To introduce and analyze guideline terminology related to clinical question formulation, evidence retrieval and appraisal, and recommendation development.

OBJECTIVE To provide a reference for standardizing the conduct of positron-emitting radiopharmaceuticals’ phase 0 clinical trials （hereinafter referred to as “phase 0 clinical trials”） and advancing the development of innovative drug by medical institutions. METHODS Initiated by the First Affiliated Hospital of Jinan University， a panel of experts consisting of pharmacy， clinical medicine and medical ethics from multiple institutions was established to investigate the current landscape， and discuss the necessary conditions， procedures， and other aspects for conducting phase 0 clinical trials in medical institutions by integrating relevant national policies， regulations and expert consensus. Finally， an agreement was reached to formulate this consensus. RESULTS & CONCLUSIONS Currently， most medical institutions have deficiencies in pharmaceutical care during the management of radiopharmaceuticals and the phase 0 clinical trials. In conjunction with the Expert Consensus on the Establishment of Nuclear Pharmacist Positions， this consensus explicitly defines the responsibilities of nuclear pharmacists in the phase 0 clinical trials on the basis of the Expert Consensus for the Application of Positron Emission Tomography Radioligands for Translational Study in the Phase 0 Clinical Trials （2020 edition）， providing a guidance for high-quality participation of nuclear pharmacists from medical institutions in China in phase 0 clinical research. Additionally， in consideration of some constraints imposed by current relevant regulations， this consensus also proposes strategic recommendations， such as encouraging medical institutions to form a consortium， leading to the establishment of dedicated bases or industrial parks， holding significant implications to strengthen institutional capacity for advancing radiopharmaceutical innovation through phase 0 clinical trials.

T7 RNA polymerase (T7 RNAP) is one of the simplest known RNA polymerases. Its unique structural features make it a critical model for studying the mechanisms of RNA synthesis. This review systematically examines the static crystal structure of T7 RNAP, beginning with an in-depth examination of its characteristic “thumb”, “palm”, and “finger” domains, which form the classic “right-hand-like” architecture. By detailing these structural elements, this review establishes a foundation for understanding the overall organization of T7 RNAP. This review systematically maps the functional roles of secondary structural elements and their subdomains in transcriptional catalysis, progressively elucidating the fundamental relationships between structure and function. Further, the intrinsic flexibility of T7 RNAP and its applications in research are also discussed. Additionally, the review presents the structural diagrams of the enzyme at different stages of the transcription process, and through these diagrams, it provides a detailed description of the complete transcription process of T7 RNAP. By integrating structural dynamics and kinetics analyses, the review constructs a comprehensive framework that bridges static structure to dynamic processes. Despite its advantages, T7 RNAP has a notable limitation: it generates double-stranded RNA (dsRNA) as a byproduct. The presence of dsRNA not only compromises the purity of mRNA products but also elicits nonspecific immune responses, which pose significant challenges for biotechnological and therapeutic applications. The review provides a detailed exploration of the mechanisms underlying dsRNA formation during T7 RNAP catalysis, reviews current strategies to mitigate this issue, and highlights recent progress in the field. A key focus is the semi-rational design of T7 RNAP mutants engineered to minimize dsRNA generation and enhance catalytic performance. Beyond its role in transcription, T7 RNAP exhibits rapid development and extensive application in fields, including gene editing, biosensing, and mRNA vaccines. This review systematically examines the structure-function relationships of T7 RNAP, elucidates the mechanisms of dsRNA formation, and discusses engineering strategies to optimize its performance. It further explores the engineering optimization and functional expansion of T7 RNAP. Furthermore, this review also addresses the pressing issues that currently need resolution, discusses the major challenges in the practical application of T7 RNAP, and provides an outlook on potential future research directions. In summary, this review provides a comprehensive analysis of T7 RNAP, ranging from its structural architecture to cutting-edge applications. We systematically examine: (1) the characteristic right-hand domains (thumb, palm, fingers) that define its minimalistic structure; (2) the structure-function relationships underlying transcriptional catalysis; and (3) the dynamic transitions during the complete transcription cycle. While highlighting T7 RNAP’s versatility in gene editing, biosensing, and mRNA vaccine production, we critically address its major limitation—dsRNA byproduct formation—and evaluate engineering solutions including semi-rationally designed mutants. By synthesizing current knowledge and identifying key challenges, this work aims to provide novel insights for the development and application of T7 RNAP and to foster further thought and progress in related fields.

