Objective: To analyze the relationship between 24 h movement behaviors and cognitive function in children and adolescents, as well as the isotemporal substitution benefits, in order to provide a basis for developing cognitive development intervention strategies among children and adolescents. Methods: Relevant studies were searched in the Web of Science, PubMed, Embase, EBSCO, and China National Knowledge Infrastructure databases from their inception to November 30, 2024. Systematic evaluation was performed after document screening, data extraction and quality assessment. Results: A total of 24 highquality studies were included, comprising 35 295 children and adolescents aged 3-18 years. Adhering to the 24 h activity guidelines was associated with better cognitive performance (19 studies). Additionally, substituting 5-30 minutes per day of moderate to vigorous physical activity (MVPA) or sleep (SLP) for sedentary behavior (SB) or light physical activity (LPA) were associated with improvements in cognitive function (7 studies). There were inconsistencies in the effects of different types of SB (learning or entertainment) on cognitive function. Conclusions Adherence to the 24 h activity guidelines supports cognitive development in children and adolescents, with MVPA and SLP as key intervention targets. Increasing the proportion of MVPA, ensuring adequate SLP, and limiting recreational SB and screen time might be helpful to enhance the combined benefits of these three behaviors.

Objective To investigate the cause of a suspected outbreak of carbapenem-resistant Klebsiella pneumoniae infection(CRKP)in the neurological ICU,to find out the reason for infection and the way of transmission to provide evidence for the prevention and control of nosocomial infection.Methods Four patients with CRKP infection in the department of neurological ICU of a hospital from Au-gust 4 to August 20,2020 were investigated epidemiologically and environmental hygiene monitoring of the ward was carried out.Compre-hensive measures were taken to control the outbreak.Results All four CRKP infection cases were hospital-acquired,and the isolated strains showed consistent drug susceptibility test results,indicating they were the same clone.Environmental hygiene monitoring revealed the presence of the same clone in samples from patient bedside items,suction devices,oxygen therapy equipment,and personal belongings of healthcare workers.After implementing comprehensive corrective measures,no new cases of CRKP infection occurred,and subsequent surface sampling did not isolate any CRKP strains.Conclusion Environmental surface contamination in the neurointensive care unit and inadequate disinfection procedures were likely the main causes of the suspected outbreak of CRKP infection.Prompt identification of the outbreak,activation of emergency response plans,and implementation of corrective measures are crucial for controlling the outbreak of multidrug-resistant bacterial infections in hospitals.After adopting comprehensive measures,there were no new CRKP infection cases.

Objective To explore the predictive value of CT radiomics and morphological features for the prognosis and survival in non-small cell lung cancer(NSCLC)patients.Methods The clinic data of 300 NSCLC patients(300 lesions)were downloaded from the Cancer Imaging Archive,with 210 randomly selected as the training set and 90 as the test set.According to the prognosis and survival,the patients were divided into two groups with survival period≤3 and＞3 years.3D Slicer software was used to delineate the regions of interest layer by layer in CT images,and the radiomics features were extracted from each region of interest.Both t-test and least absolute shrinkage and selection operator were utilized for radiomics feature screening.Three types of prediction models,namely radiomics model,morphological model and combined model,were constructed with Logistic regression,whose performances were evaluated using the receiver operating characteristic(ROC)curve.Results The differences in radiomics labels and mediastinal lymph node metastasis between the training set and the test set were statistically significant.For radiomics model,morphological model and combined model,the area under the ROC curve was 0.784(95%CI:0.722-0.847),0.734(95%CI:0.664-0.804)and 0.748(95%CI:0.680-0.815)in the training set,and 0.737(95%CI:0.630-0.844),0.665(95%CI:0.554-0.777)and 0.687(95%CI:0.578-0.797)in the test set,which demonstrated that radiomics model had the best diagnostic performance.Conclusion The CT radiomics model can effectively predict the prognosis and survival in NSCLC patients.

