The Multi-domain Lifestyle Intervention for Cognitive Impairment in Community-Dwelling Older Adults in Hangzhou (The Heritage Study): Study Design and Protocol.

BACKGROUND: The globe has been working to promote a multi-domain lifestyle intervention for dementia prevention in older adults, referring to the Worldwide-FINGERS (Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability) initiative. In China, the multi-domain lifestyle intervention has been implemented in rural communities (MIND-China), yet the adaptability of such intervention based on the urban communities in China has not been verified. OBJECTIVE: To examine the effectiveness and feasibility of the multi-domain lifestyle intervention on dementia prevention in at-risk community-dwelling older adults in China. DESIGN, SETTING, PARTICIPANTS: The multi-domain lifestyle intervention study is a community-based 2-year cluster randomized controlled trial (RCT). A total of 1200 participants aged 60-80 years old will be recruited from twelve communities in Hangzhou, Zhejiang. Inclusion criteria were the Montreal Cognitive Assessment 5 minutes protocol (5 min MoCA) score of 6-9 or the Ascertain Dementia 8 (AD 8) score of ≥2, and having modifiable lifestyle factors. INTERVENTION, MEASUREMENTS, RESULTS: Participating communities will be randomized into either the structured multi-domain intervention (SMI) arm or the self-guided intervention (SGI, general health education) arm. The SMI consists of cognitive training, physical exercise, and nutritional and dietary instruction for the first 12 months; and vascular risks monitoring and control for 24 months. The primary outcome is the global cognitive performance, measured by the comprehensive Neuropsychological Test Battery (NTB). The secondary outcomes include domain-specific cognitive performances, physical function, mental health, physiological and biochemical indices, adherence to healthy lifestyles, and neuroimaging metrics. The feasibility of intervention will be evaluated around the five dimensions of the RE-AIM framework and in conjunction with quantitative data, operational data and results of focus group discussions. CONCLUSIONS: Following the Worldwide-FINGERS, this cluster RCT will verify the adaptability of the multi-domain lifestyle intervention in the urban community settings in China. This study will add evidence for global dementia prevention and management among older adults.

Myokines and Biomarkers of Frailty in Older Inpatients with Undernutrition: A Prospective Study.

BACKGROUND: Population aging might increase the prevalence of undernutrition in older people, which increases the risk of frailty. Numerous studies have indicated that myokines are released by skeletal myocytes in response to muscular contractions and might be associated with frailty. This study aimed to evaluate whether myokines are biomarkers of frailty in older inpatients with undernutrition. METHODS: The frailty biomarkers were extracted from the Gene Expression Omnibus and Genecards datasets. Relevant myokines and health-related variables were assessed in 55 inpatients aged ≥ 65 years from the Peking Union Medical College Hospital prospective longitudinal frailty study. Serum was prepared for enzyme-linked immunosorbent assay using the appropriate kits. Correlations between biomarkers and frailty status were calculated by Spearman's correlation analysis. Multiple linear regression was performed to investigate the association between factors and frailty scores. RESULTS: The prevalence of frailty was 13.21%. The bioinformatics analysis indicated that leptin, adenosine 5'-monophosphate-activated protein kinase (AMPK), irisin, decorin, and myostatin were potential biomarkers of frailty. The frailty group had significantly higher concentrations of leptin, AMPK, and MSTN than the robust group (p < 0.05). AMPK was significantly positively correlated with frailty (p < 0.05). The pre-frailty and frailty groups had significantly lower concentrations of irisin than the robust group (p < 0.05), whereas the DCN concentration did not differ among the groups. Multiple linear regression suggested that the 15 factors influencing the coefficients of association, the top 50% were the ADL score, MNA-SF score, serum albumin concentration, urination function, hearing function, leptin concentration, GDS-15 score, and MSTN concentration. CONCLUSIONS: Proinflammatory myokines, particularly leptin, myostatin, and AMPK, negatively affect muscle mass and strength in older adults. ADL and nutritional status play major roles in the development of frailty. Our results confirm that identification of frailty relies upon clinical variables, myokine concentrations, and functional parameters, which might enable the identification and monitoring of frailty.

[Genetic characteristics and clinical analysis of 20 patients with Gaucher's disease].

