Notum, a negative feedback regulator of the Wnt signaling, has emerged as a promising target for treating glucocorticoid-induced osteoporosis (GIOP). This study showcases an efficient strategy for discovering the anti-Notum constituents from herbal medicines (HMs) as novel anti-GIOP agents. Firstly, a rapid-responding near-infrared fluorogenic substrate for Notum was rationally engineered for high-throughput identifying the anti-Notum HMs. The results showed that Bu-Gu-Zhi (BGZ), a known anti-osteoporosis herb, potently inhibited Notum in a competitive-inhibition manner. To uncover the key anti-Notum constituents in BGZ, an efficient strategy was adapted via integrating biochemical, phytochemical, computational, and pharmacological assays. Among all identified BGZ constituents, three furanocoumarins were validated as strong Notum inhibitors, while 5-methoxypsoralen (5-MP) showed the most potent anti-Notum activity and favorable safety profiles. Mechanistically, 5-MP acted as a competitive inhibitor of Notum via creating strong hydrophobic interactions with Trp128 and Phe268 in the catalytic cavity of Notum. Cellular assays showed that 5-MP remarkably promoted osteoblast differentiation and activated Wnt signaling in dexamethasone (DXMS)-challenged MC3T3-E1 osteoblasts. In dexamethasone-induced osteoporotic mice, 5-MP strongly elevated bone mineral density (BMD) and improved cancellous and cortical bone thickness. Collectively, this study constructs a high-efficient platform for discovering key anti-Notum constituents from HMs, while 5-MP emerges as a promising anti-GIOP agent.

Schizophrenia (SZ) stands as a severe psychiatric disorder. This study applied diffusion tensor imaging (DTI) data in conjunction with graph neural networks to distinguish SZ patients from normal controls (NCs) and showcases the superior performance of a graph neural network integrating combined fractional anisotropy and fiber number brain network features, achieving an accuracy of 73.79% in distinguishing SZ patients from NCs. Beyond mere discrimination, our study delved deeper into the advantages of utilizing white matter brain network features for identifying SZ patients through interpretable model analysis and gene expression analysis. These analyses uncovered intricate interrelationships between brain imaging markers and genetic biomarkers, providing novel insights into the neuropathological basis of SZ. In summary, our findings underscore the potential of graph neural networks applied to multimodal DTI data for enhancing SZ detection through an integrated analysis of neuroimaging and genetic features.
Humans ; Schizophrenia/pathology* ; Diffusion Tensor Imaging/methods* ; Male ; Female ; Adult ; Brain/metabolism* ; Young Adult ; Middle Aged ; White Matter/pathology* ; Gene Expression ; Nerve Net/diagnostic imaging* ; Graph Neural Networks

Abstract Alzheimer′s disease(AD) is a common neurodegenerative disease. It has been found that AD is related to various pathogenic factors such as genetics, cardiovascular and cerebrovascular disease, and excessive phosphorylation of tau protein. However, no definitive conclusions on its pathogenesis have been reached. In this paper, the research progress on the pathogenesis of AD inC.elegansmodel and the therapeutic effects of traditional Chinese medicine extracts on AD are reviewed, providing a basis for further research on the alleviating effects of Chinese medicine extracts on AD.

Chicken coccidia specialize in growing and reproducing within the epithelial cells of the chicken intestinal mucosa,posing a threat to the health of the chicken flock.However,traditional chemical drugs are difficult to pass through the cell barrier and can easily lead to the emergence of drug-resistant strains and residual veterinary drugs,posing a huge challenge to the prevention and control of coccidiosis.Therefore,it is necessary to develop new strategies against coccidiosis.Nano-drugs have the advantages of good biocompatibility,easy modification,and high efficiency,impro-ving the penetration of cell membranes while reducing drug toxicity and side effects.They are ex-pected to be applied in the prevention and treatment of coccidiosis.This article introduces various nanomedicines for treating chicken coccidiosis,summarizes their advantages compared to tradition-al formulations,focuses on the application of nanomedicines in the treatment of chicken coccidio-sis,elucidates the existing problems of nanomedicine treatment for chicken coccidiosis,and looks forward to the challenges and future development directions in this field,in order to provide impor-tant references for the development of nanomedicines for treating chicken coccidiosis.