Objective To summarize the liver biopsy and clinical features of patients with liver injury of unknown origin,and to investigate the value of ultrasound-guided percutaneous liver biopsy in the diagnosis of liver injury of unknown origin.Methods A retrospective analysis was performed for the clinical data and ultrasound-guided percutaneous liver biopsy results of 94 patients with liver injury of unknown origin who were admitted to Zhongshan Hospital,Xiamen University,from January 2018 to February 2023.According to the proportion of the patients with different final diagnoses,the patients were divided into autoimmune liver disease(AILD)group,metabolic associated fatty liver disease(MAFLD)group,drug-induced liver injury(DILI)group,alcoholic liver disease(ALD)group,and unknown group.An analysis of variance was used for comparison of normally distributed continuous data between multiple groups,and the Bonferroni analysis or the Dunnett'T3 test was used for further comparison between two groups;the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups;the Fisher's exact test was used for comparison of categorical data between multiple groups.Results All 94 patients with liver injury of unknown origin underwent ultrasound-guided percutaneous liver biopsy after admission,among whom 90 patients(95.7%)had a confirmed diagnosis based on liver biopsy and clinical features.There were 43 patients(45.7%)with AILD,21(22.3%)with MAFLD,15(16.0%)with DILI,6(6.4%)with ALD,1(1.1%)with AILD and MAFLD,1(1.1%)with hemochromatosis,1(1.1%)with Budd-Chiari syndrome,1(1.1%)with congenital hepatic fibrosis,and 1(1.1%)with idiopathic portal hypertension,while 4 patients(4.3%)still had an unknown etiology after liver biopsy.There were significant differences between the patients with top five diagnoses in age(F=4.457,P<0.05),body mass index(BMI)(F=3.245,P<0.05),aspartate aminotransferase(AST)(H=11.128,P<0.05),gamma-glutamyl transpeptidase(GGT)(H=24.789,P<0.05),alkaline phosphatase(ALP)(H=26.013,P<0.05),IgG(H=19.099,P<0.05),IgM(H=21.263,P<0.05),AMA-M2 positive rate(P<0.05),and ANA positive rate(P<0.05).Compared with the MAFLD group,the AILD group had significantly higher age,AST,GGT,and ALP and a significantly lower BMI;compared with the MAFLD group and the DILI group,the AILD group had significant increases in IgG and IgM;the AILD group had significant increases in the positive rates of AMA-M2 and ANA compared with the other four groups.Conclusion AILD,MAFLD,and DILI are the most common causes in patients with liver injury of unknown origin.Ultrasound-guided percutaneous liver biopsy plays an important role in determining the cause of liver injury of unknown origin,but it is still needed to make a comprehensive analysis based on clinical history,different types of liver injury,laboratory markers,and imaging data.

Objective To systematically evaluate the effect of speech and language therapies and educational interventions on chil-dren with intellectual and developmental disabilities(IDD). Methods A systematic review was conducted by searching relevant literature in PubMed,PsycINFO,ERIC,Cochrane Library and Web of Science databases,ranging from January,2018 to May,2024. Results A total of eight English articles were included,from six countries including the United States,France,Italy,Nor-way,Poland and New Zealand,involving 610 children with IDD,from journals about speech language pathology,Down syndrome research and speech language hearing research.The publication time was mainly from 2018 to 2023.The age of the subjects was two to twelve years,and the main health conditions included intellectual dis-ability,autism and Down syndrome.The intervention methods included routine speech therapy(individualized therapy and group therapy),augmentative and alternative communication(device-assisted and sign language and picture cards),family-involved language training programs(parent training and family interaction),computer-as-sisted language learning(language learning software and telehealth),and play-based interventions(interactive games and structured games);15 to 150 minutes a time,one to ten times a week,for ten to 144 weeks.The out-comes were reflected in five aspects:increasing the vocabulary in speaking;improving the language comprehen-sion,symbol recognition and vocabulary comprehension;improving both expressive and receptive language skills;improving participation in game diversity and game participation levels,communication,social interaction and interaction skills;and improving overall language and non-verbal communication skills. Conclusion Combining a variety of methods,such as individualized therapy,family participation,technologic assistance and interactive games,speech and language therapies and education are effective on spoken language production,language comprehension,speech production,social interaction and communication skills for children with IDD.

