all residents had lived in their region for more than 5 years. Various parameters were measured, included fasting blood glucose, 2-hour postprandial blood glucose, glycosylated hemoglobin (HbA 1c), blood lipids, renal function, urinary albumin/creatinine ratio (UACR), etc. Data of 5 060 subjects meeting the criteria were included in the study. CKD was defined as estimated glomerular filtration rate (eGFR)<60 ml·min -1·1.73 m -2 or UACR≥30 mg/g. Albuminuria was defined as UACR≥30 mg/g. METS-IR was calculated and categorized into quartiles: Q1, METS-IR≤32.19; Q2, METS-IR 32.20-37.10; Q3, METS-IR 37.11-42.58; and Q4, METS-IR>42.58. The correlation between METS-IR and CKD and albuminuria was analyzed by binary logistic regression, and subgroup analyses were performed. Results:There were 1 266, 1 266, 1 265, and 1 263 participants included in Q1-Q4 groups, respectively. With the increase of METS-IR quartile, various parameters increased, including age, fasting blood glucose, HbA 1c, triglycerides, serum uric acid, waist circumference, body mass index, and systolic and diastolic blood pressure, and the proportion of males also increased (all P<0.05). The proportion of patients with CKD and albuminuria increased significantly with the increase in interquartile range (Q) of METS-IR (all P<0.05). Logistic regression analysis showed that for every 1-unit increment of METS-IR, the risk of CKD and albuminuria were both increased by 2% [for both: odds ratio ( OR)=1.02, 95% confidence interval ( CI) 1.01-1.03]. Compared with the lowest METS-IR group (Q1), the ORs for CKD and albuminuria in the highest METS-IR group (Q4) were 1.57 (95% CI 1.17-2.10) and 1.46 (95% CI 1.09-1.96), respectively. In the subgroup analyses, increased METS-IR was significantly associated with CKD and albuminuria among women (CKD: OR=1.62, 95% CI 1.14-2.31; albuminuria: OR=1.53, 95% CI 1.07-2.18), individuals with HbA 1c<7% ( OR=1.64, 95% CI 1.21-2.23; OR=1.55, 95% CI 1.14-2.11), individuals with eGFR≥90 ml·min -1·1.73 m -2 ( OR=1.78, 95% CI 1.27-2.49; OR=1.80, 95% CI 1.28-2.53), and the Chinese Han population ( OR=1.56, 95% CI 1.13-2.17; OR=1.41, 95% CI 1.01-1.96). Conclusions:METS-IR is significantly associated with CKD and albuminuria in a Chinese population. Furthermore, the higher the METS-IR, the higher the risk of CKD and albuminuria.

Value of transrectal multimodal ultrasound combined with prostate specific antigen in predicting clinically organ-confined prostate cancer / 中华健康管理学杂志

Objective:To explore the predictive value of transrectal multimodal ultrasound and prostate specific antigen (PSA) in clinically organ-confined prostate cancer.Methods:It was a cross-sectional study. The clinical data of patients with suspected prostate nodules treated in the First Hospital of Shanxi Medical University from May 2014 to April 2020 were analyzed retrospectively. Of the patients, 48 cases of clinically organ-confined prostate cancer and 51 cases of benign prostatic hyperplasia confirmed by clinical data and pathology were selected as research objects. The characteristics of transrectal multimodal ultrasound in the two groups were compared. Combined with PSA, logistic regression analysis was applied to screen the statistically significant features, and then the diagnosis model was established, and odds ratio of the variables were compared. The receiver operating characteristic (ROC) curve was constructed to analyze the predicting ability of the diagnosis model.Results:Four features were obtained with logistic regression analysis finally, including enhancement type, enhancement degree, elastography mode and PSA. The odds ratio of enhancement degree was higher than those of the other independent variables. The area under ROC curve of the diagnosis model was 0.868 ( P<0.01), the cut-off value was 0.514. The sensitivity and specificity of the diagnosis model in predicting clinically organ-confined prostate cancer was 79.2% and 80.4%, respectively. Conclusions:This combined diagnosis model of transrectal multimodal ultrasound and PSA has a certain clinical value in predicting clinically organ-confined prostate cancer.

