Objective Recombinase-aided polymerase chain reaction(RAP)is a sensitive,single-tube,two-stage nucleic acid amplification method.This study aimed to develop an assay that can be used for the early diagnosis of three types of bacteremia caused by Staphylococcus aureus(SA),Pseudomonas aeruginosa(PA),and Acinetobacter baumannii(AB)in the bloodstream based on recombinant human mannan-binding lectin protein(M1 protein)-conjugated magnetic bead(M1 bead)enrichment of pathogens combined with RAP. Methods Recombinant plasmids were used to evaluate the assay sensitivity.Common blood influenza bacteria were used for the specific detection.Simulated and clinical plasma samples were enriched with M1 beads and then subjected to multiple recombinase-aided PCR(M-RAP)and quantitative PCR(qPCR)assays.Kappa analysis was used to evaluate the consistency between the two assays. Results The M-RAP method had sensitivity rates of 1,10,and 1 copies/μL for the detection of SA,PA,and AB plasmids,respectively,without cross-reaction to other bacterial species.The M-RAP assay obtained results for<10 CFU/mL pathogens in the blood within 4 h,with higher sensitivity than qPCR.M-RAP and qPCR for SA,PA,and AB yielded Kappa values of 0.839,0.815,and 0.856,respectively(P<0.05). Conclusion An M-RAP assay for SA,PA,and AB in blood samples utilizing M1 bead enrichment has been developed and can be potentially used for the early detection of bacteremia.

Endo-beta-N-acetylglucosaminidase (ENGase) is widely distributed in various organisms. The first reported ENGase activity was detected in Diplococcus pneumoniae in 1971. The protein (Endo D) was purified and its peptide sequence was determined in 1974. Three ENGases (Endo F1-F3) were discovered in Flavobacterium meningosepticum from 1982 to 1993. After that, the activity was detected from different species of bacteria, yeast, fungal, plant, mice, human, etc. Multiple ENGases were detected in some species, such as Arabidopsis thaliana and Trichoderma atroviride. The first preliminary crystallographic analysis of ENGase was conducted in 1994. But to date, only a few ENGases structures have been obtained, and the structure of human ENGase is still missing. The currently identified ENGases were distributed in the GH18 or GH85 families in Carbohydrate-Active enZyme (CAZy) database. GH18 ENGase only has hydrolytic activity, but GH85 ENGase has both hydrolytic and transglycosylation activity. Although ENGases of the two families have similar (β/α)8-TIM barrel structures, the active sites are slightly different. ENGase is an effective tool for glycan detection andglycan editing. Biochemically, ENGase can specifically hydrolyze β‑1,4 glycosidic bond between the twoN-acetylglucosamines (GlcNAc) on core pentasaccharide presented on glycopeptides and/or glycoproteins. Different ENGases may have different substrate specificity. The hydrolysis products are oligosaccharide chains and a GlcNAc or glycopeptides or glycoproteins with a GlcNAc. Conditionally, it can use the two products to produce a new glycopeptides or glycoprotein. Although ENGase is a common presentation in cell, its biological function remains unclear. Accumulated evidences demonstrated that ENGase is a none essential gene for living and a key regulator for differentiation. No ENGase gene was detected in the genomes of Saccharomyces cerevisiae and three other yeast species. Its expression was extremely low in lung. As glycoproteins are not produced by prokaryotic cells, a role for nutrition and/or microbial-host interaction was predicted for bacterium produced enzymes. In the embryonic lethality phenotype of the Ngly1-deficient mice can be partially rescued by Engase knockout, suggesting down regulation of Engase might be a solution for stress induced adaptation. Potential impacts of ENGase regulation on health and disease were presented. Rabeprazole, a drug used for stomach pain as a proton inhibitor, was identified as an inhibitor for ENGase. ENGases have been applied in vitro to produce antibodies with a designated glycan. The two step reactions were achieved by a pair of ENGase dominated for hydrolysis of substrate glycoprotein and synthesis of new glycoprotein with a free glycan of designed structure, respectively. In addition, ENGase was also been used in cell surface glycan editing. New application scenarios and new detection methods for glycobiological engineering are quickly opened up by the two functions of ENGase, especially in antibody remodeling and antibody drug conjugates. The discovery, distribution, structure property, enzymatic characteristics and recent researches in topical model organisms of ENGase were reviewed in this paper. Possible biological functions and mechanisms of ENGase, including differentiation, digestion of glycoproteins for nutrition and stress responding were hypothesised. In addition, the role of ENGase in glycan editing and synthetic biology was discussed. We hope this paper may provide insights for ENGase research and lay a solid foundation for applied and translational glycomics.

