Investigating the Impact of Tea Consumption on Cognitive Function and Exploring Tea-Genetic Interactions in Older Adults Aged 65-105 Years: Findings from the 2002-2018 CLHLS Data.

BACKGROUND: As the global population ages, cognitive impairment (CI) becomes more prevalent. Tea has been one of the most popular drinks in the world. Several studies have demonstrated that tea consumption has an impact on cognitive function. OBJECTIVE: This study aims to examine the association between tea consumption and cognitive function and explore the potential effect of genetics on the relationship between tea consumption and CI risk in older adults. DESIGN: This is a prospective longitudinal study using data from the Chinese Longitudinal Healthy Longevity Survey (CLHLS). SETTING: Six waves of data from CLHLS containing 76,270 subjects were analyzed. Generalized estimation equations (GEE) with a logit link function were adopted to estimate the effect of tea consumption on CI risk from a cross-sectional and longitudinal perspective. PARTICIPANTS: A population-based cohort of adults aged 65-105 years. MEASUREMENTS: The frequency and type of tea consumption were obtained by questionnaires. CI was measured based on MMSE. Polygenic risk was measured using the polygenic score approach described by the International Schizophrenia. RESULTS: The results showed that drinking green tea had a better protective effect on cognitive function than other types of tea, the incidence of CI gradually decreased with the increase of tea consumption frequency, and men were more likely to benefit from tea consumption. Additionally, we also found a significant interaction between tea consumption and genetic risk, measured by polygenic risk score (PRS). CONCLUSIONS: Based on current research evidence, tea consumption, may be a simple and important measure for CI prevention.

Inferring upstream regulatory genes of FOXP3 in human regulatory T cells from time-series transcriptomic data.

The discovery of upstream regulatory genes of a gene of interest still remains challenging. Here we applied a scalable computational method to unbiasedly predict candidate regulatory genes of critical transcription factors by searching the whole genome. We illustrated our approach with a case study on the master regulator FOXP3 of human primary regulatory T cells (Tregs). While target genes of FOXP3 have been identified, its upstream regulatory machinery still remains elusive. Our methodology selected five top-ranked candidates that were tested via proof-of-concept experiments. Following knockdown, three out of five candidates showed significant effects on the mRNA expression of FOXP3 across multiple donors. This provides insights into the regulatory mechanisms modulating FOXP3 transcriptional expression in Tregs. Overall, at the genome level this represents a high level of accuracy in predicting upstream regulatory genes of key genes of interest.

[Clinical characteristics of hospitalized children with respiratory syncytial virus infection and risk prediction of severe illness during the post-COVID-19 era in Kunming].