Objective:To explore the definition and connotation of the thriving in the elderly, so as to provide reference for clinical practice.Methods:This study systematically searched databases such as China National Knowledge Infrastructure, WanFangdata, CINAHL, PsycINFO, PubMed, and Web of Science using keywords such as "aged" and "thriving". The search period was from database establishment to June 10, 2023. Walker's eight-step analysis method was used to conduct concept analysis on the thriving in the elderly.Results:A total of 14 articles were included. The defining attributes of the thriving in the elderly included good self-perception, utilizing existing resources to adjust self-expectation, and achieving self-growth and development. The antecedents were a positive attitude, high-quality caregivers and care services, a good physical and humanistic environment. The consequence was that elderly people had great adaptability, subjective experience, and health level.Conclusions:The thriving in the elderly is a subjective well-being achieved by the interaction among an individual, the humanistic and physical environment, which is affected by various factors such as individuals and environment. It is a new concept that has emerged in the international field of geriatric nursing in recent years, focusing on the positive aspects of aging and providing new directions for research in geriatric nursing.

Objective:To explore the research status of artificial intelligence in nursing in China, so as to provide reference for conducting research domestically.Methods:The relevant literature collected from January 1, 2003 to May 1, 2023 was searched on China National Knowledge Infrastructure, WanFang Data, and VIP. CiteSpace and VOS viewer were used to visually analyze the research status, hotspots, and frontiers of artificial intelligence in nursing in China from the aspects of annual publication volume, region, institution, author, high-frequency keywords, and emerging words.Results:A total of 494 articles were included. In terms of publication volume, domestic research showed an overall upward trend, with publishing institutions mostly concentrated in economically developed and medically advanced regions. The authors of the articles often collaborated with research groups, with a co-authorship rate of 81.17% (401/494), but there was relatively little collaboration between groups. Research hotspots were focused on the application of artificial intelligence in geriatric nursing, rehabilitation nursing, Operating Rooms, and drug formulation, with a majority of research related to robots.Conclusions:The research enthusiasm in related fields in China is currently on the rise. Research on artificial intelligence in nursing management, nursing education, and psychological nursing can be strengthened, and the application of artificial intelligence can be enriched. At the same time, research institutions and personnel should strengthen mutual cooperation, and relevant national departments should improve laws and regulations to promote the vigorous development of this research field.

Objective To establish an ideal modeling method for diarrhea predominant irritable bowel syndrome(IBS-D)with anxiely and depression in rats,and to provide a basis for the clinical study of IBS-D.Methods 60 rats were used in this study.(1)At first,20 rats were randomly divided into blank,3%acetic acid enema,4%acetic acid enema,and 5%acetic acid enema groups.After the modeling and observation period,the diarrhea status and the degree of colon injury caused by different modeling concentrations were observed by diarrhea related index and colon histopathology.(2)After the optimal modeling concentration was assessed,40 rats were randomly divided into control(a),acetic acid enema(b),acetic acid+binding(c),and acetic acid+binding+tail clip(d)groups and correspondingly treated for 8 days.After the treatments,the general condition,diarrhea-related index,open field test(OFT)score,and colonic histopathology of rats were evaluated.Results(1)Compared with the blank group,the fecal trait score of 4%acetic acid enema group was increased on days 1 to 3 after intervention(P＜0.001),and gradually decreased on days 4 to 7 after intervention.After 1 week,there was no significant difference between the fecal trait score and that of the blank group(P＞0.05).Body weight was lower(P＜0.01),fecal water content was higher(P＜0.001).Compared with blank group,body weight of the 5%acetic acid enema group was decreased(P＜0.001),the fecal trait score and diarrhea index were increased(P＜0.01).No significant difference was found between 3%acetic acid enema and blank groups.The pathological colon tissue showed that,compared with the blank group,the mucosal structure of the 4%acetic acid enema group was complete with a small amount of inflammatory cell infiltration,and the pathological tissue score showed no significant difference(P＞0.05),whereas the 5%acetic acid enema had a medium to large amount of inflammatory cell infiltration,and the pathological tissue score was increased(P＜0.01).(2)Compared with group a,group b had lower body weight(P＜0.001),and higher fecal trait score,fecal water content and diarrhea index(P＜0.01).Compared with a and b groups,the body weight of c and d groups was lower(P＜0.001),the fecal traits score,fecal water content,and diarrhea index were increased(P＜0.01),and the colon running time was decreased(P＜0.01).Compared with group c,Fecal water content in group D was higher(P＜0.001).In the OFT score,compared with a and b groups,the OFT distance,standing times,and upright times in c and d groups were lower(P＜0.05).Compared with c,the OFT distance,standing times,and upright times in d group were lower(P＜0.05).The pathological tissue of colon showed that the mucosal structure of the four groups was complete,and there were different degrees of inflammatory cell infiltration.The pathological tissue scores of groups c and d were higher than those of groups a and b(P＜0.05).Conclusions The 4%acetic acid concentration is appropriate for IBS-D modeling.After superposition and binding,the IBS-D diarrhea and internal hypersensitivity characteristic state can be better simulated.After superposition of a tail clip,the IBS-D model of liver stagnation and spleen deficiency can be established successfully.