Objective To investigate the patterns of traditional Chinese medicine(TCM)syndrome differentiation and treatment for dengue fever by using R language data visualization technology,so as to provide reference for TCM syndrome differentiation and treatment of dengue fever.Methods The related literature of dengue fever treated by Chinese medicine was retrieved from CNKI,Wanfang Data,and VIP.R-Studio software was used to conduct descriptive statistical analysis of the TCM syndromes,treatment methods,prescriptions and Chinese medicine in the literature of dengue fever treated by oral use of Chinese medicine.Based on Apriori algorithm,association rule mining and cluster analysis were carried out to explore the TCM syndrome and treatment patters of dengue fever.Results A total of 176 prescriptions for effective cases were extracted,and the included literature involved 29 syndromes,73 TCM treatment methods,56 classical prescriptions and 35 self-formulated prescriptions,and 179 Chinese medicinals.The syndrome of comorbidity of defense phase and qi phase and the syndrome of blazing of both qi phase and nutrient phase were the high-frequency syndromes of dengue fever treated by oral use of Chinese medicine.The high-frequency treatment methods covered heat-clearing therapy,toxin-removing therapy,blood-cooling therapy and dampness-resolving therapy.Qingwen Baidu Decoction was the most frequently-used prescription.Glycyrrhizae Radix et Rhizoma,Forsythiae Fructus,Scutellariae Radix,Gypsum Fibrosum,and Lonicerae Japonicae Flos were the frequently-used Chinese medinals.There were three drug combinations containing Paeoniae Radix Rubra,Moutan Cortex,and Rehmanniae Radix,and their correlation of association rules was the highest.Bubali Cornu,Moutan Cortex,Paeoniae Radix Rubra,Rehmanniae Radix,Lonicerae Japonicae Flos,Forsythiae Fructus,Gypsum Fibrosum,Scutellariae Radix,Anemarrhenae Rhizoma,and Glycyrrhizae Radix et Rhizoma were the core Chinese medicinals for the treatment of dengue fever.Conclusion The TCM syndromes of dengue fever are predominated by the syndrome of comorbidity of defense phase and qi phase and the syndrome of blazing of both qi phase and nutrient phase.The treatment of dengue fever with TCM is based on the principle of clearing heat toxin from the qi phase,cooling the nutrient-blood excess heat,resolving pathogenic dampness,and nourishing qi and yin.The treatment focuses on clearing qi phase and blood phase,and the application of removing stasis in febrile diseases should be stressed,thus to block the progression of the disease in time.

Peroxisome proliferator-activated receptor gamma(PPAR-γ)is a member of the ligand-activated nuclear tran-scription factor superfamily.Activated PPAR-γ is involved in the regulation of many central nervous system(CNS)events,and is involved in cholesterol metabolism by inducing or inhibi-ting a series of gene pathways,thereby inhibiting the deposition of β-amyloid protein(Aβ).It plays an important neuroprotec-tive role in Alzheimer's disease(AD),improves memory and cognition in AD,and is a potential target for AD.Drug develop-ment aimed at restoring cholesterol homeostasis may be a poten-tial strategy to counteract AD.By analyzing the distribution and structure of PPAR-γ,focusing on the biological correlation be-tween PPAR-γ-mediated cholesterol metabolism and AD,this paper describes the mechanism regulation of PPAR-γ on key proteins,genes and their corresponding molecules,providing a new reference for the treatment of AD.

Chimeric antigen receptor(CAR)T cell therapy,one of the most promising tumor treatments,combines the targeted recognition of antigen and antibody with the killing effect of T cells.CAR-T has shown a strong therapeutic effect in lymphoid tumors and been applied in clinical practice.However,in the treatment of acute myeloid leukemia(AML),no effective and specific target like CD 19 in lymphoid tumors has been found.Therefore,the key research direction is to try multiple probabilities and use optimization strategies to enhance efficacy and reduce toxicity.This review introduces the latest research progress of AML targets in CAR-T therapy in recent years,analyzes the related problems that need to be solved at present,and summarizes the optimization construction strategies mentioned in the research.Hope it can provide reference for related research and clinical application of related product.