Objective: To compare the epidemiological and clinical characteristics of hospitalized children with respiratory syncytial virus (RSV) infection in Kunming among the pre-and post-COVID-19 era, and to establish a prediction model for severe RSV infection in children during the post-COVID-19 period. Methods: This was a retrospective study. Clinical and laboratory data were collected from 959 children hospitalized with RSV infection in the Department of Pulmonary and Critical Care Medicine at Kunming Children's Hospital during January to December 2019 and January to December 2023. Patients admitted in 2019 were defined as the pre-COVID-19 group, while those admitted in 2023 were classified as the post-COVID-19 group. Epidemiological and clinical characteristics were compared between the two groups. Subsequently, comparison of the clinical severity among the two groups was performed based on propensity score matching (PSM). Furthermore, the subjects in the post-COVID-19 group were divided into severe and non-severe groups based on clinical severity. Chi-square test and Mann-Whitney U test were used for pairwise comparison between groups, and multivariate Logistic regression was applied for the identification of independent risk factors and construction of the prediction model. The receiver operating characteristic (ROC) curve and calibration curve were employed to evaluate the predictive performance of this model. Results: Among the 959 children hospitalized with RSV infection, there were 555 males and 404 females, with an onset age of 15.4 (7.3, 28.5) months. Of which, there were 331 cases in the pre-COVID-19 group and 628 cases in the post-COVID-19 group. The peak period of RSV hospitalization in the post-COVID-19 group were from May to October 2023, and the monthly number of inpatients for each of these months were as follows: 72 cases (11.5%), 98 cases (15.6%), 128 cases (20.4%), 101 cases (16.1%), 65 cases (10.4%), and 61 cases (9.7%), respectively. After PSM for general data, 267 cases were matched in each group. The proportion of wheezing in the post-COVID-19 group was lower than that in the pre-COVID-19 group (109 cases (40.8%) vs. 161 cases (60.3%), χ2=20.26, P<0.001), while the incidences of fever, tachypnea, seizures, severe case, neutrophil-to-lymphocyte ratio (NLR), C-reactive protein and interleukin-6 levels were all higher than those in the pre-COVID-19 group (146 cases (54.7%) vs. 119 cases (44.6%), 117 cases (43.8%) vs. 89 cases (33.3%), 37 cases (13.9%) vs. 14 cases (5.2%), 69 cases (25.8%) vs. 45 cases (16.9%), 3.6 (1.9, 6.4) vs. 2.3 (1.8, 4.6), 9.9 (7.1, 15.2) vs. 7.8 (4.5, 13.9) mg/L, 20.5 (15.7, 30.4) vs. 17.2 (11.0, 26.9) ng/L, χ2=5.46, 6.36, 11.47, 6.42, Z=4.13, 3.06, 2.96, all P<0.05). There were 252 cases and 107 cases with co-infection in the post-and pre-COVID-19 groups, respectively. The proportion of triple and quadruple infection in the post-COVID-19 group was higher than that in the pre-COVID-19 group (59 cases (23.4%) vs. 13 cases (12.1%), 30 cases (11.9%) vs. 5 cases (4.7%), χ2=5.94, 4.46, both P<0.05). Among the 252 cases with co-infection in post-COVID-19 group, the most prevalent pathogens involving in co-infections, in order, were Mycoplasma pneumoniae 56 cases (22.2%), Influenza A virus 53 cases (21.0%), Rhinovirus 48 cases (19.0%), Parainfluenza virus 35 cases (13.9%), and Adenovirus 28 cases (11.1%).The result of multivariate Logistic regression showed that age (OR=0.70, 95%CI 0.62-0.78, P<0.001), underlying diseases (OR=10.03, 95%CI 4.10-24.55, P<0.001), premature birth (OR=6.78, 95%CI 3.53-13.04, P<0.001), NLR (OR=1.85, 95%CI 1.09-3.15, P=0.023), and co-infection (OR=1.28, 95%CI 1.18-1.38, P<0.001) were independently associated with the development of severe RSV infection in the post-COVID-19 group. The ROC curve of the prediction model integrating the above five factors indicated an area under the curve of 0.85 (95%CI 0.80-0.89, P<0.001), with an optimal cutoff of 0.21, a sensitivity of 0.83 and a specificity of 0.80. The calibration curve showed that the predicted probability in this model did not differ significantly from the actual probability (P=0.319). Conclusions: In the post-COVID-19 era in Kunming, the peak in pediatric hospitalizations for RSV infection was from May to October, with declined incidence of wheezing and increased incidence of fever, tachypnea, seizures, severe cases, and rates of triple and quadruple co-infections. Age, underlying diseases, premature birth, NLR, and co-infection were identified as independent risk factors for severe RSV infection in the post-COVID-19 period. In this study, a risk prediction model for severe pediatric RSV infection was established, which had a good predictive performance.

Longitudinal evaluation of cervical length and shear wave elastography in women with spontaneous preterm birth.

