Diffuse large B-cell lymphoma （DLBCL） is a highly heterogeneous disease. Although standard first-line regimens can cure ＞50% of patients， approximately one-third of them develop relapsed/refractory DLBCL （r/r DLBCL）. Consequently， immunotherapy targeting molecular abnormalities has become pivotal for managing r/r DLBCL. The results of this review show that with advances in understanding DLBCL pathogenesis and the tumor immune microenvironment， antibody-based therapies have evolved rapidly， progressing from monoclonal antibodies （e.g.， rituximab， tafasitamab） to bispecific antibodies（e.g.， odronextamab，glofitamab， epcoritamab） and antibody-drug conjugate （e.g.， polatuzumab vedotin， loncastuximab tesirine）. These engineered agents enhance immune cytotoxicity and tumor-specific targeting， providing novel therapeutic options for r/r DLBCL patients.

OBJECTIVE To construct an evaluation index system for the core competencies of ethics committee members of drug clinical trial institution， providing a basis for optimizing the training system for committee members， improving the quality of ethical review， and fully safeguarding the safety and rights of subjects. METHODS Using methods such as literature research and expert consultation， a preliminary core competency evaluation index system was constructed. The Delphi method was employed to revise and validate it， ultimately forming an evaluation index system for the core competencies of ethics committee members. Based on this system， a questionnaire survey was conducted among 90 ethics committee members from 29 drug clinical trial institutions nationwide， comparing their importance rating and self-assessment scores of the core competency indexes. RESULTS The evaluation system constructed included 4 primary indicators （ethics and professional knowledge， ethics review ability， communication and expression ability， moral integrity and work style） and 39 secondary indicators （familiarity with the content of clinical trial-related laws and regulations， ability to complete project ethics review and identify ethical defects in research protocols within a short period of time， ability to judge the scientific value of clinical research， etc.）. The results of questionnaire survey showed that the interviewed ethics committee members had significant capability gaps in dimensions such as regulatory knowledge， ethical norms， review efficiency， risk judgment， and problem analysis. The differences between the importance rating scores of corresponding secondary indicators and the self-assessment scores were all no less than 0.38. CONCLUSIONS This study has developed a quantifiable and stratified core competency assessment tool for ethics committee members. It can provide a scientific framework for committee member training， qualification certification， and standardized management of ethics committees.

Cultivating and inspiring students’ interests in performing experiments and improving students’ diagnostic skills and scientific research capability for infectious diseases like malaria are critical to comprehensive experimental teaching of morphology. Consequently, Soochow University initiated a problem-based hands-on inquiry-based comprehensive experiment program of blood-borne protozoa infections and diagnosis, which took students in the “5 + 3” integrated program of clinical medicine as the teaching targets, and it consisted of three parts: pre-class, in-class, and post-class. Before the experimental curriculum, students learned the theoretical knowledge and the process of modeling Plasmodium berghei and Babesia microti infections in mice through online course and virtual simulation experiments, and during the experimental curriculum, students performed exploratory experiments on differential diagnosis of P. berghei and B. microti infections with pathogenic and serological tests. After the experimental curriculum, students performed molecular biological testing and extracurricular scientific research project training through open experiments. A questionnaire survey was conducted among 99 students in the “5 + 3” integrated training program of clinical medicine in batch 2021, and a total of 93 valid questionnaires were retrieved, with a questionnaire recovery rate of 93.94%. Questionnaire survey showed that 70.97% (66/93), 70.97% (66/93), 77.42% (72/93), 70.97% (66/93), and 83.87% (78/ 93) of the students strongly agreed with the five statements in the questionnaire respectively, namely “high interest in learning during the experiment”, “reasonable experimental content settings and good classroom atmosphere”;, “teachers were good at guiding students’ practice and thinking”, “students were the main body of the classroom during the experiment” and “Comprehensive experiments had better teaching effects than traditional verification experiments”, indicating that the problem-based hands-on inquiry-based comprehensive experiment teaching has enhanced students’ learning interest, spirit of inquiry, innovative thinking, and teamwork ability.

