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Primary intrahepatic stones （PIS） is a refractory disease with a high incidence rate in Southwest China， which greatly affects the life of patients. Metabolites， such as β-glucuronidase produced by chronic biliary tract infection， play an important role in the formation of pigmented stones. In addition to exogenous β-glucuronidase produced by bacteria， endogenous β-glucuronidase produced by intrahepatic bile duct cells also plays an important role in the formation of stones. This article analyzes the research advances in the role of β-glucuronidase in the pathogenesis of PIS， in order to provide a possible method for the prevention and treatment of PIS.

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Pulmonary nodules are classified as pure ground glass nodules, part-solid nodules and solid nodules. Surgery is the main treatment for pulmonary nodules. Localization of pulmonary nodules is helpful for accurate resection. The proportion of solid component, size, pathological subtype and lymph node evaluation of pulmonary nodules are the main basis for the selection of surgical methods and the extent of lymph node dissection, but there is no unified standard at present. The management of multiple pulmonary nodules is relatively complex and often requires multidisciplinary discussion. The application of ablation technology makes the treatment of pulmonary nodules more minimally invasive. The treatment concept of pulmonary nodules is rapid recovery and overall minimal invasion.

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@#Obesity, sleep disorders, psychological stress, sedentary are modifiable cardiovascular risk factors. There is growing evidence that these risk factors may accelerate the chronic inflammatory process of atherosclerosis and lead to myocardial infarction. Studies on the role of immune cells and their related immune mechanisms in atherosclerosis have shown that the above modifiable risk factors can affect the hematopoiesis of the bone marrow system, affect the production of immune cells and phenotypes, and then affect the progress of atherosclerosis. This review will focus on the effects of modifiable cardiovascular risk factors on the progression of atherosclerosis through the role of the innate immune system.

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Ischemic stroke(IS)is a multifactorial and heterogeneous disease.Despite years of studies,effective strategies for the diagnosis,management and treatment of stroke are still lacking in clinical practice.Metabolomics is a growing field in systems biology.It is starting to show promise in the identification of biomarkers and in the use of pharmacometabolomics to help patients with certain disorders choose their course of treatment.The development of metabolomics has enabled further and more biological appli-cations.Particularly,metabolomics is increasingly being used to diagnose diseases,discover new drug targets,elucidate mechanisms,and monitor therapeutic outcomes and its potential effect on precision medicine.In this review,we reviewed some recent advances in the study of metabolomics as well as how metabolomics might be used to identify novel biomarkers and understand the mechanisms of IS.Then,the use of metabolomics approaches to investigate the molecular processes and active ingredients of Chinese herbal formulations with anti-IS capabilities is summarized.We finally summarized recent developments in single cell metabolomics for exploring the metabolic profiles of single cells.Although the field is relatively young,the development of single cell metabolomics promises to provide a powerful tool for unraveling the pathogenesis of IS.