OBJECTIVES: To compare longitudinal changes in cervical length (CL) and mean cervical shear wave elastography (CSWE) scores between women with singleton and twin pregnancies who experience spontaneous preterm birth (sPTB) and those who have term births (TB). METHODS: This was a prospective longitudinal study of 1264 unselected women with singleton (n=1143) and twin (n=121) pregnancy attending a dedicated research clinic for screening of sPTB at 4 timepoints during pregnancy including 11-15+6 (visit 1), 16-20+6 (visit 2), 21-24+6 (visit 3) and 28-32+6 (visit 4) weeks of gestation. At each visit, a transvaginal ultrasound scan was conducted to measure the CL and the CSWE scores from six regions of interest (ROI) (inner, middle, and external parts of anterior and posterior lips) in the cervix. The mean of CSWE scores from the six ROIs were calculated for data analysis. Log10 transformation was applied to make the data Gaussian prior to statistical analysis. A multilevel mixed-effects analysis was performed to compare CL and CSWE longitudinally between sPTB and TB groups. RESULTS: A total of 57 (4.99%) singleton pregnancies and 33 (27.27%) twin pregnancies were complicated with sPTB. Women with sPTB had shorter CL across gestation when controlling for history of cervical surgery, number of fetuses, gestational age at cervical assessment (GA), and the interaction between GA and sPTB. CL in the sPTB group was significantly lower than that of the TB group at 21-24+6 weeks (p=0.039) and 28-32+6 weeks (p<0.001). Twin pregnancies had significantly longer CL throughout pregnancy, compared to singleton pregnancies (coefficient=0.01864, p<0.001). Furthermore, after adjusting for maternal age, weight, height, body mass index (BMI), and GA, CSWE scores in sPTB group were significantly lower in the sPTB group across gestation, compared to the TB group (1.28265 vs 1.32832; p=0.013). However, in the individual visit analysis, CSWE scores in the sPTB group were significantly lower than that of the TB group only at 11-15+6 weeks (p=0.013). There was no difference in CSWE scores between singleton and twin pregnancies throughout pregnancy (coefficient=-0.00128, p=0.937). CONCLUSION: Women with sPTB have shorter CL and softer cervix across gestation when compared to those with TB. In the individual visit analysis, the reduction in CL in the sPTB group occurs from late second trimester onwards, while the reduction in cervical stiffness in the sPTB group is observed primarily in the first trimester. Additionally, our study has found that CL is significantly shorter in singleton pregnancies compared to twin pregnancies, while cervical stiffness does not differ between the two types of pregnancy. Our findings indicate that the cervix tends to undergo a softening process prior to shortening in the sPTB cases This article is protected by copyright. All rights reserved.

[Analysis of pre-operative factors affecting vault after posterior chamber phakic intraocular lens implantation].

Objective: To analyze the early changes in vault height and its influencing factors after implantation of posterior chamber phakic intraocular lenses (pIOL). Methods: A retrospective case series study was conducted, including patients who underwent pIOL implantation at Zhongshan Ophthalmic Center, Sun Yat-sen University, from September 2020 to August 2021, and completed a 3-month follow-up. Data were collected from myopic or myopic astigmatism patients. Preoperative ocular examinations, including Pentacam anterior segment analysis system, Sirius anterior segment analysis system, ultrasound biomicroscopy (UBM), and IOLMaster optical biometry, were performed to measure parameters such as refractive power, corneal curvature, corneal horizontal diameter, anterior chamber volume, anterior chamber depth, pupil diameter, sulcus-to-sulcus diameter (STS), and lens thickness. The degree and position of implanted pIOL, as well as vault height measured by anterior segment optical coherence tomography (AS-OCT) at 1 day, 1 week, 1 month, and 3 months postoperatively, were recorded. Statistical analyses were conducted using repeated measures analysis of variance, Pearson correlation analysis, and multiple linear regression analysis. Results: A total of 314 patients (314 eyes) were included, with 52 male (16.56%) and 262 female (83.44%) patients, and an average age of (26.44±4.60) years. The preoperative equivalent spherical power was (-8.09±2.41) D. Postoperative vault heights at 1 day, 1 week, 1 month, and 3 months were (671.88±273.02) µm, (652.26±272.21) µm, (615.08±259.69) µm, and (591.14±250.71) µm, respectively, with statistically significant differences among groups (P<0.001). Eyes with vault height>750 µm showed a greater decrease in early postoperative vault height (P<0.001). The eyes implanted with 12.1 mm pIOL had the lowest postoperative vault height, while those with 13.2 mm had the highest (P>0.05). Factors correlated with vault height at 1 day postoperatively included corneal horizontal diameter, anterior chamber depth, preoperative cylinder power, angle degree, lens thickness, and pIOL cylinder power. Factors correlated with vault height at 3 months postoperatively included corneal horizontal diameter, anterior chamber depth, preoperative cylinder power, anterior chamber volume, angle degree, lens thickness, axial length, pIOL spherical and cylinder power. Factors associated with changes in early postoperative vault height included corneal curvature K2, anterior chamber depth, anterior chamber volume, pupil diameter, horizontal STS, vertical STS, axial length, and preoperative spherical power (all P<0.05). Multiple linear regression analysis revealed that lens thickness significantly influenced vault height at 1 day postoperatively, anterior chamber volume significantly influenced vault height at 3 months postoperatively, and pupil diameter significantly influenced changes in early postoperative vault height (all P<0.05). Conclusions: Vault height after pIOL implantation is unstable in the early postoperative period and gradually decreases within 3 months. A higher baseline vault height is associated with a greater decrease. Anterior chamber volume, pupil diameter, and lens thickness are influencing factors on vault height during the first 3 months postoperatively.