Trend analysis of disease burden of gastric cancer in Chinese residents from 1990 to 2019 / 公共卫生与预防医学

Objective To analyze the trend of disease burden of gastric cancer in Chinese residents from 1990 to 2019 and to provide reference for the prevention and control of gastric cancer in China. Methods The crude incidence and crude mortality rates of gastric cancer in Chinese residents of different genders from 1990 to 2019 were calculated from the Global Burden of Disease Study (GBD) database, and the standardized incidence and mortality rates were calculated to describe the trend of incidence and mortality of gastric cancer in Chinese residents. Disability Adjusted Life year (DALY) and years lived with Disability (DALY) were used. YLD, years of life lost (YLL) and other indicators were used to analyze the age and gender distribution of the disease burden of gastric cancer in Chinese residents. Joinpoint regression model was used to analyze the trend of the disease burden of gastric cancer. Results From 1990 to 2019, the incidence and crude incidence of gastric cancer increased, while the standard incidence decreased. The number of deaths was on the rise, the crude mortality rate and the standard mortality rate were both decreased, the morbidity and mortality index values of male were higher than that of female. The average annual average of the standardized DALY rate and the standardized YLL rate in China decreased by 2.30% (AAPC= -2.30%, P < 0.001), while the trend of the standardized YLD rate was not statistically significant (P=1.000). The average annual decrease rate of standardized DALY rate, standardized YLD rate and standardized YLL rate for males was smaller than that for females. In 2019, the peak rates of normalization of disease burden indicators were mainly distributed in the 55-74 age group. Conclusion From 1990 to 2019, the disease burden of gastric cancer in China showed a downward trend, and males and middle-aged and elderly people were the key prevention and treatment groups.

Magnetic controlled capsule endoscope (MCCE)'s diagnostic performance for H. pylori infection status based on the Kyoto classification of gastritis.

BACKGROUND: Previous studies have shown that the Kyoto classification of gastritis can accurately predict H. pylori infection status on conventional gastroscopy. The aim of this study was to test whether the Kyoto classification of gastritis applies well to magnetic controlled capsule endoscopy (MCCE). METHODS: We consecutively recruited 227 participants who underwent both MCCE and urea breath tests (UBTs). Two physicians who were blinded to the UBT results independently made the diagnosis of H. pylori infection status according to 10 findings listed in the Kyoto classification of gastritis after reviewing MCCE images. We also developed 2 predictive models to assess H. pylori infection status by combining these 10 findings. RESULTS: The MCCE's overall diagnostic accuracy for H. pylori infection status was 80.2%. The sensitivity, specificity and diagnostic odds ratio (DOR) for current infection were 89.4%, 90.1% and 77.1, respectively. Major specific findings were mucosal swelling and spotty redness for current infection, regular arrangement of collecting venules (RAC), streak redness, fundic gland polyp (FGP) for noninfection, and map-like redness for past-infection. In the two prediction models, the area under the curve (AUC) values for predicting noninfection and current infection were 84.7 and 84.9, respectively. CONCLUSIONS: The Kyoto classification of gastritis applied well to MCCE. H. pylori infection status could be accurately assessed on MCCE according to the Kyoto classification of gastritis.

Erythromycin attenuates oxidative stress-induced cellular senescence via the PI3K-mTOR signaling pathway in chronic obstructive pulmonary disease.