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BackgroundDepression， anxiety， impulse control disorders， insomnia are prevalent non-motor symptoms of Parkinson's disease， severely impairing the quality of life of patients. Cognitive behavioral therapy （CBT） is a common psychological intervention for various clinical psychological conditions， which can improve anxiety， insomnia and depression in patients with Parkinson's disease. However， the current research evidence on the effects of CBT in improving quality of life in patients with Parkinson's disease remains inconsistent. ObjectiveTo assess the effects of CBT on the quality of life among patients with Parkinson's disease， so as to provide references for the clinical application of CBT in this population. MethodsOn May 25， 2023， a systematic search was conducted across PubMed， PsycINFO， Embase， CNKI， Wanfang Database and VIP Database to identify randomized controlled trials investigating the impact of CBT on the quality of life in patients with Parkinson's disease. Literature screening， quality evaluation and data extraction were performed， focusing on variables related to quality of life， anxiety， and depression. Meta-analysis was performed using Stata 13.0 and RevMan 5.3. ResultsA total of 11 studies with 456 participants were included， comprising 241 in the CBT group and 215 in the control group. The CBT group exhibited significantly higher quality of life compared with the control group （SMD=0.47， 95% CI： 0.27~0.67， P<0.01）. Anxiety and depression scores in CBT group were significantly lower than those in the control group （SMD=-0.63，95% CI：-0.84~-0.43， P<0.01； SMD=-0.83， 95% CI： -1.15~-0.51， P<0.01）. Among the 11 studies， 6 studies delivered CBT remotely and 5 studies implemented CBT face-to-face. Meta-analysis results revealed that remote CBT group yielded significantly higher quality of life （SMD=0.43， 95% CI： 0.17~0.70， P<0.01）， and lower anxiety and depression scores （SMD=-0.62， 95% CI： -0.91~-0.34， P<0.01； SMD=-0.78， 95% CI： -1.34~-0.21， P<0.01） compared with the control group. Similarly， face-to-face CBT group showed better outcomes than the control group in terms of quality of life， anxiety and depression （SMD=0.51， 95% CI： 0.22~0.81， P<0.01； SMD=-0.64， 95% CI： -0.93~-0.35， P<0.01； SMD=-0.90， 95% CI： -1.20~-0.60， P<0.01）. ConclusionCBT may contribute to alleviating anxiety and depression levels of patients with Parkinson's disease， and improving their quality of life.｛Funded by Shanghai 13th Five-Year Key Specialty Construction Project （number， shslczdzk04901）； Nature Fund Project of Shanghai Science and Technology Commission （number， 22ZR1459300）； Shanghai Municipal Health Commission Traditional Chinese Medical Science Non-drug Therapy Demonstration Center Project ［number， ZY（2021-2023） -0204-03］｝

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OBJECTIVE To systematically analyze the status of health economic evaluation studies of influenza vaccination in Guangdong-Hong Kong-Macao Greater Bay Area （GBA） of China， and to provide a methodological reference for future scholars to carry out economic evaluations of influenza vaccine in GBA. METHODS Seven English databases such as PubMed and Embase and three Chinese databases such as CNKI and Wanfang database were searched. The economic evaluation studies of influenza vaccines with the study area of GBA were collected. The search time frame was from the inception to June 30， 2022. After screening the literature and extracting key information， descriptive analysis was conducted on the study design， evaluation methods， model settings， results and conclusions of these collected papers， and the quality of the papers was evaluated using Quality of Health Economic Studies. RESULTS A total of 12 papers were included， of which 7 had a study region of Hong Kong in China， 6 had an older target group， 5 had a society-wide perspective， and the study time frame ranged from 6 months to 9 years. Besides， 8 papers used cost-utility analysis， only 2 used an epidemic model； 8 papers conducted sensitivity analyses， and most of them conducted both one-way sensitivity analysis and probabilistic sensitivity analysis. Moreover， the results of the economic evaluation of 10 papers showed that （combined） vaccination or increased vaccination rates were more economical. In addition， 4 of the 12 papers had a quality score＞75， which were considered high-quality studies. CONCLUSIONS Although most of the included studies showed that vaccination was economical， the quality of the existing paper needed to be improved. It is recommended that subsequent studies on the economic evaluation of influenza vaccines in GBA may consider adding economic evaluations for Macau and other cities in Guangdong of China， prioritizing dynamic models and recent data from local residents， and referring to relevant tools and guidelines to improve thestandardization and scientificity of the study design.

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With the high-quality development of biotechnology-related industries in China, the demand for talents and training quality in this field have received extensive attention. Several universities in Nanjing have conducted in-depth analysis on the shortcomings of talent training that does not closely match the needs of industries and enterprises. These universities have since effectively leveraged its professional characteristics, deepened university-enterprise cooperation, and encouraged the alignment of professional development with industrial growth. Biotechnology major has always focused on nurturing individuals with "right conduct, good learning, and strong ability", and capitalized on its comparative disciplinary advantages. These universities vigorously promoted and continuously optimized the model of university-enterprise collaborative training, highlighted the integration of science, industry and education, focused on innovative education teaching methods, as well as practical engineering practice to enhance its quality. The preliminary training results show that this model has promoted students' engineering practical abilities and comprehensive qualities, garnering recognition from employers and students alike.