Objective:To search, evaluate and integrate the best evidence for early recognition of patients with post-stroke cognitive impairment (PSCI).Methods:With"stroke""cognitive impairment"and"identif"as search terms, according to the 6S evidence resource pyramid model, a top-down systematic retrieval was conducted for literature on early identification of PSCI in UpToDate, BMJ Best Practice, the Joanna Briggs Institute (JBI), National institute for Health and Care Excellence (NICE), Medlive and other guideline websites, American Stroke Association (ASA), American Heart Association (AHA), European Stroke Organization (ESO), Heart and Stroke Foundation of Canada (HSFC), Australian Stroke Foundation (ASF), Royal College of Physicians (RCP) and other association networks, PubMed, Embase, Cochrane Library, CINAHL, Web of Science, CNKI, Wanfang Knowledge Data Service Platform, VIP database, Chinese Biomedical Database, Chinese Medical Journal Full Text Database and other databases. The search time was from the establishment of the databases to February 8, 2024. Two researchers trained in normative evidence-based methodology conducted literature screening, quality evaluation, and independent evidence extraction in accordance with the principle of evidence integration.Results:A total of 21 articles were included, including 1 clinical decision support, 8 guidelines, 3 expert consensus, and 9 systematic reviews. The best evidence summarized included 24 recommendations from 6 aspects, including screening objects, screening timing, screening practitioners, pre-screening assessment, screening tools and post-screening assessment, of which 70.8% was class 2b and above evidence, and 41.7% of the evidence was recommended with strength A.Conclusions:The literature on early identification of PSCI patients is of high quality and high level of evidence. The key to early identification of PSCI patients for medical professionals is to consider individual differences, select appropriate screening tools and conduct cognitive screening as soon as possible.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-positive bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-positive bacteria from blood cultures in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:A total of 3 163 strains of Gram-positive pathogens were collected from 51 member units，and the top five bacteria were Staphylococcus aureus（ n=1 147，36.3%），coagulase-negative Staphylococci（ n=928，29.3%）， Enterococcus faecalis（ n=369，11.7%）， Enterococcus faecium（ n=296，9.4%）and alpha-hemolyticus Streptococci（ n=192，6.1%）. The detection rates of methicillin-resistant Staphylococcus aureus（MRSA）and methicillin-resistant coagulase-negative Staphylococci（MRCNS）were 26.4%（303/1 147）and 66.7%（619/928），respectively. No glycopeptide and daptomycin-resistant Staphylococci were detected. The sensitivity rates of Staphylococcus aureus to cefpirome，rifampin，compound sulfamethoxazole，linezolid，minocycline and tigecycline were all >95.0%. Enterococcus faecium was more prevalent than Enterococcus faecalis. The resistance rates of Enterococcus faecium to vancomycin and teicoplanin were both 0.5%（2/369），and no vancomycin-resistant Enterococcus faecium was detected. The detection rate of MRSA in southern China was significantly lower than that in other regions（ χ2=14.578， P=0.002），while the detection rate of MRCNS in northern China was significantly higher than that in other regions（ χ2=15.195， P=0.002）. The detection rates of MRSA and MRCNS in provincial hospitals were higher than those in municipal hospitals（ χ2=13.519 and 12.136， P<0.001）. The detection rates of MRSA and MRCNS in economically more advanced regions（per capita GDP≥92 059 Yuan in 2022）were higher than those in economically less advanced regions（per capita GDP<92 059 Yuan）（ χ2=9.969 and 7.606， P=0.002和0.006）. Conclusions:Among the Gram-positive pathogens causing bloodstream infections in China， Staphylococci is the most common while the MRSA incidence decreases continuously with time；the detection rate of Enterococcus faecium exceeds that of Enterococcus faecalis. The overall prevalence of vancomycin-resistant Enterococci is still at a low level. The composition ratio of Gram-positive pathogens and resistant profiles varies slightly across regions of China，with the prevalence of MRSA and MRCNS being more pronounced in provincial hospitals and areas with a per capita GDP≥92 059 yuan.