[Multi-sequence relation attention network for diagnosing HLA-B27-negative axial spondyloarthritis].

OBJECTIVE: To develop a new 3D multi-sequence relation attention network for exploring the complementary and correlation information of different magnetic resonance imaging (MRI) modalities and improving the diagnostic performance of HLA-B27-negative axial spondyloarthropathy (axSpA). METHODS: We retrospectively collected T1-weighted imaging (T1WI) and fat suppuration MRI (FS-MRI) data and clinical data of 375 HLA-B27-negative patients from the Third Affiliated Hospital of Southern Medical University (including 164 axSpA and 211 non-axSpA patients) and 49 patients from Nanhai Hospital (including 27 axSpA and 22 non-axSpA patients) between January, 2010 and August, 2021.A 3D relation attention network MSFANet based on multi-sequence MRI was used for automatic diagnosis of axSpA against non-axSpA in these patients.MSFANet consisted of a shallow shared feature learning module and a class-aware feature learning module, and latter module used a 3D multi-sequence relation attention mechanism to refine and fuse multi-sequence MRI features.A hybrid loss function was used to enhance the recognition ability of MSFANet by learning the loss weight coefficients of different branches to improve the classification performance. RESULTS: The experimental results demonstrated that MSFANet outperformed several state-of-the-art fusion algorithms (P<0.05) with AUC, accuracy, sensitivity, and specificity of 0.840, 77.93%, 83.70%, and 70.29% in the internal validation set, and of 0.783, 74.47%, 82.43% and 70.40% in the independent external validation set, respectively.The ablation studies showed that under the same architecture, the fusion model was superior to single-sequence models, which confirmed the effectiveness and necessity of fusing multi-sequence MRI.The visualization results demonstrated that MSFANet could focus on learning information from abnormal areas on MRI during the classification. CONCLUSION: We successfully constructed a 3D deep neural network based on multi-sequence MRI for differential diagnosis of HLA-B27-negative axSpA against nonaxSpA and verified the effectiveness of the multisequence relation attention mechanism for promoting classification performance of the network.

Early-to-mid stage idiopathic Parkinson's disease shows enhanced cytotoxicity and differentiation in CD8 T-cells in females.

Neuroinflammation in the brain contributes to the pathogenesis of Parkinson's disease (PD), but the potential dysregulation of peripheral immunity has not been systematically investigated for idiopathic PD (iPD). Here we showed an elevated peripheral cytotoxic immune milieu, with more terminally-differentiated effector memory (TEMRA) CD8 T, CD8+ NKT cells and circulating cytotoxic molecules in fresh blood of patients with early-to-mid iPD, especially females, after analyzing > 700 innate and adaptive immune features. This profile, also reflected by fewer CD8+FOXP3+ T cells, was confirmed in another subcohort. Co-expression between cytotoxic molecules was selectively enhanced in CD8 TEMRA and effector memory (TEM) cells. Single-cell RNA-sequencing analysis demonstrated the accelerated differentiation within CD8 compartments, enhanced cytotoxic pathways in CD8 TEMRA and TEM cells, while CD8 central memory (TCM) and naïve cells were already more-active and transcriptionally-reprogrammed. Our work provides a comprehensive map of dysregulated peripheral immunity in iPD, proposing candidates for early diagnosis and treatments.