Objective To summarize the management challenges faced by multi-campus hospitals both domestically and internationally,to delineate the experiences in medical administration across multiple campuses,and to propose the"Zhong-zhong"multi-campus medical management pattern based on the practices of Sun Yat-sen University Cancer Center,aiming to pro-vide reference and evidence for domestic peers in the field.Methods This study uses the methods of literature research and case study analysis,and summarizes and condenses the experience of medical management in multi-campus and provides policy sug-gestions through key person interviews and expert consultation.Results SYSUCC carries out multi-campus medical management through six major measures,namely,the organizational system combining vertical and territorial management,the layout of disci-plinary clusters and specialties,multi-channel flow attraction measures,the dynamic adjustment of medical resources,the homog-enization of medical quality,and the high-effective information system.It achieves the high-quality development goals with differ-ential development of various specialties,improved resource utilization efficiency,homogeneous and incremental medical serv-ices,smooth operation of information system,and steady and orderly development of new techniques.Conclusion Domestic public specialized hospitals can achieve homogeneous management and high-quality development across multiple campuses through streamlined organizational structures to enhance management efficiency,optimizing the layout of specialized departments to pro-mote coordinated development,strict control of standards to ensure medical quality,using dynamic adjustments to guide orderly competition among specialized departments,and leveraging information systems to support homogeneous development across multi-ple campuses.

Following the reform of the professional title system for"Breaking Four One-sided Evaluation Criteria"—focu-sing on more than just papers,titles,academic qualifications,and awards-establishing a scientific,systematic,and comprehen-sive medical performance evaluation index system has become essential for developing medical talent teams and conducting profes-sional title assessments fundamentally.This study establishes a medical performance evaluation index system tailored for clinicians in various departments of a cancer hospital who are competing for senior professional titles.This system comprises six primary in-dicators and 18 secondary indicators,with results presented in a ranked format of medical performance.Additionally,we have al-so analyzed the corr-elation between clinicians'medical performance rankings and their professional title evaluation outcomes through practical application.The results indicate that clinicians with higher performance rankings have significantly higher suc-cess rates in evaluations(P＜0.05).This index system underscores clinical practice,enhances classification-based evaluations,and supports advanced information management and precision in hospital administration,thereby providing a solid foundation for strengthening the hospital's core competitiveness.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Objective: To understand the current status of diagnosis and treatment of chronic lymphocytic leukemia (CLL) /small lymphocytic lymphoma (SLL) among hematologists, oncologists, and lymphoma physicians from hospitals of different levels in China. Methods: This multicenter questionnaire survey was conducted from March 2021 to July 2021 and included 1,000 eligible physicians. A combination of face-to-face interviews and online questionnaire surveys was used. A standardized questionnaire regarding the composition of patients treated for CLL/SLL, disease diagnosis and prognosis evaluation, concomitant diseases, organ function evaluation, treatment selection, and Bruton tyrosine kinase (BTK) inhibitor was used. Results: ①The interviewed physicians stated that the proportion of male patients treated for CLL/SLL is higher than that of females, and the age is mainly concentrated in 61-70 years old. ②Most of the interviewed physicians conducted tests, such as bone marrow biopsies and immunohistochemistry, for patient diagnosis, in addition to the blood test. ③Only 13.7% of the interviewed physicians fully grasped the initial treatment indications recommended by the existing guidelines. ④In terms of cognition of high-risk prognostic factors, physicians' knowledge of unmutated immunoglobulin heavy-chain variable and 11q- is far inferior to that of TP53 mutation and complex karyotype, which are two high-risk prognostic factors, and only 17.1% of the interviewed physicians fully mastered CLL International Prognostic Index scoring system. ⑤Among the first-line treatment strategy, BTK inhibitors are used for different types of patients, and physicians have formed a certain understanding that BTK inhibitors should be preferentially used in patients with high-risk factors and elderly patients, but the actual use of BTK inhibitors in different types of patients is not high (31.6%-46.0%). ⑥BTK inhibitors at a reduced dose in actual clinical treatment were used by 69.0% of the physicians, and 66.8% of the physicians had interrupted the BTK inhibitor for >12 days in actual clinical treatment. The use of BTK inhibitors is reduced or interrupted mainly because of adverse reactions, such as atrial fibrillation, severe bone marrow suppression, hemorrhage, and pulmonary infection, as well as patients' payment capacity and effective disease progression control. ⑦Some differences were found in the perceptions and behaviors of hematologists and oncologists regarding the prognostic assessment of CLL/SLL, the choice of treatment options, the clinical use of BTK inhibitors, etc. Conclusion: At present, a gap remains between the diagnosis and treatment of CLL/SLL among Chinese physicians compared with the recommendations in the guidelines regarding the diagnostic criteria, treatment indications, prognosis assessment, accompanying disease assessment, treatment strategy selection, and rational BTK inhibitor use, especially the proportion of dose reduction or BTK inhibitor discontinuation due to high adverse events.
Female ; Humans ; Male ; Aged ; Middle Aged ; Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy* ; Prognosis ; Lymphoma, B-Cell ; Immunohistochemistry ; Immunoglobulin Heavy Chains/therapeutic use*

Humans ; Philadelphia Chromosome ; Neoplasms ; Myelodysplastic Syndromes/genetics* ; Disease Progression