Objective The objective of this study was to establish a mouse model of allergic rhinoconjunctivitis and investigate the role of the NLRP3 signaling pathway in allergic rhinoconjunctivitis.Methods Thirty-three female C57 mice(SPF)were randomLy divided into 3 groups:the control group,the experimental group,and the NLRP3-/-group.On days 0,4,7,14,and 21,the experimental group and NLRP3-/-group received a 0.2 mL intraperitoneal injection of medicine containing OVA(100 μg)and adjuvant Al(OH)3(4 mg),respectively.After an interval of 3 days,each eye and nose were dosed with 10 μL of 5%OVA for five consecutive days a week to induce allergic symptoms.During sensitization and excitation stages,the control group was replaced with an equiva-lent amount of PBS.Ocular and nasal symptoms were observed and scored.The levels of OVA-specific IgE,IL-4,IL-17,and IL-18 in serum were measured using ELISA,while changes in palpebral conjunctiva and nasal mucosa were assessed by hematoxylin-eosin staining.The expression of NLRP3 mRNA in conjunctival tissue and nasal mucosa was determined using real-time PCR analysis.Statistical analysis was performed using SPSS17.0 software with P<0.05 considered as statistically significant difference.Results The experimental group and NLRP3-/-group exhibited induced nasal and ocular allergic symptoms.In the experimental group,the duration of nasal allergy symptoms was(10.500±1.080)days,while the duration of eye allergy symptoms was(20.300±2.058)days.In the NLRP3-/-group,the duration of nasal allergy symptoms was(13.400±1.955)days,and for eye allergy symp-toms it was(20.900±2.132)days.The duration of nasal allergies in the NLRP3-/-group significantly exceeded that in the experimental group(P<0.05),whereas there were no significant differences observed in eye allergy durations between these two groups(P>0.05).Levels of OVA-specific IgE,IL-4,and IL-17 were significantly higher in both the experimental and NLRP3-/-groups compared to those in the control group(P<0.05).Additionally,serum IL-18 content increased significantly in the experimental group when compared with both control and NLRP3-/-groups(P<0.05).Conjunctival tissue lesions as well as nasal mucosa damage were evident in both experimental and NLRP3-/-groups.mRNA expression levels of NLRP3 within conjunctival tissue and nasal mucosa from the experimental group showed a significant increase when compared to those from both control and NLRP3-/-groups(P<0.05).Conclusion Allergic rhinoconjunctivitis pathogenesis is influenced by various factors;however,the involvement of NLPR3 signaling pathway promotes its development.

Objective:This study aims to compare the antiviral treatment similarities and differences in the population covered by the 2024 version of the World Health Organization's (WHO) hepatitis B prevention and treatment guidelines and the current Chinese hepatitis B prevention and treatment guidelines, so as to explore their impact on the indications for antiviral therapy in Chinese patients with chronic hepatitis B (CHB).Methods:The information of patients with chronic hepatitis B virus infection who did not receive antiviral treatment was collected through the registration database of the China Clinical Research Platform for Hepatitis B Elimination. Descriptive statistics were conducted on the demographic, blood, biochemical, and virological levels of patients according to the treatment recommendations of the two versions of the guidelines. The Mann-Whitney U test and χ2 test were used to compare the differences and proportional distribution of the treatment populations covered by the two guidelines. The χ2 test was used to analyze the coverage rate of different antiviral treatment indications.Results:A total of 21,134 CHB patients without antiviral treatment were enrolled. 69.4% of patients met the 2024 versions of the WHO guidelines' recommendations. 85.0% of patients met the current Chinese hepatitis B prevention and treatment guidelines. The WHO guidelines for antiviral therapy indications were met in younger patients with higher levels of ALT, AST, and APRI scores, as well as greater proportion of patients with higher viral loads (P<0.001). The WHO guidelines recommended a cut-off value of APRI>0.5, which raised the proportion of patients on antiviral therapy from 6.6% to 30.9%. 45.7% of patients met the antiviral indications for HBV DNA >2000 IU/ml with abnormal transaminase (ALT>30 U/L for males and ALT>19 U/L for females). The reduced APRI diagnostic cut-off value and ALT treatment threshold had further increased the treatment coverage rate by 91.6% in patients with chronic HBV infection in line with the 2024 versions of WHO guidelines.Conclusion:The reduction of the APRI diagnostic cut-off value and the ALT treatment threshold, based on the current hepatitis B guidelines of China, will further improve the treatment coverage of CHB patients.