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OBJECTIVE@#To observe the ferroptosis triggered by in different pathways during cecal ligation and puncture (CLP)-induced liver injury in septic mice, and to investigate whether mitochondrial aldehyde dehydrogenase 2 (ALDH2) can alleviate sepsis-induced liver injury by inhibiting ferroptosis.@*METHODS@#Sixty 8-week-old male C57BL/6J mice were randomly divided into sham operation group (Sham group), CLP group, ferroptosis inhibitor ferrostain-1 (Fer-1) group, ALDH2-specific agonist Alda-1 group, iron chelator deferasirox Fe3+ chelate (DXZ) group and dimethyl sulfoxide (DMSO) group, with 10 mice in each group. The septic liver injury was induced by CLP in mice model. In the Sham group, only laparotomy was performed without ligation and puncture of the cecum. 10 mL/kg 5% DMSO, 5 mg/kg Fer-1, 50 mg/kg DXZ and 10 mg/kg Alda-1 were injected intraperitoneally 1 hour before CLP in the DMSO, Fer-1, DXZ and Alda-1 groups respectively. At 24 hours after operation, eyeball blood and liver tissue were collected from anesthetized mice. The hepatic structure and inflammatory infiltration were observed by hematoxylin-eosin (HE) staining. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) in serum, the levels of hepatic malondialdehyde (MDA), superoxide dismutase (SOD) and reactive oxygen species (ROS) were detected. Western blotting was used to detect the protein expressions of ALDH2, ferroptosis-related proteins glutathione peroxidase 4 (GPX4), ferroptosis suppressor protein 1 (FSP1) and transferrin receptor 1 (TFR1) in liver tissue.@*RESULTS@#Compared with Sham group, the mice in CLP group showed varying degrees of congestion, disorganized hepatocyte arrangement, inflammatory cell infiltration at 24 hours after operation. Compared with the CLP group, the mice in the Fer-1 group, DXZ group and Alda-1 group liver morphology, liver injury and inflammatory cell infiltration was improved. Compared with Sham group, the serum levels of ALT and AST, the contents of MDA and ROS, and the expression of TFR1 protein in CLP group were significantly increased, while the activity of SOD and the expressions of ALDH2, GPX4 and FSP1 protein in CLP group were significantly decreased. Compared with CLP group, serum ALT and AST levels in Fer-1, DXZ and Alda-1 groups were significantly decreased [ALT (U/L): 45.76±10.81, 37.30±2.98, 36.40±12.75 vs. 73.06±12.20, AST (U/L): 61.57±2.69, 52.41±6.92, 56.05±8.29 vs. 81.59±5.46, all P < 0.05], and the contents of MDA, ROS and TFR1 protein expression in liver tissue were significantly decreased [MDA (μmol/L): 0.60±0.10, 0.57±0.18, 0.83±0.39 vs. 1.61±0.30, ROS (fluorescence intensity): 270.34±9.64, 276.02±62.33, 262.05±18.55 vs. 455.38±36.07, TFR1/GAPDH: 0.90±0.04, 1.01±0.09, 0.55±0.08 vs. 1.18±0.06, all P < 0.05], and the SOD activity and ALDH2, GPX4 and FSP1 protein expressions in liver tissue were significantly increased [SOD (kU/g): 88.77±8.20, 88.37±4.47, 93.43±7.24 vs. 50.27±3.57, ALDH2/GAPDH: 1.10±0.15, 1.02±0.07, 1.14±0.07 vs. 0.70±0.04, GPX4/GAPDH: 1.02±0.12, 0.99±0.08, 1.05±0.19 vs. 0.71±0.10, FSP1/GAPDH: 1.06±0.24, 1.02±0.08, 0.93±0.09 vs. 0.66±0.03, all P < 0.05]. There was no significant difference in the parameters between DMSO group and CLP group.@*CONCLUSIONS@#Both GPX4 and FSP1 mediated ferroptosis are involved in liver injury in septic mice. Activation of ALDH2 and inhibition of ferroptosis can alleviatehepatic injury. ALDH2 may play a protective role by regulating FSP1 and GPX4 mediated ferroptosis.