Objective:To investigate the predictive value of controlling nutritional status (CONUT) score in the prognosis of patients with advanced diffuse large B-cell lymphoma (DLBCL).Methods:A retrospective case series study was performed. The clinical data of 654 patients newly diagnosed with advanced DLBCL diagnosed in 7 medical centers in Huaihai Lymphoma Working Group from October 2009 to January 2022 were retrospectively collected. All the patients received rituximab-based immune chemotherapy regimens. The patients were randomly assigned to the training set (458 cases) and the validation set (196 cases) in a 7:3 ratio. The clinicopathological data of patients were collected, and the CONUT score was calculated based on albumin, lymphocyte count, and total cholesterol. The optimal critical value of CONUT scote was determined by using MaxStat method. Kaplan-Meier method was used to draw survival curves; Cox proportional hazards model was used to make univariate analysis and multivariate analysis on the factors influencing overall survival (OS). The efficacy of CONUT score in combination with the International prognostic index (IPI) and an enhanced IPI (NCCN-IPI) in predicting OS was evaluated by using receiver operating characteristic (ROC) curves.Results:The median follow-up time of 654 patients was 38.1 months (95% CI: 35.3 months- 40.9 months), and the 5-year OS rate was 49.2%. According to the MaxStat method, the optimal critical value for CONUT score was determined to be 6 points. All the patients were classified into the normal nutritional status group (CONUT score ≤ 6 points, 489 cases) and the poor nutritional status group (CONUT score > 6 points, 165 cases). The results of the multivariate analysis showed that CONUT score > 6 points, male, lactate dehydrogenase >240 U/L, high white blood cell count, low hemoglobin level and age > 60 years were independent risk factors for OS of patients with advanced DLBCL (all P < 0.05). Patients in the poor nutritional status group (CONUT score > 6 points) had worse OS compared with that in the normal nutritional status group in the overall cohort of advanced DLBCL. Subgroup analysis revealed that among patients with Eastern Cooperative Oncology Group-performance status (ECOG PS) score < 2 points, IPI low-intermediate risk, IPI intermediate-high risk, NCCN-IPI low-intermediate risk, and NCCN-IPI intermediate-high risk, the patients in the poor nutritional status group (CONUT score > 6 points) had worse OS compared with that in the normal nutritional status group (CONUT score ≤ 6 points) (all P < 0.05). Conclusions:CONUT score has a certain value in the assessment of the prognosis of patients with advanced DLBCL, and its predictive efficacy is further improved when combined with IPI and NCCN-IPI.

Objective:To analyze the epidemiological characteristics of human respiratory syncytial virus (HRSV) in cases of febrile respiratory syndrome in China from 2010 to 2020.Methods:Based on the sub-project of the National Science and Technology Major Project for Infectious Disease Prevention and Control "Infectious Disease Monitoring Technology Platform", active monitoring of febrile respiratory syndrome cases was conducted in sentinel hospitals in 31 provinces across China (excluding Hong Kong, Macau, and Chinese Taiwan) from January 2010 to December 2020, resulting in the inclusion of 191 441 cases. Clinical specimens of monitored cases were screened for HRSV nucleic acid, and the differences in HRSV detection rates among different age groups, regions, and time periods were analyzed using the χ 2 test/Fisher exact probability method. Results:Among the 191 441 cases of febrile respiratory syndrome in China from 2010 to 2020, the age group M ( Q1, Q3) was 9 (2, 40) years old, with 83 773 cases (43.8%) in the <5 years old group. There were 113 660 males, with a male-to-female ratio of 1.5∶1.0. There were as many as 105 508 cases (55.2%) of scattered children and preschool children. About 70 565 cases (36.9%) lived in the northern region. There were 13 858 HRSV positive cases, with a total positive rate of 7.2%. The positive rate of HRSV detection in the northern population was 5.7% (4 004/70 565), which was lower than that in the southern population (8.2%, 9 854/120 876), and the difference was statistically significant (χ 2=407.4, P<0.001). HRSV was detected in all age groups, with the highest positive rate of 23.9% in the <6 months age group. The month with the highest positive rate was December, and autumn and winter were the main epidemic seasons. Both northern and southern HRSV subtypes were mainly infected with type A, with a low proportion of mixed infections of type A and type B. Conclusion:HRSV is a common pathogen causing respiratory infections in children from 2010 to 2020. It can be detected throughout the year and shows the main peak of prevalence in autumn and winter. The HRSV strain is mainly classified as a type A infection.