Gaucher Disease (GD) is an autosomal recessive lysosomal storage disorder characterized by high heterogeneity. This study aimed to further understand the correlation between clinical phenotypes and genotypes in GD patients through a retrospective analysis of 20 cases in Shanxi Bethune Hospital, including their clinical manifestations, laboratory tests, enzyme studies, and genetic results. Among the 20 GD patients, 16 were classified as Type Ⅰ GD with a median age of diagnosis of 24 years, and 4 were classified as Type Ⅲ GD with a median age of diagnosis of 19 years. All patients exhibited splenomegaly and thrombocytopenia, with 16 patients showing skeletal imaging changes, and 5 of them presenting with bone pain symptoms. Genetic analysis revealed 15 distinct mutations, predominantly missense mutations, with L483P being the most prevalent (35.7%), followed by V414L, L303I, and F252I. Mutation sites were predominantly located in exon 7. Noteworthy findings included the first report of the S310G mutation by our research group and the first occurrence of the K196R mutation in the Chinese population. Additionally, the N227S mutation was implicated in a potential association with neuropathy. Despite advancements, Uncertainties still exist in the correlation between clinical phenotypes and genotypes in GD patients.

Application of deep learning in radiation therapy for cancer.

In recent years, with the development of artificial intelligence, deep learning has been gradually applied to clinical treatment and research. It has also found its way into the applications in radiotherapy, a crucial method for cancer treatment. This study summarizes the commonly used and latest deep learning algorithms (including transformer, and diffusion models), introduces the workflow of different radiotherapy, and illustrates the application of different algorithms in different radiotherapy modules, as well as the defects and challenges of deep learning in the field of radiotherapy, so as to provide some help for the development of automatic radiotherapy for cancer.

Development and validation of a nomogram to predict postsurgical intra-abdominal infection in blunt abdominal trauma patients: A multicenter retrospective study.

BACKGROUND: Intra-abdominal infection is a common complication of blunt abdominal trauma. Early detection and intervention can reduce the incidence of intra-abdominal infection and improve patients' prognoses. This study aims to construct a clinical model predicting postsurgical intra-abdominal infection after blunt abdominal trauma. METHODS: This study is a retrospective analysis of 553 patients with blunt abdominal trauma from the Department of General Surgery of 7 medical centers (2011-2021). A 7:3 ratio was used to assign patients to the derivation and validation cohorts. Patients were divided into 2 groups based on whether intra-abdominal infection occurred after blunt abdominal trauma. Multivariate logistic regression and least absolute shrinkage and selection operator regression were used to select variables to establish a nomogram. The nomogram was evaluated, and the validity of the model was further evaluated by the validation cohort. RESULTS: A total of 113 were diagnosed with intra-abdominal infection (20.4%). Age, prehospital time, C-reactive protein, injury severity score, operation duration, intestinal injury, neutrophils, and antibiotic use were independent risk factors for intra-abdominal infection in blunt abdominal trauma patients (P < .05). The area under the receiver operating curve (area under the curve) of derivation cohort and validation cohort was 0.852 (95% confidence interval, 0.784-0.912) and 0.814 (95% confidence interval, 0.751-0.902). The P value for the Hosmer-Lemeshow test was .135 and .891 in the 2 cohorts. The calibration curve demonstrated that the nomogram had a high consistency between prediction and practical observation. The decision curve analysis also showed that the nomogram had a better potential for clinical application. To facilitate clinical application, we have developed an online at https://nomogramcgz.shinyapps.io/IAIrisk/. CONCLUSION: The nomogram is helpful in predicting the risk of postoperative intra-abdominal infection in patients with blunt abdominal trauma and provides guidance for clinical decision-making and treatment.

Use of TSAR, Thermal Shift Analysis in R, to identify Folic Acid as a Molecule that Interacts with HIV-1 Capsid.