Background and Purpose: Chronic obstructive pulmonary disease (COPD) is proposed to hasten lung aging. Erythromycin protects against oxidative stress and inflammatory responses. However, the potential anti-senescence effect of erythromycin remains disclosed. In the present study, we investigated whether erythromycin influenced oxidative stress-induced cellular senescence and investigated its related mechanisms. Methods: A cigarrete smoke (CS) -induced emphysema mouse model and a H2O2-induced premature senescence model in human bronchial epithelial cell line (BEAS-2B) were established. Senescence-related markers (P53, P21 and SA-ß-Gal activity), and levels of oxidative stress biomarkers (MDA, SOD and ROS) were measured. Additionally, cells were pretreated with rapamycin (mTOR inhibitor) or erythromycin, and the expression levels of components of the PI3K-mTOR signaling pathway were measured in BEAS-2B cells. Results: Exposed to H2O2, increased SA-ß-gal activity was observed in BEAS-2B cells suggesting premature senescence. Erythromycin inhibited the expression of P53 and P21 in the CS-induced emphysema mouse model. MDA levels significantly increased and SOD levels decreased in the CS-exposed mice and H2O2-induced BEAS-2B cells. Rapamycin and erythromycin significantly suppressed the expression of P53 and P21. Additionally, rapamycin and erythromycin inhibited the PI3K-mTOR signaling pathway. Conclusion: Our findings suggest that erythromycin ameliorates oxidative stress-induced cellular senescence via the PI3K-mTOR signaling pathway. Hence, we establish a theoretical foundation for the clinical application of erythromycin for COPD prevention and treatment.

A cocktail containing two synergetic antibodies broadly neutralizes SARS-CoV-2 and its variants including Omicron BA.1 and BA.2

Neutralizing antibodies (NAbs) can prevent and treat infections caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, continuously emerging variants, such as Omicron, have significantly reduced the potency of most known NAbs. The selection of NAbs with broad neutralizing activities and the identification of conserved critical epitopes are still urgently needed. Here, we identified an extremely potent antibody (55A8) by single B-cell sorting from convalescent SARS-CoV-2-infected patients that recognized the receptor-binding domain (RBD) in the SARS-CoV-2 spike (S) protein. 55A8 could bind to wild-type SARS-CoV-2, Omicron BA.1 and Omicron BA.2 simultaneously with 58G6, a NAb previously identified by our group. Importantly, an antibody cocktail containing 55A8 and 58G6 (2-cocktail) showed synergetic neutralizing activity with a half-maximal inhibitory concentration (IC50) in the picomolar range in vitro and prophylactic efficacy in hamsters challenged with Omicron (BA.1) through intranasal delivery at an extraordinarily low dosage (25 g of each antibody daily) at 3 days post-infection. Structural analysis by cryo-electron microscopy (cryo-EM) revealed that 55A8 is a Class III NAb that recognizes a highly conserved epitope. It could block angiotensin-converting enzyme 2 (ACE2) binding to the RBD in the S protein trimer via steric hindrance. The epitopes in the RBD recognized by 55A8 and 58G6 were found to be different and complementary, which could explain the synergetic mechanism of these two NAbs. Our findings not only provide a potential antibody cocktail for clinical use against infection with current SARS-CoV-2 strains and future variants but also identify critical epitope information for the development of better antiviral agents.

Molecular basis of broad neutralization against SARS-CoV-2 variants including Omicron by a human antibody

Omicron, a newly emerging SARS-CoV-2 variant, carried a large number of mutations in the spike protein leading to an unprecedented evasion from many neutralizing antibodies (nAbs). Here, we performed a head-to-head comparison of Omicron with other existing highly evasive variants in terms of their reduced sensitivities to antibodies, and found that Omicron variant is significantly more evasive than Beta and Mu variants. Of note, some key mutations occur in the conserved epitopes identified previously, especially in the binding sites of Class 4 nAbs, contributing to the increased Ab evasion. We also reported a broadly nAb (bnAb), VacW-209, which effectively neutralized all tested SARS-CoV-2 variants and even SARS-CoV. Finally, we determined six cryo-electron microscopy structures of VacW-209 complexed with the spike ectodomains of wild-type, Delta, Mu, C.1.2, Omicron, and SARS-CoV, and revealed the molecular basis of the broadly neutralizing activities of VacW-209 against SARS-CoV-2 variants. Overall, Omicron has once again raised the alarm over virus variation with significantly compromised neutralization. BnAbs targeting more conserved epitopes among variants will continue to play a key role in pandemic control and prevention. One sentence summaryStructural and functional analyses reveal that a human antibody named VacW-209 confers broad neutralization against SARS-CoV-2 variants including Omicron by recognizing a highly conserved epitope.