Objective:To compare the prognosis of patients with hepatolithiasis-associated intrahepatic cholangiocarcinoma (ICC) and hepatitis B virus (HBV)-associated ICC after radical resection.Methods:The clinicopathological and survival data of 69 patients with ICC undergoing radical resection in the Department of Hepatobiliary and Pancreatic Surgery, Lihuili Hospital Affiliated to Ningbo University from January 2012 to February 2024 were retrospectively analyzed, including 40 males and 29 females, aged (62.9±10.2) years. Patients were divided into the stone group ( n=40, with hepatolithiasis) and HBV group ( n=29, with HBV). Kaplan-Meier method was used for survival analysis, and log-rank test was used for survival rate comparison. Cox proportional hazard regression model was used for multivariate analysis to analyze the effect of hepatolithiasis and HBV on the prognosis. Results:The median overall survival of ICC patients in the stone group was 16 months, and that in the HBV group was 27 months. The 1-, 3-, and 5-year cumulative survivals of the stone group were 56.6%, 23.2%, and 10.3%, respectively, which were lower than those of the HBV group (72.0%, 50.7%, and 43.4%, respectively, χ2=5.95, P=0.015). The median recurrence-free survivals (RFS) of the stone group and the HBV group were 12 months and 23 months, respectively. The 1-year and 3-year RFS of the stone group were 49.2% and 18.1%, which were lower than those of the HBV group (65.0% and 39.8%, respectively, χ2=3.94, P=0.047). Univariate analysis showed that hepatolithiasis was assciated with prognosis ( χ2=5.95, P=0.015). Multivariate Cox regression analysis showed that hepatolithiasis and hepatitis B virus infection had no effect on the prognosis of ICC patients after surgery (all P>0.05). Conclusion:Compared to HBV infection, ICC patients with hepatolithiasis have a worse prognosis. Hepatolithiasis and HBV infection have no effect on the prognosis of ICC after radical resection.

The C-glycosidic bond that connects the sugar moiety with aglycone is difficult to be broken or made due to its inert nature. The knowledge of C-glycoside breakdown and synthesis is very limited. Recently, the enzyme DgpA/B/C cascade from a human intestinal bacterium PUE was identified to specifically cleave the C-glycosidic bond of puerarin (daidzein-8-C-glucoside). Here we investigated how puerarin is recognized and oxidized by DgpA based on crystal structures of DgpA with or without substrate and biochemical characterization. More strikingly, we found that apart from being a C-glycoside cleaving enzyme, DgpA/B/C is capable of efficiently converting O- to C-glycoside showing the activity as a structure isomerase. A possible mechanistic model was proposed dependently of the simulated complex structure of DgpB/C with 3″-oxo-daidzin and structure-based mutagenesis. Our findings not only shed light on understanding the enzyme-mediated C-glycosidic bond breakage and formation, but also may help to facilitate stereospecific C-glycoside synthesis in pharmaceutical industry.

Background Flurochloridone (FLC) is toxic to male reproduction and can induce apoptosis of testicular tissue and supporting cells under oxidative stress. Of particular concern is whether nuclear factor-erythrocyte 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) signaling pathway and nuclear factor kappa B (NFκB) signaling pathway participate this process. Objective To observe apoptosis of testicular tissue and sertoli TM4 cells and alterations of Nrf2/HO-1 and NFκB signaling pathways in mice treated with FLC in vivo/in vitro. Methods (1) Animal experiment. Testis samples were harvested from male C57BL/6 mice after 28-day FLC (0, 3, 15, 75, and 375 mg·kg⁻¹ per day) exposure via oral route. Malondialdehyde (MDA) and superoxide dismutase (SOD) in homogenate of testicular tissue were measured by colorimetry. Apoptosis of testicular tissue was evaluated by TUNEL staining. Expression and distribution of Nrf2 and NFκB were detected by immunohistochemistry. Protein expression levels of Nrf2, HO-1, NAD(P)H: quinone oxidoreductase 1 (NQO1), NFκB, inhibitor of nuclear factor kappa-B kinase subunit beta (IKKβ), and phosphorylated recombinant inhibitory subunit of nuclear factor kappa-B alpha (P-IκBα) in testicular tissue homogenate were determined by Western blotting. (2) Cell experiment. TM4 cell lines were treated with 40, 80, 120, 160, and 200 μmol·L⁻¹ FLC for 6 h, and cell viability was detected by CCK-8. After 6 h exposure to 40, 80, and 160 μmol·L⁻¹ FLC, the apoptosis rate was detected by flow cytometry, and the protein expression levels of Nrf2, HO-1, NQO1, NFκB, IKKβ, and IκBα were detected by Western blotting. Results (1) Animal experiment. Apoptosis occurred in the interstitial and basal parts of spermatogenic tubules in male C57BL/6 mice after 28 days of oral FLC exposure. Compared with the control group, the MDA level in testicular tissue of the 375 mg·kg⁻¹ FLC-treated group was significantly increased (P<0.05), and the SOD activity was significantly decreased (P<0.05). After 375 mg·kg⁻¹ FLC exposure, apoptosis occurred in the interstitial and basal parts of spermatogenic tubules. The results of immunohistochemistry showed the expression of Nrf2 and NFκB in the interstitium and basal part of spermatogenic tubules of the treated groups. Compared with the control group, the protein levels of Nrf2, NQO1, P-IκBα, NFκB, and IKKβ in the 15, 75, and 375 mg·kg^-1 groups were significantly increased (P<0.001), and the HO-1 protein level was significantly increased in the 375 mg·kg⁻¹ group (P<0.001). (2) Cell experiment. Compared with the control group, the TM4 cell viabilities in the 40, 80, 120, 160, and 200 μmol·L⁻¹ FLC-treated groups significantly decreased (P<0.01). The apoptosis rates were significantly increased (P<0.05), and the apoptosis rates increased from 5.7% in the control group to 7.4%, 9.4%, and 11.7% in the 40, 80, and 160 μmol·L⁻¹, respectively. The Nrf2 protein level in the 40 μmol·L⁻¹ group was significantly increased (P<0.01), while the levels significantly decreased in the 80 and 160 μmol·L⁻¹ groups (P<0.01). The HO-1 protein levels in the 40, 80, and 160 μmol·L⁻¹ groups were significantly increased (P<0.01). The level of NQO1 protein in the 40 μmol·L⁻¹ group was significantly increased (P<0.01). The NFκB protein levels were significantly increased in the 80 and 160 μmol·L⁻¹ groups (P<0.001). The IκBα protein levels were significantly decreased in all treated groups (P<0.001). The IKKβ protein had no significant change. Conclusion FLC induces testicular tissue apoptosis, and the process affects Nrf2/HO-1 signaling pathway and NFκB signaling pathway. The in vitro study confirms that FLC could induce apoptosis of TM4 cells and activate Nrf2/HO-1 and NFκB signaling pathways.