[A 3D/2D registration method based on reconstruction of orthogonal-view Xray images].

OBJECTIVE: To establish a 3D/2D registration method for preoperative CT and intra-operative X-ray images in imageguided spine surgery. METHODS: We propose a 3D/2D registration algorithm based on 3D image reconstruction. The algorithm performs 3D image reconstruction of 2D orthogonal view X-ray images, thus converting the problem into 3D/3D registration. By constructing an end-to-end framework that combines the two tasks of reconstruction and registration, the geodesic distance is measured in the 3D manifold space to complete the registration. RESULTS: We conducted experiments on the public dataset CTSpine1k. The tests on two test sets with different initial registration errors showed that for data with small initial errors, the proposed algorithm achieved a rotation estimation error of 0.115±0.095° and a translation estimation error of 0.144±0.124 mm; for data with larger initial errors, a rotation estimation error of 0.792±0.659° and a translation estimation error of 0.867±0.701 mm were achieved. CONCLUSION: The proposed method can achieve robust and accurate 3D/2D registration at a speed that meets real-time requirements to improve the performance of spine surgery navigation.

[Standardized nomenclature of oral microorganisms in Chinese: the 2023 update].

Oral microbial community, as an important part of human microbial community, is closely related to oral and general health. Oral microbiological research has become the forefront of international microbiological research. Standardized and unified nomenclature for oral microorganisms in Chinese is of great significance to support the development of oral medicine research. Standardized translation of microbial names is the basis for writing canonical and authoritative professional textbooks and reference books, which helps students to accurately acquire the characteristics and classifications of oral microbes. Unified translation of oral microorganisms is also conducive to academic communication and cooperation, and plays an important role in oral health education and science popularization, which enables oral microbiology knowledge to be accurately disseminated to the public. Therefore, in order to standardize the words in scientific research, funding application, publications, academic exchanges and science popularization within the field of oral medicine, we have fully discussed and revised the Chinese names of oral microorganisms in 2017 edition and ones of newly discovered oral microbes, finally reaching a consensus to form the 2023 edition of Chinese names of oral microorganisms.

[Deep learning-based dose prediction in radiotherapy planning for head and neck cancer].

OBJECTIVE: To propose an deep learning-based algorithm for automatic prediction of dose distribution in radiotherapy planning for head and neck cancer. METHODS: We propose a novel beam dose decomposition learning (BDDL) method designed on a cascade network. The delivery matter of beam through the planning target volume (PTV) was fitted with the pre-defined beam angles, which served as an input to the convolution neural network (CNN). The output of the network was decomposed into multiple sub-fractions of dose distribution along the beam directions to carry out a complex task by performing multiple simpler sub-tasks, thus allowing the model more focused on extracting the local features. The subfractions of dose distribution map were merged into a distribution map using the proposed multi-voting mechanism. We also introduced dose distribution features of the regions-of-interest (ROIs) and boundary map as the loss function during the training phase to serve as constraining factors of the network when extracting features of the ROIs and areas of dose boundary. Public datasets of radiotherapy planning for head and neck cancer were used for obtaining the accuracy of dose distribution of the BDDL method and for implementing the ablation study of the proposed method. RESULTS: The BDDL method achieved a Dose score of 2.166 and a DVH score of 1.178 (P < 0.05), demonstrating its superior prediction accuracy to that of current state-ofthe-art (SOTA) methods. Compared with the C3D method, which was in the first place in OpenKBP-2020 Challenge, the BDDL method improved the Dose score and DVH score by 26.3% and 30%, respectively. The results of the ablation study also demonstrated the effectiveness of each key component of the BDDL method. CONCLUSION: The BDDL method utilizes the prior knowledge of the delivery matter of beam and dose distribution in the ROIs to establish a dose prediction model. Compared with the existing methods, the proposed method is interpretable and reliable and can be potentially applied in clinical radiotherapy.

[General anesthesia versus deep sedation for dental treatment in children: comparison of parental acceptance, oral health-related quality of life, and treatment efficacy].