Thermal shift assay (TSA) is a versatile biophysical technique for studying protein interactions. Here, we report a free, open-source software tool TSAR (Thermal Shift Analysis in R) to expedite and automate the analysis of thermal shift data derived either from individual experiments or large screens of chemical libraries. The TSAR package incorporates multiple, dynamic workflows to facilitate the analysis of TSA data and returns publication-ready graphics or processed results. Further, the package includes a graphic user interface (GUI) that enables easy use by non-programmers, aiming to simplify TSA analysis while diversifying visualization. To exemplify the utility of TSAR we screened a chemical library of vitamins to identify molecules that interact with the capsid protein (CA) of human immunodeficiency virus type 1 (HIV-1). Our data show that hexameric CA interacts with folic acid in vitro.

[Reference values for carotid artery intima-media thickness among community adult dwellers in Shenzhen City].

Objective: To establish reference values for carotid intima-media thickness (CIMT) of adult dwellers in Shenzhen City. Methods: The study was conducted based on the Shenzhen heart failure epidemiological survey from 2021 to 2022. In this survey, residents aged 18 years and above in Shenzhen were selected by using a multi-stage stratified random sampling method. General information, cardiovascular disease (CVD) related behavior and carotid ultrasound examination and etc. were collected from the participants. People with CVD factors, a history of atherosclerotic cardiovascular disease, carotid plaque or having no carotid ultrasound examination results were excluded. The parameter regression model based on fractional polynomial was used to establish the reference values of CIMT by age and sex. Results: A total of 2 163 healthy individuals were enrolled in the final analysis, including 576 males (26.6%) and 1 587 females (73.4%). The fractional polynomial regression of the CIMT mean and standard deviation was obtained. For men, the regression was meanCIMT=0.324 7+0.006 9×age and SDCIMT=0.076 9+0.001 2×age. For women, the regression was meanCIMT=0.354 9+0.005 4×age and SDCIMT=0.041 6+0.002 0×age. Conclusion: The age and sex reference values for CIMT of adult people in Shenzhen established in this study could provide the latest reference standards for early screening of subclinical CVD.

[Comprehensive clinical evaluation of bedaquiline in the treatment of multidrug-resistant tuberculosis].

Objective: To assess the clinical value of bedaquiline in five dimensions: effectiveness, safety, economics, appropriateness, and social benefits, to provide a reference for medical and health insurance-related decisions. Methods: A total of 792 patients with multidrug-resistant tuberculosis who were hospitalized at Wuhan Pulmonary Hospital, Ganzhou Fifth People's Hospital and Jiangxi Chest Hospital between January 2018 and December 2020 were included in the study. Based on a retrospective survey of case data, and each evaluation dimension of bedaquiline was statistically analyzed by causal analysis or chi-square test, using linezolid as the reference drug. Results: In terms of effectiveness, bedaquiline significantly increased treatment success by 23.9% (95%CI:4.8%-43.0%) and shortened treatment duration by 64 days(95%CI:18-109 days). In terms of safety, the incidence of adverse reactions to bedaquiline and the discontinuation rate of adverse reactions (5.11%,4.55%) were significantly lower than those for linezolid (22.49%,15.24%), with statistically significant differences (χ2=27.50,P<0.001;χ2=14.09,P<0.001). In terms of economics, patients treated with bedaquiline had a significantly higher anti-TB drug course cost of RMB 48 209.4 Yuan(95%CI: 28 336.0-68 082.8 Yuan). In terms of appropriateness, the proportion of bedaquiline in patients' initial treatment regimens was lower than that of linezolid (16.7% vs. 86.5%) in the 2020 observation sample, with a statistically significant difference (χ2=238.96,P<0.001). In terms of social benefits, the infection control rate was significantly increased by 27.8% (95%CI:8.2%-47.5%) in patients using bedaquiline. Conclusions: Bedaquiline performed well in terms of efficacy, safety, and social benefits. However, it was less economical and the actual use rate of bedaquiline in clinical practice was lower than that of its counterpart drug, linezolid. Price reductions might be needed to increase the clinical use and performance of bedaquiline in the future.