Objective:To analyze the epidemiological characteristics of human respiratory syncytial virus (HRSV) in cases of febrile respiratory syndrome in China from 2010 to 2020.Methods:Based on the sub-project of the National Science and Technology Major Project for Infectious Disease Prevention and Control "Infectious Disease Monitoring Technology Platform", active monitoring of febrile respiratory syndrome cases was conducted in sentinel hospitals in 31 provinces across China (excluding Hong Kong, Macau, and Chinese Taiwan) from January 2010 to December 2020, resulting in the inclusion of 191 441 cases. Clinical specimens of monitored cases were screened for HRSV nucleic acid, and the differences in HRSV detection rates among different age groups, regions, and time periods were analyzed using the χ 2 test/Fisher exact probability method. Results:Among the 191 441 cases of febrile respiratory syndrome in China from 2010 to 2020, the age group M ( Q1, Q3) was 9 (2, 40) years old, with 83 773 cases (43.8%) in the <5 years old group. There were 113 660 males, with a male-to-female ratio of 1.5∶1.0. There were as many as 105 508 cases (55.2%) of scattered children and preschool children. About 70 565 cases (36.9%) lived in the northern region. There were 13 858 HRSV positive cases, with a total positive rate of 7.2%. The positive rate of HRSV detection in the northern population was 5.7% (4 004/70 565), which was lower than that in the southern population (8.2%, 9 854/120 876), and the difference was statistically significant (χ 2=407.4, P<0.001). HRSV was detected in all age groups, with the highest positive rate of 23.9% in the <6 months age group. The month with the highest positive rate was December, and autumn and winter were the main epidemic seasons. Both northern and southern HRSV subtypes were mainly infected with type A, with a low proportion of mixed infections of type A and type B. Conclusion:HRSV is a common pathogen causing respiratory infections in children from 2010 to 2020. It can be detected throughout the year and shows the main peak of prevalence in autumn and winter. The HRSV strain is mainly classified as a type A infection.

Objective:To investigate the occurrence of frailty and its influencing factors in patients with lung cancer.Methods:Patients with lung cancer receiving treatment at Xiangya Hospital of Central South University were recruited between March 2022 and March 2023.The FRAIL scale was employed to categorize the patients into non-frailty, pre-frailty, and frailty groups.A comparison of their basic data, disease data, and relevant laboratory indicators before treatment was conducted to identify factors influencing frailty in lung cancer patients.Results:A total of 240 patients with lung cancer were analyzed in this study, comprising 46 patients(19.2%)in the non-frailty group, 121 patients(50.4%)in the pre-frailty group, and 73 patients(30.4%)in the frailty group.The average age of the frailty and pre-frailty groups was significantly higher than that of the non-frailty group( P<0.05).Additionally, the body mass index(BMI)of the frailty group was significantly lower compared to both the non-frailty and pre-frailty groups( P=0.005).The proportion of male patients in the frailty group was lower than that of female patients, while the proportion of pre-frailty patients was higher among females( P=0.017).Furthermore, the percentage of patients receiving family care was lower in both the frailty and pre-frailty groups compared to those without family care( P<0.001).Various blood markers such as white blood cells(WBC), neutrophils(NEUT), N terminal pro B type natriuretic peptide(NT-proBNP), carcinoembryonic antigen(CEA), neuron-specific enolase(NSE), neurophil to lymphocyte ratio(NLR), monocyte-lymphocyte ratio(MLR), and systemic inflammatory index(SII)were significantly elevated in the frailty group compared to the non-frailty group, whereas red blood cells(RBC), hemoglobin(Hb), hematocrit(HCT), lymphocytes(LYMPH), total protein(TP), albumin(Alb), total cholesterol(TC), high-density lipoprotein cholesterol(HDL-C), and low-desity lipoprotein cholesterol(LDL-C)were notably lower in the frailty group(all P<0.05).Similarly, NEUT, NLR, platelet to lymphocyte ratio(PLR), MLR, and SII were higher in the frailty group compared to the pre-frailty group, while RBC, Hb, HCT, LYMPH, TP, Alb, TC, HDL-C, and LDL-C were lower in the frailty group than the pre-frailty group( P<0.05).Moreover, NT-proBNP levels were higher in the pre-frailty group than in the non-frailty group, with all these differences being statistically significant(all P<0.05).The results of multifactorial Logistic regression analyses revealed several significant associations with frailty in lung cancer patients.Males had an increased risk of frailty( OR=2.80, P=0.033), while family care was linked to a decreased risk( OR=0.37, P=0.004).Additionally, advancing age was associated with a higher risk of frailty( OR=1.06, P=0.004).Furthermore, higher Alb levels were correlated with a reduced risk of frailty( OR=0.91, P=0.023), elevated LDL-C levels were associated with a lower risk( OR=0.59, P=0.027), and increased CEA levels were linked to a higher risk of frailty( OR=1.01, P=0.003)in lung cancer patients. Conclusions:In lung cancer patients, older age, male gender, and higher CEA levels were linked to a higher risk of frailty, whereas family care, higher Alb levels, and high LDL-C levels were associated with a lower risk of frailty.These findings imply the importance of intensifying frailty screening in lung cancer patients to identify and intervene in frailty risk early on.