The spillover of tourism development on CO2 emissions: a spatial econometric analysis.

Climate change and tourism's interaction and vulnerability have been among the most hotly debated topics recently. In this context, the study focuses on how CO2 emissions, the primary cause of global warming and climate change, respond to changes in tourism development. In order to do so, the impact of tourism development on CO2 emissions in the most visited countries is investigated. A panel data from 2000 to 2017 for top 70 tourist countries are analysed using a spatial econometric method to investigate the spatial effect of tourism on environmental pollution. The direct, indirect, and overall impact of tourism on CO2 emissions are estimated using the most appropriate generalized nested spatial econometric (GNS) method. The findings reveal that tourism has a positive direct effect and a negative indirect effect; both are significant at the 1% level. The negative indirect effect of tourism is greater than its direct positive effect, implying an overall significantly negative impact. Further, the outcome of financial development and CO2 emissions have an inverted U-shaped and U-shaped relationship in direct and indirect impacts. Population density, trade openness, and economic growth significantly influence environmental pollution. In addition, education expenditure and infrastructure play a significant moderating role among tourism and environmental pollution. The results have important policy implications as they establish an inverted-U-shaped relationship among tourism and CO2 emissions and indicate that while a country's emissions initially rise with the tourism industry's growth, it begins declining after a limit.

Analysis of risk factors of postoperative acute respiratory distress syndrome in patients with esophageal cancer / 肿瘤研究与临床

Objective:To investigate the risk factors of postoperative acute respiratory distress syndrome (ARDS) in patients with esophageal cancer.Methods:The clinical data of patients with esophageal cancer who underwent surgery in the Affiliated Huai'an No. 1 People's Hospital of Nanjing Medical University from January 2020 to April 2021 were retrospectively analyzed, 223 patients were enrolled. The patients were divided into ARDS group (28 cases) and non-ARDS group (195 cases) according to whether ARDS occurred after surgery. The clinicopathological features of the two groups were compared, and the risk factors of postoperative ARDS were analyzed by univariate and multivariate logistic regression.Results:The age of patients in the ARDS group was higher than that in the non-ARDS group [(70±4) years old vs. (66±7) years old, P = 0.024]. The proportion of patients with history of chronic obstructive pulmonary disease (COPD) in the ARDS group was higher than that in the non-ARDS group [25.0% (7/28) vs. 4.6% (9/195), P < 0.001]. There were no statistical differences in gender, systolic pressure, body mass index, left ventricular ejection fraction, laboratory related examinations, history of smoking, history of diabetes, history of hypertension, history of cardiovascular disease, history of cerebrovascular disease, pathological type, tumor location, tumor stage and postoperative complications between the two groups (all P > 0.05). After further adjusting for gender, multivariate logistic regression analysis showed that the old age (≥65 years old) ( OR = 4.581, 95% CI 1.299-16.154, P = 0.018) and the history of COPD ( OR= 5.493, 95% CI 1.644-18.358, P = 0.006) were independent risk factors for postoperative ARDS in patients with esophageal cancer. Conclusions:Esophageal cancer patients with an age of ≥65 years old or history of COPD have a high risk of postoperative ARDS. Age and history of COPD may have certain significances in judging the occurrence of postoperative ARDS in patients with esophageal cancer.