Objective:To explore the changes of large-scale functional brain networks and network topological properties in patients with major depressive disorder (MDD) whose diagnosis had not changed after 5 years of follow-up.Methods:Totally 521 cases of hospitalized MDD patients were recruited from January 2012 to August 2018, and another 204 cases of gender- and age-matched healthy controls were recruited. All participants completed resting-state functional magnetic resonance scanning and clinical assessment. Their diagnosis were reviewed 5 years after discharge.A total of 258 participants whose diagnosis had not changed were counted into the MDD group for analysis. The differences in large-scale brain network connectivity between the two groups were analyzed by constructing a whole-brain functional network, on the basis of which the altered topological properties of the sensorimotor network (SMN), visual network (VN) and default mode network (DMN) were further analyzed between the two groups.The SPSS 24.0 software was used for data analysis and the independent sample t-test and χ2 test were used for the data comparison of the two groups. Results:Compared with the healthy controls, the MDD group had significantly decreased network clustering, mainly involving the SMN, VN and DMN (edge P<0.001, cluster P<0.05). The MDD group had decreased functional connectivity(FC) strength within the SMN, VN and DMN networks, the FC strength between the SMN and VN networks, between the frontoparietal network (FPN) and the DAN networks were decreased(all P<0.05, FDR corrected). Graph-theory analysis showed that local efficiency, clustering coefficient, and normalized shortest path length were decreased in the MDD group, node efficiency was decreased in the left ventral medial prefrontal cortex and the middle of the bilateral insula, node centrality was decreased in the middle of the bilateral insula and occipital lobe, and the betweenness was decreased in the middle of the right insula (all P<0.05, FDR corrected). Conclusion:MDD exhibits abnormal network functional connectivity, disruption of network topological properties, diminished optimal information processing, and to some extent reflects the severity of depressive symptoms. The decreased ability of information transfer flow in the insula plays an important role for the functional abnormality of the network.