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OBJECTIVE: The present study aimed to develop a nomogram to predict long-term outcomes of uterine artery embolisation (UAE) for treating adenomyosis. MATERIALS AND METHODS: We reviewed data of 221 patients with adenomyosis who underwent UAE between May 2016 and January 2018. Predictive factors were identified using multivariate logistic regression analysis. A nomogram to predict the outcome of UAE was created for the training set. The performance of the predictive model was assessed by discrimination (quantified using the area under the curve, AUC) and calibration (evaluated by calibration curves and Hosmer-Lemeshow test) internally within the training set. Finally, an independent external validation was conducted using the validation set. RESULTS: In total, 201 patients were included. In the training set (n = 137), 96 (70.1%) exhibited a good response (GR), and 41 (39.9%) showed a poor response (PR). In the validation set (n = 64), 44 (68.7%) showed GR and 20 (31.3%) showed PR. The dysmenorrhoea score, T2 signal type, CA125, apparent diffusion coefficient, accompanying endometriosis, and accompanying fibroids were identified as associated factors and used in the nomogram. The AUC of the nomogram was 0.800 (95% confidence interval [CI] 0.724-0.877) and 0.798 (95% CI 0.686-0.909) in the training and validation sets, respectively. The calibration curves and Hosmer-Lemeshow test showed optimal agreement between predicted and actual probabilities (training set: P = 0.754; validation set: P = 0.453). CONCLUSIONS: We developed a nomogram that could predict the outcome of UAE in patients with adenomyosis. This model has the potential to select patients for UAE.

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The ongoing evolution of SARS-CoV-2 has resulted in the emergence of Omicron, which displays striking immune escape potential. Many of its mutations localize to the spike protein ACE2 receptor-binding domain, annulling the neutralizing activity of most therapeutic monoclonal antibodies. Here we describe a receptor-blocking human monoclonal antibody, 87G7, that retains ultrapotent neutralization against SARS-CoV-2 variants including the Alpha, Beta, Gamma, Delta and Omicron (BA.1/BA.2) Variants-of-Concern (VOCs). Structural analysis reveals that 87G7 targets a patch of hydrophobic residues in the ACE2-binding site that are highly conserved in SARS-CoV-2 variants, explaining its broad neutralization capacity. 87G7 protects mice and/or hamsters against challenge with all current SARS-CoV-2 VOCs. Our findings may aid the development of sustainable antibody-based strategies against COVID-19 that are more resilient to SARS-CoV-2 antigenic diversity. One sentence summaryA human monoclonal antibody confers broad neutralization and protection against Omicron and other SARS-CoV-2 variants

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Objective:To understand the status quo of subthreshold depression and its influencing factors among students in comprehensive universities, and then provide a research basis for promoting their mental health and effectively controlling the occurrence of depression.Methods:From October 2020 to January 2021, 450 undergraduates from 45 comprehensive universities in China were selected as research objects by convenient sampling and snowball sampling, and were investigated by a general information questionnaire and Self-Subthreshold Depression Scale (STDS).Results:The subthreshold depression score of the investigated college students was (83.28 ± 24.81), and the incidence of subthreshold depression was 40.8%(164/450). There were statistically significant differences in the incidence of subthreshold depression among different genders, grades, life satisfaction, family economic status, love status, understanding degree of subthreshold depression, time of depression, psychological counseling related to depression, and behavior after depression ( χ2 values were 5.68-19.48, all P<0.05). Conclusions:The incidence of subthreshold depression among the investigated undergraduates is high, and never falling in love is the protective factor of subthreshold depression. The risk factors of subthreshold depression are freshmen, who think they have never had depression and don′t know much about subthreshold depression.Attention should be paid to the present situation of college students' subthreshold depression, early detection and intervention should be made to prevent the development of depression, so as to improve the mental health level of college students.

