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 investigate long-term auditory changes and characteristics of Alport syndrome（AS） patients with different degrees of renal injury. Methods:Retrospectively analyzing clinical data of patients diagnosed AS from January 2007 to September 2022, including renal pathology, genetic detection and hearing examination. A long-term follow-up focusing on hearing and renal function was conducted. Results:This study included 70 AS patients, of which 33（25 males, 8 females, aged 3.4-27.8 years） were followed up, resulting in a loss rate of 52.9%.The follow-up period ranged from 1.1to 15.8 years, with 16 patients followed-up for over 10 years. During the follow-up, 10 patients presenting with hearing abnormalities at the time of diagnosis of AS had progressive hearing loss, and 3 patients with new hearing abnormalities were followed up, which appeared at 5-6 years of disease course. All of which were sensorineural deafness. While only 3 patients with hearing abnormalities among 13 patients received hearing aid intervention. Of these patients,7 developed end-stage renal disease（ESRD）, predominantly males （6/7）. The rate of long-term hearing loss was significantly different between ESRD group and non-ESRD group（P=0.013）. There was no correlation between the progression of renal disease and long-term hearing level（P>0.05）. kidney biopsies from 28 patients revealed varying degrees of podocyte lesion and uneven thickness of basement membrane. The severity of podocyte lesion was correlated with the rate of long-term hearing loss（P=0.048）, and there was no correlation with the severity of hearing loss（P>0.05）. Among 11 cases, theCOL4A5mutationwas most common （8 out of 11）, but there was no significant correlation between the mutation type and hearing phenotype（P>0.05）. Conclusion:AS patients exhibit progressive hearing loss with significant heterogeneity over the long-term.. THearing loss is more likely to occur 5-6 years into the disease course. Hearing abnormalities are closely related to renal disease status, kidney tissue pathology, and gene mutations, emphasizing the need for vigilant long-term hearing follow-up and early intervention.
Male ; Child ; Female ; Humans ; Nephritis, Hereditary/pathology* ; Retrospective Studies ; Kidney ; Deafness ; Hearing Loss/genetics* ; Kidney Failure, Chronic/pathology* ; Mutation

Tuberculosis （TB） and human immunodeficiency virus infection / acquired immune deficiency syndrome （HIV/AIDS） are both serious global public health threats. Early detection of infected persons and/or patients through TB/HIV bi-directional screening is crucial for prevention and control strategy in China and globally. In recent years， with the promotion and application of new TB and HIV detection technologies worldwide， TB/HIV bi-directional screening technologies and strategies have made remarkable changes. This expert consensus introduces the significance and challenges of TB/HIV bi-directional screening， summarizes important progress of research and applications， and makes recommendations on screening measures and procedures to further strengthen TB/HIV bi-directional screening in China.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To investigate the change of collagen fibers in locally recurrent esophageal squamous cell carcinoma after radical chemoradiotherapy and the discrepancy of adverse effects and survival outcomes among groups with different salvage treatments, provide references for the options of salvage therapy.Methods:Medical records of 137 patients with esophageal squamous cell carcinoma who received radical chemoradiotherapy and had local recurrence admitted to Cancer Center of Renmin Hospital of Wuhan University from January 2015 to September 2022 were retrospectively collected. The expression of collagen fibers in paraffin samples of cases with different recurrence time was determined by Masson staining, and the differences of the average optical density were calculated. According to the salvage treatment after local recurrence, all cases were divided into the salvage surgery group, second-course chemoradiotherapy group and immunochemotherapy group. The differences of survival outcomes and incidence rates of esophageal tracheal fistula, hemorrhage, pericardial effusion, radiation pneumonitis, radiation esophagitis were analyzed among the three groups. The differences of survival rates were analyzed by Kaplan-Meier method and compared by log-rank test among groups.Results:The expression of collagen fibers in recurrent esophageal squamous cell carcinoma was significantly higher than that in primary esophageal squamous cell carcinoma. Collagen fiber expression was gradually down-regulated with the prolongation of recurrence time. The expression of collagen fibers in recurrent cases after 7 years was similar to that of primary esophageal squamous cell carcinoma. The 1-, 2- and 3-year survival rates of patients in the salvage surgery group, the second-course chemoradiotherapy group and the immunochemotherapy group were 47%, 30%, 20%; 50%, 27%, 15% and 72.5%, 50%, 50%, respectively; Immunochemotherapy was more effective in salvage treatment for recurrent esophageal squamous cell carcinoma, but there was no statistical difference.Conclusions:Collagen fibers are abundant in recurrent esophageal squamous cell carcinoma after radical chemoradiotherapy. With prolongation of recurrent interval, the expression of collagen fibers is down-regulated. The survival outcomes of patients in the immunochemotherapy group, salvage surgery group and second-course chemoradiotherapy group were comparable.