Intravital imaging of three different microvascular beds in SARS-CoV-2-infected mice.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) enters the respiratory tract, where it infects the alveoli epithelial lining. However, patients have sequelae that extend well beyond the alveoli into the pulmonary vasculature and, perhaps, beyond to the brain and other organs. Because of the dynamic events within blood vessels, histology does not report platelet and neutrophil behavior. Because of the rapid nontranscriptional response of these cells, neither single-cell RNA sequencing nor proteomics report robustly on their critical behaviors. We used intravital microscopy in level-3 containment to examine the pathogenesis of SARS-CoV-2 within 3 organs in mice expressing human angiotensin converting enzyme 2 (ACE-2) ubiquitously (CAG-AC-70) or on epithelium (K18-promoter). Using a neon-green SARS-CoV-2, we observed both the epithelium and endothelium infected in AC70 mice but only the epithelium in K18 mice. There were increased neutrophils in the microcirculation but not in the alveoli of the lungs of AC70 mice. Platelets formed large aggregates in the pulmonary capillaries. Despite only neurons being infected within the brain, profound neutrophil adhesion forming the nidus of large platelet aggregates were observed in the cerebral microcirculation, with many nonperfused microvessels. Neutrophils breached the brain endothelial layer associated with a significant disruption of the blood-brain-barrier. Despite ubiquitous ACE-2 expression, CAG-AC-70 mice had very small increases in blood cytokine, no increase in thrombin, no infected circulating cells, and no liver involvement suggesting limited systemic effects. In summary, our imaging of SARS-CoV-2-infected mice gave direct evidence that there is a significant perturbation locally in the lung and brain microcirculation induced by local viral infection leading to increased local inflammation and thrombosis in these organs.

[Oncologic outcomes of surgical treatments of advanced sinonasal malignancies].

Objective: To investigate the prognoses of advanced (T3-T4) sinonasal malignancies (SNM). Methods: The clinical data of 229 patients with advanced (T3-4) SNM who underwent surgical treatments in the First Affiliated Hospital of Sun Yat-sen University from 2000 to 2018 were retrospectively analyzed, including 162 males and 67 females, aged (46.8±18.5) years old. Among them, 167 cases received endoscopic surgery alone, 30 cases received assisted incision endoscopic surgery, and 32 cases received open surgery. The Kaplan-Meier method was used to estimate the 3-year and 5-year overall survival (OS) and event-free survival (EFS). Univariate and multivariate Cox regression analyses were performed to explore significant prognostic factors. Results: The 3-year and 5-year OS were respectively 69.7% and 64.0%. The median OS time was 43 months. The 3-year and 5-year EFS were respectively 57.8% and 47.4%. The median EFS time was 34 months. The 5-year OS of the patients with epithelial-derived tumors was better than that of the patients with mesenchymal-derived tumors and malignant melanoma (5-year OS was respectively 72.3%, 47.8% and 30.0%, χ2=36.01, P<0.001). Patients with microscopically margin-negative resection (R0 resection) had the best prognosis, followed by macroscopically margin-negative resection (R1 resection), and debulking surgery was the worst (5-year OS was respectively 78.4%, 55.1% and 37.4%, χ2=24.63, P<0.001). There was no significant difference in 5-year OS between the endoscopic surgery group and the open surgery group (65.8% vs. 53.4%, χ2=2.66, P=0.102). Older patients had worse OS (HR=1.02, P=0.011) and EFS (HR=1.01, P=0.027). Patients receiving adjuvant therapy had a lower risk of death (HR=0.62, P=0.038). Patients with a history of nasal radiotherapy had a higher risk of recurrence (HR=2.48, P=0.002) and a higher risk of death (HR=2.03, P=0.020). Conclusion: For patients with advanced SNM, the efficacy of endoscopic surgery can be comparable to that of open surgery when presence of safe surgical margins, and a treatment plan based on transnasal endoscopic surgery as the main comprehensive treatment is recommended.

Association of pectoralis muscle area on computed tomography with airflow limitation severity and respiratory outcomes in COPD: A population-based prospective cohort study.