OBJECTIVE: To compare the parental acceptance of dental treatment under general anesthesia and deep sedation in children and assess the changes in postoperative oral health-related quality of life and treatment efficacy. METHODS: The parents of 131 children undergoing dental treatment in the Department of Stomatology of Sichuan Provincial People's Hospital from January, 2022 to June, 2022 were surveyed using a questionnaire of children's advanced oral behavior management, and 83 children receiving general anesthesia or deep sedation for dental treatment between January, 2018 and December, 2021 were also investigated for changes in quality of life after the treatment using a questionnaire. The treatment efficacy was assessed at the 1-year follow-up visit in 149 children who received dental treatment under general anesthesia or deep sedation during the same period. RESULTS: The survey of perantal acceptance showed that 62.6% of the parents preferred deep sedation, 29.01% preferred general anesthesia, and 8.4% preferred compulsory treatment. Dental treatments under general anesthesia and deep sedation both significantly improved oral health-related quality of life of the children. While dental surgeries under general anesthesia resulted in the most significant improvement of pain symptoms, deep sedation was associated with both obvious relief of the children's pain symptoms and reduction of the parents' pressure level. No significant difference was found in the efficacy of treatments under general anesthesia and deep sedation at the 1-year follow-up. CONCLUSION: Dental treatment in children under deep sedation has the highest parental acceptance, followed by treatment under general anesthesia, and the acceptance of compulsory treatment is the lowest. The treatments under general anesthesia and deep sedation significantly improve the quality of life of the children and their parents and both have good treatment efficacy.

[Application of Rotarex catheter system in femoropopliteal artery stenosis accompanied with thrombosis].

OBJECTIVE: To evaluate the effectiveness and safety of Rotarex catheter system in treating femoropopliteal artery stenosis accompanied with thrombosis. METHODS: From Jun. 2017 to Dec. 2019, the clinical data of 32 femoropopliteal artery stenosis accompanied with thrombosis cases treated with Rotarex catheter system were retrospectively analyzed. There were 23 males and 9 females aged from 50 to 89 years and the mean age was (70.7±10.3) years. Six cases had acute course of disease (≤2 weeks), 17 cases had subacute course of disease (>2 weeks, ≤3 months), and 9 cases had chronic course of disease (>3 months). Mean lesion length was (23.4±13.7) cm, mean occlusion length was (19.9±13.3) cm, and in-stent occlusion 7 cases. The superficial femoral artery (SFA) was involved in 13 cases, the popliteal artery (PA) was involved in 8 cases, and both SFA and PA were involved in the other 11 cases. All the cases were treated with Rotarex catheter system. When necessary, suction with large lumen catheter was enabled. Residual stenosis was treated with percutaneous transluminal angioplasty (PTA). Drug-coated balloon (DCB) was only used in patients with financial status, and stent was used only when it was necessary. Heparin was used for 24 h after procedures, and after that, antiplatelet agents were used. Doppler ultrasonography was taken during the followed-up. RESULTS: Technical success was 100%, and mean procedure time was (107.4±21.5) min. 8F (1F≈0.33 mm) and 6F Rotarex catheter were used in 27 and 5 cases respectively. In 27 cases, forward flow was obtained immediately after debulking with Rotarex catheter, and in the other 5 cases, suction with large lumen catheters were used. PTA was used in all 32 cases. DCB were used in 8 cases, of which 4 were used in in-stent stenosis. Twelve cases were implanted stents. There were no perioperative deaths. The only one procedure related complication was distal embolism. We took out the thrombus with guiding catheter. In all cases, mean hospital stay were (4.6±1.5) d. The ankle brachial index increased from 0.32±0.15 to 0.86±0.10 after treatment (t=-16.847, P < 0.001). The Rutherford stages decreased significantly (Z=-4.518, P < 0.001). All the patients were followed up for 6.0-36.0 months, and the median time was 16.0 months. 2 cases stopped antiplatelet agents, which resulted in acute thrombosis. Another percutaneous mechanical thrombectomy and PTA were taken in one of them. Two cases died of cardiovascular disease during the follow-up, and no amputation was observed. Target lesion restenosis occurred in 7 cases during the follow-up, and target lesion revascularization (TLR) was taken in two of them. CONCLUSION: In treating femoropopliteal artery stenosis accompanied with thrombosis, Rotarex catheter can remove thrombus effectively, and that can expose underlying lesions and reduce stent use and complications rates. It is a safe and effective method.