Objective:To investigate the impacts of fatty acid binding protein 4(FABP4)silencing on endoplasmic reticulum stress(ERS)and insulin resistance(IR)in gestational diabetes mellitus(GDM)rats by regulating protein kinase R-like endoplasmic reticulum kinase(PERK)/eukaryotic initiation factor 2α(eIF2α)/transcription factor 4(ATF4)/C/EBP homologous protein(CHOP)signaling pathway.Methods:GDM rat model was established by intraperitoneal injection of streptozotocin(STZ).Rats were injected with FABP4 siRNA plasmid(si-FABP4),negative control plasmid(NC)and PERK activator(CCT020312)via tail vein,and were randomly grouped into Normal group,GDM group,GDM+NC group,GDM+si-FABP4 group and GDM+si-FABP4+CCT020312 group.The levels of FABP4,blood lipids,inflammatory markers and oxidative stress markers in pancreatic tissue were detected,the expres-sions of PERK/eIF2α/ATF4/CHOP signaling pathway-related proteins in pancreatic tissue were detected.HTR-8/SVneo cells were divided into 5 groups:Control group,high glucose(HG)group,HG+NC group,HG+si-FABP4 group,HG+si-FABP4+CCT020312 group.After 24 h,the expressions of FABP4 and PERK/eIF2α/ATF4/CHOP signaling pathway related proteins were detected.Results:Compared with Normal group,the level of FABP4 in the serum and pancreatic tissue of the GDM group were obviously up-regu-lated(P<0.05).FABP4 silencing obviously reduced FBG and IR,decreased the levels of blood lipids,CRP,TNF-α,IL-6 and MDA,and increased the levels of SOD and CAT(P<0.05).Furthermore,FABP4 silencing attenuated pancreatic and placental tissue damages.After CCT020312 up-regulated the phosphorylation levels of PERK and eIF2α and the protein expressions of ATF4 and CHOP,the inhibitory effects of FABP4 silencing on IR,inflammation,oxidative stress,and pancreatic and placental damages in GDM rats were reversed(P<0.05).FABP4 was up-regulated in HTR-8/SVneo cells induced by HG,and silencing FABP4 inhibited the protein ex-pression of the PERK/eIF2α/ATF4/CHOP pathway,while CCT020312 reversed this change(P<0.05).Conclusion:FABP4 silencing improves IR and ERS in GDM rats by inhibiting inflammation and oxidative stress,and the mechanism is related to the inhibition of PERK/eIF2α/ATF4/CHOP signaling pathway.

Objective:To investigate two cases of rare pathogenic genes,initiation codon mutations in HBA2 gene,combined with Southeast Asian deletion and their family members to understand the relationship of HBA2:c.2T＞C and HBA2:c.2delT mutations with clinical phenotype.Methods:The peripheral blood of family members was obtained for blood cell analysis and capillary electrophoresis hemoglobin analysis.Gap-PCR and reverse dot blotting(RDB)were used to detect common types of mutations in α-thalassaemia gene.Sanger sequencing was used to analyze HBA1 and HBA2 gene sequence.Results:Two proband genotypes were identified as--SEA/αα with HBA2:c.2T＞C and--SEA/αα with HBA2:c.2delT.HBA2:c.2T＞C/WT and HBA2:c.2delT/WT was detected in family members.They all presented with microcytic hypochromic anemia.Conclusion:When HBA2:c.2T＞C and HBA2:c.2delT are heterozygous that can lead to static α-thalassemia phenotype,and when combined with mild α-thalassemia,they can lead to the clinical manifestations of hemoglobin H disease.This study provides a basis for genetic counseling.