BACKGROUND: Previous studies have shown that patients with chronic obstructive pulmonary disease (COPD) of severe or very severe airflow limitation have a reduced pectoralis muscle area (PMA), which is associated with mortality. However, whether patients with COPD of mild or moderate airflow limitation also have a reduced PMA remains unclear. Additionally, limited evidence is available regarding the associations between PMA and respiratory symptoms, lung function, computed tomography (CT) imaging, lung function decline, and exacerbations. Therefore, we conducted this study to evaluate the presence of PMA reduction in COPD and to clarify its associations with the referred variables. METHODS: This study was based on the subjects enrolled from July 2019 to December 2020 in the Early Chronic Obstructive Pulmonary Disease (ECOPD) study. Data including questionnaire, lung function, and CT imaging were collected. The PMA was quantified on full-inspiratory CT at the aortic arch level using predefined -50 and 90 Hounsfield unit attenuation ranges. Multivariate linear regression analyses were performed to assess the association between the PMA and airflow limitation severity, respiratory symptoms, lung function, emphysema, air trapping, and the annual decline in lung function. Cox proportional hazards analysis and Poisson regression analysis were used to evaluate the PMA and exacerbations after adjustment. RESULTS: We included 1352 subjects at baseline (667 with normal spirometry, 685 with spirometry-defined COPD). The PMA was monotonically lower with progressive airflow limitation severity of COPD after adjusting for confounders (vs. normal spirometry; Global Initiative for Chronic Obstructive Lung Disease [GOLD] 1: ß=-1.27, P=0.028; GOLD 2: ß=-2.29, P<0.001; GOLD 3: ß=-4.88, P<0.001; GOLD 4: ß=-6.47, P=0.014). The PMA was negatively associated with the modified British Medical Research Council dyspnea scale (ß=-0.005, P=0.026), COPD Assessment Test score (ß=-0.06, P=0.001), emphysema (ß=-0.07, P<0.001), and air trapping (ß=-0.24, P<0.001) after adjustment. The PMA was positively associated with lung function (all P<0.05). Similar associations were discovered for the pectoralis major muscle area and pectoralis minor muscle area. After the 1-year follow-up, the PMA was associated with the annual decline in the post-bronchodilator forced expiratory volume in 1 s percent of predicted value (ß=0.022, P=0.002) but not with the annual rate of exacerbations or the time to first exacerbation. CONCLUSION: Patients with mild or moderate airflow limitation exhibit a reduced PMA. The PMA is associated with airflow limitation severity, respiratory symptoms, lung function, emphysema, and air trapping, suggesting that PMA measurement can assist with COPD assessment.

Enhanced diesel emissions at low ambient temperature: hazardous materials in fine particles.

The emission of fine particles (PM2.5) from diesel trucks is enhanced by low ambient temperatures, which is a fact that has attracted considerable attention. Carbonaceous matter and polycyclic aromatic hydrocarbons (PAHs) are the dominant hazardous materials in PM2.5. These materials induce severe adverse effects on air quality and human health and contribute to climate change. The emissions from heavy- and light-duty diesel trucks were tested at an ambient temperature of - 20 to - 13 â„ƒ and 18-24 â„ƒ. This is the first study to quantify the enhanced carbonaceous matter and PAH emissions from diesel trucks at very low ambient temperatures based on an on-road emission test system. Features affecting diesel emissions, including driving speed, vehicle type, and engine certification level, were considered. The emissions of organic carbon, elemental carbon, and PAHs significantly increased from - 20 to - 13 â„ƒ. The empirical results revealed that intensive abatement of diesel emissions at low ambient temperatures could benefit human health and have a positive influence on climate change. Considering the widespread applications worldwide, an investigation into diesel emissions of carbonaceous matter and PAHs in fine particles at low ambient temperatures is urgently required.

Observing flow of He II with unsupervised machine learning.

Time dependent observations of point-to-point correlations of the velocity vector field (structure functions) are necessary to model and understand fluid flow around complex objects. Using thermal gradients, we observed fluid flow by recording fluorescence of [Formula: see text] excimers produced by neutron capture throughout a ~ cm3 volume. Because the photon emitted by an excited excimer is unlikely to be recorded by the camera, the techniques of particle tracking (PTV) and particle imaging (PIV) velocimetry cannot be applied to extract information from the fluorescence of individual excimers. Therefore, we applied an unsupervised machine learning algorithm to identify light from ensembles of excimers (clusters) and then tracked the centroids of the clusters using a particle displacement determination algorithm developed for PTV.

[Effects of insulin glargine at different times on organ oxidative stress in burned rats with delayed resuscitation].