Objective To investigate the mechanism of Dayuan Decoction in the treatment of Helicobacter pylori(Hp)-positive perioral acne based on network pharmacology and animal experiments.Methods The effective active components and their corresponding targets of Dayuan Decoction were obtained from TCMSP.Targets related to Hp and perioral acne were retrieved from GeneCards,OMIM and TTD databases,and the intersection of drug targets and disease targets was considered as the target of Dayuan Decoction in the treatment of Hp-positive perioral acne.A protein-protein interaction network for the drug-disease intersection targets was constructed by using Cytoscape 3.7.2 and the STRING database,and the core targets were screened.GO and KEGG pathway enrichment analyses of the core target genes were performed using the DAVID database and the bioinformatics platform.By establishing an Hp-positive perioral acne rat model through gastric gavage with Hp bacterial liquid and intradermal injection of Propionibacterium acnes suspension,the intervention effect of Dayuan Decoction was observed and the core targets and related pathways were preliminary validated.Morphology in the perioral skin and gastric tissue were observed through HE staining.The expressions of TLR4,MyD88,NF-κB in perioral skin tissue,the contents of TNF-α and IL-6 in serum were measured using ELISA.Results A total of 145 active components were screened from Dayuan Decoction,corresponding to 253 targets,with 57 targets overlapping between drugs and diseases.The core targets for the treatment of Hp-positive perioral acne with Dayuan Decoction were identified as IL6,TNF,IL1B,AKT1,TP53,etc.KEGG pathway enrichment analysis revealed 153 signaling pathways,primarily involved in pathways in cancer,lipids and atherosclerosis,AGE-RAGE signaling pathway in diabetic complications,TLR signaling pathway and TNF signaling pathway.Dayuan Decoction attenuated the expression of TLR4,MyD88 and NF-κB in the perioral skin of the Hp-positive perioral acne rat model,as well as reduced the contents of TNF-α and IL-6 in serum(P<0.01).Conclusion Dayuan Decoction may exert therapeutic effects on Hp-positive perioral acne by modulating the TLR4/NF-κB signaling pathway,reducing the levels of inflammatory factors TNF-α and IL-6,and alleviating the inflammatory damage in the perioral skin.

Objective To explore the mechanism of Dayuan Decoction in treating Helicobacter pylori(Hp)positive oral ulcer based on network pharmacology and experimental validation.Methods Active components of Dayuan Decoction and its targets were collected using the TCMSP database;relevant targets for Hp positive oral ulcer were screened through the GeneCards database;the Venny 2.1.0 online platform was used to screen the intersection targets of drug active components and diseases;a protein-protein interaction network was built using STRING 11.0 database and core key targets were screened using Cytoscape 3.7.1 software;GO and KEGG enrichment analysis was conducted on intersection targets using the DAVID database.Oral administration of standard Hp bacterial solution and burning of oral mucosa with glacial acetic acid were used to construct an animal model of Hp positive oral ulcer,and the model rats were intervented with Dayuan Decoction by gavage.The morphology of oral and gastric mucosal tissues was observed,and the expression of core targets in oral and gastric mucosal tissues were detected.Results A total of 165 targets were obtained for the treatment of Hp positive oral ulcer with Dayuan Decoction.The main active components were quercetin,kaempferol,5,8,2'-trihydroxy-7-methoxyflavone,etc.,the core targets were AKT1,IL6,TP53,TNF,etc.GO and KEGG enrichment analysis suggested that Dayuan Decoction in the treatment of Hp positive oral ulcer was mainly related to the inflammatory pathway.Animal experiments showed that compared with the blank group,the structure of the oral and gastric tissues in the model group rats were significantly disrupted,with significant infiltration of inflammatory cells;the contents of IL-6 and TNF-α in the serum significantly increased(P<0.05),the contents of TLR4 and NLRP3 in oral and gastric mucosal tissues significantly increased(P<0.05),and the protein expression of TLR4 and NF-κB in oral mucosal tissues significantly increased(P<0.05).Compared with the model group,the histopathological manifestations of rats in all doseage of Dayuan Decoction groups significantly improved,the contents of IL-6 and TNF-α in the serum,and the contents of TLR4 and NLRP3 in the oral and gastric mucosal tissues significantly decreased,the protein expression of TLR4 and NF-κB in the oral mucosal tissue significantly decreased(P<0.05).Conclusion Dayuan Decoction is possible to regulate the inflammatory development of Hp positive oral ulcer and improve their symptoms by downregulating TLR4 and NF-κB levels.

Mitochondria are the main site of energy metabolism in cardiomyocytes， and at the same time mediate apoptosis and immune response， so mitochondrial dysfunction is closely related to the development of heart failure. Combined with the pathogenesis of mitochondrial dysfunction and heart failure， it is proposed that the mitochondrial function is similar to "sweat pore - collaterals - zang and fu organs"， according to which the treatment of heart failure is based on the theory of "sweat pore - collaterals - zang and fu organs". It is believed that the core mechanism of heart failure is qi deficiency， and qi deficiency leads to the weakness of the sweat pore opening and closing， or even the sweat pore closure， then resulting in qi deficiency and blood stasis， collaterals stagnation fail to flourish， and qi， blood， and body fluids can not infiltrate and nourish zang-fu organs， so that the heart fail to be nourished， and the disease will develop. The treatment should be based on the method of boosting qi and opening sweat pore， using acridity to unblock the collaterals， and invigorating blood and draining water， with medicinal of boosting qi， invigorating blood， and draining water as treatment.