Altered infective competence of the human gut microbiome in COVID-19.

BACKGROUND: Infections with SARS-CoV-2 have a pronounced impact on the gastrointestinal tract and its resident microbiome. Clear differences between severe cases of infection and healthy individuals have been reported, including the loss of commensal taxa. We aimed to understand if microbiome alterations including functional shifts are unique to severe cases or a common effect of COVID-19. We used high-resolution systematic multi-omic analyses to profile the gut microbiome in asymptomatic-to-moderate COVID-19 individuals compared to a control group. RESULTS: We found a striking increase in the overall abundance and expression of both virulence factors and antimicrobial resistance genes in COVID-19. Importantly, these genes are encoded and expressed by commensal taxa from families such as Acidaminococcaceae and Erysipelatoclostridiaceae, which we found to be enriched in COVID-19-positive individuals. We also found an enrichment in the expression of a betaherpesvirus and rotavirus C genes in COVID-19-positive individuals compared to healthy controls. CONCLUSIONS: Our analyses identified an altered and increased infective competence of the gut microbiome in COVID-19 patients. Video Abstract.

Evaluation of the allocation efficiency of medical and health resources in China's rural three-tier healthcare system.

OBJECTIVES: Evaluating the efficiency of health resource allocations is critical to improving China's rural three-level health service network. STUDY DESIGN: This was a prospective panel data study. METHODS: Based on panel data of the medical and health resources of 31 provinces within rural China, collected from 2003 to 2020, this study uses a three-stage Data Envelopment Analysis-Malmquist index to analyze the evolution of efficiency and productivity. RESULTS: The efficiency and productivity of county and county-level medical and health institutions rank highest, followed by township hospitals, whereas village clinics are shown to be in great need of improvement. A decline in technical advancement appears as a crucial factor exacerbating loss of factor productivity. CONCLUSIONS: Policy makers should further optimize the efficiency of medical resource allocation and promote the coordinated development of rural health in China.

Observation of Monoenergetic Electrons from Two-Pulse Ionization Injection in Quasilinear Laser Wakefields.

The generation of low emittance electron beams from laser-driven wakefields is crucial for the development of compact x-ray sources. Here, we show new results for the injection and acceleration of quasimonoenergetic electron beams in low amplitude wakefields experimentally and using simulations. This is achieved by using two laser pulses decoupling the wakefield generation from the electron trapping via ionization injection. The injection duration, which affects the beam charge and energy spread, is found to be tunable by adjusting the relative pulse delay. By changing the polarization of the injector pulse, reducing the ionization volume, the electron spectra of the accelerated electron bunches are improved.

[Long-term outcomes and failure patterns of definitive radiotherapy for cervical esophageal carcinoma].

Objective: To evaluate the long-term outcomes, failure patterns and prognostic factors of definitive radiotherapy in patients with cervical esophageal carcinoma (CEC). Methods: We retrospectively reviewed the clinical data of 148 CEC patients who treated with definitive radiotherapy in Cancer Hospital of Chinese Academy of Medical Sciences from January 2001 to December 2017. The median radiation dose was 66 Gy (59.4-70 Gy) and 33.1% of patients received concurrent chemotherapy. The Kaplan-Meier method was used to calculate survival rates. The log rank test was used for survival comparison and univariate prognostic analysis. The Cox model was used for multivariate prognostic analysis. Results: The median follow-up time was 102.6 months. The median survival time, 2- and 5-year overall survival (OS) were 22.7 months, 49.9% and 28.3%. The median, 2- and 5-year progression-free survival were 12.6 months, 35.8% and 25.8%. The 2- and 5-year locoregional recurrence-free survival were 59.1% and 50.8%. The 2- and 5-year distant metastases-free survival were 74.6% and 65.9%. Multivariate analysis showed that EQD(2)>66 Gy was the only independent prognostic indicator for OS (P=0.040). The median survival time and 5-year OS rate significantly improved in patients who received EQD(2)>66 Gy than those who received≤66 Gy (31.2 months vs. 19.2 months, 40.1% vs. 19.1%, P=0.027). A total of 87 patients (58.8%) developed tumor progression. There were 50 (33.8%), 23 (15.5%) and 39 (26.4%) patients developed local, regional recurrence and distant metastases, respectively. Eleven patients (7.4%) underwent salvage surgery, and the laryngeal preservation rate for entire group was 93.9%. Conclusions: Definitive radiotherapy is an effective treatment for cervical esophageal carcinoma with the advantage of larynx preservation. Local recurrence is the major failure pattern. EQD(2)>66 Gy is associated with the improved overall survival.