Objective: To examine the antioxidant effect of low dosage insulin glargine intervention at different time in rats with delayed resuscitation after burn, in order to acquire a better time of antioxidant intervention during delayed resuscitation following burn injury. Methods: With 10 rats in each group, 50 male SD rats were assigned to sham injury group, delayed resuscitation group, immediate post-burn insulin glargine treatment group (immediate treatment group), 2 hours post-burn insulin glargine treatment group(2 h treatment group), and 6 hours post-burn insulin treatment group(6 h treatment group) with random number table. Each treatment group received subcutaneous injections of insulin glargine (1.0 U·kg-1·d-1) immediately, two hours and six hours after the burn, while the delayed resuscitation group received the same amount of normal saline six hours after the burn. To imitate delayed fluid resuscitation, the delayed resuscitation group and each therapy group were intraperitoneally injected with normal saline (40 ml/kg) 6 hours after injury. No medicine and fluid resuscitation was administered to the sham injury group. Rats in the sham injury group had their abdominal aortic blood, hearts, and kidney tissues collected immediately after injury, while rats in the other groups had their blood and tissues collected 24 hours later. To analyze the timing of antioxidant intervention, the activities of CuZn-superoxide dismutase (CuZn-SOD), catalase (CAT), glutathione peroxidase (GSH-Px), total antioxidant capacity (T-AOC), xanthine oxidase (XOD) and myeloperoxidase (MPO) in blood glucose and myocardial and renal tissues were measured by spectrophotometry. Results: Compared with the sham group, blood glucose levels in the delayed resuscitation group increased [(10.72±0.80) vs (6.57±0.82)mmol/L,P<0.001], while in the myocardium and kidney, the activities of CuZn-SOD, CAT, GSH-Px and T-AOC decreased (all P<0.05) and the activities of XOD and MPO increased (all P<0.05). Compared with the delayed resuscitation group, blood glucose decreased in the immediate, 2 h, and 6 h treatment groups (all P<0.05). In the immediate and 2 h treatment group, the activities of CuZn-SOD, CAT, GSH-Px and T-AOC in the myocardium and kidney increased(all P<0.05). In the 6 h treatment group, only the activities of GSH-Px in myocardium, CAT and GSH-Px in kidney increased (all P<0.05). Compared with the delayed resuscitation group, in the immediate treatment group, the activities of MPO and XOD in myocardial tissue and XOD in renal tissue decreased (all P<0.05). The activities of MPO and XOD in myocardial and renal tissues of the 2 h treatment group both decreased (all P<0.05). In the 6 h treatment group, the activities of MPO in myocardial tissue and XOD in renal tissue both decreased (all P<0.05). Compared with the immediate treatment group, the activity of GSH-Px in myocardial tissue increased (P<0.05), and the activities of CuZn-SOD, CAT, GSH-Px and T-AOC in renal tissue increased in the 2 h treatment group (all P<0.05). The activities of CuZn-SOD, CAT, GSH-Px and T-AOC in myocardium of 6 h treatment group decreased (all P<0.05). Compared with the immediate treatment group, the activities of XOD and MPO in myocardial tissue and XOD in renal tissue of the 2 h treatment group had no significant difference (all P>0.05), but the activity of MPO in renal tissue decreased (P<0.05). The activities of XOD and MPO in myocardial tissue of the 6 h treatment group increased (all P<0.05). Compared with the 2 h treatment group, the activities of CuZn-SOD, CAT and GSH-Px and T-AOC in myocardium and kidney tissues in the 6 h treatment group decreased (all P<0.05), while the activities of XOD and MPO in myocardium and kidney tissues increased [myocardium: (374±8) vs (290±19) U/g, (0.021 8±0.003 9) vs (0.010 7±0.002 4) U/g, kidney: (157±6) vs (128±9) U/g, (0.026 8±0.004 3) vs (0.013 4±0.003 1) U/g, all P<0.05]. Conclusions: The timing of the intervention is related to the antioxidant effect of insulin glargine during delayed burn resuscitation. The intervention immediately and 2 hours after burn could have a better antioxidant effect compared to the intervention at 6 hours after burn.

[The diagnostic potential of Golgi protein 73 for cirrhosis in patients with chronic hepatitis C].