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SARS-CoV-2 has infected millions of people globally and continues to undergo evolution. Emerging variants can be partially resistant to vaccine induced immunity and therapeutic antibodies, emphasizing the urgent need for accessible, broad-spectrum therapeutics. Here, we report a comprehensive study of ensovibep, the first trispecific clinical DARPin candidate, that can simultaneously engage all three units of the spike protein trimer to potently inhibit ACE2 interaction, as revealed by structural analyses. The cooperative binding of the individual modules enables ensovibep to retain inhibitory potency against all frequent SARS-CoV-2 variants, including Omicron BA.1 and BA.2, as of February 2022. Moreover, viral passaging experiments show that ensovibep, when used as a single agent, can prevent development of escape mutations comparably to a cocktail of monoclonal antibodies (mAb). Finally, we demonstrate that the very high in vitro antiviral potency also translates into significant therapeutic protection and reduction of pathogenesis in Roborovski dwarf hamsters infected with either the SARS-CoV-2 wild-type or the Alpha variant. In this model, ensovibep prevents fatality and provides substantial protection equivalent to the standard of care mAb cocktail. These results support further clinical evaluation and indicate that ensovibep could be a valuable alternative to mAb cocktails and other treatments for COVID-19.

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This paper reviews and analyzes the development process of nursing practice in response to natural disasters and public health emergencies, as well as the development process of disaster nursing education and disaster nursing discipline in China, and shows the continuous progress and improvement of disaster nursing. In view of the law of disaster development, the situation and challenges of disaster medicine and disaster nursing science, the development of disaster nursing in China in the future is prospected.

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Under the leadership of the Communist Party of China, China has been actively dealing with population aging and issued a series of elderly-oriented policies to provide effective guidance for the elderly-oriented development of the whole society. Elderly-oriented environment promotes the safe activities for the elderly, the elderly-oriented auxiliary devices improve the quality of life for the elderly, and the elderly-oriented services could meet the needs of the elderly for better lives. Elderly-oriented development of the whole society plays a positive role in promoting the health of the elderly in China.

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@#The World Health Organization (WHO) released the WHO 2020 guidelines on physical activity and sedentary behaviour in November 2020. Compared with the 2010 WHO guidelines, this guideline has incorporated more extensive medical evidence and made targeted recommendations for special populations. The main content includes physical activity and sedentary behaviour advice for children and adolescents, adults, older adults, pregnant and postpartum women, people with chronic conditions, and disability. This review will interpret the 2020 WHO guidelines in detail.

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Heterogeneous immunoassays such as ELISA have become indispensable in modern bioanalysis, yet translation into easy-to-use point-of-care assays is hindered by their dependence on external calibration and multiple washing and incubation steps. Here, we introduce RAPPID (Ratiometric Plug-and-Play Immunodiagnostics), a "mix-and-measure" homogeneous immunoassay platform that combines highly specific antibody-based detection with a ratiometric bioluminescent readout that can be detected using a basic digital camera. The concept entails analyte-induced complementation of split NanoLuc luciferase fragments, photoconjugated to an antibody sandwich pair via protein G adapters. We also introduce the use of a calibrator luciferase that provides a robust ratiometric signal, allowing direct in-sample calibration and quantitative measurements in complex media such as blood plasma. We developed RAPPID sensors that allow low-picomolar detection of several protein biomarkers, anti-drug antibodies, therapeutic antibodies, and both SARS-CoV-2 spike protein and anti-SARS-CoV-2 antibodies. RAPPID combines ratiometric bioluminescent detection with antibody-based target recognition into an easy-to-implement standardized workflow, and therefore represents an attractive, fast, and low-cost alternative to traditional immunoassays, both in an academic setting and in clinical laboratories for point-of-care applications.