Objective:To perform molecular diagnosis and pedigree analysis for one case with α-thalassemia who does not conform to the genetic laws,and explore the effects of a newly discovered rare mutation(HBA2:c.*12G＞A)on clinical phenotypes.Methods:Blood samples of the proband and her family members were collected for blood routine analysis,and the hemoglobin components were analyzed by capillary electrophoresis.The common α-and β-globin gene loci in Chinese population were detected by conventional techniques(Gap-PCR,RDB-PCR).The α-globin gene sequences(HBA1,HBA2)were analyzed by Sanger sequencing.Results:By analyzing the test results of proband and her family members,the genotype of the proband was-α3,7/HBA2:c.*12G＞A,her father was HBA2:c.*12G＞A heterozygous mutation carrier.Conclusion:This study identifies a rare α-globin gene mutation(HBA2:c.*12G＞A)that has not been reported before.It is found that heterozygous mutation carriers present with static α-thalassemia.

Objective:To investigate the genotype,mutation type,and ethnic distribution characteristics of thalassemia in the population of Hechi area,Guangxi,and to provide a reference basis for prevention and control of thalassemia and eugenic counseling in the region.Methods:Gap-polymerase chain reaction(gap-PCR)and reverse dot blot(RDB)were used for genetic testing on suspected thalassemia persons,and the results were analyzed.Results:Among 29 136 samples,a total of 17 016(58.40％)positive samples for thalassemia genes were detected,with a higher detection rate in males than in females(X2=49.917,P＜0.001).The detection rates of thalassemia genes were significant different among Zhuang,Han,Yao,Mulao,and Maonan ethnic groups(x2=546.121,P＜0.001).The α-thalassemia genotypes were mainly--SEA/αα(16.67％),-α3.7/αα(8.90％),αCSα/αα(6.00％).Additionally,four rare genotypes were detected,including--THAI/αα(47 cases),HKαα/αα(2 cases),--SEA/-α21.9(2 cases),and--THAI/αcsα(1 case).The β-thalassemia genotypes were mainly βCD17/βN(7.49％),βCD41-42/βN(6.70％),βCD71-72/βN(0.44％).108 cases of moderate and severeβ-thalassemia were detected,of which 81 cases had a history of blood transfusion,the transfusion frequency of 60 cases was more than 10 times/year,and 10 cases received bone marrow transplantation.Conclusion:Thalassemia in Hechi area is predominantly deletion type--SEA/αα,the detection rate of thalassemia in ethnic minorities is higher than that in Han population.In this area,moderate and severe β-thalassemia have certain incidence,these patients mostly need regular blood transfusion and iron removal treatment,and very few patients have received bone marrow transplantation.This study provides a certain reference basis for prevention and control of thalassemia and eugenic counseling in the region.

Purpose: The risk stratification of pediatric anaplastic large cell lymphoma (ALCL) has not been standardized. In this study, new risk factors were included to establish a new risk stratification system for ALCL, and its feasibility in clinical practice was explored. Materials and Methods: On the basis of the non-Hodgkin’s lymphoma Berlin–Frankfurt–Munster 95 (NHL-BFM-95) protocol, patients with minimal disseminated disease (MDD), high-risk tumor site (multiple bone, skin, liver, and lung involvement), and small cell/lymphohistiocytic (SC/LH) pathological subtype were enrolled in risk stratification. Patients were treated with a modified NHL-BFM-95 protocol combined with an anaplastic lymphoma kinase inhibitor or vinblastine (VBL). Results: A total of 136 patients were enrolled in this study. The median age was 8.8 years. The 3-year event-free survival (EFS) and overall survival of the entire cohort were 77.7% (95% confidence interval [CI], 69.0% to 83.9%) and 92.3% (95% CI, 86.1% to 95.8%), respectively. The 3-year EFS rates of low-risk group (R1), intermediate-risk group (R2), and high-risk group (R3) patients were 100%, 89.5% (95% CI, 76.5% to 95.5%), and 67.9% (95% CI, 55.4% to 77.6%), respectively. The prognosis of patients with MDD (+), stage IV cancer, SC/LH lymphoma, and high-risk sites was poor, and the 3-year EFS rates were 45.3% (95% CI, 68.6% to 19.0%), 65.7% (95% CI, 47.6% to 78.9%), 55.7% (95% CI, 26.2% to 77.5%), and 70.7% (95% CI, 48.6% to 84.6%), respectively. At the end of follow-up, one of the five patients who received maintenance therapy with VBL relapsed, and seven patients receiving anaplastic lymphoma kinase inhibitor maintenance therapy did not experience relapse. Conclusion This study has confirmed the poor prognostic of MDD (+), high-risk site and SC/LH, but patients with SC/LH lymphoma and MDD (+) at diagnosis still need to receive better treatment (ClinicalTrials.gov number, NCT03971305).