Objective: To explore the diagnostic value and model of serum Golgi protein 73 (GP73) in patients with hepatitis C cirrhosis. Methods: 271 cases with chronic hepatitis C virus infection who were treated in the Fifth Medical Center of PLA General Hospital from January 2010 to December 2017 were retrospectively collected as the research objects, including 126 cases with hepatitis and 145 cases with liver cirrhosis. Serum GP73 and liver stiffness measurement (LSM) based on transient elastography test were performed in all patients. Simultaneously, blood routine, liver function, coagulation function and other related indicators were collected. GP73 diagnostic efficiency for liver cirrhosis was evaluated by receiver operating characteristic curve (ROC). GP73 diagnostic value was clarified after comparison with aspartate aminotransferase/platelet ratio index (APRI), FIB-4 index (FIB-4) and LSM. Compensated hepatitis C virus-related cirrhosis diagnostic model based on serological index was established by logistic regression analysis. Results: The area under the receiver operating characteristic curve (AUC) of GP73, LSM, FIB-4 and APRI in the diagnosis of compensated hepatitis C virus-related cirrhosis were 0.923, 0.839, 0.836 and 0.800 respectively, and GP73 had the best diagnostic efficiency (P <0.001). LSM and GP73 combined use had improved the diagnostic sensitivity of cirrhosis to 97.24%. Multivariate logistic regression analysis revealed that GP73, age, and platelets were independent predictors of cirrhosis.Compensated hepatitis C virus-related cirrhosis diagnostic model (GAP) was established based on the result: LogitP=1/[1+exp(6.145+0.013×platelet-0.059×age-0.059×GP73)].AUC model for diagnosing compensated liver cirrhosis was 0.944, and the optimal cut-off value was 0.56, with sensitivity and specificity of 84.03% and 92.06%, respectively, and the diagnostic efficiency of this model was better than that of APRI, FIB-4, LSM and GP73 alone (P<0.05). Conclusion: GP73 is a reliable serum biomarker for the diagnosis of compensated hepatitis C virus-related cirrhosis. The GAP diagnostic model based on GP73, platelet count, and age can further improve the diagnostic efficiency and help to diagnose patients with compensated hepatitis C virus-related cirrhosis.

[Analysis on the epidemic characteristics and genetic characteristics of varicella in Beijing from 2019 to 2021].

The reported incidence of varicella in Beijing from 2019 to 2021 were 63.8/100 000, 32.2/100 000 and 38.6/100 000, respectively. There were two VZV epidemics in Beijing each year, one peaked in May and the other in November. However, the first VZV epidemic almost disappeared in 2020. Among the cases involved in the varicella outbreaks in school, the proportion of the students with no history of vaccine immunization, 1 dose of immunization and 2 doses of immunization were 33.12%, 44.79% and 22.08%, respectively. The major body of VZV breakthrough cases was children aged 6-14 years (523/755, 69.27%). The proportion of moderate- or severe-rash were 55.32%, 39.06%, 29.96% in the three groups of cases with no immunization history, 1 dose of immunization and 2 doses of immunization, respectively (P<0.001). A total of 1 089 varicella samples were collected, and 837 (76.86%) were confirmed to be PCR-positive for VZV and were identified as VZV wild strains. 311 VZV strains were sequenced successfully, and 307 strains were clade 2 (98.72%), 1 clade 3 (0.32%) and 3 Clade 5 (0.96%). Compared with the representative strains, the nucleotide similarities of ORF22 fragments were between 99.4% and 100%, and amino acid similarities were between 99.4% and 100%.

Toxicity profiles and protective effects of antifreeze proteins from insect in mammalian models.