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The coronavirus spike glycoprotein, located on the virion surface, is the key mediator of cell entry. As such, it is an attractive target for the development of protective antibodies and vaccines. Here we describe two human monoclonal antibodies, 1.6C7 and 28D9, that display a remarkable cross-reactivity against distinct species from three Betacoronavirus subgenera, capable of binding the spike proteins of SARS-CoV and SARS-CoV-2, MERS-CoV and the endemic human coronavirus HCoV-OC43. Both antibodies, derived from immunized transgenic mice carrying a human immunoglobulin repertoire, blocked MERS-CoV infection in cells, whereas 28D9 also showed weak cross-neutralizing potential against HCoV-OC43, SARS-CoV and SARS-CoV-2 in a neutralization-sensitive virus pseudotyping system, but not against authentic virus. Both cross-reactive monoclonal antibodies were found to target the stem helix in the spike protein S2 fusion subunit which, in the prefusion conformation of trimeric spike, forms a surface exposed membrane-proximal helical bundle, that is antibody-accessible. We demonstrate that administration of these antibodies in mice protects from a lethal MERS-CoV challenge in both prophylactic and/or therapeutic models. Collectively, these antibodies delineate a conserved, immunogenic and vulnerabe site on the spike protein which spurs the development of broad-range diagnostic, preventive and therapeutic measures against coronaviruses.

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SARS-CoV-2 has caused a global outbreak of severe respiratory disease (COVID-19), leading to an unprecedented public health crisis. To date, there has been over thirty-three million diagnosed infections, and over one million deaths. No vaccine or targeted therapeutics are currently available. We previously identified a human monoclonal antibody, 47D11, capable of cross-neutralising SARS-CoV-2 and the related 2002/2003 SARS-CoV in vitro, and preventing SARS-CoV-2 induced pneumonia in a hamster model. Here we present the structural basis of its neutralization mechanism. We describe cryo-EM structures of trimeric SARS-CoV and SARS-CoV-2 spike ectodomains in complex with the 47D11 Fab. These data reveal that 47D11 binds specifically to the closed conformation of the receptor binding domain, distal to the ACE2 binding site. The CDRL3 stabilises the N343 glycan in an upright conformation, exposing a conserved and mutationally constrained hydrophobic pocket, into which the CDRH3 loop inserts two aromatic residues. Interestingly, 47D11 preferentially selects for the partially open conformation of the SARS-CoV-2 spike, suggesting that it could be used effectively in combination with other antibodies that target the exposed receptor-binding motif. Taken together, these results expose a cryptic site of vulnerability on the SARS-CoV-2 RBD and provide a structural roadmap for the development of 47D11 as a prophylactic or post-exposure therapy for COVID-19.

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Globally accessible therapeutics against SARS-CoV-2 are urgently needed. Here, we report the generation of the first anti-SARS-CoV-2 DARPin molecules with therapeutic potential as well as rapid large-scale production capabilities. Highly potent multivalent DARPin molecules with low picomolar virus neutralization efficacies were generated by molecular linkage of three different monovalent DARPin molecules. These multivalent DARPin molecules target various domains of the SARS-CoV-2 spike protein, thereby limiting possible viral escape. Cryo-EM analysis of individual monovalent DARPin molecules provided structural explanations for the mode of action. Analysis of the protective efficacy of one multivalent DARPin molecule in a hamster SARS-CoV-2 infection model demonstrated a significant reduction of pathogenesis. Taken together, the multivalent DARPin molecules reported here, one of which has entered clinical studies, constitute promising therapeutics against the COVID-19 pandemic.

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Effective clinical intervention strategies for COVID-19 are urgently needed. Although several clinical trials have evaluated the use of convalescent plasma containing virus-neutralizing antibodies, the effectiveness has not been proven. We show that hamsters treated with a high dose of human convalescent plasma or a monoclonal antibody were protected against weight loss showing reduced pneumonia and pulmonary virus replication compared to control animals. However, a ten-fold lower dose of convalescent plasma showed no protective effect. Thus, variable and relatively low levels of virus neutralizing antibodies in convalescent plasma may limit their use for effective antiviral therapy, favouring concentrated, purified (monoclonal) antibodies.