Objective:To investigate the value and clinical significance of fasting plasma glucose (FPG) in early pregnancy (8-12 gestational weeks) as a predictor of gestational diabetes mellitus (GDM) among women with different pre-pregnancy body mass index (pre-BMI) categories.Methods:A retrospective study was conducted including 9 710 singleton pregnant women (FPG levels in early pregnancy ≤5.6 mmol/L) who underwent prenatal screening and delivery in Yuyao People's Hospital from January 2020 to December 2022. Participants were stratified based on their pre-BMI as follows: <18.5 ( n=1 406), ≥18.5 to <25.0 ( n=7 162), ≥25.0 to <30.0 ( n=978), and ≥30.0 kg/m 2 ( n=164). Within each pre-BMI category, women were further divided into four groups based on FPG levels in early pregnancy (<4.5, ≥4.5 to <4.8, ≥4.8 to <5.1, and ≥5.1 mmol/L). Univariate and multivariate logistic regression analysis were used to identify risk factors for GDM, and receiver operating characteristic (ROC) curve was applied to evaluate the efficacy of FPG in early pregnancy based on different pre-BMI in predicting GDM. Results:The overall incidence of GDM in the singleton pregnancy women with FPG levels in early pregnancy ≤5.6 mmol/L was 12.3% (1 197/9 710). For a pre-BMI of <18.5 kg/m 2, the ORs with 95% CIs for GDM within the different FPG categories (<4.5, ≥4.5 to <4.8, ≥4.8 to <5.1, and ≥5.1 mmol/L) were 0.041 (95% CI: 0.015-0.409), 1.834 (95% CI: 1.089-3.088), 6.779 (95% CI: 4.041-11.371), and 13.723 (95% CI: 5.560-33.871), respectively. For pre-BMI of ≥18.5 to <25.0 kg/m 2, the respective the ORs with 95% CIs were 0.048 (95% CI: 0.012-0.203), 2.573 (95% CI: 2.091-3.168), 9.023 (95% CI: 7.240-11.245), and 9.158 (95% CI: 6.484-12.937). For pre-BMI of ≥25.0 to <30.0 kg/m 2, the ORs with 95% CIs were 0.108 (95% CI: 0.053-0.446), 1.698 (95% CI: 1.064-2.654), 7.537 (95% CI: 5.285-13.080), and 9.994 (95% CI: 5.613-18.218). For pre-BMI of ≥30.0 kg/m 2, the ORs with 95% CIs were 0.098 (95% CI: 0.072-1.015), 2.888 (95% CI: 0.911-9.157), 13.674 (95% CI: 3.480-53.736), and 20.509 (95% CI: 6.674-63.019). The optimal cutoff value of FPG in early pregnancy for GDM prediction was 4.7 mmol/L with an area under the curve of 0.752, the risk of GDM significantly increased with FPG levels ≥4.7 mmol/L in early pregnancy across all pregnant women ( OR=17.356, 95% CI: 13.757-21.896, P<0.001). Conclusions:In the singleton pregnancy women with FPG levels in early pregnancy ≤5.6 mmol/L, FPG in early pregnancy is an independent risk factor for the occurrence of GDM; for pregnant women stratified by the same pre-BMI, the risk of developing GDM increases progressively with the rise of FPG in early pregnancy. FPG in early pregnancy has a certain value in predicting the occurrence of GDM.