Antifreeze proteins (AFPs), found in many cold-adapted organisms, can protect them from cold and freezing damages and have thus been considered as additional protectants in current cold tissue preservation solutions that generally include electrolytes, osmotic agents, colloids and antioxidants, to reduce the loss of tissue viability associated with cold-preservation. Due to the lack of toxicity profile studies on AFPs, their inclusion in cold preservation solutions has been a trial-and-error process limiting the development of AFPs' application in cold preservation. To assess the feasibility of translating the technology of AFPs for mammalian cell cold or cryopreservation, we determined the toxicity profile of two highly active beetle AFPs, DAFP1 and TmAFP, from Dendroides canadensis and Tenebrio molitor in this study. Toxicity was examined on a panel of representative mammalian cell lines including testicular spermatogonial stem cells and Leydig cells, macrophages, and hepatocytes. Treatments with DAFP1 and TmAFP at up to 500 µg/mL for 48 and 72 h were safe in three of the cell lines, except for a 20% decrease in spermatogonia treated with TmAFP. However, both AFPs at 500 µg/mL or below reduced hepatocyte viability by 20-40% at 48 and 72 h. At 1000 µg/mL, DAFP1 and TmAFP reduced viability in most cell lines. While spermatogonia and Leydig cell functions were not affected by 1000 µg/mL DAFP1, this treatment induced inflammatory responses in macrophages. Adding 1000 µg/mL DAFP1 to rat kidneys stored at 4 °C for 48 h protected the tissues from cold-related damage, based on tissue morphology and gene and protein expression of two markers of kidney function. However, DAFP1 and TmAFP did not prevent the adverse effects of cold on kidneys over 72 h. Overall, DAFP1 is less toxic at high dose than TmAFP, and has potential for use in tissue preservation at doses up to 500 µg/mL. However, careful consideration must be taken due to the proinflammatory potential of DAFP1 on macrophages at higher doses and the heighten susceptibility of hepatocytes to both AFPs.

[Two-dimensional equivalent mechanical modeling and finite element analysis of normal female pelvic floor system].

Objective: To construct the geometric model of the pelvic floor by a two-dimensional equivalent mechanics method, and to explore the effect of the shape and position of pelvic floor organs and tissues on the biomechanical properties of the pelvic floor under different abdominal pressure. Methods: A 28-year-old healthy and symmetrical married infertile female volunteer was included. The pelvic floor tissue was scanned in the supine position using a 3.0T magnetic resonance scanner (Philips Company, Holland). Based on the method of magnetic resonance imaging (MRI) two-dimensional parameter measurement and computer aided design, the geometric model and finite element model of the female pelvic floor were established, and the biomechanical characteristics of the pelvic floor support system under different abdominal pressure were analyzed. Results: In this study, four different working conditions of the pelvic floor force were simulated under 60, 99, 168, and 208 cmH2O (1 cmH2O=0.098 kPa) abdominal pressure loads. The trend was as follows: under the abdominal pressure load, the retrograde flexion of the uterus occurred, the cervical, the middle and upper vaginal segment and the levator anus muscle had the characteristic change of mechanical axial direction pointing to the sacrum and coccyx, and the deformation of the levator anus muscle in the horizontal direction was greater than that in the vertical direction. With the increase of the abdominal pressure, the maximum stress values of the pelvic floor whole system of healthy subjects under four different working conditions were 0.194 3, 0.389 6, 0.557 1, and 0.627 5 MPa, respectively, and the maximum displacement values were 10, 14, 21 and 25 mm, respectively. The maximum stress values of the cervical and vaginal middle and upper segment were 0.111 7, 0.161 8, 0.250 6, and 0.304 1 MPa, respectively, and the maximum displacement values were 3, 6, 9, and 11 mm, respectively. The maximum stress of the perineal body was 0.063 4, 0.119 6, 0.235 2, and 0.288 0 MPa, and the maximum displacement was 1, 2, 4, and 5 mm. The maximum stress values of the levator anus muscle were 0.194 3, 0.389 6, 0.557 1, and 0.627 5 MPa, and the maximum displacement values were 2, 4, 7, and 8 mm, respectively. The maximum stress and maximum displacement of pelvic organs increased with the increase of the abdominal pressure under different working conditions. The stress axial relationship of normal female pelvic floor was that the middle and upper segment of uterus and vagina mainly acted on the sacrococcyx and the levator anus muscle, and the lower vaginal segment acts on the perineal body. Conclusions: The two-dimensional equivalent mechanical modeling and finite element analysis of the female pelvic floor system can accurately reflect the biomechanical characteristics of the female pelvic floor, and the resultant stress direction of the pelvic organs points to the sacrum and coccyx. The sacrum and coccyx, levator anus and perineal body play important stress supporting roles in the pelvic floor system.