Objective:To analyze the gene mutation type and clinical phenotype of patients with PRRT2 mutation, and explore their relations with prognosis. Methods:A total of 18 patients with PRRT2 gene mutation (1 patient with novel mutation in PRRT2 gene, and 17 probands in 17 families with PRRT2 gene mutation) were enrolled in Department of Neurology, First Affiliated Hospital of Air Force Medical University from January 2018 to July 2023. Serum of the patients was collected for whole exon sequencing, and mutation sites and types of PRRT2 gene were analyzed. SWISS-MODEL website was used to predict the changes in protein structure caused by PRRT2 gene mutation. The relations of gene mutation type and clinical phenotype with prognosis of these patients were analyzed. Results:(1) All 18 patients with PRRT2 gene mutation were heterozygous mutation, including 12 frameshift mutations, 5 missense mutations, and 1 integer mutation. The clinical phenotype included benign familial infantile epilepsy (BFIE) in 5 patients, epilepsy in 6 patients, exercise-induced paroxysmal kinesigenic dyskinesia (PKD) in 5 patients, and infantile convulsion and choreoathetosis (ICCA) in 2 patients. A total of 8 mutation sites were found in 18 patients with PRRT2 gene mutation, of which 3 mutation sites have been reported, and 5 mutation sites have not been reported, including c.647(exon2)C>A, c.647(exon2)C>G, c.170(exon2)delC, c.981(exon3)C>G, and lossl(EXON: 2)(all). (2) Eighteen patients mainly accepted oxcarbazepine, levetiracetam, and sodium valproate in combination or monotherapy. Among them, 5 BFIE patients, 2 ICCA patients and 3 epilepsy patients were seizure-free after treatment. PKD patients did not respond well to oxcarbazepine. (3) Three frameshift mutations (mutation sites: c.649 [exon2]_c.650 [exon2] insC, c.640 [exon2]_c.641 [exon2] insC, and c.170 [exon2] delC) led to premature termination of protein translation, resulting in significant changes in protein structure. Four missense mutations (mutation sites: c.640[exo2]G>C, c.647[exon2]C>A, c.647[exon2]C>G, and c.981[exon3]C>G) had little effect on protein structure changes. No relation was found between changes of protein structure caused by different mutation types and prognosis. Conclusion:PRRT2 gene mutation patients with clinical phenotypes of BFIE and ICCA have good prognosis, but the mutation type is not related with the prognosis of patients.

Respiratory syncytial virus (RSV) is an enveloped, negative-sense, single-stranded RNA virus of the Orthopneumovirus  genus of the Pneumoviridae family in the order Mononegavirales. RSV can cause acute upper and lower respiratory tract infections, sometimes with extrapulmonary complications. The disease burden of RSV infection is enormous, mainly affecting infants and older adults aged 75 years or above. Currently, treatment options for RSV are largely supportive. Prevention strategies remain a critical focus, with efforts centered on vaccine development and the use of prophylactic monoclonal antibodies. To date, three RSV vaccines have been approved for active immunization among individuals aged 60 years and above. For children who are not eligible for these vaccines, passive immunization is recommended. A newly approved prophylactic monoclonal antibody, Nirsevimab, which offers enhanced neutralizing activity and an extended half-life, provides exceptional protection for high-risk infants and young children. This review provides a comprehensive and detailed exploration of RSV's virology, immunology, pathogenesis, epidemiology, clinical manifestations, treatment options, and prevention strategies.
Humans ; Respiratory Syncytial Virus Infections/prevention & control* ; Respiratory Syncytial Viruses/pathogenicity* ; Respiratory Syncytial Virus, Human/pathogenicity* ; Antiviral Agents/therapeutic use*