Objective To investigate the regulatory effect of Jianpi Huayu Prescription(Ginseng Radix et Rhizoma,Poria,Atractylodis Macrocephalae Rhizoma,Salviae Miltiorrhizae Radix et Rhizoma,etc.)on epithelial-mesenchymal transition(EMT)and angiogenesis of hepatocellular carcinoma through TGF-β1/Smad7 pathway.Methods(1)Hep3B tumor-bearing mouse model was established by BALB/C-nu nude mice.The mice were randomly divided into control group and Jianpi Huayu Prescription low-,medium-and high-dose groups(3.844,7.689,15.378 g·kg-1·d-1),with five mice in each group.Intragastric administration was performed once a day for 21 days.(2)Hep3B cells were divided into blank group,model group(10 ng·mL-1 TGF-β1),low-concentration group(10 ng·mL-1 TGF-β1+4 mg·mL-1 Jianpi Huayu Prescription),and high-concentration group(10 ng·mL-1 TGF-β1+6 mg·mL-1 Jianpi Huayu Prescription).After 48 hours of TGF-β1 induction,the cells were replaced with the corresponding concentration of Jianpi Huayu Prescription complete culture medium(0,4,6 mg·mL-1)and cultured for 24 hours.(3)HUVEC cells were divided into normal group,model group,Chinese medicine group,model plus Chinese medicine group.The cells in the normal group were cultured with conditioned medium without TGF-β1;the cells in the model group were cultured with conditioned medium containing TGF-β1.The cells in the Chinese medicine group were cultured in conditioned medium containing 4 mg·mL-1 Jianpi Huayu Prescription without TGF-β 1.The cells in the model plus Chinese medicine group were cultured with conditioned medium containing 4 mg·mL-1 Jianpi Huayu Prescription and TGF-β1.After 24 hours of continuous culture,the cells were collected for subsequent experiments.(4)The tumor mass index and tumor inhibition rate of subcutaneous transplantation tumor of Hep3B tumor-bearing nude mice were calculated.The expression of CD31 in subcutaneous xenografts of tumor-bearing nude mice was detected by immunofluorescence.The microvessel density of subcutaneous transplanted tumor in nude mice was detected by immunohistochemistry.The migration ability of Hep3B cells was detected by cell scratch test.Transwell assay was used to detect the invasion ability of Hep3B/HUVEC cells.The tube formation ability of HUVEC cells was detected.The expression levels of related proteins in subcutaneous transplanted tumors,Hep3B and HUVEC cells of tumor-bearing nude mice were detected by Western Blot.Results(1)Compared with the control group,the weight and tumor mass index of subcutaneous transplanted tumor in nude mice in the medium-and high-dose groups of Jianpi Huayu Prescription were significantly decreased(P＜0.01).The expression of CD31 and microvessel density in subcutaneous transplanted tumors of nude mice in low-,medium-and high-dose groups were significantly decreased(P＜0.05,P＜0.01),the protein expressions of VE-cadherin,EphA2 and N-cadherin were significantly down-regulated(P＜0.05,P＜0.01),and the protein expressions of E-cadherin and Smad7 was significantly up-regulated(P＜0.01).(2)Compared with the blank group,the relative migration rate of Hep3B cells in the model group was significantly increased(P＜0.05),and the number of invasive cells was significantly increased(P＜0.01).The protein expressions of Vimentin and N-cadherin were significantly up-regulated(P＜0.01),and the protein expressions of E-cadherin and Smad7 was significantly down-regulated(P＜0.01).Compared with the model group,the relative migration rate of Hep3B cells in the low-and high-concentration groups of Jianpi Huayu Prescription was significantly decreased(P＜0.01),and the number of invasive cells was significantly decreased(P＜0.01).The protein expressions of Vimentin and N-cadherin was significantly down-regulated(P＜0.01),and the protein expressions of E-cadherin and Smad7 were significantly up-regulated(P＜0.01).(3)Compared with the normal group,the number of tubular branching points formed by HUVEC cells in the model group was significantly increased(P＜0.01),the length of tubular branching was significantly increased(P＜0.01),and the number of invasive cells was significantly increased(P＜0.01).The protein expressions of VE-cadherin and EphA2 were significantly up-regulated(P＜0.01),and the protein expression of Smad7 was significantly down-regulated(P＜0.01).Compared with the model group,the number of tubular branching points formed by HUVEC cells in the model plus Chinese medicine group was significantly reduced(P＜0.01),the length of tubular branching was significantly shortened(P＜0.01),and the number of invasive cells was significantly reduced(P＜0.01).The protein expressions of VE-cadherin and EphA2 were significantly down-regulated(P＜0.01),and the protein expression of Smad7 was significantly up-regulated(P＜0.01).Conclusion Jianpi Huayu Prescription can significantly inhibit the growth,invasion and migration of hepatocellular carcinoma,which may be related to the regulation of EMT and angiogenesis mediated by TGF-β1/Smad7 pathway.

Objective:To further improve the understanding of paroxysmal nocturnal hemoglobinuria (PNH), we retrospectively analyzed and summarized the clinical characteristics, treatment status, and survival status of patients with PNH in Zhejiang Province.Methods:This study included 289 patients with PNH who visited 20 hospitals in Zhejiang Province. Their clinical characteristics, comorbidity, laboratory test results, and medications were analyzed and summarized.Results:Among the 289 patients with PNH, 148 males and 141 females, with a median onset age of 45 (16-87) years and a peak onset age of 20-49 years (57.8% ). The median lactic dehydrogenase (LDH) level was 1 142 (604-1 925) U/L. Classified by type, 70.9% (166/234) were classical, 24.4% (57/234) were PNH/bone marrow failure (BMF), and 4.7% (11/234) were subclinical. The main clinical manifestations included fatigue or weakness (80.8%, 235/289), dizziness (73.4%, 212/289), darkened urine color (66.2%, 179/272), and jaundice (46.2%, 126/270). Common comorbidities were hemoglobinuria (58.7% ), renal dysfunction (17.6% ), and thrombosis (15.0% ). Moreover, 82.3% of the patients received glucocorticoid therapy, 70.9% required blood transfusion, 30.7% used immunosuppressive agents, 13.8% received anticoagulant therapy, and 6.3% received allogeneic hematopoietic stem cell transplantation. The 10-year overall survival (OS) rate was 84.4% (95% CI 78.0% -91.3% ) . Conclusion:Patients with PNH are more common in young and middle-aged people, with a similar incidence rate between men and women. Common clinical manifestations include fatigue, hemoglobinuria, jaundice, renal dysfunction, and recurrent thrombosis. The 10-year OS of this group is similar to reports from other centers in China.