Altered infective competence of the human gut microbiome in COVID-19

ObjectivesInfections with SARS-CoV-2 have a pronounced impact on the gastrointestinal tract and its resident microbiome. Clear differences between severe cases of infection and healthy individuals have been reported, including the loss of commensal taxa. We aimed to understand if microbiome alterations including functional shifts are unique to severe cases or a common effect of COVID-19. DesignWe used high-resolution systematic multi-omic analyses to profile the gut microbiome in asymptomatic-to-moderate COVID-19 individuals compared to a control group. ResultsWe found a striking increase in the overall abundance and expression of both virulence factors and antimicrobial resistance genes in COVID-19. Importantly, these genes are encoded and expressed by commensal taxa from families such as Acidaminococcaceae and Erysipelatoclostridiaceae, which we found to be enriched in COVID-19 positive individuals. We also found an enrichment in the expression of a betaherpesvirus and rotavirus C genes in COVID-19 positive individuals compared to healthy controls. ConclusionOur analyses identified an altered and increased infective competence of the gut microbiome in COVID-19 patients.

[FUT8 modulates galectin-3 expression to regulate TGF-ß1-mediated fibrosis of lung fibroblasts].

OBJECTIVE: To investigate the regulatory role of α-1, 6-fucosyltransferase (FUT8) in TGF-ß1-induced proliferation, migration and fibrosis of human embryonic lung fibroblasts (MRC-5 cells) and explore the underlying molecular mechanism. METHODS: C57/BL6 mice were randomized into 4 groups for treatment with saline (control group), bleomycin, bleomycin+sh-NC or bleomycin+sh-FUT8, and pulmonary fibrosis was observed using Masson staining.MRC-5 cells were transfected with si-NC, FUT8 siRNA (si-FUT8), or both si-FUT8 and a galectin-3(Gal-3) overexpression plasmid (pcDNA3.1-Gal) prior to TGF-ß1 treatment, and the changes in cell proliferation and migration were assessed using CCK-8 assay, BrdU assay, and wound healing assay; the changes in the expression levels of α-SMA, collagen I (COLIA1) and extracellular matrix fibronectin (FN) were detected with real-time quantitative PCR (RT-qPCR) and Western blotting.The interaction of FUT8 and Gal-3 was tested using coimmunoprecipitation (Co-IP) assay, and the effect of FUT8 silencing on Gal-3 and FAK/Akt signaling pathways was analyzed. RESULTS: FUT8 knockdown significantly reduced bleomycin-induced extracellular collagen deposition in the lung tissues of the mice.Silencing FUT8 obviously inhibited cell proliferation (P < 0.05) and migration mediated by TGF-ß1.FUT8 knockdown down-regulated the mRNA and protein levels of α-SMA, COLIA1 and FN (P < 0.05) in the cells.Coimmunoprecipitation analysis showed that FUT8 interacted with Gal-3.Silencing FUT8 significantly down-regulated Gal-3 expression and inhibited the activation of the FAK/Akt signaling pathway (P < 0.05).Overexpression of Gal-3 obviously reversed the effects of FUT8 silencing on cell proliferation, migration and fibrosis (P < 0.05). CONCLUSION: FUT8 regulates TGF-ß1-induced proliferation, migration and fibrosis of MRC-5 cells by modulating Gal-3 expression, in which the FAK/Akt pathway may play a role.