Via an insufficient coat protein complex I (COPI) retrieval signal, the majority of SARS-CoV-2 spike (S) is resident in host early secretory organelles and a tiny amount is leaked out in cell surface. Only surface-exposed S can be recognized by B cell receptor (BCR) or anti-S therapeutic monoclonal antibodies (mAbs) that is the trigger step for B cell activation after S mRNA vaccination or infected cell clearance by S mAbs. Now, a drug strategy to promote S host surface exposure is absent. Here, we first combined structural and biochemical analysis to characterize S COPI sorting signals. A potent S COPI sorting inhibitor was then invented, evidently capable of promoting S surface exposure and facilitating infected cell clearance by S antibody-dependent cellular cytotoxicity (ADCC). Importantly, with the inhibitor as a probe, we revealed Omicron BA.1 S is less cell surface exposed than prototypes because of a constellation of S folding mutations, possibly corresponding to its ER chaperone association. Our findings not only suggest COPI is a druggable target against COVID-19, but also highlight SARS-CoV-2 evolution mechanism driven by S folding and trafficking mutations.

As an important complementary form of decoction pieces of traditional Chinese medicine（TCM）， TCM dispensing granules has the advantages of being free of decoction， easy to take， easy to carry and easy to be dispensed， which greatly improves the capacity of emergency services of TCM and is more in line with the needs of modern society. With the end of the pilot project of TCM dispensing granules， the market has been fully liberalized， the competition has been intensified， and it is in the transition period of switching between the new standard and the old one， and there are some problems such as the shortage of varieties， the change of specifications and the difference of quality， and the production enterprises are facing new opportunities and challenges. Based on this， the authors intend to systematically sort out the policies and regulations， enterprise layout and standard formulation since the pilot of TCM dispensing granules. In view of the problems in the post-pilot stage and from the perspective of survival and development of enterprises， it is suggested that enterprises should establish a quality control system for the whole industry chain of TCM dispensing granules to reduce process costs and increase enterprise competitiveness， further increase the investment in scientific research， overcome the key technical problems of difficult varieties， actively and orderly promote the research of national standards， in order to ensure the integrity of clinical formula varieties， and establish and improve the efficacy evaluation mechanism of TCM dispensing granules， build a consistency evaluation system between TCM dispensing granules and decoction pieces. Government departments should strengthen the guidance， fully mobilize the enthusiasm of scientific research institutions， enterprises and hospitals， and explore the establishment of "government-industry-study-research-application" mode to promote the development of TCM dispensing granule industry.